Samuel J. Ridout

Depression and telomere length: A meta-analysis

BACKGROUND Several recent studies have investigated the relationship between telomere length and depression with inconsistent results. This meta-analysis examined whether telomere length and depression are associated and explored factors that might affect this association. METHODS Studies measuring telomere length in subjects with clinically significant unipolar depression were included. A comprehensive search strategy identified studies in PubMed, MEDLINE, PsycINFO, Global Health, The Cochrane Library, and Web of Science. A structured data abstraction form was used and studies were appraised for inclusion or exclusion using a priori conditions. Analyses were conducted using standardized mean differences in a continuous random effects model. RESULTS Thirty-eight studies (N=34,347) met the inclusion criteria. The association between depression and telomere length was significant, with a Cohens d effect size of -0.205 (p<0.0001, I(2)=42%). Depression severity significantly associated with telomere length (p=0.03). Trim and fill analysis indicated the presence of publication bias (p=0.003), but that the association remained highly significant after accounting for the bias. Subgroup analysis revealed depression assessment tools, telomere measurement techniques, source tissue and comorbid medical conditions significantly affected the relationship. LIMITATIONS Other potentially important sub-groups, including antidepressant use, have not been investigated in sufficient detail or number yet and thus were not addressed in this meta-analysis. CONCLUSIONS There is a negative association between depression and telomere length. Further studies are needed to clarify potential causality underlying this association and to elucidate the biology linking depression and this cellular marker of stress exposure and aging.

Association of telomere length and mitochondrial DNA copy number in a community sample of healthy adults.

Cellular aging plays a role in longevity and senescence, and has been implicated in medical and psychiatric conditions, including heart disease, cancer, major depression and posttraumatic stress disorder. Telomere shortening and mitochondrial dysfunction are thought to be central to the cellular aging process. The present study examined the association between mitochondrial DNA (mtDNA) copy number and telomere length in a sample of medically healthy adults. Participants (total n=392) were divided into 4 groups based on the presence or absence of early life adversity and lifetime psychopathology: No Adversity/No Disorder, n=136; Adversity/No Disorder, n=91; No Adversity/Disorder, n=46; Adversity/Disorder, n=119. Telomere length and mtDNA copy number were measured using quantitative polymerase chain reaction. There was a positive correlation between mtDNA and telomere length in the entire sample (r=0.120, p<0.001) and in each of the four groups of participants (No Adversity/No Disorder, r=0.291, p=0.001; Adversity/No Disorder r=0.279, p=0.007; No Adversity/Disorder r=0.449, p=0.002; Adversity/Disorder, r=0.558, p<0.001). These correlations remained significant when controlling for age, smoking, and body mass index and establish an association between mtDNA and telomere length in a large group of women and men both with and without early adversity and psychopathology, suggesting co-regulation of telomeres and mitochondrial function. The mechanisms underlying this association may be important in the pathophysiology of age-related medical conditions, such as heart disease and cancer, as well as for stress-associated psychiatric disorders.

5-Hz Transcranial Magnetic Stimulation for Comorbid Posttraumatic Stress Disorder and Major Depression.

Current treatment options for posttraumatic stress disorder (PTSD) offer modest benefits, underscoring the need for new treatments. Repetitive transcranial magnetic stimulation (rTMS) depolarizes neurons in a targeted brain region with magnetic fields typically pulsed at low (1 Hz) or high (10 Hz) frequency to relieve major depressive disorder (MDD). Prior work suggests an intermediate pulse frequency, 5 Hz, is also efficacious for treating comorbid depressive and anxiety symptoms. In this chart review study, we systematically examined the clinical and safety outcomes in 10 patients with comorbid MDD and PTSD syndromes who received 5-Hz rTMS therapy at the Providence VA Medical Center Neuromodulation Clinic. Self-report scales measured illness severity prior to treatment, after every 5 treatments, and upon completion of treatment. Results showed significant reduction in symptoms of PTSD (p = .003, effect size = 1.12, 8/10 with reliable change) and MDD (p = .005, effect size = 1.09, 6/10 with reliable change). Stimulation was well tolerated and there were no serious adverse events. These data indicate 5-Hz rTMS may be a useful option to treat these comorbid disorders. Larger, controlled trials are needed to confirm the benefits of 5-Hz protocols observed in this pilot study.

5 Hz Repetitive transcranial magnetic stimulation to left prefrontal cortex for major depression

BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) to left prefrontal cortex at 10Hz is the most commonly utilized protocol for major depressive disorder (MDD). Published data suggests that left sided 5Hz rTMS may be efficacious and well tolerated. OBJECTIVE We analyzed outcomes in a naturalistic cohort of MDD patients who could not tolerate 10Hz rTMS and were routinely switched to 5Hz. We hypothesized that the efficacy of 5Hz rTMS would be equivalent to 10Hz. METHODS Records were reviewed for patients (n=98) who received 15 or more acute rTMS treatments. The sample was split based upon the frequency (10 or 5Hz) at which the majority of treatments were delivered. The Inventory of Depressive Symptoms (IDS-SR) and 9-Item Patient Health Questionnaire (PHQ-9) were used to evaluate outcomes. RESULTS Baseline IDS-SR was higher in the 5Hz (n=27) than in the 10Hz (n=71) group (p<.05), as was frequency of comorbid anxiety (p=.002). Depression outcomes did not differ between groups, and there were no differences in response or remission rates (all p>.1). Statistical power was sufficient to detect small group differences (d=.26). LIMITATIONS Open-label data in a naturalistic setting. CONCLUSION Outcomes associated with 5Hz rTMS did not differ from 10Hz, despite higher baseline depressive symptom severity and anxiety in 5Hz patients. 5Hz stimulation may be an alternative treatment option for patients unable to tolerate 10Hz rTMS.

Sudden-onset dystonia in a patient taking asenapine: interaction between ciprofloxacin and asenapine metabolism.

Asenapine is a newer second generation antipsychotic (SGA) that is primarily metabolized by Uridine 5′-diphospho-glucuronosyltransferase 1A4 (UGT1A4) and cytochrome p450 (CYP)1A2 (1). When co-administered with inducers or inhibitors of CYP enzymes, antipsychotic plasma levels may be reduced or increased, respectively, resulting in a reduced effectiveness of the antipsychotic or an increased risk of adverse events (2). Here, we report a potential drug-drug interaction leading to an adverse effect during a psychiatric inpatient hospitalization.

Heart Rate Variability Responses to a Standardized Virtual Reality Exposure in Veterans with PTSD

Opinion StatementPurpose In this article, we present data incorporating heart rate variability (HRV) into a graded virtual reality protocol performed in both a combat environment and an active control (classroom) environment, for combat Veterans with and without PTSD. Recent Findings Exposure therapy for PTSD has proven effective. There is increasing interest in the use of virtual reality exposure therapy (VRET)-customized environments incorporating auditory, visual, and olfactory sensory modalities, to augment exposure-based treatment for PTSD. Particularly for combat Veterans, VRET may offer the advantage of a more realistic in vivo exposure for treatment. When combined with concurrent psychophysiological data, VRET has the potential to inform PTSD diagnosis, predict therapeutic responsiveness, and provide objective indicators of treatment response. HRV was not different between Veteran with and without PTSD, but our group recently found that Veterans with PTSD had differential skin conductance responses compared with Veterans without PTSD. Summary Virtual reality is a promising treatment for PTSD. Methodological factors may have influenced the absence of significant findings in the current data. Future research which optimizes the potential use of psychophysiological assessments for the development of biomarkers and prediction of PTSD treatment response, or to inform the process of PTSD treatment, remain important.