HPA-axis genes as potential risk variants for neurocognitive decline in trauma-exposed, HIV-positive females

Figures & data

Figure 1 Haplotype block structure for CRHBP and CRHR1.

Note: The numbers in the squares refer to pairwise linkage disequilibrium (LD) measured as D, with darker colors depicting stronger LD.

Table 1 Demographic and clinical characteristics of study participants (n=128) showing differences between those with/without childhood trauma exposure

Variable	Overall (n=128)	Childhood trauma exposure
		No (n=40)	Yes (n=88)	T	χ^2	P-value
Mean age in years (SD)	33.2 (6.8)	32.0 (6.8)	33.7 (6.8)	−1.33	–	0.19
Mean years of education (SD)	10.1 (1.7)	10.5 (1.3)	10.0 (1.8)	1.70		0.09
Marital status, n (%)
Single/separate	102 (79.7)	30 (29.4)	72 (70.6)	–	0.790	0.48
Married/cohabiting	26 (20.3)	10 (38.5)	16 (61.5)
Unemployed	85 (66.4)	24 (60.0)	61 (69.3)		1.070	0.32
Median CD4 T lymphocyte count (IQR)	396.0 (237.8–587.5)	347.0 (195.3–587.5)	416.0 (259.5–604.8)	−0.94	–	0.35
On ARVs, n (%)	58 (41.4)	14 (31.1)	41 (46.3)	–	1.508	0.25
Median CTQ-SF (IQR)	53.0 (37.5–70.5)	325.5 (29–36)	61.5 (53–77.75)	−18.09	–	<0.01
Depression (MDD, single), n (%)	6 (5)	0 (0)	6 (7)			0.09
Depression (MDD, recurrent), n (%)	9 (7)	0 (0)	9 (10)			0.04*
Median CES-D total score (IQR)	8.5 (0–27)	4 (0–11.75)	14 (0–48.1)	−3.70	–	<0.01

Notes:

* Indicates a significant chi-squared or t-test at P<0.05.

Abbreviations: ARV, antiretroviral; CD4, cluster of differentiation 4 glycoprotein; CES-D, Center for Epidemiologic Studies Depression Scale; CTQ-SF, Childhood Trauma Questionnaire - short form; MDD, major depressive disorder, single or recurrent episode; IQR, interquartile range.

Table 2 Differences in mean global NCI scores (z-scores) by ART status

Neurocognitive domain	Mean NCI z-scores (± SD)		T value	df	P-value
	ARVs	No ARVs
Motora	−0.159 (1.500)	0.097 (0.700)	−1.170	69.8	0.246
Verbal fluency	−0.101 (0.802)	−0.204 (0.761)	0.743	126	0.459
Working memory	−0.067 (0.735)	−0.090 (0.959)	0.143	126	0.886
Speed	−0.076 (0.731)	−0.018 (0.679)	−0.463	126	0.644
Learning	−0.172 (0.870)	0.067 (0.827)	−1.578	126	0.117
Recall	−0.235 (0.938)	0.063 (0.733)	−2.017	126	0.046*
Executive functions	−0.157 (0.827)	0.078 (0.546)	−1.934	126	0.055
Global	−0.125 (0.577)	−0.011 (0.533)	−1.157	126	0.250

Notes:

a Not normally distributed. Median scores (IQR) for this domain: Not on ART = 0.241 (−0.284 to 0.550); participants on ARV = 0.278 (−0.425 to 0.702).

* Indicates a significant t-test at P<0.05.

Abbreviations: ART, antiretroviral therapy; ARV, antiretroviral; IQR, interquartile range; NCI, neurocognitive impairment.

Table 3 Differences in neurocognitive impairment (z-scores) across genotypes for CRHBP rs10062367

Genotype	Frequency, n (%)	Neurocognitive impairment
		z-score (± SD)	P-value
Codominant			0.106
G/G	40 (32.26)	0.00551 (±0.592)
G/A	57 (45.97)	−0.00474 (±0.554)
A/A	27 (21.77)	−0.25484 (±0.454)
Dominant			0.396
G/G	40 (32.26)	0.00551 (±0.592)
G/A-A/A	84 (67.74)	−0.08513 (±0.534)
Recessive			0.034*
G/G-G/A	97 (78.23)	−0.00052 (±0.567)
A/A	24 (19.35)	−0.25484 (±0.454)
Additive			0.080

Note:

* Indicates statistical significance at P<0.05.

Table 4 Predictive value of CRHR1 variants × childhood trauma interactions on cognitive domain scores

Interaction	df	Deviance residual	df residual	Deviance	P (>χ^2)
Learning
rs110402 + CTQ	122	88.690
rs110402 + CTQ + rs110402^*CTQ	121	85.212	1	3.478	0.03
rs7209436 + CTQ	123	88.864
rs7209436 + CTQ + rs7209436^*CTQ	122	85.502	1	3.362	0.03
Recall
rs110402 + CTQ	122	84.998
rs110402 + CTQ + rs110402^*CTQ	121	79.703	1	5.295	0.01
rs7209436 + CTQ	123	85.273
rs7209436 + CTQ + rs7209436^*CTQ	122	80.158	1	5.114	0.01
rs4792888 + CTQ	123	85.943
rs4792888 + CTQ + rs4792888^*CTQ	122	82.918	1	3.025	0.04

Abbreviation: CTQ, Childhood Trauma Questionnaire.