SUPPLEMENTARY DATA

Stress Challenge

Using a Chi square (χ2) test, we found no associations between diagnosis and COMT (χ2 = 0.658, p = 0.720, df = 2), between diagnosis and MAOA (χ2 = 0.812, p = 0.368, df = 1), diagnosis and 5-HTT (χ2 = 1.590, p = 0.45, df = 4) and between diagnosis and Sex (χ2 = 3.182, p = 0.074, df = 1). Likewise, no significant associations between MDRisk and COMT (χ2= 2.609, p = 0.271, df = 2), MDRisk and MAOA (χ2= 0.065, p = 0.799, df = 1), MDRisk and 5-HTT (χ2 = 0.245, p = 0.885, df = 2), and between MDRisk and sex (χ2 = 2.610, p = 0.106, df = 1) were observed. We found no association between COMT and Sex using (χ2 = 2.651, p = 0.266, df = 2), however, a significant association between MAOA and Sex was found (χ2 = 5.833, p = 0.016, df = 1) suggesting higher frequency of male representation within the group carrying the low activity MAOA while high activity allelic carriers were predominantly women (table 1h), this was not surprising given that MAOA is an X linked gene. No significant association between 5-HTT and sex was found (χ2 = 3.873, p = 0.144, df = 2). Finally, we found no significant COMT by MAOA associations (χ2 = 2.080, p = 0.353, df = 2; table 2i)n COMT and 5-HTT (χ2 = 4.909, p = 0.297, df = 4) and between MAOA and 5-HTT (χ2 = 0.078, p = 0.962, df = 2). For a summary of the demographics see TableS1.

Table1. COMT By Diagnosis

MD no MD (i.e., HRPs and healthy controls) Total

COMT

met/met 8 13 21

val/met 10 26 36

val/val 4 9 13

Total 22 48 70

. MAOA By diagnosis

COMT

Low 3 11 14

High 19 37 56

Total 22 48 70

Sex By diagnosis

COMT

male 6 24 30

female 16 24 40

Total 22 48 70

COMT By MDRisk MDRisk no MDRisk (i.e., healthy controls)

COMT

met/met 16 5 21

val/met 21 15 36

val/val 10 3 13

Total 47 23 70

MAOA By MDRisk

COMT

Low 9 5 14

High 38 18 56

Total 47 23 70

Sex By MDRisk

Sex

male 17 13 30

female 30 10 40

Total 47 23 70

COMT By Sex male female

COMT

met/met 7 14 21

val/met 15 21 36

val/val 8 5 13

Total 30 40 70

MAOA By Sex

MAOA

Low 10 4 14

High 20 36 56

Total 30 40 70

COMT By MAOA Low High

COMT

met/met 2 19 21

val/met 9 27 36

val/val 3 10 13

Total 14 56 70

5-HTT By diagnosis MD no MD

SS 13 3 16

LS 23 13 36

LL 6 12 18

48 24

5-HTT By MDRisk MDRisk no MDRisk

SS 10 6 16

LS 11 25 36

LL 12 6 18

33 37

5-HTT By sex male female

SS 10 6 16

LS 12 24 36

LL 8 10 18

30 40

5-HTT By MAO Low High

SS 3 13 16

LS 7 29 36

LL 4 14 18

14 56

5-HTT By COMT met/met val/met val/val

SS 5 10 1 16

LS 11 15 10 36

LL 5 11 2 18 21 36 13

Table 1. (a) Mean of group demographics by genotypes.

DEX/CRH Challenge

We found no associations between diagnosis and COMT (χ2, p = 0.693, df = 2; see table 3a), between diagnosis and MAOA (χ2, p = 0.158, df = 1; see table 3b) and between diagnosis and Sex (χ2, p = 0.077 (df = 1; table 3c). Likewise, no significant associations between the existence of MDRisk and COMT (χ2, p = 0.415, df = 2; table 3d), MDRisk and MAOA (χ2, p = 0.158, df = 1; table 3e) and no association was found between Sex and MDRisk (χ2, p = 0.081, df = 1; see table 3f). We found no association between COMT and Sex using (χ2, p = 0.978, df = 2; table 3g), however, a near significant association between MAOA and Sex was found (χ2, p < 0.067, df = 1; table 3h), this was not surprising given that MAOA is an X linked gene, with only females in the heterozygous group, while males can only be homozygous. Finally, we found no significant COMT by MAOA associations (χ2, p = 0.186, df = 2; table 1i). For a summary of the demographics see TableS1.

Table 2a. COMT By Diagnosis

MD no MD (i.e., HRPs and healthy controls) Total

COMT

met/met 7 11 18

val/met 9 24 33

val/val 4 9 13

Total 20 44 64

2b. MAOA By diagnosis

MAOA

Low 3 14 17

High 17 30 47

Total 20 44 64

2c. Sex By diagnosis

Sex

male 7 26 33

female 13 18 31

Total 20 44 64

2d. COMT By MDRisk MDRisk no MDRisk (i.e., healthy controls)

COMT

met/met 15 3 18

val/met 22 11 33

val/val 10 3 13

Total 47 17 64

2e. MAOA By MDRisk

MAOA

Low 12 5 17

High 35 12 47

Total 47 17 64

2f. Sex By MDRisk

Sex

male 21 12 33

female 26 5 31

Total 47 17 64

1g. COMT By Sex

male female

COMT

met/met 9 9 18

val/met 17 16 33

val/val 7 6 13

Total 33 31 64

1h. MAOA By Sex

COMT

Low activity 12 5 17

High 21 26 47

Total 33 31 64

1i. COMT by MAOA

Low High

COMT

met/met 3 15 18

val/met 12 21 33

val/val 2 11 13

Total 17 47 64

Table 2. Mean of group demographics by genotypes.