Mark J Niciu1, Chadi G Abdallah2, Lisa R Fenton3, Madonna K Fasula4, Anne Black3, George M Anderson5, Gerard Sanacora4. 1. National Institutes of Health, National Institute of Mental Health, Experimental Therapeutics and Pathophysiology Branch, Building 10/CRC, 10 Center Dr., Bethesda, MD 20892, USA. Electronic address: mark.niciu@nih.gov. 2. Yale University Department of Psychiatry/Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, 34 Park St., 3rd floor, New Haven, CT 06519, USA; Clinical Neuroscience Division, Veterans Affairs National Center for PTSD, Veterans Affairs Connecticut Healthcare System, 950 Campbell Ave., West Haven, CT 06516, USA. 3. Veterans Affairs Connecticut Healthcare System, 950 Campbell Ave., West Haven, CT 06516, USA. 4. Yale University Department of Psychiatry/Connecticut Mental Health Center, Abraham Ribicoff Research Facilities, 34 Park St., 3rd floor, New Haven, CT 06519, USA. 5. Yale Child Study Center, 230 South Frontage Rd., New Haven, CT 06519, USA.
Abstract
BACKGROUND: There is a clinical need for evidence-based psychotherapy response biomarkers in major depressive disorder (MDD). Based on previous studies, we hypothesized that lower 24-h urinary cortisol levels and a history of early life stress/trauma would predict an improved antidepressant response to cognitive-behavioral therapy (CBT). METHODS: 50 currently depressed MDD subjects were enrolled. 24-h urine was collected and measured for cortisol levels by radioimmunoassay (RIA). Subjects were also administered early life stress/trauma measures at baseline: Global Perceived Early-Life Stress (GPELS), The Early Life Trauma Inventory (ELTI) and Klein Loss Scale (KLS). The efficacy of a twelve-week course of once-weekly CBT was evaluated by the primary outcome measure, the 24-item Hamilton Depression Rating Scale (HDRS24), at baseline and every four weeks, and the Beck Depression Inventory at baseline and weekly thereafter. 42 subjects had at least one complete follow-up visit (≥4 weeks of CBT), and 30 subjects completed the full 12-week course. RESULTS: Baseline 24-h urinary cortisol levels did not correlate with CBT's antidepressant response. Higher KLS scores, a measure of early life parental loss or separation, correlated with delta HDRS24 (rs=-0.39, padjusted=0.05). Complementary general linear model analysis revealed enhanced CBT efficacy in patients with a history of early life parental loss or separation [F(1,35)=6.65, p=0.01]. LIMITATIONS: Small sample size, Treatment-naïve population. CONCLUSIONS: Early life parental separation or loss positively correlated with CBT's antidepressant efficacy in our sample and may warrant further study in larger clinical samples.
BACKGROUND: There is a clinical need for evidence-based psychotherapy response biomarkers in major depressive disorder (MDD). Based on previous studies, we hypothesized that lower 24-h urinary cortisol levels and a history of early life stress/trauma would predict an improved antidepressant response to cognitive-behavioral therapy (CBT). METHODS: 50 currently depressed MDD subjects were enrolled. 24-h urine was collected and measured for cortisol levels by radioimmunoassay (RIA). Subjects were also administered early life stress/trauma measures at baseline: Global Perceived Early-Life Stress (GPELS), The Early Life Trauma Inventory (ELTI) and Klein Loss Scale (KLS). The efficacy of a twelve-week course of once-weekly CBT was evaluated by the primary outcome measure, the 24-item Hamilton Depression Rating Scale (HDRS24), at baseline and every four weeks, and the Beck Depression Inventory at baseline and weekly thereafter. 42 subjects had at least one complete follow-up visit (≥4 weeks of CBT), and 30 subjects completed the full 12-week course. RESULTS: Baseline 24-h urinary cortisol levels did not correlate with CBT's antidepressant response. Higher KLS scores, a measure of early life parental loss or separation, correlated with delta HDRS24 (rs=-0.39, padjusted=0.05). Complementary general linear model analysis revealed enhanced CBT efficacy in patients with a history of early life parental loss or separation [F(1,35)=6.65, p=0.01]. LIMITATIONS: Small sample size, Treatment-naïve population. CONCLUSIONS: Early life parental separation or loss positively correlated with CBT's antidepressant efficacy in our sample and may warrant further study in larger clinical samples.
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