Project description:BackgroundConventional pharmacotherapies and psychotherapies for major depression are associated with limited adherence to care and relatively low remission rates. Yoga may offer an alternative treatment option, but rigorous studies are few. This randomized controlled trial with blinded outcome assessors examined an 8-week hatha yoga intervention as mono-therapy for mild-to-moderate major depression.MethodsInvestigators recruited 38 adults in San Francisco meeting criteria for major depression of mild-to-moderate severity, per structured psychiatric interview and scores of 14-28 on Beck Depression Inventory-II (BDI). At screening, individuals engaged in psychotherapy, antidepressant pharmacotherapy, herbal or nutraceutical mood therapies, or mind-body practices were excluded. Participants were 68% female, with mean age 43.4 years (SD = 14.8, range = 22-72), and mean BDI score 22.4 (SD = 4.5). Twenty participants were randomized to 90-minute hatha yoga practice groups twice weekly for 8 weeks. Eighteen participants were randomized to 90-minute attention control education groups twice weekly for 8 weeks. Certified yoga instructors delivered both interventions at a university clinic. Primary outcome was depression severity, measured by BDI scores every 2 weeks from baseline to 8 weeks. Secondary outcomes were self-efficacy and self-esteem, measured by scores on the General Self-Efficacy Scale (GSES) and Rosenberg Self-Esteem Scale (RSES) at baseline and at 8 weeks.ResultsIn intent-to-treat analysis, yoga participants exhibited significantly greater 8-week decline in BDI scores than controls (p-value = 0.034). In sub-analyses of participants completing final 8-week measures, yoga participants were more likely to achieve remission, defined per final BDI score ≤ 9 (p-value = 0.018). Effect size of yoga in reducing BDI scores was large, per Cohen's d = -0.96 [95%CI, -1.81 to -0.12]. Intervention groups did not differ significantly in 8-week change scores for either the GSES or RSES.ConclusionIn adults with mild-to-moderate major depression, an 8-week hatha yoga intervention resulted in statistically and clinically significant reductions in depression severity.Trial registrationClinicalTrials.gov NCT01210651.
Project description:BackgroundThe objective of this study was to determine whether hatha yoga is an efficacious adjunctive intervention for individuals with continued depressive symptoms despite antidepressant treatment.MethodWe conducted a randomized controlled trial of weekly yoga classes (n = 63) v. health education classes (Healthy Living Workshop; HLW; n = 59) in individuals with elevated depression symptoms and antidepressant medication use. HLW served as an attention-control group. The intervention period was 10 weeks, with follow-up assessments 3 and 6 months afterwards. The primary outcome was depression symptom severity assessed by blind rater at 10 weeks. Secondary outcomes included depression symptoms over the entire intervention and follow-up periods, social and role functioning, general health perceptions, pain, and physical functioning.ResultsAt 10 weeks, we did not find a statistically significant difference between groups in depression symptoms (b = -0.82, s.e. = 0.88, p = 0.36). However, over the entire intervention and follow-up period, when controlling for baseline, yoga participants showed lower levels of depression than HLW participants (b = -1.38, s.e. = 0.57, p = 0.02). At 6-month follow-up, 51% of yoga participants demonstrated a response (⩾50% reduction in depression symptoms) compared with 31% of HLW participants (odds ratio = 2.31; p = 0.04). Yoga participants showed significantly better social and role functioning and general health perceptions over time.ConclusionsAlthough we did not see a difference in depression symptoms at the end of the intervention period, yoga participants showed fewer depression symptoms over the entire follow-up period. Benefits of yoga may accumulate over time.
Project description:The neurobiology underlying depression in older adults is less extensively evaluated than in younger adults, despite the putative influence of aging on depression neuropathology. Studies using transcranial magnetic stimulation (TMS), a neurophysiological tool capable of probing inhibitory and excitatory cortical neurotransmission, have identified dysfunctional GABAergic inhibitory activity in younger adults with depression. However, GABAergic and glutamatergic cortical neurotransmission have not yet been studied in late-life depression (LLD). Here, we used single- and paired-pulse TMS to measure cortical inhibition and excitation in 92 LLD patients and 41 age-matched healthy controls. To differentiate the influence of age and depression, we also compared these TMS indices to those of 30 younger depressed adults and 30 age- and sex-matched younger healthy adults. LLD patients, older healthy adults, and younger depressed adults demonstrated significantly lower GABAA receptor-mediated cortical inhibition than younger healthy controls. By contrast, no significant differences in cortical inhibition were observed between older adults with and without depression. No significant differences in GABAB receptor-mediated inhibition or cortical excitation were found between the groups. Altogether, these findings suggest that reduced cortical inhibition may be associated with both advancing age and depression, which (i) supports the model of depression as a disease of accelerated aging, and (ii) prompts future investigation into diminished GABAergic neurotransmission in late-life as a biological predisposing factor to the development of depression. Given that cortical neurophysiology was similar in depressed and healthy older adults, future prospective studies need to establish the relative influence of age and depression on cortical inhibition deficits.
Project description:Bipolar disorder (BD) is a psychiatric disorder with high morbidity and mortality that cannot be distinguished from major depressive disorder (MDD) until the first manic episode. A biomarker able to differentiate BD and MDD could help clinicians avoid risks of treating BD with antidepressants without mood stabilizers.Cortical thickness differences were assessed using magnetic resonance imaging in BD depressed patients (n = 18), MDD depressed patients (n = 56), and healthy volunteers (HVs) (n = 54). A general linear model identified clusters of cortical thickness difference between diagnostic groups.Compared to the HV group, the BD group had decreased cortical thickness in six regions, after controlling for age and sex, located within the frontal and parietal lobes, and the posterior cingulate cortex. Mean cortical thickness changes in clusters ranged from 7.6 to 9.6% (cluster-wise p-values from 1.0 e-4 to 0.037). When compared to MDD, three clusters of lower cortical thickness in BD were identified that overlapped with clusters that differentiated the BD and HV groups. Mean cortical thickness changes in the clusters ranged from 7.5 to 8.2% (cluster-wise p-values from 1.0 e-4 to 0.023). The difference in cortical thickness was more pronounced when the subgroup of subjects with bipolar I disorder (BD-I) was compared to the MDD group.Cortical thickness patterns were distinct between BD and MDD. These results are a step toward developing an imaging test to differentiate the two disorders.
Project description:BACKGROUND:Suicide is a leading cause of death among youth. Prior research using transcranial magnetic stimulation (TMS) has implicated deficits in GABAergic cortical inhibition in adolescent suicidal behavior, yet no studies have assessed whether cortical inhibition varies over time in conjunction with changes in suicidal ideation (SI). This study examined dynamic changes in long-interval intracortical inhibition (LICI), a TMS measure of GABAB-mediated inhibition, and their relationship with changes in SI in a small sample of adolescents undergoing pharmacologic treatment for depression. METHODS:Ten depressed adolescents (aged 13-17) underwent clinical assessment and TMS testing at baseline and again at follow-up. All were treated with antidepressant medication in the interim. SI was measured with the Columbia Suicide Severity Rating Scale (C-SSRS) Intensity of Ideation subscale. LICI was measured at interstimulus intervals of 100 and 150?ms. RESULTS:There was a significant partial correlation, controlling for change in depression severity, between ?LICI-100 and change in SI as measured by ?C-SSRS (??=?.746, df?=?7, p?=?.021), which remained after also controlling for time to follow-up assessment (??=?.752, df?=?6, p?=?.032). No significant correlation was observed between ?LICI-150 and change in SI. LIMITATIONS:Sample size; variable follow-up interval; inability to control for age, sex, and potential treatment effects. CONCLUSIONS:These data offer preliminary signal of an association between increases in GABAB-mediated cortical inhibition and reduction in SI over time in adolescents treated for depression. Further studies are warranted to explore the role of cortical inhibition in adolescent suicidal ideation and behavior.
Project description:BackgroundEarly diagnosis of adolescent psychiatric disorder is crucial for early intervention. However, there is extensive comorbidity between affective and psychotic disorders, which increases the difficulty of precise diagnoses among adolescents.MethodsWe obtained structural magnetic resonance imaging scans from 150 adolescents, including 67 and 47 patients with major depressive disorder (MDD) and schizophrenia (SCZ), as well as 34 healthy controls (HC) to explore whether psychiatric disorders could be identified using a machine learning technique. Specifically, we used the support vector machine and the leave-one-out cross-validation method to distinguish among adolescents with MDD and SCZ and healthy controls.ResultsWe found that cortical thickness was a classification feature of a) MDD and HC with 79.21% accuracy where the temporal pole had the highest weight; b) SCZ and HC with 69.88% accuracy where the left superior temporal sulcus had the highest weight. Notably, adolescents with MDD and SCZ could be classified with 62.93% accuracy where the right pars triangularis had the highest weight.ConclusionsOur findings suggest that cortical thickness may be a critical biological feature in the diagnosis of adolescent psychiatric disorders. These findings might be helpful to establish an early prediction model for adolescents to better diagnose psychiatric disorders.
Project description:ObjectivesRecent research has found abnormalities in reward-related neural activation in bipolar disorder (BD), during both manic and euthymic phases. However, reward-related neural activation in currently depressed individuals with BD and that in currently depressed individuals with major depressive disorder (MDD) have yet to be directly compared. Here, we studied these groups, examining the neural activation elicited during a guessing task in fronto-striatal regions identified by previous studies.MethodsWe evaluated neural activation during a reward task using fMRI in two groups of depressed individuals, one with bipolar I disorder (BD-I) (n = 23) and one with MDD (n = 40), with similar levels of illness severity, and a group of healthy individuals (n = 37).ResultsReward expectancy-related activation in the anterior cingulate cortex was observed in the healthy individuals, but was significantly reduced in depressed patients (BD-I and MDD together). Anticipation-related activation was increased in the left ventrolateral prefrontal cortex in the BD-I depressed group compared with the other two groups. There were no significant differences in prediction error-related activation in the ventral striatum across the three groups.ConclusionsThe findings extend previous research which has identified dysfunction within the ventrolateral prefrontal cortex in BD, and show that abnormally elevated activity in this region during anticipation of either reward or loss may distinguish depressed individuals with BD-I from those with MDD. Altered activation of the anterior cingulate cortex during reward expectancy characterizes both types of depression. These findings have important implications for identifying both common and distinct properties of the neural circuitry underlying BD-I and MDD.
Project description:While exposure to adverse life events and subsequent dysregulation of the stress hormone response broadly confer risk for depression, the specific molecular mechanisms mediating this risk are poorly understood. Through pharmacologic activation of the stress hormone response in blood cells we demonstrate that common genetic variants in long-range enhancer elements moderate the immediate transcriptome response to stress, and that these genetic differences are associated with increased risk for depression in the context of early adversity. Using imaging genetics we then link these common risk variants with dysregulated amygdala reactivity, an important trigger of the stress hormone response. The transcripts regulated by these risk variants in peripheral blood were also responsive to stress and stress hormone receptor activation in murine brain. Network modeling approaches suggest that these differences in transcriptional activation may mediate stress-related risk for depression by altering a functional gene network related to proteasome degradation and synaptic plasticity. A Dexamethasone Suppression Test was performed in 160 male subjects. Baseline and stimulated (3 hours after 1.5 mg dexamethasone p.o.) whole blood samples were analyzed using Illumina Human HT-12 v3 arrays.
Project description:Deficits in GABAergic inhibitory neurotransmission are a reliable finding in schizophrenia (SCZ) patients. Previous studies have reported that unaffected first-degree relatives of patients with SCZ demonstrate neurophysiological abnormalities that are intermediate between probands and healthy controls. In this study, first-degree relatives of patients with SCZ and their related probands were investigated to assess frontal cortical inhibition. Long-interval cortical inhibition (LICI) was measured from the dorsolateral prefrontal cortex (DLPFC) using combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG). The study presents an extended sample of 129 subjects (66 subjects have been previously reported): 19 patients with SCZ or schizoaffective disorder, 30 unaffected first-degree relatives of these SCZ patients, 13 obsessive-compulsive disorder (OCD) patients, 18 unaffected first-degree relatives of these OCD patients and 49 healthy subjects. In the DLPFC, cortical inhibition was significantly decreased in patients with SCZ compared to healthy subjects. First-degree relatives of patients with SCZ showed significantly more cortical inhibition than their SCZ probands. No differences were demonstrated between first-degree relatives of SCZ patients and healthy subjects. Taken together, these findings show that more studies are needed to establish an objective biological marker for potential diagnostic usage in severe psychiatric disorders.