Insula activity in resting-state differentiates bipolar from unipolar depression: a systematic review and meta-analysis.

Symptomatic overlap of depressive episodes in bipolar disorder (BD) and major depressive disorder (MDD) is a major diagnostic and therapeutic problem. Mania in medical history remains the only reliable distinguishing marker which is problematic given that episodes of depression compared to episodes of mania are more frequent and predominantly present at the beginning of BD. Resting-state functional magnetic resonance imaging (rs-fMRI) is a non-invasive, task-free, and well-tolerated method that may provide diagnostic markers acquired from spontaneous neural activity. Previous rs-fMRI studies focused on differentiating BD from MDD depression were inconsistent in their findings due to low sample power, heterogeneity of compared samples, and diversity of analytical methods. This meta-analysis investigated resting-state activity differences in BD and MDD depression using activation likelihood estimation. PubMed, Web of Science, Scopus and Google Scholar databases were searched for whole-brain rs-fMRI studies which compared MDD and BD currently depressed patients between Jan 2000 and August 2020. Ten studies were included, representing 234 BD and 296 MDD patients. The meta-analysis found increased activity in the left insula and adjacent area in MDD compared to BD. The finding suggests that the insula is involved in neural activity patterns during resting-state that can be potentially used as a biomarker differentiating both disorders.

Testing the Analytical Rumination Hypothesis: Exploring the Longitudinal Effects of Problem Solving Analysis on Depression.

Depression is a mental health condition for which individuals commonly seek treatment. However, depressive episodes often resolve on their own, even without treatment. One evolutionary perspective, the analytical rumination hypothesis (ARH), suggests that depression occurs in response to complex problems. According to this perspective, depressive symptoms promote analytical rumination, i.e., distraction-resistant thoughts about the causes of problems [causal analysis (CA)] and how they can be solved [problem-solving analysis (PSA)]. By helping individuals solve complex problems, analytical rumination may contribute to remission from depression. The aim of this study was to investigate (1) whether clinically-depressed individuals have more complex problems and engage in more CA and PSA than non-depressed and (2) the effects of CA and PSA on decreases in problem complexity, depressive symptoms, and remission from the depression. Samples of 85 patients were treated for depression with antidepressants and psychotherapy, and 49 healthy subjects were assessed three times over a 4-month period (at Weeks 1, 5, and 16). At each assessment, they completed measures of depression, analytical rumination, and problem complexity. Depressed individuals reported having more complex problems and engaging in more CA than non-depressed participants. The two groups engaged in a similar degree of PSA. Findings from a multiple regression suggested that more PSA at Week 1 was related to a decrease in depressive symptoms at Week 5, even after controlling for baseline depression, problem number, and complexity. PSA at Week 1 did not predict the remission after hospitalization or at follow-up; however, having less complex problems at the baseline made it more likely that a patient would later remit. Engaging in more CA or PSA at Week 1 did not affect perceived problem complexity at Week 5 or at follow-up. However, these findings were not statistically significant when influential observations (or outliers) were included in the analysis. Our findings suggest that PSA may contribute to a decrease in symptoms of depression over time. However, alleviations in problem complexity and remission might only be achieved if problems are initially less complex. Future directions involve exploring how PSA might contribute to decreases in depressive symptoms and other mechanisms underlying remission from depression.