Rumination in bipolar disorder associated with brain network and behavioural measures of inhibitory executive control.

OBJECTIVE: Rumination is a passive form of negative self-focused cognition that predicts depressive episodes for individuals with bipolar disorder (BD). Individuals with BD also have impaired inhibitory executive control; rumination in BD may therefore reflect executive dysfunction. We investigated the relationship between a neural measure of executive functioning (functional connectivity between the frontoparietal control network [FPCN] and the default mode network [DMN] during an effortful task), behavioural measures of executive functioning (the Behavior Rating Inventory of Executive Function) and rumination (the Ruminative Responses Scale). METHODS: Fifteen individuals with BD and fifteen healthy controls underwent MRI scans during mental distraction. Using CONN toolbox, between-network FPCN-DMN connectivity values were calculated. We conducted Pearson's r bivariate correlations between connectivity values, BRIEF and RRS scores. RESULTS: RRS scores were positively correlated with BRIEF Behavioral Regulation Index (BRI) scores. In individuals with BD, there was a positive correlation between FPCN-DMN functional connectivity during distraction and BRIEF BRI scores. FPCN-DMN functional connectivity was also positively correlated with RRS ruminative brooding scores. Healthy controls did not show significant correlations between these behavioural and neural measures of executive functioning and rumination. CONCLUSION: For individuals with BD, the greater the tendency to ruminate and the higher the executive dysfunction, the stronger the connectivity between an executive control network and a network involved in rumination during an unrelated cognitive task. This could reflect continual attempts to inhibit ruminative thinking and shift back to the distraction task. Therefore, engagement in rumination may reflect failed inhibitory executive control.

Neural predictors of successful brief psychodynamic psychotherapy for persistent depression.

BACKGROUND: Psychodynamic psychotherapy has been used to treat depression for more than a century. However, not all patients respond equally well, and there are few reliable predictors of treatment outcome. METHODS: We used resting (18)F-fluorodeoxyglucose positron emission tomography ((18)FDG-PET) scans immediately before and after a structured, open trial of brief psychodynamic psychotherapy (n = 16) in conjunction with therapy process ratings and clinical outcome measures to identify neural correlates of treatment response. RESULTS: Pretreatment glucose metabolism within the right posterior insula correlated with depression severity. Reductions in depression scores correlated with a pre- to posttreatment reduction in right insular metabolism, which in turn correlated with higher objective measures of patient insight obtained from videotaped therapy sessions. Pretreatment metabolism in the right precuneus was significantly higher in patients who completed treatment and correlated with psychological mindedness. CONCLUSIONS: Resting brain metabolism predicted both clinical course and relevant psychotherapeutic process during short-term psychodynamic psychotherapy for depression.

Management of Rumination and Obsessions in Primary Care.

The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry.Prim Care Companion CNS Disord 2024;26(3):23f03653. Author affiliations are listed at the end of this article.

Medical Uses and Adverse Effects of Psilocybin.

The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds repors that will prove useful for clinicians practicing at the interface of medicine and psychiatry.Prim Care Companion CNS Disord 2024;26(3):23f03652. Author affiliations are listed at the end of this article.

Differential patterns of default mode network activity associated with negative and positive rumination in bipolar disorder.

BACKGROUND: Patients with bipolar disorder (BD) engage in both negative and positive rumination, defined as maladaptive self-focused thinking, and this tendency predicts depressive and manic episodes, respectively. Prior research in patients with major depression implicates regions of the default mode network (DMN) consistent with the self-focused nature of rumination. Little is known about the neural correlates of rumination in bipolar disorder. METHODS: Fifteen euthymic patients with BD (twelve with Type I) and 17 healthy controls (HC) performed negative and positive rumination induction tasks, as well as a distraction task, followed by a self-related trait judgment task while undergoing functional magnetic resonance imaging (fMRI). Participants also underwent resting state scans. We examined functional connectivity at rest and during the induction tasks, as well as task-based activation during the trait judgment task, in core regions of the DMN. RESULTS: Compared to HC, patients with BD showed greater functional connectivity between the posterior cingulate cortex (PCC) and medial prefrontal cortex (MPFC) at rest and during positive rumination, compared to distraction. They also showed greater activity in the PCC and MPFC during processing of positive traits, following positive rumination. At rest and during negative rumination compared to distraction, patients with BD showed greater functional connectivity between the PCC and inferior parietal lobule than HC. CONCLUSIONS: These findings demonstrate that negative and positive rumination are subserved by different patterns of connectivity within the DMN in BD. Additionally, the PCC and MPFC are key regions involved in the processing of positive self-relevant traits following positive rumination.

Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha as a Novel Target for Bipolar Disorder and Other Neuropsychiatric Disorders.

Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) is a protein that regulates metabolism and inflammation by activating nuclear receptors, especially the family of peroxisome proliferator-activated receptors (PPARs). PGC-1 alpha and PPARs also regulate mitochondrial biogenesis, cellular energy production, thermogenesis, and lipid metabolism. Brain energy metabolism may also be regulated in part by the interaction between PGC-1 alpha and PPARs. Because neurodegenerative diseases (Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis) and bipolar disorder have been associated with dysregulated mitochondrial and brain energy metabolism, PGC-1 alpha may represent a potential drug target for these conditions. The purpose of this article is to review the physiology of PGC-1 alpha, PPARs, and the role of PPAR agonists to target PGC-1 alpha to treat neurodegenerative diseases and bipolar disorder. We also review clinical trials of repurposed antidiabetic thiazolidines and anti-triglyceride fibrates (PPAR agonists) for neurodegenerative diseases and bipolar disorder. PGC-1 alpha and PPARs are innovative potential targets for bipolar disorder and warrant future clinical trials.

Rumination in bipolar disorder: evidence for an unquiet mind.

Depression in bipolar disorder has long been thought to be a state characterized by mental inactivity. However, recent research demonstrates that patients with bipolar disorder engage in rumination, a form of self-focused repetitive cognitive activity, in depressed as well as in manic states. While rumination has long been associated with depressed states in major depressive disorder, the finding that patients with bipolar disorder ruminate in manic states is unique to bipolar disorder and challenges explanations put forward for why people ruminate. We review the research on rumination in bipolar disorder and propose that rumination in bipolar disorder, in both manic and depressed states, reflects executive dysfunction. We also review the neurobiology of bipolar disorder and recent neuroimaging studies of rumination, which is consistent with our hypothesis that the tendency to ruminate reflects executive dysfunction in bipolar disorder. Finally, we relate the neurobiology of rumination to the neurobiology of emotion regulation, which is disrupted in bipolar disorder.