Feasibility of Computerized Cognitive-Behavioral Therapy Combined With Bifrontal Transcranial Direct Current Stimulation for Treatment of Major Depression.

BACKGROUND: Cognitive behavioral therapy (CBT) is effective in the treatment of major depressive disorder (MDD). Transcranial Direct Current Stimulation (tDCS) has demonstrated preliminary antidepressant effects and beneficial effects on cognitive function. OBJECTIVE: We investigated the feasibility and acceptability of using tDCS to enhance the effects of computer-based CBT for treatment of MDD. MATERIALS AND METHODS: In a randomized, double-blind, sham-controlled study, 14 patients with MDD on stable or no pharmacotherapy received active or sham bifrontal tDCS for four weeks with concurrent CBT. RESULTS: Ten participants completed the protocol. Three withdrew from the study because of lack of efficacy or dislike of the eCBT program. One was discontinued from the protocol by the investigators. Treatment was well tolerated, and most side-effects were mild and consistent with prior tDCS research. Pooled data from both groups showed significant baseline to endpoint improvement in depression (p = 0.008). Overall percent change on the HAMD-21 was 28.98%. The study was underpowered to detect differences in tDCS treatment groups. CONCLUSIONS: Combining tDCS with computer-based CBT is feasible for MDD. Further work is needed to evaluate potential synergistic effects of combined tDCS and CBT.

5 Hz Repetitive transcranial magnetic stimulation for posttraumatic stress disorder comorbid with major depressive disorder.

BACKGROUND: Standard clinical protocols for repetitive transcranial magnetic stimulation (rTMS) for major depressive disorder (MDD) apply 10 Hz pulses over left prefrontal cortex, yet little is known about the effects of rTMS in more diagnostically complex depressed patients. OBJECTIVE/HYPOTHESIS: Posttraumatic stress disorder (PTSD) is commonly comorbid with MDD, and while rTMS has been shown to alleviate PTSD symptoms in preliminary studies, ideal parameters remain unclear. We conducted a prospective, open-label study of 5 Hz rTMS for patients with comorbid PTSD + MDD and hypothesized stimulation would reduce symptoms of both disorders. METHODS: Outpatients (N = 40) with PTSD + MDD and at least moderate global severity were enrolled. 5 Hz rTMS included up to 40 daily sessions followed by a 5-session taper. Symptoms were measured using the PTSD Checklist (PCL-5) and Inventory of Depressive Symptomatology, Self-Report (IDS-SR). Baseline-to-endpoint changes were analyzed. RESULTS: The intent-to-treat population included 35 participants. Stimulation significantly reduced PTSD symptoms (PCL-5 baseline mean ±â€¯SD score 52.2 ±â€¯13.1 versus endpoint 34.0 ±â€¯21.6; p < .001); 23 patients (48.6%) met a pre-defined categorical PTSD response criteria. MDD symptoms also improved significantly (IDS-SR, baseline 47.8 ±â€¯11.9 to endpoint 30.9 ±â€¯18.9; p < .001); 15 patients (42.9%) demonstrated categorical response and 12 (34.3%) remitted. PTSD and MDD symptom change was highly correlated (r = 0.91, p < .001). LIMITATIONS: Unblinded single-arm study, with modest sample size. CONCLUSION: Significant and clinically meaningful reductions in both MDD and PTSD symptoms were observed following stimulation. The preliminary efficacy of 5 Hz rTMS for both symptom domains in patients with comorbid disorders supports future controlled studies.

Alterations of Mitochondrial DNA Copy Number and Telomere Length With Early Adversity and Psychopathology.

BACKGROUND: Telomere shortening and alterations of mitochondrial biogenesis are involved in cellular aging. Childhood adversity is associated with telomere shortening, and several investigations have shown short telomeres in psychiatric disorders. Recent studies have examined whether mitochondria might be involved in neuropsychiatric conditions; findings are limited and no prior work has examined this in relation to stress exposure. METHODS: Two-hundred ninety healthy adults provided information on childhood parental loss and maltreatment and completed diagnostic interviews. Participants were categorized into four groups based upon the presence or absence of childhood adversity and the presence or absence of lifetime psychopathology (depressive, anxiety, and substance use disorders). Telomere length and mitochondrial DNA (mtDNA) copy number were measured from leukocyte DNA by quantitative polymerase chain reaction. RESULTS: Childhood adversity and lifetime psychopathology were each associated with shorter telomeres (p < .01) and higher mtDNA copy numbers (p < .001). Significantly higher mtDNA copy numbers and shorter telomeres were seen in individuals with major depression, depressive disorders, and anxiety disorders, as well as those with parental loss and childhood maltreatment. A history of substance disorders was also associated with significantly higher mtDNA copy numbers. CONCLUSIONS: This study provides the first evidence of an alteration of mitochondrial biogenesis with early life stress and with anxiety and substance use disorders. We replicate prior work on telomere length and psychopathology and show that this effect is not secondary to medication use or comorbid medical illness. Finally, we show that early life stress and psychopathology are each associated with these markers of cellular aging.

Pavlovian contextual and instrumental biconditional discrimination learning in mice.

Genetically-modified animal models are a powerful tool for investigating the link between neurological and behavioral changes and for the development of therapeutic interventions. Executive function deficits are symptomatic of many human clinical disorders but few tasks exist for studying executive functions in mice. To address this need, we describe procedures for establishing Pavlovian contextual and instrumental biconditional discriminations (BCDs) in C57BL/6J mice. In the first experiment, contextual cues disambiguated when two short duration stimulus targets would be followed by food pellets. In the second experiment, discrete visual cues signaled when lever press or nose poke responses would be continuously reinforced with food pellets. Mice learned both BCDs as evidenced by differential responding in each cue during training and, more critically, during extinction testing. The implications of these findings for using BCD tasks to analyze the neural substrates of executive processing in animal models are discussed.