1 Sample characteristics by Remission

compareGroups::descrTable(Remission~.
                          , Biok_vert_df_raw, 
                          hide.no = '0', 
                          show.p.overall = FALSE,
                          include.label = TRUE)
## Warning in compareGroups.fit(X = X, y = y, include.label = include.label, :
## Variables 'Sample_ID' have been removed since some errors occurred
## 
## --------Summary descriptives table by 'Remission'---------
## 
## ______________________________________________________________________ 
##                                              No remission   Remitter   
##                                                  N=77        N=138     
## ¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯ 
## sex:                                                                   
##     male                                      23 (29.9%)   56 (40.6%)  
##     female                                    54 (70.1%)   82 (59.4%)  
## age                                          43.7 (13.9)  44.5 (12.4)  
## BMI                                          28.6 (6.46)  28.7 (5.01)  
## race:                                                                  
##     asian                                     0 (0.00%)    3 (2.17%)   
##     black                                     3 (3.90%)    1 (0.72%)   
##     white                                     74 (96.1%)  134 (97.1%)  
## patientno                                    1000 (1365)  1045 (1377)  
## Site_Location:                                                         
##     Johns Hopkins                             7 (9.09%)    15 (10.9%)  
##     Univeristy of Michigan                    24 (31.2%)   45 (32.6%)  
##     Mayo Clinic                               39 (50.6%)   72 (52.2%)  
##     Pine Rest                                 7 (9.09%)    6 (4.35%)   
## infusionno:                                                            
##     BL                                        26 (33.8%)   46 (33.3%)  
##     1st                                       25 (32.5%)   46 (33.3%)  
##     3rd                                       26 (33.8%)   46 (33.3%)  
## Blood_Draw_Event:                                                      
##     Acute Infusion #1 Baseline 100            18 (23.4%)   30 (21.7%)  
##     Acute Infusion #1 Baseline 40             8 (10.4%)    16 (11.6%)  
##     Acute Infusion #1 Stop 100                17 (22.1%)   30 (21.7%)  
##     Acute Infusion #1 Stop 40                 8 (10.4%)    16 (11.6%)  
##     Acute Infusion #3 Stop 100                11 (14.3%)   16 (11.6%)  
##     Acute Infusion #3 Stop 40                 15 (19.5%)   30 (21.7%)  
## Batch_Number                                 3.34 (1.74)  3.62 (1.71)  
## BSS_Score                                    6.51 (7.29)  3.43 (6.12)  
## MADRS_Score                                  21.8 (8.46)  14.4 (10.8)  
## TRP_nM                                       26255 (5646) 25152 (6045) 
## five_HT_nM                                    302 (362)    154 (215)   
## KYN_nM                                        940 (238)    914 (244)   
## three_HK_nM                                  16.1 (6.15)  16.4 (8.09)  
## KYNA_nM                                      19.0 (7.09)  20.0 (7.80)  
## PIC_nM                                       19.2 (9.98)  19.3 (15.2)  
## Quin_nM                                       141 (39.6)   150 (44.5)  
## AA_nM                                        5.28 (1.79)  6.39 (3.62)  
## KYN_TRP_ratio                                0.04 (0.01)  0.04 (0.01)  
## KYN_SER_ratio                                30.6 (74.7)  34.8 (71.7)  
## QUIN_PIC_ratio                               8.57 (3.64)  9.50 (4.77)  
## QUIN_KYNA_ratio                              8.20 (3.51)  8.16 (3.07)  
## threeHK_KYN_ratio                            0.02 (0.00)  0.02 (0.01)  
## threeHK_KYNA_ratio                           0.95 (0.53)  0.88 (0.37)  
## IL1B_pg_mL                                   0.32 (0.43)  0.26 (0.48)  
## IL1B_pg_mL_LLOD                              0.34 (0.15)  0.34 (0.21)  
## IL2_pg_mL                                    2.89 (10.1)  0.43 (0.27)  
## IL2_pg_mL_LLOD                               1.98 (8.39)  0.34 (0.27)  
## IL4_pg_mL                                    0.09 (0.03)  0.09 (0.03)  
## IL4_pg_mL_LLOD                               0.09 (0.03)  0.09 (0.03)  
## IL6_pg_mL                                    1.13 (0.69)  1.00 (0.51)  
## IL8_pg_mL                                    4.18 (1.82)  4.48 (1.57)  
## IL10_pg_mL                                   0.39 (0.14)  0.78 (2.44)  
## IL12p70_pg_mL                                0.46 (0.25)   34.3 (233)  
## IL12p70_pg_mL_LLOD                           0.46 (0.25)   34.0 (232)  
## IL13_pg_mL                                   3.62 (0.74)  5.93 (14.5)  
## IL13_pg_mL_LLOD                              3.62 (0.74)  5.81 (14.3)  
## TNFa_pg_mL                                   1.37 (0.28)  1.48 (0.54)  
## IFNy_pg_mL                                   6.78 (5.63)  7.12 (5.49)  
## CRP_ng_mL                                    4004 (6567)  2141 (3292)  
## NIC_nM                                        113 (568)   2.29 (5.43)  
## NIC_nM_LLOD                                   113 (568)   2.29 (5.43)  
## NTA_nM                                        297 (152)    313 (155)   
## SAA_ng_mL                                    3187 (2304)  2699 (2063)  
## VCAM_1_ng_mL                                  310 (68.5)   309 (68.4)  
## ICAM_1_ng_mL                                  325 (86.5)   300 (79.3)  
## ¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯

2 Sample characteristics (biomarkers only) in whole group

compareGroups::descrTable(~.
                          , Biok_biomarkers_df, 
                          hide.no = '0', 
                          show.p.overall = FALSE,
                          include.label = TRUE)
## 
## --------Summary descriptives table ---------
## 
## ___________________________________ 
##                       [ALL]      N  
##                       N=218         
## ¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯ 
## TRP_nM             25449 (5942) 218 
## five_HT_nM          205 (284)   218 
## KYN_nM              917 (244)   218 
## three_HK_nM        16.2 (7.44)  218 
## KYNA_nM            19.5 (7.68)  218 
## PIC_nM             19.2 (13.5)  218 
## Quin_nM             146 (43.0)  218 
## AA_nM              5.95 (3.12)  218 
## KYN_TRP_ratio      0.04 (0.01)  218 
## KYN_SER_ratio      33.2 (72.1)  218 
## QUIN_PIC_ratio     9.14 (4.39)  218 
## QUIN_KYNA_ratio    8.30 (3.40)  218 
## threeHK_KYN_ratio  0.02 (0.01)  218 
## threeHK_KYNA_ratio 0.91 (0.44)  218 
## IL1B_pg_mL         0.28 (0.47)  42  
## IL1B_pg_mL_LLOD    0.34 (0.19)  218 
## IL2_pg_mL          1.27 (6.00)  152 
## IL2_pg_mL_LLOD     0.92 (5.03)  218 
## IL4_pg_mL          0.09 (0.03)  217 
## IL4_pg_mL_LLOD     0.09 (0.03)  218 
## IL6_pg_mL          1.04 (0.58)  218 
## IL8_pg_mL          4.36 (1.66)  218 
## IL10_pg_mL         0.64 (1.95)  218 
## IL12p70_pg_mL       21.8 (186)  217 
## IL12p70_pg_mL_LLOD  21.7 (185)  218 
## IL13_pg_mL         5.07 (11.5)  215 
## IL13_pg_mL_LLOD    5.01 (11.4)  218 
## TNFa_pg_mL         1.44 (0.46)  218 
## IFNy_pg_mL         6.97 (5.50)  218 
## CRP_ng_mL          2835 (4774)  218 
## NIC_nM              41.4 (340)  218 
## NIC_nM_LLOD         41.4 (340)  218 
## NTA_nM              306 (153)   218 
## SAA_ng_mL          2870 (2145)  218 
## VCAM_1_ng_mL        309 (67.9)  218 
## ICAM_1_ng_mL        308 (82.3)  218 
## ¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯

3 Sample missingness counts by variable

missingTable(compareGroups(infusionno~., data=Biok_vert_df_raw))
## Warning in compareGroups.fit(X = X, y = y, include.label = include.label, :
## Variables 'Sample_ID' have been removed since some errors occurred
## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero

## Warning in cor(as.integer(x), as.integer(y)): the standard deviation is zero
## 
## --------Missingness table by 'infusionno'---------
## 
## _____________________________________________________________ 
##                        BL        1st        3rd     p.overall 
##                       N=73       N=72       N=73              
## ¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯ 
## sex                0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## age                0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## BMI                0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## race               0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## patientno          0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## Site_Location      0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## Blood_Draw_Event   0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## Sample_ID          0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## Batch_Number       0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## BSS_Score          0 (0.00%)  2 (2.78%)  3 (4.11%)    0.291   
## MADRS_Score        0 (0.00%)  0 (0.00%)  1 (1.37%)    1.000   
## Remission          1 (1.37%)  1 (1.39%)  1 (1.37%)    1.000   
## TRP_nM             0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## five_HT_nM         0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## KYN_nM             0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## three_HK_nM        0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## KYNA_nM            0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## PIC_nM             0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## Quin_nM            0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## AA_nM              0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## KYN_TRP_ratio      0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## KYN_SER_ratio      0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## QUIN_PIC_ratio     0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## QUIN_KYNA_ratio    0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## threeHK_KYN_ratio  0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## threeHK_KYNA_ratio 0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## IL1B_pg_mL         57 (78.1%) 61 (84.7%) 58 (79.5%)   0.565   
## IL1B_pg_mL_LLOD    0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## IL2_pg_mL          28 (38.4%) 20 (27.8%) 18 (24.7%)   0.168   
## IL2_pg_mL_LLOD     0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## IL4_pg_mL          0 (0.00%)  1 (1.39%)  0 (0.00%)    0.330   
## IL4_pg_mL_LLOD     0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## IL6_pg_mL          0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## IL8_pg_mL          0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## IL10_pg_mL         0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## IL12p70_pg_mL      0 (0.00%)  1 (1.39%)  0 (0.00%)    0.330   
## IL12p70_pg_mL_LLOD 0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## IL13_pg_mL         1 (1.37%)  2 (2.78%)  0 (0.00%)    0.327   
## IL13_pg_mL_LLOD    0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## TNFa_pg_mL         0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## IFNy_pg_mL         0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## CRP_ng_mL          0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## NIC_nM             0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## NIC_nM_LLOD        0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## NTA_nM             0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## SAA_ng_mL          0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## VCAM_1_ng_mL       0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## ICAM_1_ng_mL       0 (0.00%)  0 (0.00%)  0 (0.00%)      .     
## ¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯

4 Outcome inspection - Depressive severity (MADRS_Score)

mu <- ddply(Biok_vert_df, "infusionno", summarise, grp.mean=mean(MADRS_Score))
ggplot(Biok_vert_df, aes(x=MADRS_Score))+
  geom_histogram(color="black", fill="orange")+
  facet_grid(infusionno ~ .)+
  theme(legend.position="none")+
  geom_vline(data=mu, aes(xintercept=grp.mean, color=infusionno),linetype="dashed")+
  labs(title="Distribution of MADRS total score by Ketamine infusion (timepoint)", x="Depressive severity (MADRS)", y="Count")+
  theme_gray()
## `stat_bin()` using `bins = 30`. Pick better value with `binwidth`.
## Warning: Removed 1 rows containing non-finite values (stat_bin).
## Warning: Removed 1 rows containing missing values (geom_vline).

ggplot(Biok_vert_df, aes(x=MADRS_Score,fill=Remission))+
  geom_histogram(color="black")+
  facet_grid(infusionno ~ .)+
  theme(legend.position="none")+
  geom_vline(data=mu, aes(xintercept=grp.mean, color=infusionno),linetype="dashed")+
  labs(title="Distribution of MADRS total score by Ketamine infusion (timepoint)", x="Depressive severity (MADRS)", y="Count")+
  theme_gray()
## `stat_bin()` using `bins = 30`. Pick better value with `binwidth`.
## Warning: Removed 1 rows containing non-finite values (stat_bin).

## Warning: Removed 1 rows containing missing values (geom_vline).

Biok_vert_df %>% 
    filter(!is.na(Remission)) %>%
ggplot(aes(x = as.numeric(infusionno), y = MADRS_Score)) + 
  # geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 ) +
  ggtitle("Depression by Ketamine Infusion (timeseries)")+
  geom_line(aes(group=patientno, color=Remission)) +
  geom_point(aes(color=Remission))+
  labs(x = "infusionno") +
  scale_x_continuous(breaks = 1:3)

my_comparisons <- list( c("BL", "1st"), c("1st", "3rd"), c("BL", "3rd") )

Biok_vert_df %>%
  filter(!is.na(Remission)) %>%
ggplot(aes(x = infusionno, y = MADRS_Score))+
  geom_boxplot(aes(fill=Remission))+
 geom_jitter(width = 0.1)+ 
  facet_wrap(~Remission)+
  theme_bw()+
  theme(legend.position = "none")+
  ggpubr::stat_compare_means(method="t.test", ref.group="BL", comparisons=my_comparisons)+
  ggpubr::stat_compare_means(method="anova", label.y=70)

Biok_vert_df %>%
  filter(!is.na(Remission)) %>%
ggplot(aes(x = Remission, y = MADRS_Score))+
  geom_boxplot(aes(fill=Remission))+
 geom_jitter(width = 0.1)+ 
  facet_wrap(~infusionno)+
  theme_bw()+
  theme(legend.position = "none")+
  ggpubr::stat_compare_means(method="t.test", label.y=50)

5 Outcome inspection - suicidality (BSS_Score)

mu <- ddply(Biok_vert_df, "infusionno", summarise,grp.mean=mean(log(BSS_Score)))
ggplot(Biok_vert_df, aes(x=log(BSS_Score)))+
  geom_histogram(color="black", fill="orange")+
  facet_grid(infusionno ~ .)+
  theme(legend.position="none")+
  geom_vline(data=mu, aes(xintercept=grp.mean, color=infusionno),linetype="dashed")+
  labs(title="Distribution of BSS total score by Ketamine infusion (timepoint)", x="Suicidal severity (BSS)", y="Count")+
  theme_gray()
## `stat_bin()` using `bins = 30`. Pick better value with `binwidth`.
## Warning: Removed 112 rows containing non-finite values (stat_bin).
## Warning: Removed 2 rows containing missing values (geom_vline).

Biok_vert_df %>% 
    filter(!is.na(Remission)) %>%
ggplot(aes(x = as.numeric(infusionno), y = BSS_Score)) + 
  # geom_boxplot(aes(group = infusionno), lwd=1.25, fatten=1, outlier.shape = "triangle", outlier.size = 3 ) +
  ggtitle("Suicidality by Ketamine Infusion (timeseries)")+
  geom_line(aes(group=patientno, color=Remission)) +
  geom_point(aes(color=Remission))+
  labs(x = "infusionno") +
  scale_x_continuous(breaks = 1:3)
## Warning: Removed 4 row(s) containing missing values (geom_path).
## Warning: Removed 5 rows containing missing values (geom_point).

Biok_vert_df %>%
  filter(!is.na(Remission)) %>%
ggplot(aes(x = infusionno, y = BSS_Score))+
  geom_boxplot(aes(fill=Remission))+
 geom_jitter(width = 0.1)+ 
  facet_wrap(~Remission)+
  theme_bw()+
  theme(legend.position = "none")+
  ggpubr::stat_compare_means(method="t.test", ref.group="BL", comparisons=my_comparisons)+
  ggpubr::stat_compare_means( label.y=40)
## Warning: Removed 5 rows containing non-finite values (stat_boxplot).
## Warning: Removed 5 rows containing non-finite values (stat_signif).
## Warning: Removed 5 rows containing non-finite values (stat_compare_means).
## Warning: Removed 5 rows containing missing values (geom_point).

Biok_vert_df %>%
  filter(!is.na(Remission)) %>%
ggplot(aes(x = Remission, y = BSS_Score))+
  geom_boxplot(aes(fill=Remission))+
 geom_jitter(width = 0.1)+ 
  facet_wrap(~infusionno)+
  theme_bw()+
  theme(legend.position = "none")+
  ggpubr::stat_compare_means( label.y=30)
## Warning: Removed 5 rows containing non-finite values (stat_boxplot).
## Warning: Removed 5 rows containing non-finite values (stat_compare_means).
## Warning: Removed 5 rows containing missing values (geom_point).

6 Univariate screen (whole group, Pearson’s matrix)

Bx_spearmans<- Biok_vert_df %>% 
  select("age", "BMI","MADRS_Score", "BSS_Score",
         all_of(Biok_biomarkers)) %>% 
  select(!starts_with("IL1"))%>% 
  select(!starts_with("IL2")) %>% 
  select(!starts_with("IL4")) %>% 
  select(!contains("LLOD"))

mydata.cor = cor(Bx_spearmans, method = c("pearson"), use="complete.obs")
matrix<-Hmisc::rcorr(as.matrix(mydata.cor))
corrplot::corrplot(mydata.cor, 
                   addCoef.col = 'black', 
                   p.mat=matrix$P,
                   insig="blank", 
                   order="hclust",
                   method="color", 
                   type="upper", 
                   diag=FALSE, 
                   number.cex=0.8, 
                   na.label.col = "gray",
                   addgrid.col=TRUE,
                   tl.col = 'red',
                   tl.srt = 45,
                   title="Pearson's matrix of age, BMI, and log transformed biomarkers (whole sample)")

7 Model 1: Biomarker by Remission:infusionno

8 Model 1a (clmm): ordinal regressions for IL1B

#IL1B

rlmer_IL1B<-ordinal::clmm(as.factor(IL1B_pg_mL)~sex+age+BMI+Remission*infusionno+(1|patientno), data=Biok_vert_df,nAGQ=10)
## Warning: Using formula(x) is deprecated when x is a character vector of length > 1.
##   Consider formula(paste(x, collapse = " ")) instead.
pairwise_remission<-emmeans(rlmer_IL1B, pairwise~Remission|infusionno)
## Note: Use 'contrast(regrid(object), ...)' to obtain contrasts of back-transformed estimates
pairwise_remission$contrasts
## infusionno = BL:
##  contrast                estimate   SE  df z.ratio p.value
##  No remission - Remitter     2.14 1.79 Inf   1.196  0.2315
## 
## infusionno = 1st:
##  contrast                estimate   SE  df z.ratio p.value
##  No remission - Remitter    -1.69 2.23 Inf  -0.757  0.4491
## 
## infusionno = 3rd:
##  contrast                estimate   SE  df z.ratio p.value
##  No remission - Remitter     0.98 1.70 Inf   0.575  0.5651
## 
## Results are averaged over the levels of: sex 
## Note: contrasts are still on the as.factor scale
pairwise_remission<-emmeans(rlmer_IL1B, pairwise~infusionno|Remission)
## Note: Use 'contrast(regrid(object), ...)' to obtain contrasts of back-transformed estimates
pairwise_remission$contrasts
## Remission = No remission:
##  contrast  estimate    SE  df z.ratio p.value
##  BL - 1st    1.8590 2.118 Inf   0.878  0.6544
##  BL - 3rd   -0.0128 1.361 Inf  -0.009  1.0000
##  1st - 3rd  -1.8717 2.028 Inf  -0.923  0.6257
## 
## Remission = Remitter:
##  contrast  estimate    SE  df z.ratio p.value
##  BL - 1st   -1.9737 1.121 Inf  -1.761  0.1830
##  BL - 3rd   -1.1767 0.941 Inf  -1.251  0.4234
##  1st - 3rd   0.7970 1.106 Inf   0.721  0.7513
## 
## Results are averaged over the levels of: sex 
## Note: contrasts are still on the as.factor scale 
## P value adjustment: tukey method for comparing a family of 3 estimates

9 Model 1: ordinal regressions for IL2

Note: error for IL2 model “cannot compute vcov: Hessian is not positive”

10 Model 2: Depression by biomarker:infusionno

Varnames_bx<-Biok_vert_df %>% 
  dplyr::select(-all_of(vars_demo),
                -all_of(vars_tx),
                -all_of(vars_cx),
                vars_KP,
                vars_inflam,
                vars_vasc) %>% names()
## Note: Using an external vector in selections is ambiguous.
## ℹ Use `all_of(vars_KP)` instead of `vars_KP` to silence this message.
## ℹ See <https://tidyselect.r-lib.org/reference/faq-external-vector.html>.
## This message is displayed once per session.
## Note: Using an external vector in selections is ambiguous.
## ℹ Use `all_of(vars_inflam)` instead of `vars_inflam` to silence this message.
## ℹ See <https://tidyselect.r-lib.org/reference/faq-external-vector.html>.
## This message is displayed once per session.
## Note: Using an external vector in selections is ambiguous.
## ℹ Use `all_of(vars_vasc)` instead of `vars_vasc` to silence this message.
## ℹ See <https://tidyselect.r-lib.org/reference/faq-external-vector.html>.
## This message is displayed once per session.
model2<-list()
model2_nobmi<-list()
emtrends_mod2<-list()
emtrend_contrasts<-list()
emtrend_confint<-list()

for (x in Varnames_bx){
    
    mod2<-rlmer(substitute(MADRS_Score~age+sex+BMI+i*infusionno+(1|patientno)+(1|Site_Location), list(i=as.name(x))), data=Biok_vert_df)
    # model2[[x]]<-summary(mod2)$coefficients
    emtrend<-emtrends(mod2, pairwise~infusionno, x)
      emtrend_contrasts[[x]]<-emtrend$contrasts
      emtrend_confint[[x]]<-confint(emtrend)
    
    # mod2_nobmi<-rlmer(substitute(MADRS_Score~age+sex+i*infusionno+(1|patientno)+(1|Site_Location), list(i=as.name(x))), data=Biok_vert_df)
    # model2_nobmi[[x]]<-summary(mod2_nobmi)$coefficients
    
}
## Warning: Some predictor variables are on very different scales: consider
## rescaling

## Warning: Some predictor variables are on very different scales: consider
## rescaling

## Warning: Some predictor variables are on very different scales: consider
## rescaling

## Warning: Some predictor variables are on very different scales: consider
## rescaling

## Warning: Some predictor variables are on very different scales: consider
## rescaling
emtrend_contrasts
## $TRP_nM
##  contrast   estimate       SE  df z.ratio p.value
##  BL - 1st  -0.000180 0.000185 Inf  -0.973  0.5940
##  BL - 3rd  -0.000244 0.000187 Inf  -1.303  0.3932
##  1st - 3rd -0.000064 0.000186 Inf  -0.343  0.9372
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $five_HT_nM
##  contrast  estimate      SE  df z.ratio p.value
##  BL - 1st   -0.0029 0.00370 Inf  -0.785  0.7122
##  BL - 3rd   -0.0107 0.00373 Inf  -2.866  0.0116
##  1st - 3rd  -0.0078 0.00399 Inf  -1.955  0.1235
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $KYN_nM
##  contrast  estimate      SE  df z.ratio p.value
##  BL - 1st  -0.00469 0.00450 Inf  -1.040  0.5514
##  BL - 3rd  -0.00611 0.00441 Inf  -1.385  0.3486
##  1st - 3rd -0.00142 0.00461 Inf  -0.309  0.9487
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $three_HK_nM
##  contrast  estimate    SE  df z.ratio p.value
##  BL - 1st   -0.0663 0.134 Inf  -0.496  0.8733
##  BL - 3rd   -0.1336 0.145 Inf  -0.921  0.6272
##  1st - 3rd  -0.0673 0.160 Inf  -0.421  0.9071
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $KYNA_nM
##  contrast  estimate    SE  df z.ratio p.value
##  BL - 1st   -0.1183 0.142 Inf  -0.835  0.6814
##  BL - 3rd   -0.0803 0.128 Inf  -0.627  0.8054
##  1st - 3rd   0.0380 0.149 Inf   0.256  0.9646
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $PIC_nM
##  contrast  estimate    SE  df z.ratio p.value
##  BL - 1st   -0.2443 0.109 Inf  -2.248  0.0634
##  BL - 3rd   -0.0939 0.090 Inf  -1.044  0.5491
##  1st - 3rd   0.1503 0.129 Inf   1.164  0.4746
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $Quin_nM
##  contrast  estimate     SE  df z.ratio p.value
##  BL - 1st   0.00363 0.0262 Inf   0.139  0.9895
##  BL - 3rd   0.01751 0.0251 Inf   0.698  0.7646
##  1st - 3rd  0.01387 0.0258 Inf   0.537  0.8531
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $AA_nM
##  contrast  estimate    SE  df z.ratio p.value
##  BL - 1st    -0.455 0.334 Inf  -1.361  0.3616
##  BL - 3rd    -0.078 0.401 Inf  -0.194  0.9794
##  1st - 3rd    0.377 0.440 Inf   0.856  0.6683
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $KYN_TRP_ratio
##  contrast  estimate  SE  df z.ratio p.value
##  BL - 1st     -59.8 111 Inf  -0.536  0.8534
##  BL - 3rd     -91.7 110 Inf  -0.835  0.6813
##  1st - 3rd    -31.9 107 Inf  -0.298  0.9523
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $KYN_SER_ratio
##  contrast  estimate     SE  df z.ratio p.value
##  BL - 1st   0.02829 0.0174 Inf   1.628  0.2339
##  BL - 3rd   0.02675 0.0130 Inf   2.052  0.1001
##  1st - 3rd -0.00153 0.0176 Inf  -0.087  0.9958
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $QUIN_PIC_ratio
##  contrast  estimate    SE  df z.ratio p.value
##  BL - 1st    0.3292 0.254 Inf   1.299  0.3959
##  BL - 3rd    0.2846 0.246 Inf   1.157  0.4793
##  1st - 3rd  -0.0447 0.245 Inf  -0.182  0.9819
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $QUIN_KYNA_ratio
##  contrast  estimate    SE  df z.ratio p.value
##  BL - 1st     0.578 0.327 Inf   1.769  0.1802
##  BL - 3rd     0.359 0.304 Inf   1.182  0.4638
##  1st - 3rd   -0.219 0.322 Inf  -0.679  0.7755
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $threeHK_KYN_ratio
##  contrast  estimate  SE  df z.ratio p.value
##  BL - 1st      7.83 187 Inf   0.042  0.9990
##  BL - 3rd     29.64 186 Inf   0.159  0.9861
##  1st - 3rd    21.82 187 Inf   0.117  0.9925
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $threeHK_KYNA_ratio
##  contrast  estimate   SE  df z.ratio p.value
##  BL - 1st      1.95 2.49 Inf   0.782  0.7142
##  BL - 3rd     -1.32 2.41 Inf  -0.545  0.8492
##  1st - 3rd    -3.27 2.67 Inf  -1.222  0.4404
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $IL1B_pg_mL
##  contrast  estimate    SE  df z.ratio p.value
##  BL - 1st     2.870 12.19 Inf   0.235  0.9699
##  BL - 3rd     2.486  5.22 Inf   0.476  0.8824
##  1st - 3rd   -0.384 11.74 Inf  -0.033  0.9994
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $IL1B_pg_mL_LLOD
##  contrast  estimate    SE  df z.ratio p.value
##  BL - 1st     12.89 17.63 Inf   0.731  0.7449
##  BL - 3rd      1.93  5.86 Inf   0.330  0.9418
##  1st - 3rd   -10.96 17.08 Inf  -0.641  0.7973
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $IL2_pg_mL
##  contrast  estimate    SE  df z.ratio p.value
##  BL - 1st   -0.0299 0.214 Inf  -0.139  0.9894
##  BL - 3rd   -0.1524 0.208 Inf  -0.733  0.7438
##  1st - 3rd  -0.1226 0.216 Inf  -0.566  0.8380
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $IL2_pg_mL_LLOD
##  contrast  estimate    SE  df z.ratio p.value
##  BL - 1st   -0.0363 0.217 Inf  -0.168  0.9846
##  BL - 3rd   -0.1332 0.210 Inf  -0.634  0.8014
##  1st - 3rd  -0.0969 0.219 Inf  -0.442  0.8979
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $IL4_pg_mL
##  contrast  estimate   SE  df z.ratio p.value
##  BL - 1st    -30.01 36.7 Inf  -0.817  0.6927
##  BL - 3rd    -37.54 40.6 Inf  -0.925  0.6247
##  1st - 3rd    -7.54 39.3 Inf  -0.192  0.9799
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $IL4_pg_mL_LLOD
##  contrast  estimate   SE  df z.ratio p.value
##  BL - 1st   -36.516 36.0 Inf  -1.014  0.5679
##  BL - 3rd   -37.167 40.7 Inf  -0.914  0.6314
##  1st - 3rd   -0.651 38.5 Inf  -0.017  0.9998
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $IL6_pg_mL
##  contrast  estimate   SE  df z.ratio p.value
##  BL - 1st    -1.070 1.82 Inf  -0.589  0.8258
##  BL - 3rd    -0.768 2.14 Inf  -0.359  0.9316
##  1st - 3rd    0.302 2.02 Inf   0.149  0.9878
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $IL8_pg_mL
##  contrast  estimate    SE  df z.ratio p.value
##  BL - 1st    -1.318 0.639 Inf  -2.063  0.0975
##  BL - 3rd    -0.891 0.674 Inf  -1.322  0.3830
##  1st - 3rd    0.427 0.756 Inf   0.564  0.8390
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $IL10_pg_mL
##  contrast  estimate    SE  df z.ratio p.value
##  BL - 1st     0.336 0.536 Inf   0.627  0.8052
##  BL - 3rd     0.469 0.572 Inf   0.819  0.6911
##  1st - 3rd    0.132 0.599 Inf   0.221  0.9734
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $IL12p70_pg_mL
##  contrast   estimate      SE  df z.ratio p.value
##  BL - 1st  -0.002773 0.00712 Inf  -0.390  0.9197
##  BL - 3rd  -0.003045 0.00526 Inf  -0.579  0.8316
##  1st - 3rd -0.000272 0.00730 Inf  -0.037  0.9992
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $IL12p70_pg_mL_LLOD
##  contrast   estimate      SE  df z.ratio p.value
##  BL - 1st  -2.99e-03 0.00714 Inf  -0.419  0.9080
##  BL - 3rd  -3.06e-03 0.00528 Inf  -0.579  0.8311
##  1st - 3rd -7.19e-05 0.00732 Inf  -0.010  0.9999
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $IL13_pg_mL
##  contrast   estimate     SE  df z.ratio p.value
##  BL - 1st  -0.057479 0.0968 Inf  -0.594  0.8233
##  BL - 3rd  -0.056513 0.0921 Inf  -0.614  0.8127
##  1st - 3rd  0.000966 0.0978 Inf   0.010  0.9999
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $IL13_pg_mL_LLOD
##  contrast  estimate     SE  df z.ratio p.value
##  BL - 1st   -0.0671 0.0973 Inf  -0.690  0.7695
##  BL - 3rd   -0.0562 0.0928 Inf  -0.606  0.8170
##  1st - 3rd   0.0109 0.0984 Inf   0.111  0.9932
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $TNFa_pg_mL
##  contrast  estimate   SE  df z.ratio p.value
##  BL - 1st    -0.955 2.39 Inf  -0.399  0.9158
##  BL - 3rd    -2.445 2.36 Inf  -1.038  0.5527
##  1st - 3rd   -1.490 2.31 Inf  -0.644  0.7955
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $IFNy_pg_mL
##  contrast  estimate    SE  df z.ratio p.value
##  BL - 1st    0.2681 0.183 Inf   1.464  0.3082
##  BL - 3rd    0.0506 0.208 Inf   0.244  0.9678
##  1st - 3rd  -0.2175 0.217 Inf  -1.001  0.5764
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $CRP_ng_mL
##  contrast   estimate       SE  df z.ratio p.value
##  BL - 1st  -1.94e-04 0.000215 Inf  -0.902  0.6391
##  BL - 3rd  -2.34e-04 0.000243 Inf  -0.965  0.5989
##  1st - 3rd -4.04e-05 0.000247 Inf  -0.163  0.9854
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $NIC_nM
##  contrast   estimate      SE  df z.ratio p.value
##  BL - 1st  -3.22e-03 0.00300 Inf  -1.075  0.5299
##  BL - 3rd  -3.24e-03 0.00338 Inf  -0.960  0.6022
##  1st - 3rd -2.05e-05 0.00361 Inf  -0.006  1.0000
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $NIC_nM_LLOD
##  contrast   estimate      SE  df z.ratio p.value
##  BL - 1st  -3.22e-03 0.00300 Inf  -1.075  0.5299
##  BL - 3rd  -3.24e-03 0.00338 Inf  -0.960  0.6022
##  1st - 3rd -2.05e-05 0.00361 Inf  -0.006  1.0000
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $NTA_nM
##  contrast  estimate      SE  df z.ratio p.value
##  BL - 1st  -0.00379 0.00709 Inf  -0.534  0.8544
##  BL - 3rd  -0.00969 0.00724 Inf  -1.338  0.3739
##  1st - 3rd -0.00590 0.00786 Inf  -0.750  0.7335
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $SAA_ng_mL
##  contrast   estimate       SE  df z.ratio p.value
##  BL - 1st   5.19e-05 0.000513 Inf   0.101  0.9944
##  BL - 3rd  -5.90e-04 0.000521 Inf  -1.134  0.4930
##  1st - 3rd -6.42e-04 0.000519 Inf  -1.237  0.4314
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $VCAM_1_ng_mL
##  contrast  estimate     SE  df z.ratio p.value
##  BL - 1st  -0.00397 0.0166 Inf  -0.239  0.9690
##  BL - 3rd  -0.01008 0.0159 Inf  -0.633  0.8021
##  1st - 3rd -0.00611 0.0160 Inf  -0.381  0.9231
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates 
## 
## $ICAM_1_ng_mL
##  contrast   estimate     SE  df z.ratio p.value
##  BL - 1st  -0.003287 0.0131 Inf  -0.251  0.9658
##  BL - 3rd  -0.004180 0.0131 Inf  -0.318  0.9457
##  1st - 3rd -0.000892 0.0134 Inf  -0.067  0.9975
## 
## Results are averaged over the levels of: sex 
## P value adjustment: tukey method for comparing a family of 3 estimates
emtrend_confint
## $TRP_nM
## $TRP_nM$emtrends
##  infusionno TRP_nM.trend       SE  df asymp.LCL asymp.UCL
##  BL             3.18e-05 0.000134 Inf -2.31e-04  0.000295
##  1st            2.12e-04 0.000132 Inf -4.77e-05  0.000472
##  3rd            2.76e-04 0.000139 Inf  4.29e-06  0.000547
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $TRP_nM$contrasts
##  contrast   estimate       SE  df asymp.LCL asymp.UCL
##  BL - 1st  -0.000180 0.000185 Inf -0.000614  0.000254
##  BL - 3rd  -0.000244 0.000187 Inf -0.000683  0.000195
##  1st - 3rd -0.000064 0.000186 Inf -0.000501  0.000373
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $five_HT_nM
## $five_HT_nM$emtrends
##  infusionno five_HT_nM.trend      SE  df asymp.LCL asymp.UCL
##  BL                 -0.00114 0.00245 Inf  -0.00595   0.00367
##  1st                 0.00176 0.00281 Inf  -0.00375   0.00727
##  3rd                 0.00956 0.00291 Inf   0.00386   0.01526
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $five_HT_nM$contrasts
##  contrast  estimate      SE  df asymp.LCL asymp.UCL
##  BL - 1st   -0.0029 0.00370 Inf   -0.0116   0.00576
##  BL - 3rd   -0.0107 0.00373 Inf   -0.0195  -0.00195
##  1st - 3rd  -0.0078 0.00399 Inf   -0.0171   0.00155
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $KYN_nM
## $KYN_nM$emtrends
##  infusionno KYN_nM.trend      SE  df asymp.LCL asymp.UCL
##  BL             -0.00088 0.00315 Inf  -0.00705   0.00529
##  1st             0.00381 0.00351 Inf  -0.00307   0.01068
##  3rd             0.00523 0.00336 Inf  -0.00136   0.01182
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $KYN_nM$contrasts
##  contrast  estimate      SE  df asymp.LCL asymp.UCL
##  BL - 1st  -0.00469 0.00450 Inf   -0.0152   0.00587
##  BL - 3rd  -0.00611 0.00441 Inf   -0.0164   0.00423
##  1st - 3rd -0.00142 0.00461 Inf   -0.0122   0.00938
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $three_HK_nM
## $three_HK_nM$emtrends
##  infusionno three_HK_nM.trend     SE  df asymp.LCL asymp.UCL
##  BL                   -0.0396 0.0853 Inf    -0.207     0.128
##  1st                   0.0267 0.1138 Inf    -0.196     0.250
##  3rd                   0.0940 0.1269 Inf    -0.155     0.343
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $three_HK_nM$contrasts
##  contrast  estimate    SE  df asymp.LCL asymp.UCL
##  BL - 1st   -0.0663 0.134 Inf    -0.380     0.247
##  BL - 3rd   -0.1336 0.145 Inf    -0.474     0.207
##  1st - 3rd  -0.0673 0.160 Inf    -0.442     0.308
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $KYNA_nM
## $KYNA_nM$emtrends
##  infusionno KYNA_nM.trend     SE  df asymp.LCL asymp.UCL
##  BL              -0.07769 0.0897 Inf    -0.253    0.0981
##  1st              0.04059 0.1227 Inf    -0.200    0.2811
##  3rd              0.00257 0.1010 Inf    -0.195    0.2005
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $KYNA_nM$contrasts
##  contrast  estimate    SE  df asymp.LCL asymp.UCL
##  BL - 1st   -0.1183 0.142 Inf     -0.45     0.214
##  BL - 3rd   -0.0803 0.128 Inf     -0.38     0.220
##  1st - 3rd   0.0380 0.149 Inf     -0.31     0.386
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $PIC_nM
## $PIC_nM$emtrends
##  infusionno PIC_nM.trend     SE  df asymp.LCL asymp.UCL
##  BL             -0.00822 0.0390 Inf   -0.0847    0.0682
##  1st             0.23606 0.1017 Inf    0.0366    0.4355
##  3rd             0.08573 0.0814 Inf   -0.0738    0.2453
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $PIC_nM$contrasts
##  contrast  estimate    SE  df asymp.LCL asymp.UCL
##  BL - 1st   -0.2443 0.109 Inf    -0.499    0.0104
##  BL - 3rd   -0.0939 0.090 Inf    -0.305    0.1170
##  1st - 3rd   0.1503 0.129 Inf    -0.152    0.4529
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $Quin_nM
## $Quin_nM$emtrends
##  infusionno Quin_nM.trend     SE  df asymp.LCL asymp.UCL
##  BL              0.000521 0.0186 Inf   -0.0360    0.0370
##  1st            -0.003113 0.0202 Inf   -0.0427    0.0364
##  3rd            -0.016985 0.0183 Inf   -0.0529    0.0189
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $Quin_nM$contrasts
##  contrast  estimate     SE  df asymp.LCL asymp.UCL
##  BL - 1st   0.00363 0.0262 Inf   -0.0578    0.0651
##  BL - 3rd   0.01751 0.0251 Inf   -0.0413    0.0763
##  1st - 3rd  0.01387 0.0258 Inf   -0.0467    0.0744
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $AA_nM
## $AA_nM$emtrends
##  infusionno AA_nM.trend    SE  df asymp.LCL asymp.UCL
##  BL              -0.242 0.202 Inf    -0.638     0.155
##  1st              0.213 0.279 Inf    -0.334     0.760
##  3rd             -0.164 0.357 Inf    -0.863     0.535
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $AA_nM$contrasts
##  contrast  estimate    SE  df asymp.LCL asymp.UCL
##  BL - 1st    -0.455 0.334 Inf    -1.237     0.328
##  BL - 3rd    -0.078 0.401 Inf    -1.019     0.863
##  1st - 3rd    0.377 0.440 Inf    -0.655     1.408
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $KYN_TRP_ratio
## $KYN_TRP_ratio$emtrends
##  infusionno KYN_TRP_ratio.trend   SE  df asymp.LCL asymp.UCL
##  BL                       -73.8 84.4 Inf      -239      91.6
##  1st                      -14.0 80.8 Inf      -172     144.4
##  3rd                       17.8 78.8 Inf      -137     172.2
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $KYN_TRP_ratio$contrasts
##  contrast  estimate  SE  df asymp.LCL asymp.UCL
##  BL - 1st     -59.8 111 Inf      -321       202
##  BL - 3rd     -91.7 110 Inf      -349       166
##  1st - 3rd    -31.9 107 Inf      -283       219
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $KYN_SER_ratio
## $KYN_SER_ratio$emtrends
##  infusionno KYN_SER_ratio.trend      SE  df asymp.LCL asymp.UCL
##  BL                      0.0151 0.01026 Inf  -0.00502   0.03521
##  1st                    -0.0132 0.01591 Inf  -0.04438   0.01800
##  3rd                    -0.0117 0.00881 Inf  -0.02893   0.00561
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $KYN_SER_ratio$contrasts
##  contrast  estimate     SE  df asymp.LCL asymp.UCL
##  BL - 1st   0.02829 0.0174 Inf   -0.0124    0.0690
##  BL - 3rd   0.02675 0.0130 Inf   -0.0038    0.0573
##  1st - 3rd -0.00153 0.0176 Inf   -0.0427    0.0396
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $QUIN_PIC_ratio
## $QUIN_PIC_ratio$emtrends
##  infusionno QUIN_PIC_ratio.trend    SE  df asymp.LCL asymp.UCL
##  BL                       0.0209 0.185 Inf    -0.342    0.3842
##  1st                     -0.3083 0.182 Inf    -0.665    0.0479
##  3rd                     -0.2636 0.174 Inf    -0.604    0.0767
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $QUIN_PIC_ratio$contrasts
##  contrast  estimate    SE  df asymp.LCL asymp.UCL
##  BL - 1st    0.3292 0.254 Inf    -0.265     0.923
##  BL - 3rd    0.2846 0.246 Inf    -0.292     0.861
##  1st - 3rd  -0.0447 0.245 Inf    -0.620     0.530
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $QUIN_KYNA_ratio
## $QUIN_KYNA_ratio$emtrends
##  infusionno QUIN_KYNA_ratio.trend    SE  df asymp.LCL asymp.UCL
##  BL                         0.166 0.221 Inf    -0.267    0.5980
##  1st                       -0.412 0.244 Inf    -0.891    0.0665
##  3rd                       -0.193 0.213 Inf    -0.612    0.2246
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $QUIN_KYNA_ratio$contrasts
##  contrast  estimate    SE  df asymp.LCL asymp.UCL
##  BL - 1st     0.578 0.327 Inf    -0.188     1.343
##  BL - 3rd     0.359 0.304 Inf    -0.353     1.071
##  1st - 3rd   -0.219 0.322 Inf    -0.973     0.536
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $threeHK_KYN_ratio
## $threeHK_KYN_ratio$emtrends
##  infusionno threeHK_KYN_ratio.trend  SE  df asymp.LCL asymp.UCL
##  BL                           -42.4 133 Inf      -304       219
##  1st                          -50.2 134 Inf      -313       213
##  3rd                          -72.0 133 Inf      -332       188
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $threeHK_KYN_ratio$contrasts
##  contrast  estimate  SE  df asymp.LCL asymp.UCL
##  BL - 1st      7.83 187 Inf      -430       446
##  BL - 3rd     29.64 186 Inf      -407       466
##  1st - 3rd    21.82 187 Inf      -417       460
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $threeHK_KYNA_ratio
## $threeHK_KYNA_ratio$emtrends
##  infusionno threeHK_KYNA_ratio.trend   SE  df asymp.LCL asymp.UCL
##  BL                           0.0503 1.61 Inf     -3.10      3.20
##  1st                         -1.9000 1.95 Inf     -5.71      1.91
##  3rd                          1.3653 1.87 Inf     -2.31      5.04
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $threeHK_KYNA_ratio$contrasts
##  contrast  estimate   SE  df asymp.LCL asymp.UCL
##  BL - 1st      1.95 2.49 Inf     -3.90      7.80
##  BL - 3rd     -1.32 2.41 Inf     -6.97      4.34
##  1st - 3rd    -3.27 2.67 Inf     -9.53      3.00
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $IL1B_pg_mL
## $IL1B_pg_mL$emtrends
##  infusionno IL1B_pg_mL.trend    SE  df asymp.LCL asymp.UCL
##  BL                    -1.03  4.61 Inf    -10.07      8.01
##  1st                   -3.90 11.18 Inf    -25.80     18.00
##  3rd                   -3.52  2.88 Inf     -9.17      2.14
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $IL1B_pg_mL$contrasts
##  contrast  estimate    SE  df asymp.LCL asymp.UCL
##  BL - 1st     2.870 12.19 Inf    -25.70      31.4
##  BL - 3rd     2.486  5.22 Inf     -9.74      14.7
##  1st - 3rd   -0.384 11.74 Inf    -27.91      27.1
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $IL1B_pg_mL_LLOD
## $IL1B_pg_mL_LLOD$emtrends
##  infusionno IL1B_pg_mL_LLOD.trend    SE  df asymp.LCL asymp.UCL
##  BL                         -0.36  5.18 Inf    -10.51      9.79
##  1st                       -13.25 16.83 Inf    -46.23     19.73
##  3rd                        -2.29  2.79 Inf     -7.76      3.17
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $IL1B_pg_mL_LLOD$contrasts
##  contrast  estimate    SE  df asymp.LCL asymp.UCL
##  BL - 1st     12.89 17.63 Inf     -28.4      54.2
##  BL - 3rd      1.93  5.86 Inf     -11.8      15.7
##  1st - 3rd   -10.96 17.08 Inf     -51.0      29.1
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $IL2_pg_mL
## $IL2_pg_mL$emtrends
##  infusionno IL2_pg_mL.trend    SE  df asymp.LCL asymp.UCL
##  BL                  0.0937 0.151 Inf   -0.2025     0.390
##  1st                 0.1236 0.164 Inf   -0.1974     0.445
##  3rd                 0.2462 0.155 Inf   -0.0569     0.549
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $IL2_pg_mL$contrasts
##  contrast  estimate    SE  df asymp.LCL asymp.UCL
##  BL - 1st   -0.0299 0.214 Inf    -0.532     0.473
##  BL - 3rd   -0.1524 0.208 Inf    -0.640     0.335
##  1st - 3rd  -0.1226 0.216 Inf    -0.630     0.385
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $IL2_pg_mL_LLOD
## $IL2_pg_mL_LLOD$emtrends
##  infusionno IL2_pg_mL_LLOD.trend    SE  df asymp.LCL asymp.UCL
##  BL                       0.0928 0.150 Inf    -0.202     0.387
##  1st                      0.1291 0.163 Inf    -0.191     0.449
##  3rd                      0.2260 0.154 Inf    -0.076     0.528
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $IL2_pg_mL_LLOD$contrasts
##  contrast  estimate    SE  df asymp.LCL asymp.UCL
##  BL - 1st   -0.0363 0.217 Inf    -0.544     0.471
##  BL - 3rd   -0.1332 0.210 Inf    -0.626     0.359
##  1st - 3rd  -0.0969 0.219 Inf    -0.610     0.417
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $IL4_pg_mL
## $IL4_pg_mL$emtrends
##  infusionno IL4_pg_mL.trend   SE  df asymp.LCL asymp.UCL
##  BL                   -13.2 27.9 Inf     -68.0      41.5
##  1st                   16.8 25.8 Inf     -33.8      67.4
##  3rd                   24.3 31.3 Inf     -37.1      85.7
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $IL4_pg_mL$contrasts
##  contrast  estimate   SE  df asymp.LCL asymp.UCL
##  BL - 1st    -30.01 36.7 Inf    -116.1      56.1
##  BL - 3rd    -37.54 40.6 Inf    -132.7      57.6
##  1st - 3rd    -7.54 39.3 Inf     -99.6      84.5
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $IL4_pg_mL_LLOD
## $IL4_pg_mL_LLOD$emtrends
##  infusionno IL4_pg_mL_LLOD.trend   SE  df asymp.LCL asymp.UCL
##  BL                        -13.0 28.0 Inf     -67.8      41.8
##  1st                        23.5 24.5 Inf     -24.6      71.6
##  3rd                        24.2 31.4 Inf     -37.4      85.7
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $IL4_pg_mL_LLOD$contrasts
##  contrast  estimate   SE  df asymp.LCL asymp.UCL
##  BL - 1st   -36.516 36.0 Inf    -120.9      47.9
##  BL - 3rd   -37.167 40.7 Inf    -132.5      58.1
##  1st - 3rd   -0.651 38.5 Inf     -90.9      89.6
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $IL6_pg_mL
## $IL6_pg_mL$emtrends
##  infusionno IL6_pg_mL.trend   SE  df asymp.LCL asymp.UCL
##  BL                   0.701 1.46 Inf    -2.159      3.56
##  1st                  1.771 1.14 Inf    -0.457      4.00
##  3rd                  1.469 1.71 Inf    -1.886      4.82
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $IL6_pg_mL$contrasts
##  contrast  estimate   SE  df asymp.LCL asymp.UCL
##  BL - 1st    -1.070 1.82 Inf     -5.32      3.18
##  BL - 3rd    -0.768 2.14 Inf     -5.79      4.25
##  1st - 3rd    0.302 2.02 Inf     -4.43      5.03
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $IL8_pg_mL
## $IL8_pg_mL$emtrends
##  infusionno IL8_pg_mL.trend    SE  df asymp.LCL asymp.UCL
##  BL                  -0.267 0.391 Inf   -1.0326     0.499
##  1st                  1.051 0.519 Inf    0.0347     2.068
##  3rd                  0.624 0.563 Inf   -0.4790     1.728
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $IL8_pg_mL$contrasts
##  contrast  estimate    SE  df asymp.LCL asymp.UCL
##  BL - 1st    -1.318 0.639 Inf     -2.81     0.179
##  BL - 3rd    -0.891 0.674 Inf     -2.47     0.689
##  1st - 3rd    0.427 0.756 Inf     -1.35     2.199
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $IL10_pg_mL
## $IL10_pg_mL$emtrends
##  infusionno IL10_pg_mL.trend    SE  df asymp.LCL asymp.UCL
##  BL                 -0.00326 0.361 Inf     -0.71     0.704
##  1st                -0.33972 0.401 Inf     -1.13     0.447
##  3rd                -0.47215 0.448 Inf     -1.35     0.407
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $IL10_pg_mL$contrasts
##  contrast  estimate    SE  df asymp.LCL asymp.UCL
##  BL - 1st     0.336 0.536 Inf    -0.921      1.59
##  BL - 3rd     0.469 0.572 Inf    -0.873      1.81
##  1st - 3rd    0.132 0.599 Inf    -1.270      1.54
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $IL12p70_pg_mL
## $IL12p70_pg_mL$emtrends
##  infusionno IL12p70_pg_mL.trend      SE  df asymp.LCL asymp.UCL
##  BL                   -0.003392 0.00362 Inf  -0.01048   0.00369
##  1st                  -0.000619 0.00629 Inf  -0.01294   0.01171
##  3rd                  -0.000346 0.00398 Inf  -0.00815   0.00746
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $IL12p70_pg_mL$contrasts
##  contrast   estimate      SE  df asymp.LCL asymp.UCL
##  BL - 1st  -0.002773 0.00712 Inf   -0.0195   0.01391
##  BL - 3rd  -0.003045 0.00526 Inf   -0.0154   0.00929
##  1st - 3rd -0.000272 0.00730 Inf   -0.0174   0.01683
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $IL12p70_pg_mL_LLOD
## $IL12p70_pg_mL_LLOD$emtrends
##  infusionno IL12p70_pg_mL_LLOD.trend      SE  df asymp.LCL asymp.UCL
##  BL                        -0.003281 0.00363 Inf  -0.01039   0.00382
##  1st                       -0.000293 0.00630 Inf  -0.01264   0.01206
##  3rd                       -0.000221 0.00399 Inf  -0.00805   0.00760
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $IL12p70_pg_mL_LLOD$contrasts
##  contrast   estimate      SE  df asymp.LCL asymp.UCL
##  BL - 1st  -2.99e-03 0.00714 Inf   -0.0197   0.01374
##  BL - 3rd  -3.06e-03 0.00528 Inf   -0.0154   0.00932
##  1st - 3rd -7.19e-05 0.00732 Inf   -0.0172   0.01708
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $IL13_pg_mL
## $IL13_pg_mL$emtrends
##  infusionno IL13_pg_mL.trend     SE  df asymp.LCL asymp.UCL
##  BL                 -0.06336 0.0659 Inf    -0.192    0.0657
##  1st                -0.00588 0.0738 Inf    -0.151    0.1387
##  3rd                -0.00685 0.0673 Inf    -0.139    0.1251
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $IL13_pg_mL$contrasts
##  contrast   estimate     SE  df asymp.LCL asymp.UCL
##  BL - 1st  -0.057479 0.0968 Inf    -0.284     0.169
##  BL - 3rd  -0.056513 0.0921 Inf    -0.272     0.159
##  1st - 3rd  0.000966 0.0978 Inf    -0.228     0.230
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $IL13_pg_mL_LLOD
## $IL13_pg_mL_LLOD$emtrends
##  infusionno IL13_pg_mL_LLOD.trend     SE  df asymp.LCL asymp.UCL
##  BL                      -0.06194 0.0662 Inf    -0.192    0.0679
##  1st                      0.00518 0.0741 Inf    -0.140    0.1504
##  3rd                     -0.00574 0.0678 Inf    -0.139    0.1272
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $IL13_pg_mL_LLOD$contrasts
##  contrast  estimate     SE  df asymp.LCL asymp.UCL
##  BL - 1st   -0.0671 0.0973 Inf    -0.295     0.161
##  BL - 3rd   -0.0562 0.0928 Inf    -0.274     0.161
##  1st - 3rd   0.0109 0.0984 Inf    -0.220     0.242
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $TNFa_pg_mL
## $TNFa_pg_mL$emtrends
##  infusionno TNFa_pg_mL.trend   SE  df asymp.LCL asymp.UCL
##  BL                   -2.647 1.75 Inf     -6.07     0.777
##  1st                  -1.692 1.69 Inf     -5.00     1.616
##  3rd                  -0.201 1.64 Inf     -3.41     3.009
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $TNFa_pg_mL$contrasts
##  contrast  estimate   SE  df asymp.LCL asymp.UCL
##  BL - 1st    -0.955 2.39 Inf     -6.56      4.65
##  BL - 3rd    -2.445 2.36 Inf     -7.97      3.08
##  1st - 3rd   -1.490 2.31 Inf     -6.91      3.93
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $IFNy_pg_mL
## $IFNy_pg_mL$emtrends
##  infusionno IFNy_pg_mL.trend    SE  df asymp.LCL asymp.UCL
##  BL                   0.1424 0.124 Inf   -0.0997     0.384
##  1st                 -0.1257 0.140 Inf   -0.3994     0.148
##  3rd                  0.0918 0.169 Inf   -0.2387     0.422
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $IFNy_pg_mL$contrasts
##  contrast  estimate    SE  df asymp.LCL asymp.UCL
##  BL - 1st    0.2681 0.183 Inf    -0.161     0.697
##  BL - 3rd    0.0506 0.208 Inf    -0.436     0.537
##  1st - 3rd  -0.2175 0.217 Inf    -0.727     0.292
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $CRP_ng_mL
## $CRP_ng_mL$emtrends
##  infusionno CRP_ng_mL.trend       SE  df asymp.LCL asymp.UCL
##  BL               -4.33e-05 0.000154 Inf -0.000345  0.000258
##  1st               1.50e-04 0.000162 Inf -0.000166  0.000467
##  3rd               1.91e-04 0.000201 Inf -0.000203  0.000584
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $CRP_ng_mL$contrasts
##  contrast   estimate       SE  df asymp.LCL asymp.UCL
##  BL - 1st  -1.94e-04 0.000215 Inf -0.000697  0.000310
##  BL - 3rd  -2.34e-04 0.000243 Inf -0.000802  0.000334
##  1st - 3rd -4.04e-05 0.000247 Inf -0.000620  0.000540
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $NIC_nM
## $NIC_nM$emtrends
##  infusionno NIC_nM.trend      SE  df asymp.LCL asymp.UCL
##  BL            -0.000999 0.00192 Inf  -0.00477   0.00277
##  1st            0.002223 0.00232 Inf  -0.00231   0.00676
##  3rd            0.002244 0.00279 Inf  -0.00323   0.00771
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $NIC_nM$contrasts
##  contrast   estimate      SE  df asymp.LCL asymp.UCL
##  BL - 1st  -3.22e-03 0.00300 Inf  -0.01025   0.00381
##  BL - 3rd  -3.24e-03 0.00338 Inf  -0.01116   0.00467
##  1st - 3rd -2.05e-05 0.00361 Inf  -0.00849   0.00845
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $NIC_nM_LLOD
## $NIC_nM_LLOD$emtrends
##  infusionno NIC_nM_LLOD.trend      SE  df asymp.LCL asymp.UCL
##  BL                 -0.000999 0.00192 Inf  -0.00477   0.00277
##  1st                 0.002223 0.00232 Inf  -0.00231   0.00676
##  3rd                 0.002244 0.00279 Inf  -0.00323   0.00771
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $NIC_nM_LLOD$contrasts
##  contrast   estimate      SE  df asymp.LCL asymp.UCL
##  BL - 1st  -3.22e-03 0.00300 Inf  -0.01025   0.00381
##  BL - 3rd  -3.24e-03 0.00338 Inf  -0.01116   0.00467
##  1st - 3rd -2.05e-05 0.00361 Inf  -0.00849   0.00845
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $NTA_nM
## $NTA_nM$emtrends
##  infusionno NTA_nM.trend      SE  df asymp.LCL asymp.UCL
##  BL            -0.003672 0.00455 Inf  -0.01260   0.00526
##  1st            0.000118 0.00547 Inf  -0.01060   0.01083
##  3rd            0.006015 0.00575 Inf  -0.00525   0.01729
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $NTA_nM$contrasts
##  contrast  estimate      SE  df asymp.LCL asymp.UCL
##  BL - 1st  -0.00379 0.00709 Inf   -0.0204   0.01283
##  BL - 3rd  -0.00969 0.00724 Inf   -0.0267   0.00728
##  1st - 3rd -0.00590 0.00786 Inf   -0.0243   0.01253
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $SAA_ng_mL
## $SAA_ng_mL$emtrends
##  infusionno SAA_ng_mL.trend       SE  df asymp.LCL asymp.UCL
##  BL                6.37e-05 0.000381 Inf -0.000683  0.000811
##  1st               1.17e-05 0.000379 Inf -0.000731  0.000754
##  3rd               6.54e-04 0.000397 Inf -0.000123  0.001432
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $SAA_ng_mL$contrasts
##  contrast   estimate       SE  df asymp.LCL asymp.UCL
##  BL - 1st   5.19e-05 0.000513 Inf  -0.00115  0.001255
##  BL - 3rd  -5.90e-04 0.000521 Inf  -0.00181  0.000630
##  1st - 3rd -6.42e-04 0.000519 Inf  -0.00186  0.000575
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $VCAM_1_ng_mL
## $VCAM_1_ng_mL$emtrends
##  infusionno VCAM_1_ng_mL.trend     SE  df asymp.LCL asymp.UCL
##  BL                   -0.00150 0.0118 Inf   -0.0246    0.0216
##  1st                   0.00247 0.0120 Inf   -0.0210    0.0259
##  3rd                   0.00858 0.0110 Inf   -0.0130    0.0302
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $VCAM_1_ng_mL$contrasts
##  contrast  estimate     SE  df asymp.LCL asymp.UCL
##  BL - 1st  -0.00397 0.0166 Inf   -0.0429    0.0349
##  BL - 3rd  -0.01008 0.0159 Inf   -0.0474    0.0273
##  1st - 3rd -0.00611 0.0160 Inf   -0.0437    0.0315
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates 
## 
## 
## $ICAM_1_ng_mL
## $ICAM_1_ng_mL$emtrends
##  infusionno ICAM_1_ng_mL.trend      SE  df asymp.LCL asymp.UCL
##  BL                    0.00835 0.00938 Inf  -0.01004    0.0267
##  1st                   0.01164 0.00969 Inf  -0.00736    0.0306
##  3rd                   0.01253 0.00963 Inf  -0.00635    0.0314
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## 
## $ICAM_1_ng_mL$contrasts
##  contrast   estimate     SE  df asymp.LCL asymp.UCL
##  BL - 1st  -0.003287 0.0131 Inf   -0.0340    0.0274
##  BL - 3rd  -0.004180 0.0131 Inf   -0.0349    0.0266
##  1st - 3rd -0.000892 0.0134 Inf   -0.0322    0.0304
## 
## Results are averaged over the levels of: sex 
## Confidence level used: 0.95 
## Conf-level adjustment: tukey method for comparing a family of 3 estimates

emtrends(rlmer,pairwise~infusionno,”TRP_nM”) The $contrats portion of this will let us know if MADRS:Marker correlations change at any timepoint Also this confint(emtrends(rlmer,pairwise~infusionno,”TRP_nM”)) will help us determine which markers are correlated with MADRS score within each timepoint.

11 Model 3: MADRS_3rd by Biomarker_BL + MADRS_BL

Biok_wide_new_bx<-Biok_wide_new %>% 
  select(-contains("MADRS"), -contains("BSS"), -contains("_1st"), -contains("_3rd"),-sex, -age, -BMI, -race, -patientno, -Remission) %>% names()

model3<-list()
model3_nobmi<-list()

for (x in Biok_wide_new_bx){
  mod3<-lm(substitute(MADRS_Score_3rd~age+sex+BMI+MADRS_Score_BL+i, list(i=as.name(x))), data=Biok_wide_new)
  mod3_nobmi<-lm(substitute(MADRS_Score_3rd~age+sex+MADRS_Score_BL+i, list(i=as.name(x))), data=Biok_wide_new)

  # model3[[x]]<-summary(mod3)$coefficients[,4]
  # model3_nobmi[[x]]<-summary(mod3_nobmi)$coefficients[,4]
  
  model3[[x]]<-summary(mod3)$coefficients
  model3_nobmi[[x]]<-summary(mod3_nobmi)$coefficients

}

model3
## $TRP_nM_BL
##                     Estimate   Std. Error    t value   Pr(>|t|)
## (Intercept)    -1.396762e+01 8.1228237326 -1.7195520 0.09034704
## age             4.179664e-02 0.0670903528  0.6229902 0.53550469
## sexfemale       3.041263e+00 1.7926754348  1.6964938 0.09465160
## BMI             5.317539e-02 0.1519152765  0.3500332 0.72746313
## MADRS_Score_BL  2.914078e-01 0.1471370494  1.9805197 0.05194696
## TRP_nM_BL       3.310841e-04 0.0001489956  2.2221062 0.02981799
## 
## $five_HT_nM_BL
##                   Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)    -7.63252324 6.75073813 -1.1306205 0.26243408
## age             0.05679040 0.06755990  0.8405933 0.40370541
## sexfemale       1.49991029 1.73133855  0.8663299 0.38954556
## BMI             0.05471647 0.15109741  0.3621271 0.71845003
## MADRS_Score_BL  0.35004726 0.14676261  2.3851255 0.02004546
## five_HT_nM_BL   0.00640233 0.00268956  2.3804377 0.02028071
## 
## $KYN_nM_BL
##                    Estimate Std. Error     t value   Pr(>|t|)
## (Intercept)    -6.588392712 7.08316683 -0.93014789 0.35578980
## age            -0.007690056 0.07266740 -0.10582540 0.91605188
## sexfemale       2.545490779 1.81067161  1.40582685 0.16461196
## BMI            -0.006840197 0.15586869 -0.04388435 0.96513322
## MADRS_Score_BL  0.314930690 0.15000704  2.09943938 0.03972686
## KYN_nM_BL       0.005475453 0.00387667  1.41241143 0.16267321
## 
## $three_HK_nM_BL
##                   Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)    -3.38171551 6.88393075 -0.4912478 0.62493168
## age             0.02676339 0.06954423  0.3848398 0.70163203
## sexfemale       1.98540031 1.79362340  1.1069215 0.27247106
## BMI             0.01777757 0.15937982  0.1115422 0.91153550
## MADRS_Score_BL  0.31713742 0.15362581  2.0643498 0.04304262
## three_HK_nM_BL  0.01322423 0.10026952  0.1318868 0.89548758
## 
## $KYNA_nM_BL
##                   Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)    -2.87988061 7.36405858 -0.3910725 0.69704257
## age             0.02910535 0.07060239  0.4122431 0.68153883
## sexfemale       1.92789327 1.85718947  1.0380703 0.30314345
## BMI             0.02118385 0.15696637  0.1349579 0.89306875
## MADRS_Score_BL  0.31085312 0.15545005  1.9996977 0.04978139
## KYNA_nM_BL     -0.01289453 0.11029460 -0.1169099 0.90729756
## 
## $PIC_nM_BL
##                   Estimate Std. Error     t value   Pr(>|t|)
## (Intercept)    -2.69043621 6.88842851 -0.39057329 0.69740973
## age             0.03125663 0.06983331  0.44758919 0.65596104
## sexfemale       2.00404601 1.79222852  1.11818666 0.26766700
## BMI             0.01547450 0.15745976  0.09827591 0.92202036
## MADRS_Score_BL  0.30875099 0.15279225  2.02072412 0.04749662
## PIC_nM_BL      -0.01744039 0.04312656 -0.40440011 0.68726684
## 
## $Quin_nM_BL
##                   Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)    -0.85659070 7.05474999 -0.1214204 0.90373847
## age             0.04572793 0.07069860  0.6468011 0.52007375
## sexfemale       1.37174220 1.86497465  0.7355286 0.46470469
## BMI             0.03933210 0.15641473  0.2514603 0.80226390
## MADRS_Score_BL  0.32157996 0.15108518  2.1284679 0.03715378
## Quin_nM_BL     -0.02373179 0.02186506 -1.0853750 0.28182706
## 
## $AA_nM_BL
##                   Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)    -2.70741738 6.54162059 -0.4138756 0.68034891
## age             0.05198952 0.06785436  0.7661928 0.44637845
## sexfemale       2.24467975 1.73579127  1.2931738 0.20059943
## BMI             0.12135123 0.15840141  0.7660994 0.44643358
## MADRS_Score_BL  0.26029793 0.14915927  1.7451007 0.08576719
## AA_nM_BL       -0.49032451 0.22658529 -2.1639732 0.03420502
## 
## $KYN_TRP_ratio_BL
##                      Estimate   Std. Error    t value   Pr(>|t|)
## (Intercept)       -2.89383580   7.06298488 -0.4097185 0.68338060
## age                0.03194778   0.07450963  0.4287738 0.66952763
## sexfemale          1.99219920   1.79416400  1.1103774 0.27099089
## BMI                0.02694105   0.16060067  0.1677518 0.86730754
## MADRS_Score_BL     0.31157712   0.15335958  2.0316769 0.04634262
## KYN_TRP_ratio_BL -16.58757345 102.78713100 -0.1613779 0.87230412
## 
## $KYN_SER_ratio_BL
##                     Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)      -4.89516457 6.84606171 -0.7150337 0.47718858
## age               0.03912899 0.06925148  0.5650275 0.57403040
## sexfemale         2.20713892 1.78429670  1.2369798 0.22061435
## BMI               0.02051913 0.15526841  0.1321526 0.89527815
## MADRS_Score_BL    0.36775974 0.15720962  2.3392954 0.02245341
## KYN_SER_ratio_BL -0.01352328 0.01138615 -1.1876961 0.23934239
## 
## $QUIN_PIC_ratio_BL
##                      Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)       -3.76025019 6.73532899 -0.5582875 0.57859603
## age                0.03758971 0.06939909  0.5416456 0.58994341
## sexfemale          2.17833575 1.78843136  1.2180147 0.22768979
## BMI                0.05985463 0.15993415  0.3742455 0.70945881
## MADRS_Score_BL     0.34216657 0.15335170  2.2312539 0.02917473
## QUIN_PIC_ratio_BL -0.21745779 0.20819200 -1.0445060 0.30018057
## 
## $QUIN_KYNA_ratio_BL
##                       Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)        -2.98611505 6.76227692 -0.4415843 0.66027849
## age                 0.02865775 0.06912639  0.4145704 0.67984275
## sexfemale           2.14197733 1.80638193  1.1857832 0.24009180
## BMI                 0.03213408 0.15744043  0.2041031 0.83892057
## MADRS_Score_BL      0.34165695 0.15803555  2.1618993 0.03437146
## QUIN_KYNA_ratio_BL -0.18184659 0.29258644 -0.6215141 0.53646907
## 
## $threeHK_KYN_ratio_BL
##                           Estimate   Std. Error     t value   Pr(>|t|)
## (Intercept)            -0.60858425   7.29999938 -0.08336771 0.93381937
## age                     0.01878377   0.06950729  0.27024179 0.78784379
## sexfemale               2.19928810   1.79730196  1.22366088 0.22556624
## BMI                     0.04522989   0.15806284  0.28615135 0.77568642
## MADRS_Score_BL          0.29137596   0.15339262  1.89954349 0.06200119
## threeHK_KYN_ratio_BL -137.21891617 148.96524565 -0.92114718 0.36043292
## 
## $threeHK_KYNA_ratio_BL
##                          Estimate Std. Error     t value   Pr(>|t|)
## (Intercept)           -3.26389662 6.72836405 -0.48509513 0.62926523
## age                    0.02850468 0.06886739  0.41390671 0.68032626
## sexfemale              1.51822871 1.85307951  0.81930036 0.41565566
## BMI                   -0.01145057 0.16001020 -0.07156152 0.94317402
## MADRS_Score_BL         0.30246451 0.15190023  1.99120506 0.05073063
## threeHK_KYNA_ratio_BL  1.70469966 1.85758127  0.91769856 0.36222220
## 
## $IL1B_pg_mL_BL
##                   Estimate  Std. Error    t value  Pr(>|t|)
## (Intercept)     3.11086256 12.53070121  0.2482593 0.8089576
## age            -0.06081348  0.09780974 -0.6217528 0.5480164
## sexfemale      -3.35825420  2.65579847 -1.2644989 0.2347267
## BMI            -0.03428727  0.26161366 -0.1310607 0.8983265
## MADRS_Score_BL  0.28791096  0.24265070  1.1865243 0.2628392
## IL1B_pg_mL_BL   4.55287631  2.98492361  1.5252907 0.1581699
## 
## $IL1B_pg_mL_LLOD_BL
##                       Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)        -4.07972810 7.11564261 -0.5733464 0.56841941
## age                 0.02751741 0.06922851  0.3974866 0.69233129
## sexfemale           1.91473132 1.80054277  1.0634190 0.29158803
## BMI                 0.02374712 0.15689385  0.1513579 0.88016952
## MADRS_Score_BL      0.31777959 0.15237977  2.0854447 0.04102171
## IL1B_pg_mL_LLOD_BL  2.18458359 5.59997969  0.3901056 0.69775378
## 
## $IL2_pg_mL_BL
##                  Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)    -0.9815982 7.37724238 -0.1330576 0.89484996
## age             0.0958955 0.08075374  1.1875053 0.24239844
## sexfemale      -1.3524518 1.97905588 -0.6833823 0.49851119
## BMI            -0.1301561 0.19321390 -0.6736372 0.50461903
## MADRS_Score_BL  0.3294784 0.15151026  2.1746276 0.03595144
## IL2_pg_mL_BL    0.2506601 0.14278872  1.7554616 0.08723961
## 
## $IL2_pg_mL_LLOD_BL
##                      Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)       -3.59807980 6.69233622 -0.5376418 0.59268900
## age                0.03597533 0.06873831  0.5233665 0.60252672
## sexfemale          1.83649361 1.77464151  1.0348533 0.30463195
## BMI                0.03566807 0.15535658  0.2295884 0.81914380
## MADRS_Score_BL     0.29617683 0.15105012  1.9607852 0.05425905
## IL2_pg_mL_LLOD_BL  0.20842750 0.16149755  1.2905923 0.20148814
## 
## $IL4_pg_mL_BL
##                    Estimate  Std. Error    t value   Pr(>|t|)
## (Intercept)    -5.048480105  7.70547048 -0.6551813 0.51469916
## age             0.037291461  0.07193747  0.5183871 0.60597585
## sexfemale       1.904431353  1.79766795  1.0593899 0.29340416
## BMI             0.006255084  0.15964547  0.0391811 0.96886797
## MADRS_Score_BL  0.332501623  0.15633530  2.1268493 0.03729334
## IL4_pg_mL_BL   15.651769690 31.63521051  0.4947579 0.62246527
## 
## $IL4_pg_mL_LLOD_BL
##                       Estimate  Std. Error    t value   Pr(>|t|)
## (Intercept)       -5.048480105  7.70547048 -0.6551813 0.51469916
## age                0.037291461  0.07193747  0.5183871 0.60597585
## sexfemale          1.904431353  1.79766795  1.0593899 0.29340416
## BMI                0.006255084  0.15964547  0.0391811 0.96886797
## MADRS_Score_BL     0.332501623  0.15633530  2.1268493 0.03729334
## IL4_pg_mL_LLOD_BL 15.651769690 31.63521051  0.4947579 0.62246527
## 
## $IL6_pg_mL_BL
##                   Estimate Std. Error    t value  Pr(>|t|)
## (Intercept)    -4.11643560 6.90668098 -0.5960078 0.5532722
## age             0.03443219 0.07000074  0.4918832 0.6244849
## sexfemale       2.24884767 1.83901612  1.2228537 0.2258689
## BMI             0.06187122 0.16961613  0.3647720 0.7164842
## MADRS_Score_BL  0.32823815 0.15349353  2.1384495 0.0363032
## IL6_pg_mL_BL   -1.08820078 1.76001557 -0.6182904 0.5385782
## 
## $IL8_pg_mL_BL
##                   Estimate Std. Error    t value  Pr(>|t|)
## (Intercept)    -3.82617510 7.11305925 -0.5379085 0.5925059
## age             0.02371607 0.07061518  0.3358494 0.7380830
## sexfemale       2.05530880 1.81093437  1.1349438 0.2606316
## BMI             0.02283202 0.15695406  0.1454695 0.8847974
## MADRS_Score_BL  0.31788370 0.15272475  2.0814158 0.0414012
## IL8_pg_mL_BL    0.12566987 0.45224933  0.2778774 0.7820022
## 
## $IL10_pg_mL_BL
##                   Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)    -3.18095466 6.65549107 -0.4779444 0.63431826
## age             0.03700499 0.06840489  0.5409700 0.59040626
## sexfemale       2.29688663 1.77508001  1.2939623 0.20032856
## BMI             0.01669625 0.15429187  0.1082121 0.91416597
## MADRS_Score_BL  0.30970712 0.14973188  2.0684113 0.04264696
## IL10_pg_mL_BL  -0.58014509 0.38529472 -1.5057177 0.13705952
## 
## $IL12p70_pg_mL_BL
##                      Estimate  Std. Error     t value   Pr(>|t|)
## (Intercept)      -3.587447668 6.795085553 -0.52794739 0.59936165
## age               0.036257652 0.071165971  0.50948018 0.61216800
## sexfemale         2.138294014 1.814343512  1.17854971 0.24294085
## BMI               0.005676360 0.159533076  0.03558109 0.97172714
## MADRS_Score_BL    0.324523302 0.153221561  2.11800023 0.03806439
## IL12p70_pg_mL_BL  0.002096697 0.004025941  0.52079670 0.60430566
## 
## $IL12p70_pg_mL_LLOD_BL
##                           Estimate  Std. Error     t value   Pr(>|t|)
## (Intercept)           -3.587447668 6.795085553 -0.52794739 0.59936165
## age                    0.036257652 0.071165971  0.50948018 0.61216800
## sexfemale              2.138294014 1.814343512  1.17854971 0.24294085
## BMI                    0.005676360 0.159533076  0.03558109 0.97172714
## MADRS_Score_BL         0.324523302 0.153221561  2.11800023 0.03806439
## IL12p70_pg_mL_LLOD_BL  0.002096697 0.004025941  0.52079670 0.60430566
## 
## $IL13_pg_mL_BL
##                    Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)    -3.200874311 6.90918512 -0.4632781 0.64476153
## age             0.035035021 0.07181870  0.4878259 0.62736661
## sexfemale       1.912385079 1.84453069  1.0367868 0.30379841
## BMI             0.004513109 0.16048036  0.0281225 0.97765334
## MADRS_Score_BL  0.317423997 0.15453581  2.0540482 0.04412592
## IL13_pg_mL_BL   0.033951121 0.07441843  0.4562193 0.64980121
## 
## $IL13_pg_mL_LLOD_BL
##                        Estimate Std. Error     t value   Pr(>|t|)
## (Intercept)        -3.755304691 6.83673314 -0.54928350 0.58472244
## age                 0.036910053 0.07148447  0.51633668 0.60739880
## sexfemale           2.128446038 1.81149130  1.17496895 0.24436016
## BMI                 0.004895886 0.15984304  0.03062934 0.97566046
## MADRS_Score_BL      0.325548445 0.15349127  2.12095744 0.03780519
## IL13_pg_mL_LLOD_BL  0.038361309 0.07385905  0.51938534 0.60528369
## 
## $TNFa_pg_mL_BL
##                   Estimate Std. Error    t value  Pr(>|t|)
## (Intercept)    -4.16933336 7.66672345 -0.5438221 0.5884534
## age             0.02562159 0.06964844  0.3678702 0.7141838
## sexfemale       2.09137969 1.83820633  1.1377285 0.2594753
## BMI             0.02018692 0.15695406  0.1286167 0.8980643
## MADRS_Score_BL  0.32249785 0.15523460  2.0774869 0.0417742
## TNFa_pg_mL_BL   0.53226141 2.01496816  0.2641538 0.7925102
## 
## $IFNy_pg_mL_BL
##                     Estimate Std. Error      t value   Pr(>|t|)
## (Intercept)    -2.6292929633 6.76054409 -0.388917361 0.69862823
## age             0.0307674720 0.06896274  0.446146332 0.65699737
## sexfemale       1.8979394667 1.78497884  1.063284011 0.29164873
## BMI            -0.0005491233 0.15784519 -0.003478873 0.99723509
## MADRS_Score_BL  0.3456727424 0.15521950  2.226993009 0.02947281
## IFNy_pg_mL_BL  -0.1246916174 0.13756804 -0.906399613 0.36812436
## 
## $CRP_ng_mL_BL
##                     Estimate   Std. Error    t value   Pr(>|t|)
## (Intercept)    -1.7813590219 6.8839998939 -0.2587680 0.79664468
## age             0.0304355096 0.0688711642  0.4419195 0.66003716
## sexfemale       1.7917329459 1.7917850711  0.9999709 0.32109046
## BMI            -0.0419214847 0.1689418180 -0.2481416 0.80481935
## MADRS_Score_BL  0.3094710001 0.1513057215  2.0453357 0.04493743
## CRP_ng_mL_BL    0.0001687193 0.0001738043  0.9707430 0.33533081
## 
## $NIC_nM_BL
##                    Estimate  Std. Error    t value   Pr(>|t|)
## (Intercept)    -3.381528093 6.760945340 -0.5001561 0.61868064
## age             0.028147308 0.069141571  0.4070967 0.68529531
## sexfemale       1.875668548 1.799218450  1.0424907 0.30110624
## BMI             0.016876143 0.156767692  0.1076506 0.91460959
## MADRS_Score_BL  0.324384348 0.152912368  2.1213742 0.03776878
## NIC_nM_BL       0.001207579 0.002104615  0.5737765 0.56813002
## 
## $NIC_nM_LLOD_BL
##                    Estimate  Std. Error    t value  Pr(>|t|)
## (Intercept)    -3.381520731 6.760945663 -0.5001550 0.6186814
## age             0.028147108 0.069141573  0.4070938 0.6852974
## sexfemale       1.875667914 1.799219104  1.0424900 0.3011066
## BMI             0.016876353 0.156767695  0.1076520 0.9146085
## MADRS_Score_BL  0.324384191 0.152912388  2.1213729 0.0377689
## NIC_nM_LLOD_BL  0.001207557 0.002104616  0.5737659 0.5681372
## 
## $NTA_nM_BL
##                    Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)    -5.418335166 7.48642642 -0.7237545 0.47185367
## age             0.035720353 0.07010948  0.5094939 0.61215841
## sexfemale       2.172853110 1.80891166  1.2011936 0.23410267
## BMI             0.030710230 0.15700237  0.1956036 0.84554014
## MADRS_Score_BL  0.324482897 0.15249448  2.1278337 0.03720841
## NTA_nM_BL       0.003462993 0.00510282  0.6786431 0.49981075
## 
## $SAA_ng_mL_BL
##                     Estimate   Std. Error     t value   Pr(>|t|)
## (Intercept)    -2.4765203774 6.9171637355 -0.35802541 0.72150246
## age             0.0260651955 0.0692344875  0.37647705 0.70780753
## sexfemale       1.7863089736 1.8328207457  0.97462285 0.33341687
## BMI            -0.0132857740 0.1711293592 -0.07763585 0.93835993
## MADRS_Score_BL  0.3071804954 0.1527144231  2.01147010 0.04849082
## SAA_ng_mL_BL    0.0002218888 0.0004401364  0.50413643 0.61589669
## 
## $VCAM_1_ng_mL_BL
##                     Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)     -1.471003878 8.88657677 -0.1655310 0.86904784
## age              0.023636516 0.07043971  0.3355567 0.73830270
## sexfemale        1.867636448 1.83327623  1.0187425 0.31216093
## BMI              0.023362329 0.15698399  0.1488198 0.88216375
## MADRS_Score_BL   0.306464718 0.15449751  1.9836224 0.05159122
## VCAM_1_ng_mL_BL -0.004247904 0.01400303 -0.3033561 0.76260243
## 
## $ICAM_1_ng_mL_BL
##                    Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)     -5.48884313 7.06911764 -0.7764538 0.44034131
## age              0.02315177 0.06887415  0.3361460 0.73786039
## sexfemale        2.29665702 1.80480964  1.2725204 0.20779204
## BMI              0.01718406 0.15573712  0.1103402 0.91248488
## MADRS_Score_BL   0.28079018 0.15457825  1.8164921 0.07397828
## ICAM_1_ng_mL_BL  0.01063176 0.01031879  1.0303301 0.30673318
model3_nobmi
## $TRP_nM_BL
##                     Estimate  Std. Error    t value   Pr(>|t|)
## (Intercept)    -1.259723e+01 7.068875006 -1.7820695 0.07940858
## age             4.782093e-02 0.064406093  0.7424907 0.46046494
## sexfemale       2.995822e+00 1.775859301  1.6869703 0.09640307
## MADRS_Score_BL  2.933018e-01 0.146041675  2.0083433 0.04876535
## TRP_nM_BL       3.261805e-04 0.000147331  2.2139309 0.03034763
## 
## $five_HT_nM_BL
##                    Estimate  Std. Error    t value   Pr(>|t|)
## (Intercept)    -6.323749780 5.663565895 -1.1165668 0.26829014
## age             0.062796642 0.065053133  0.9653131 0.33796585
## sexfemale       1.476070200 1.718484394  0.8589372 0.39353174
## MADRS_Score_BL  0.351144325 0.145747355  2.4092672 0.01882651
## five_HT_nM_BL   0.006312212 0.002660063  2.3729556 0.02061377
## 
## $KYN_nM_BL
##                    Estimate  Std. Error    t value   Pr(>|t|)
## (Intercept)    -6.729540045 6.262174347 -1.0746331 0.28651205
## age            -0.008345423 0.070568194 -0.1182604 0.90622604
## sexfemale       2.547052605 1.796369315  1.4178892 0.16099949
## MADRS_Score_BL  0.314730800 0.148782270  2.1153784 0.03823487
## KYN_nM_BL       0.005453602 0.003814929  1.4295421 0.15763736
## 
## $three_HK_nM_BL
##                   Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)    -3.00962657 5.97575411 -0.5036396 0.61621732
## age             0.02869020 0.06685097  0.4291665 0.66922120
## sexfemale       1.97583482 1.77791017  1.1113243 0.27052262
## MADRS_Score_BL  0.31803524 0.15224491  2.0889712 0.04063016
## three_HK_nM_BL  0.01517094 0.09798599  0.1548276 0.87743697
## 
## $KYNA_nM_BL
##                   Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)    -2.38778792 6.34947192 -0.3760609 0.70809629
## age             0.03163618 0.06755037  0.4683346 0.64111206
## sexfemale       1.91502985 1.84068132  1.0403919 0.30201239
## MADRS_Score_BL  0.31141916 0.15421543  2.0193774 0.04757525
## KYNA_nM_BL     -0.01309930 0.10944810 -0.1196850 0.90510182
## 
## $PIC_nM_BL
##                   Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)    -2.32593577 5.76027525 -0.4037890 0.68769328
## age             0.03315619 0.06659188  0.4979014 0.62023394
## sexfemale       1.99582919 1.77658650  1.1234067 0.26539692
## MADRS_Score_BL  0.30907221 0.15158912  2.0388813 0.04553269
## PIC_nM_BL      -0.01783720 0.04260878 -0.4186274 0.67686849
## 
## $Quin_nM_BL
##                   Estimate Std. Error      t value   Pr(>|t|)
## (Intercept)    -0.02044511 6.17696479 -0.003309896 0.99736923
## age             0.04988518 0.06824130  0.731011495 0.46739916
## sexfemale       1.36471917 1.85127942  0.737176223 0.46366791
## MADRS_Score_BL  0.32255220 0.14994340  2.151159671 0.03518582
## Quin_nM_BL     -0.02315221 0.02158599 -1.072557159 0.28743586
## 
## $AA_nM_BL
##                   Estimate Std. Error     t value   Pr(>|t|)
## (Intercept)    -0.20837636  5.6522219 -0.03686627 0.97070462
## age             0.06260267  0.0662137  0.94546407 0.34792345
## sexfemale       2.15504810  1.7263319  1.24833941 0.21638467
## MADRS_Score_BL  0.26916008  0.1482367  1.81574489 0.07402210
## AA_nM_BL       -0.43972615  0.2160559 -2.03524224 0.04590795
## 
## $KYN_TRP_ratio_BL
##                      Estimate  Std. Error    t value  Pr(>|t|)
## (Intercept)       -2.37426883  6.30003428 -0.3768660 0.7075007
## age                0.03401586  0.07293123  0.4664101 0.6424814
## sexfemale          1.97589490  1.77808588  1.1112483 0.2705551
## MADRS_Score_BL     0.31297725  0.15198318  2.0592887 0.0434769
## KYN_TRP_ratio_BL -12.92528731 99.68818984 -0.1296572 0.8972381
## 
## $KYN_SER_ratio_BL
##                     Estimate Std. Error    t value  Pr(>|t|)
## (Intercept)      -4.42456758 5.80267044 -0.7625054 0.4485167
## age               0.04156298 0.06625088  0.6273574 0.5326226
## sexfemale         2.19566670 1.76866271  1.2414276 0.2189092
## MADRS_Score_BL    0.36839350 0.15594430  2.3623402 0.0211641
## KYN_SER_ratio_BL -0.01353077 0.01129962 -1.1974529 0.2354788
## 
## $QUIN_PIC_ratio_BL
##                      Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)       -2.41285518 5.65454097 -0.4267111 0.67099981
## age                0.04346763 0.06714983  0.6473230 0.51970264
## sexfemale          2.13030248 1.77198087  1.2022153 0.23364160
## MADRS_Score_BL     0.34155526 0.15232527  2.2422758 0.02836161
## QUIN_PIC_ratio_BL -0.19953907 0.20126686 -0.9914154 0.32515915
## 
## $QUIN_KYNA_ratio_BL
##                      Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)        -2.2648221 5.72271064 -0.3957604 0.69357785
## age                 0.0323736 0.06619247  0.4890829 0.62642935
## sexfemale           2.1183700 1.78933670  1.1838856 0.24076977
## MADRS_Score_BL      0.3416165 0.15686609  2.1777589 0.03305891
## QUIN_KYNA_ratio_BL -0.1753178 0.28868070 -0.6073071 0.54576293
## 
## $threeHK_KYN_ratio_BL
##                           Estimate   Std. Error     t value  Pr(>|t|)
## (Intercept)             0.27057732   6.57504195  0.04115218 0.9673007
## age                     0.02443601   0.06616923  0.36929575 0.7131076
## sexfemale               2.16349114   1.78023547  1.21528369 0.2286538
## MADRS_Score_BL          0.29384566   0.15206417  1.93237941 0.0576726
## threeHK_KYN_ratio_BL -130.25293691 145.92107330 -0.89262595 0.3753503
## 
## $threeHK_KYNA_ratio_BL
##                          Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)           -3.51303813 5.71337423 -0.6148798 0.54078079
## age                    0.02720087 0.06590342  0.4127383 0.68115662
## sexfemale              1.53251305 1.82814411  0.8382890 0.40494056
## MADRS_Score_BL         0.30235417 0.15072550  2.0059921 0.04902221
## threeHK_KYNA_ratio_BL  1.67492806 1.79648645  0.9323355 0.35461346
## 
## $IL1B_pg_mL_BL
##                   Estimate Std. Error    t value  Pr(>|t|)
## (Intercept)     1.94840463  8.4467840  0.2306682 0.8218065
## age            -0.06432802  0.0897615 -0.7166549 0.4885241
## sexfemale      -3.45150235  2.4417385 -1.4135430 0.1851657
## MADRS_Score_BL  0.30153935  0.2092171  1.4412748 0.1773626
## IL1B_pg_mL_BL   4.65878301  2.7420909  1.6989893 0.1173910
## 
## $IL1B_pg_mL_LLOD_BL
##                       Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)        -3.52216904 6.04197722 -0.5829497 0.56194421
## age                 0.03032311 0.06619738  0.4580712 0.64842901
## sexfemale           1.90234800 1.78511278  1.0656738 0.29051364
## MADRS_Score_BL      0.31842971 0.15117004  2.1064340 0.03903206
## IL1B_pg_mL_LLOD_BL  2.15258209 5.55376780  0.3875895 0.69958616
## 
## $IL2_pg_mL_BL
##                   Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)    -3.66265246 6.16791543 -0.5938234 0.55605914
## age             0.08433111 0.07835339  1.0762918 0.28840993
## sexfemale      -1.40935759 1.96335717 -0.7178305 0.47713997
## MADRS_Score_BL  0.31240954 0.14832673  2.1062255 0.04167179
## IL2_pg_mL_BL    0.26292895 0.14062719  1.8696879 0.06904819
## 
## $IL2_pg_mL_LLOD_BL
##                      Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)       -2.77774855 5.61729527 -0.4944993 0.62262084
## age                0.04006734 0.06590189  0.6079847 0.54531620
## sexfemale          1.81830336 1.75990594  1.0331821 0.30534756
## MADRS_Score_BL     0.29745317 0.14984381  1.9850882 0.05135752
## IL2_pg_mL_LLOD_BL  0.20579568 0.15991206  1.2869303 0.20268283
## 
## $IL4_pg_mL_BL
##                   Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)    -4.93790457  7.1147701 -0.6940357 0.49013289
## age             0.03815275  0.0679684  0.5613307 0.57650232
## sexfemale       1.89981288  1.7799686  1.0673294 0.28977130
## MADRS_Score_BL  0.33295323  0.1547077  2.1521434 0.03510509
## IL4_pg_mL_BL   15.89000399 30.8060198  0.5158084 0.60773837
## 
## $IL4_pg_mL_LLOD_BL
##                      Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)       -4.93790457  7.1147701 -0.6940357 0.49013289
## age                0.03815275  0.0679684  0.5613307 0.57650232
## sexfemale          1.89981288  1.7799686  1.0673294 0.28977130
## MADRS_Score_BL     0.33295323  0.1547077  2.1521434 0.03510509
## IL4_pg_mL_LLOD_BL 15.89000399 30.8060198  0.5158084 0.60773837
## 
## $IL6_pg_mL_BL
##                   Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)    -2.70166264 5.67659952 -0.4759298 0.63572018
## age             0.03909381 0.06836381  0.5718495 0.56939635
## sexfemale       2.15888097 1.81020824  1.1926147 0.23735582
## MADRS_Score_BL  0.32666145 0.15240601  2.1433633 0.03583147
## IL6_pg_mL_BL   -0.84066672 1.61306677 -0.5211605 0.60402606
## 
## $IL8_pg_mL_BL
##                   Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)    -3.29183959 6.04521446 -0.5445364 0.58793572
## age             0.02647845 0.06749994  0.3922737 0.69613930
## sexfemale       2.04122779 1.79467791  1.1373783 0.25955555
## MADRS_Score_BL  0.31849852 0.15151239  2.1021285 0.03942092
## IL8_pg_mL_BL    0.12356452 0.44860130  0.2754440 0.78384892
## 
## $IL10_pg_mL_BL
##                   Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)    -2.79737419 5.59000500 -0.5004243 0.61846656
## age             0.03899341 0.06538784  0.5963404 0.55301911
## sexfemale       2.28791359 1.75961071  1.3002385 0.19811085
## MADRS_Score_BL  0.31019161 0.14852278  2.0885120 0.04067294
## IL10_pg_mL_BL  -0.58099577 0.38227481 -1.5198380 0.13340137
## 
## $IL12p70_pg_mL_BL
##                      Estimate  Std. Error    t value   Pr(>|t|)
## (Intercept)      -3.466481542 5.838077681 -0.5937711 0.55472607
## age               0.037018177 0.067356746  0.5495838 0.58448826
## sexfemale         2.137198554 1.800091511  1.1872722 0.23944111
## MADRS_Score_BL    0.324814518 0.151822804  2.1394317 0.03616096
## IL12p70_pg_mL_BL  0.002123869 0.003922363  0.5414768 0.59003021
## 
## $IL12p70_pg_mL_LLOD_BL
##                           Estimate  Std. Error    t value   Pr(>|t|)
## (Intercept)           -3.466481542 5.838077681 -0.5937711 0.55472607
## age                    0.037018177 0.067356746  0.5495838 0.58448826
## sexfemale              2.137198554 1.800091511  1.1872722 0.23944111
## MADRS_Score_BL         0.324814518 0.151822804  2.1394317 0.03616096
## IL12p70_pg_mL_LLOD_BL  0.002123869 0.003922363  0.5414768 0.59003021
## 
## $IL13_pg_mL_BL
##                   Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)    -3.10702106 6.00232041 -0.5176367 0.60649648
## age             0.03564911 0.06788236  0.5251602 0.60128652
## sexfemale       1.91146877 1.82978949  1.0446386 0.30011973
## MADRS_Score_BL  0.31767033 0.15307822  2.0752157 0.04199115
## IL13_pg_mL_BL   0.03436600 0.07236991  0.4748658 0.63649911
## 
## $IL13_pg_mL_LLOD_BL
##                       Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)        -3.65357191 5.92960864 -0.6161573 0.53994254
## age                 0.03757651 0.06756711  0.5561362 0.58002728
## sexfemale           2.12748386 1.79724562  1.1837469 0.24082432
## MADRS_Score_BL      0.32581687 0.15205866  2.1427052 0.03588644
## IL13_pg_mL_LLOD_BL  0.03881203 0.07181994  0.5404074 0.59076308
## 
## $TNFa_pg_mL_BL
##                   Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)    -3.71980764 6.77189500 -0.5493008 0.58468128
## age             0.02797976 0.06668156  0.4196026 0.67615940
## sexfemale       2.08155451 1.82267125  1.1420351 0.25762902
## MADRS_Score_BL  0.32320935 0.15395791  2.0993358 0.03967494
## TNFa_pg_mL_BL   0.54007101 1.99875857  0.2702032 0.78785998
## 
## $IFNy_pg_mL_BL
##                   Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)    -2.64196136 5.65200131 -0.4674382 0.64174972
## age             0.03070213 0.06584321  0.4662915 0.64256580
## sexfemale       1.89829334 1.76831688  1.0735029 0.28701473
## MADRS_Score_BL  0.34563856 0.15371198  2.2486117 0.02793366
## IFNy_pg_mL_BL  -0.12461807 0.13488439 -0.9238880 0.35896172
## 
## $CRP_ng_mL_BL
##                     Estimate   Std. Error    t value   Pr(>|t|)
## (Intercept)    -2.7428400710 5.6487622234 -0.4855648 0.62890852
## age             0.0259289978 0.0659522219  0.3931482 0.69549654
## sexfemale       1.8308947880 1.7718902557  1.0333003 0.30529268
## MADRS_Score_BL  0.3089160464 0.1501931166  2.0567923 0.04372399
## CRP_ng_mL_BL    0.0001520577 0.0001591488  0.9554432 0.34289364
## 
## $NIC_nM_BL
##                    Estimate  Std. Error    t value   Pr(>|t|)
## (Intercept)    -2.996258698 5.692243733 -0.5263757 0.60041880
## age             0.030144683 0.066097184  0.4560661 0.64986262
## sexfemale       1.865123625 1.782838193  1.0461542 0.29936467
## MADRS_Score_BL  0.324974211 0.151647841  2.1429531 0.03586572
## NIC_nM_BL       0.001219065 0.002085866  0.5844405 0.56094709
## 
## $NIC_nM_LLOD_BL
##                    Estimate  Std. Error    t value   Pr(>|t|)
## (Intercept)    -2.996246422 5.692243274 -0.5263736 0.60042026
## age             0.030144506 0.066097190  0.4560633 0.64986456
## sexfemale       1.865122863 1.782838848  1.0461534 0.29936504
## MADRS_Score_BL  0.324974059 0.151647861  2.1429518 0.03586583
## NIC_nM_LLOD_BL  0.001219043 0.002085868  0.5844296 0.56095435
## 
## $NTA_nM_BL
##                    Estimate  Std. Error    t value  Pr(>|t|)
## (Intercept)    -4.662755308 6.365279199 -0.7325296 0.4664787
## age             0.039120683 0.067415775  0.5802897 0.5637256
## sexfemale       2.150896705 1.792019255  1.2002643 0.2343930
## MADRS_Score_BL  0.325129700 0.151326538  2.1485306 0.0354024
## NTA_nM_BL       0.003376117 0.005045707  0.6691068 0.5057970
## 
## $SAA_ng_mL_BL
##                     Estimate   Std. Error    t value   Pr(>|t|)
## (Intercept)    -2.7783468351 5.6773446094 -0.4893744 0.62622413
## age             0.0248387002 0.0668905969  0.3713332 0.71159701
## sexfemale       1.8048660835 1.8032200084  1.0009129 0.32058059
## MADRS_Score_BL  0.3073054741 0.1515338590  2.0279657 0.04666631
## SAA_ng_mL_BL    0.0002081363 0.0003998231  0.5205710 0.60443446
## 
## $VCAM_1_ng_mL_BL
##                     Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)     -0.969674261 8.16123638 -0.1188146 0.90578866
## age              0.026473244 0.06729958  0.3933642 0.69533785
## sexfemale        1.856768158 1.81798999  1.0213302 0.31088431
## MADRS_Score_BL   0.307310789 0.15322713  2.0055899 0.04906627
## VCAM_1_ng_mL_BL -0.004163622 0.01388593 -0.2998447 0.76525243
## 
## $ICAM_1_ng_mL_BL
##                    Estimate Std. Error    t value   Pr(>|t|)
## (Intercept)     -5.10066886 6.08480841 -0.8382629 0.40495512
## age              0.02517098 0.06589206  0.3820032 0.70370509
## sexfemale        2.28783944 1.78928647  1.2786323 0.20557313
## MADRS_Score_BL   0.28120026 0.15335482  1.8336578 0.07128362
## ICAM_1_ng_mL_BL  0.01066193 0.01023648  1.0415619 0.30147346

12 Model 4: Bayesian models

model1 <- brms::brm(MADRS_Score_3rd~age+sex+MADRS_Score_BL+TRP_nM_BL+five_HT_nM_BL+AA_nM_BL+IL2_pg_mL_BL, data=Biok_wide_new, family = "gaussian", prior = c(brms::set_prior("horseshoe(1)")))
## Warning: Rows containing NAs were excluded from the model.
## Compiling Stan program...
## Trying to compile a simple C file
## Running /Library/Frameworks/R.framework/Resources/bin/R CMD SHLIB foo.c
## clang -mmacosx-version-min=10.13 -I"/Library/Frameworks/R.framework/Resources/include" -DNDEBUG   -I"/Library/Frameworks/R.framework/Versions/4.1/Resources/library/Rcpp/include/"  -I"/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/"  -I"/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported"  -I"/Library/Frameworks/R.framework/Versions/4.1/Resources/library/BH/include" -I"/Library/Frameworks/R.framework/Versions/4.1/Resources/library/StanHeaders/include/src/"  -I"/Library/Frameworks/R.framework/Versions/4.1/Resources/library/StanHeaders/include/"  -I"/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppParallel/include/"  -I"/Library/Frameworks/R.framework/Versions/4.1/Resources/library/rstan/include" -DEIGEN_NO_DEBUG  -DBOOST_DISABLE_ASSERTS  -DBOOST_PENDING_INTEGER_LOG2_HPP  -DSTAN_THREADS  -DBOOST_NO_AUTO_PTR  -include '/Library/Frameworks/R.framework/Versions/4.1/Resources/library/StanHeaders/include/stan/math/prim/mat/fun/Eigen.hpp'  -D_REENTRANT -DRCPP_PARALLEL_USE_TBB=1   -I/usr/local/include   -fPIC  -Wall -g -O2  -c foo.c -o foo.o
## In file included from <built-in>:1:
## In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/StanHeaders/include/stan/math/prim/mat/fun/Eigen.hpp:13:
## In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:1:
## In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Core:88:
## /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/Macros.h:628:1: error: unknown type name 'namespace'
## namespace Eigen {
## ^
## /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/Macros.h:628:16: error: expected ';' after top level declarator
## namespace Eigen {
##                ^
##                ;
## In file included from <built-in>:1:
## In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/StanHeaders/include/stan/math/prim/mat/fun/Eigen.hpp:13:
## In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:1:
## /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Core:96:10: fatal error: 'complex' file not found
## #include <complex>
##          ^~~~~~~~~
## 3 errors generated.
## make: *** [foo.o] Error 1
## Start sampling
## 
## SAMPLING FOR MODEL '52c8d97328160311a61f9b26e277b9f1' NOW (CHAIN 1).
## Chain 1: 
## Chain 1: Gradient evaluation took 5.1e-05 seconds
## Chain 1: 1000 transitions using 10 leapfrog steps per transition would take 0.51 seconds.
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## Chain 1: 
## 
## SAMPLING FOR MODEL '52c8d97328160311a61f9b26e277b9f1' NOW (CHAIN 2).
## Chain 2: 
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## Chain 2: 
## 
## SAMPLING FOR MODEL '52c8d97328160311a61f9b26e277b9f1' NOW (CHAIN 3).
## Chain 3: 
## Chain 3: Gradient evaluation took 5.5e-05 seconds
## Chain 3: 1000 transitions using 10 leapfrog steps per transition would take 0.55 seconds.
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## Chain 3: 
## 
## SAMPLING FOR MODEL '52c8d97328160311a61f9b26e277b9f1' NOW (CHAIN 4).
## Chain 4: 
## Chain 4: Gradient evaluation took 2e-05 seconds
## Chain 4: 1000 transitions using 10 leapfrog steps per transition would take 0.2 seconds.
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## Chain 4:
## Warning: There were 486 divergent transitions after warmup. See
## https://mc-stan.org/misc/warnings.html#divergent-transitions-after-warmup
## to find out why this is a problem and how to eliminate them.
## Warning: Examine the pairs() plot to diagnose sampling problems
## Warning: Bulk Effective Samples Size (ESS) is too low, indicating posterior means and medians may be unreliable.
## Running the chains for more iterations may help. See
## https://mc-stan.org/misc/warnings.html#bulk-ess
## Warning: Tail Effective Samples Size (ESS) is too low, indicating posterior variances and tail quantiles may be unreliable.
## Running the chains for more iterations may help. See
## https://mc-stan.org/misc/warnings.html#tail-ess
model1
## Warning: There were 486 divergent transitions after warmup. Increasing
## adapt_delta above 0.8 may help. See http://mc-stan.org/misc/
## warnings.html#divergent-transitions-after-warmup
##  Family: gaussian 
##   Links: mu = identity; sigma = identity 
## Formula: MADRS_Score_3rd ~ age + sex + MADRS_Score_BL + TRP_nM_BL + five_HT_nM_BL + AA_nM_BL + IL2_pg_mL_BL 
##    Data: Biok_wide_new (Number of observations: 44) 
##   Draws: 4 chains, each with iter = 2000; warmup = 1000; thin = 1;
##          total post-warmup draws = 4000
## 
## Population-Level Effects: 
##                Estimate Est.Error l-95% CI u-95% CI Rhat Bulk_ESS Tail_ESS
## Intercept         -2.18      5.28   -12.92     7.78 1.01     1393     1372
## age                0.01      0.03    -0.02     0.12 1.00      660     2177
## sexfemale         -0.00      0.14    -0.17     0.15 1.01      725     1661
## MADRS_Score_BL     0.03      0.07    -0.03     0.26 1.00      475     1169
## TRP_nM_BL          0.00      0.00     0.00     0.00 1.01     1822      525
## five_HT_nM_BL      0.00      0.00    -0.00     0.01 1.01      797     2027
## AA_nM_BL          -0.03      0.09    -0.36     0.04 1.00      723     1245
## IL2_pg_mL_BL       0.01      0.05    -0.04     0.16 1.00     1428     1841
## 
## Family Specific Parameters: 
##       Estimate Est.Error l-95% CI u-95% CI Rhat Bulk_ESS Tail_ESS
## sigma     5.83      0.62     4.81     7.22 1.00     1585     1564
## 
## Draws were sampled using sampling(NUTS). For each parameter, Bulk_ESS
## and Tail_ESS are effective sample size measures, and Rhat is the potential
## scale reduction factor on split chains (at convergence, Rhat = 1).
model2 <- brms::brm(MADRS_Score_3rd~age+sex+MADRS_Score_BL, data=Biok_wide_new, family = "gaussian", prior = c(brms::set_prior("horseshoe(1)")))
## Warning: Rows containing NAs were excluded from the model.
## Compiling Stan program...
## Trying to compile a simple C file
## Running /Library/Frameworks/R.framework/Resources/bin/R CMD SHLIB foo.c
## clang -mmacosx-version-min=10.13 -I"/Library/Frameworks/R.framework/Resources/include" -DNDEBUG   -I"/Library/Frameworks/R.framework/Versions/4.1/Resources/library/Rcpp/include/"  -I"/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/"  -I"/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/unsupported"  -I"/Library/Frameworks/R.framework/Versions/4.1/Resources/library/BH/include" -I"/Library/Frameworks/R.framework/Versions/4.1/Resources/library/StanHeaders/include/src/"  -I"/Library/Frameworks/R.framework/Versions/4.1/Resources/library/StanHeaders/include/"  -I"/Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppParallel/include/"  -I"/Library/Frameworks/R.framework/Versions/4.1/Resources/library/rstan/include" -DEIGEN_NO_DEBUG  -DBOOST_DISABLE_ASSERTS  -DBOOST_PENDING_INTEGER_LOG2_HPP  -DSTAN_THREADS  -DBOOST_NO_AUTO_PTR  -include '/Library/Frameworks/R.framework/Versions/4.1/Resources/library/StanHeaders/include/stan/math/prim/mat/fun/Eigen.hpp'  -D_REENTRANT -DRCPP_PARALLEL_USE_TBB=1   -I/usr/local/include   -fPIC  -Wall -g -O2  -c foo.c -o foo.o
## In file included from <built-in>:1:
## In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/StanHeaders/include/stan/math/prim/mat/fun/Eigen.hpp:13:
## In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:1:
## In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Core:88:
## /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/Macros.h:628:1: error: unknown type name 'namespace'
## namespace Eigen {
## ^
## /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/src/Core/util/Macros.h:628:16: error: expected ';' after top level declarator
## namespace Eigen {
##                ^
##                ;
## In file included from <built-in>:1:
## In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/StanHeaders/include/stan/math/prim/mat/fun/Eigen.hpp:13:
## In file included from /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Dense:1:
## /Library/Frameworks/R.framework/Versions/4.1/Resources/library/RcppEigen/include/Eigen/Core:96:10: fatal error: 'complex' file not found
## #include <complex>
##          ^~~~~~~~~
## 3 errors generated.
## make: *** [foo.o] Error 1
## Start sampling
## 
## SAMPLING FOR MODEL 'ab9e8ab03165e24c9459e4812c601265' NOW (CHAIN 1).
## Chain 1: 
## Chain 1: Gradient evaluation took 4.6e-05 seconds
## Chain 1: 1000 transitions using 10 leapfrog steps per transition would take 0.46 seconds.
## Chain 1: Adjust your expectations accordingly!
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## Chain 1: 
## 
## SAMPLING FOR MODEL 'ab9e8ab03165e24c9459e4812c601265' NOW (CHAIN 2).
## Chain 2: 
## Chain 2: Gradient evaluation took 1.9e-05 seconds
## Chain 2: 1000 transitions using 10 leapfrog steps per transition would take 0.19 seconds.
## Chain 2: Adjust your expectations accordingly!
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## Chain 2: 
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## Chain 2: 
## 
## SAMPLING FOR MODEL 'ab9e8ab03165e24c9459e4812c601265' NOW (CHAIN 3).
## Chain 3: 
## Chain 3: Gradient evaluation took 2e-05 seconds
## Chain 3: 1000 transitions using 10 leapfrog steps per transition would take 0.2 seconds.
## Chain 3: Adjust your expectations accordingly!
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## Chain 3: 
## 
## SAMPLING FOR MODEL 'ab9e8ab03165e24c9459e4812c601265' NOW (CHAIN 4).
## Chain 4: 
## Chain 4: Gradient evaluation took 1.7e-05 seconds
## Chain 4: 1000 transitions using 10 leapfrog steps per transition would take 0.17 seconds.
## Chain 4: Adjust your expectations accordingly!
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## Chain 4:
## Warning: There were 255 divergent transitions after warmup. See
## https://mc-stan.org/misc/warnings.html#divergent-transitions-after-warmup
## to find out why this is a problem and how to eliminate them.
## Warning: Examine the pairs() plot to diagnose sampling problems
model2
## Warning: There were 255 divergent transitions after warmup. Increasing
## adapt_delta above 0.8 may help. See http://mc-stan.org/misc/
## warnings.html#divergent-transitions-after-warmup
##  Family: gaussian 
##   Links: mu = identity; sigma = identity 
## Formula: MADRS_Score_3rd ~ age + sex + MADRS_Score_BL 
##    Data: Biok_wide_new (Number of observations: 70) 
##   Draws: 4 chains, each with iter = 2000; warmup = 1000; thin = 1;
##          total post-warmup draws = 4000
## 
## Population-Level Effects: 
##                Estimate Est.Error l-95% CI u-95% CI Rhat Bulk_ESS Tail_ESS
## Intercept          0.28      5.71   -11.12    10.41 1.00     1733     2245
## age                0.01      0.06    -0.09     0.13 1.00     2711     2929
## sexfemale          0.57      1.04    -1.00     3.04 1.00      832      706
## MADRS_Score_BL     0.26      0.16    -0.02     0.59 1.00     1731     1533
## 
## Family Specific Parameters: 
##       Estimate Est.Error l-95% CI u-95% CI Rhat Bulk_ESS Tail_ESS
## sigma     6.98      0.59     6.00     8.20 1.01      696     2600
## 
## Draws were sampled using sampling(NUTS). For each parameter, Bulk_ESS
## and Tail_ESS are effective sample size measures, and Rhat is the potential
## scale reduction factor on split chains (at convergence, Rhat = 1).

This will fit two Bayesian models to predict MADRS_Score_3rd using all the markers or none of the markers. Now we’ll begin to quantify how accurate we can be by comparing the two model’s accuracy. When this is fit, we can discuss how to turn it into something we can more easily interpret.