Neurotrophic factors in women with crack cocaine dependence during early abstinence: the role of early life stress

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Fig. 1
General linear models, adjusted for age and body mass index, showing differences in neurotrophic factors plasma levels between women with crack cocaine dependence with (CSA+) and without (CSA−) a history of childhood sexual abuse and healthy controls. All data are presented raw (means and standard errors of the mean). Repeated-measures analyses of covariance (ANCOVAs) showed independent pairwise comparisons among the estimated marginal means. (A) Effect of group: CSA+ > CSA−, p = 0.001; effect of time: [18 d], [11 d] > [4 d], all p < 0.001. (B–D) No specific effect of group or time. (E) No specific effect of group; effect of time: day 18 and day 11 greater than day 4, all p < 0.005. These analyses revealed a significant group × time interaction effect for glial cell line–derived neurotrophic factor (GDNF; p = 0.001) and neurotrophic factor-4/5 (NT-4/5; p = 0.004) levels and a significant general effect of time for nerve growth factor (NGF; p = 0.026). The examination of group differences at separate time points using ANCOVAs with revealed significant differences among the 3 groups: (A) c greater than f (p < 0.001); d greater than g and a (all p < 0.05); (B) h–m greater than n (all p < 0.005); (C) o greater than p–u (all p < 0.005); (D) no pairwise comparison effects; and (E) f″ greater than i″ (p = 0.012). NT-3 = neurotrophic factor-3.

Table 1

Demographic, clinical and psychosocial characteristics of the groups

	Group; no. (%)^*

Characteristic	CSA+, n = 22	CSA−, n = 82	Control, n = 20	Statistic	p value
Age, mean ± SD yr	31.8 ± 6.2	28.1 ± 7.6	29.5 ± 8.8	F_2,120 = 2.12	0.12
Menstrual cycle				χ^2₂ = 0.42	0.80
Follicular phase	13 (59.1)	47 (57.3)	10 (50)	—	—
Luteal phase	9 (40.9)	35 (42.6)	10 (50)	—	—
Comorbidities
Depressive episode	6 (27.2)	13 (15.8)	—	χ^2₁ = 1.35	0.24
Bipolar disorder	1 (4.5)	11 (13.4)	—	χ^2₁ = 1.16	0.28
Posttraumatic stress disorder	5 (22.7)	7 (8.5)	—	χ^2₁ = 2.98	0.08
Other axis I disorder	4 (18.1)	8 (9.7)	—	χ^2₁ = 1.53	0.21
Medication
Mood stabilizers	10 (45.5)	44 (53.7)	—	χ^2₁ = 0.46	0.49
Neuroleptics	10 (45.5)	48 (58.5)	—	χ^2₁ = 1.21	0.27
Antidepressants	1 (4.5)	7 (8.5)	—	χ^2₁ = 0.38	0.53
CTQ–CSA, mean ± SD	18.31 ± 5.25	6.08 ± 2.52	—	U = 98^†	< 0.001
BMI, mean ± SD
Baseline	22.8 ± 3.1	22.3 ± 3.5	23.7 ± 3.2	F_2,121 = 1.40	0.24
11 d	23.7 ± 3.2	23.1 ± 3.7	—	F_2,121 = 0.43^‡	0.65
18 d	24.3 ± 3.5	23.9 ± 3.4	—	F_2,121 = 0.14^‡	0.86

BMI = Body Mass Index; CSA+ = crack cocaine dependence with a history of childhood sexual abuse; CSA− = crack cocaine dependence without a history of childhood sexual abuse; CTQ = Childhood Trauma Questionnaire; SD = standard deviation.
↵* Unless otherwise indicated.
↵† U = Wilcoxon Mann Whitney test.
↵‡ Phase of menstrual cycle during first week of hospitalization.

Table 2

Clinical characteristics of groups

	Group; mean ± SD^*

Characteristic	CSA+, n = 22	CSA−, n = 82	Statistic^*	p value
ASI-6
Drugs	60.7 ± 8.8	63.2 ± 10.1	U = 790	0.36
Family/child	67.5 ± 8.3	66.9 ± 8.9	U = 861	0.74
Alcohol	50.8 ± 9.7	50.4 ± 9.7	U = 871	0.80
Psychiatric diagnosis	59.0 ± 6.0	56.4 ± 5.3	U = 618	0.017
Medical	47.8 ± 7.7	47.0 ± 6.7	U = 807	0.45
Legal	58.7 ± 9.5	62.4 ± 8.1	U = 677	0.07
Employment	44.0 ± 6.9	44.0 ± 8.2	U = 899	0.98
Family social support	46.9 ± 12.4	45.6 ± 11.8	U = 834	0.58
Family social problem	56.4 ± 9.0	56.4 ± 9.2	U = 898	0.97
Prior hospital admissions in last 6 mo owing to relapse, no. (%)	10 (45.5)	15 (19.5)^†	χ^2₁ = 6.11	0.013
Age at first crack cocaine use, yr	19.2 ± 6.4	18.5 ± 5.2	U = 657	0.92
Duration, yr, of crack use ≥ 3 times/wk	5.5 ± 5.3	4.6 ± 3.4	U = 703	0.99
Days of consumption in last mo	15.6 ± 13.5	16.2 ± 13.2	U = 614	0.79
Withdrawal prior to admission, d	3.9 ± 7.3	2.3 ± 3.8	U = 750	0.85
Alcohol use > 50 times, no. (%)	11 (50)	37 (45.1)	χ^2₁ = 0.39	0.53
Powder cocaine use > 50 times, no. (%)	10 (45.4)	58 (70.7)	χ^2₁ = 3.44	0.06
Marijuana use > 50 times, no. (%)	22 (100)	82 (100)	—	—
Beck Depression Inventory
4 d	33.5 ± 15.5	29.0 ± 14.6	t₁₀₂ = −1.28	0.20
11 d	24.2 ± 14.2	20.7 ± 13.5	t₁₀₂ = −1.07	0.28
18 d	18.7 ± 12.3	17.4 ± 11.3	t₁₀₂ = −1.28	0.63
Cocaine Selective Severity Assessment
4 d	60.9 ± 17.6	55.6 ± 17.4	t₁₀₁ = −1.22	0.22
11 d	53.4 ± 30.0	47.6 ± 18.5	t₁₀₁ = −1.11	0.26
18 d	53.0 ± 20.3	45.3 ± 16.4	t₁₀₀ = −1.81	0.07

ASI-6 = Addiction Severity Index; CSA+ = crack cocaine dependence with a history of childhood sexual abuse; CSA− = crack cocaine dependence without a history of childhood sexual abuse; SD = standard deviation.
↵* Wilcoxon Mann Whitney test unless otherwise indicated.
↵† n = 77.