Objective: The comorbidity of alcohol and substance use disorders among persons with bipolar disorder is elevated, as indicated by epidemiological and clinical studies. Following alcohol use, cannabis is the most frequently used and abused illicit substance among bipolar individuals, and such use may lead to comorbid cannabis use disorders (CUD). Previous research indicated that CUDs were related to a more severe course of bipolar disorder and higher rates of other comorbid alcohol and substance use disorders. Few studies, however, have conducted longitudinal research on this comorbidity. The aim of this study is to investigate the influence of CUD on the course of bipolar I and II individuals during a 5-year follow-up. Methods: The characteristics of bipolar disorder, cannabis use disorders, and other alcohol and substance use disorders, as well as comorbid mental disorders, were assessed using a standardized semi-structured interview (SSAGA) at both baseline and the 5-year follow-up. N = 180 bipolar I and II patients were subdivided into groups of with and without comorbid cannabis use disorders (CUD). Results: Of the 77 bipolar I and 103 bipolar II patients, n = 65 (36.1%) had a comorbid diagnosis of any CUD (DSM-IV cannabis abuse or dependence). Comorbid bipolar patients with CUD had higher rates of other substance use disorders and posttraumatic stress disorders, more affective symptoms, and less psychosocial functioning at baseline and at 5-year follow-up. In contrast to previously reported findings, higher rates of anxiety disorders and bipolar disorder complications (e.g., mixed episodes, rapid cycling, and manic or hypomanic episodes) were not found. The effect of CUD on other substance use disorders was confirmed using moderation analyses. Conclusions: A 5-year prospective evaluation of bipolar patients with and without CUD confirmed previous investigations, suggesting that the risk of other substance use disorders is significantly increased in comorbid individuals. CUD has a moderation effect, while no effect was found for other mental disorders. Findings from this study and previous research may be due to the examination of different phenotypes (Cannabis use vs. CUD) and sample variation (family study vs. clinical and epidemiological populations). Full article

The pathophysiology of bipolar disorder (BD) remains mostly unclear. Yet, a valid biomarker is necessary to improve upon the early detection of this serious disorder. Patients with manifest BD display reduced volumes of the hippocampal subfields and amygdala nuclei. In this pre-registered analysis, we used structural MRI (n = 271, 7 sites) to compare volumes of hippocampus, amygdala and their subfields/nuclei between help-seeking subjects divided into risk groups for BD as estimated by BPSS-P, BARS and EPIbipolar. We performed between-group comparisons using linear mixed effects models for all three risk assessment tools. Additionally, we aimed to differentiate the risk groups using a linear support vector machine. We found no significant volume differences between the risk groups for all limbic structures during the main analysis. However, the SVM could still classify subjects at risk according to BPSS-P criteria with a balanced accuracy of 66.90% (95% CI 59.2–74.6) for 10-fold cross-validation and 61.9% (95% CI 52.0–71.9) for leave-one-site-out. Structural alterations of the hippocampus and amygdala may not be as pronounced in young people at risk; nonetheless, machine learning can predict the estimated risk for BD above chance. This suggests that neural changes may not merely be a consequence of BD and may have prognostic clinical value. Full article

The connection between cognitive function and the “Big Five” personality traits (openness, conscientiousness, extraversion, agreeableness, and neuroticism) in the general population is well known; however, studies researching bipolar disorder (BD) are scarce. Therefore, this study aimed to investigate the Big Five as predictors of executive function, verbal memory, attention, and processing speed in euthymic individuals with BD (cross-sectional: n = 129, including time point t1; longitudinal: n = 35, including t1 and t2). Participants completed the NEO Five-Factor Inventory, the Color and Word Interference Test, the Trail Making Test, the d2 Test of Attention Revised, and the California Verbal Learning Test. The results showed a significant negative correlation between executive function and neuroticism at t1. Changes in cognitive function between t1 and t2 did not correlate with and could not be predicted by the Big Five at t1. Additionally, worse executive function at t2 was predicted by higher neuroticism and lower conscientiousness at t1, and high neuroticism was a predictor of worse verbal memory at t2. The Big Five might not strongly impact cognitive function over short periods; however, they are significant predictors of cognitive function. Future studies should include a higher number of participants and more time in between points of measurement. Full article

(1) Cognitive impairments such as working memory (WM) deficits are amongst the most common dysfunctions characterizing bipolar disorder (BD) patients, severely contributing to functional impairment. We aimed to investigate WM performance and associated brain activation during the acute phase of BD and to observe changes in the same patients during remission. (2) Frontal brain activation was recorded using functional near-infrared spectroscopy (fNIRS) during n-back task conditions (one-back, two-back and three-back) in BD patients in their acute depressive (n = 32) and remitted (n = 15) phases as well as in healthy controls (n = 30). (3) Comparison of BD patients during their acute phase with controls showed a trend (p = 0.08) towards lower dorsolateral prefrontal cortex (dlPFC) activation. In the remitted phase, BD patients showed lower dlPFC and ventrolateral prefrontal cortex (vlPFC) activation (p = 0.02) compared to controls. No difference in dlPFC and vlPFC activation between BD patients’ phases was found. (4) Our results showed decreased working memory performance in BD patients during the working memory task in the acute phase of disease. Working memory performance improved in the remitted phase of the disease but was still particularly attenuated for the more demanding conditions. Full article

It is hypothesized that factors associated with bipolar disorder could, uer defined conditions, produce adaptive behaviors. The aim is to verify whether a genetic feature associated with bipolar disorder can be found in people without bipolar disorder but with hyperactivity/exploration traits. Healthy old adults (N = 40) recruited for a previous study on exercise were subdivided using a previously validated tool into those with and without hyperactivity/exploration traits and compared with a group of old patients with bipolar disorder (N = 21). The genetic variant RS1006737 of CACNA1C was analyzed using blood samples, DNA extraction, real-time PCR, FRET probes, and SANGER method sequencing. People with hyperactivity/exploration traits and without bipolar disorder were like people with bipolar disorder regarding the frequency of the genetic variant (OR = 0.79, CI95%: 0.21–2.95), but were different from people without either hyperactivity/exploration traits and bipolar disorder (OR = 4.75, CI95%: 1.19–18.91). The combined group of people with hyperactivity/exploration traits without bipolar disorder plus people with bipolar disorder had a higher frequency of the variant than people without either hyperactivity/exploration traits or bipolar disorder (OR = 4.25, CI95%: 1.24–14.4). To consider the genetic profile of bipolar disorder not an aberrant condition opens the way to a new approach in which the adaptive potential would be a central point in psychosocial treatment in addition to drug therapy. Future research can confirm the results of our study. Full article

In patients with bipolar disorder, we do not only see a cycling of mood episodes, but also a shift in circadian rhythm. In the present overview, the circadian rhythm, the “internal clock”, and their disruptions are briefly described. In addition, influences on circadian rhythms such as sleep, genetics, and environment are discussed. This description is conducted with a translational focus covering human patients as well as animal models. Concluding the current knowledge on chronobiology and bipolar disorder, implications for specificity and the course of bipolar disorder and treatment options are given at the end of this article. Taken together, circadian rhythm disruption and bipolar disorder are strongly correlated; the exact causation, however, is still unclear. Full article