Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen’s d =−0.293; P = 1.71 × 10−21), left fusiform gyrus (d =−0.288; P = 8.25 × 10−21) and left rostral middle frontal cortex (d =−0.276; P =2.99 × 10−19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.

Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case–control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=−0.232; P=3.50 × 10−7) and thalamus (d=−0.148; P=4.27 × 10−3) and enlarged lateral ventricles (d=−0.260; P=3.93 × 10−5) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons.

How cognition influences the affective brain representations of the taste and flavor of a food is important not only for understanding top-down influences in the brain, but also in relation to the topical issues of appetite control and obesity. We found using functional magnetic resonance imaging that activations related to the affective value of umami taste and flavor (as shown by correlations with pleasantness ratings) in the orbitofrontal cortex were modulated by word-level descriptors. Affect-related activations to taste were modulated in a region that receives from the orbitofrontal cortex, the pregenual cingulate cortex, and to taste and flavor in another region that receives from the orbitofrontal cortex, the ventral striatum. Affect-related cognitive modulations were not found in the insular taste cortex, where the intensity but not the pleasantness of the taste was represented. We conclude that top-down language-level cognitive effects reach far down into the earliest cortical areas that represent the appetitive value of taste and flavor. This is an important way in which cognition influences the neural mechanisms that control appetite.

BackgroundTraditionally, assessment of psychiatric symptoms has been relying on their retrospective report to a trained interviewer. The emergence of smartphones facilitates passive sensor-based monitoring and active real-time monitoring through time-stamped prompts; however there are few validated self-report measures designed for this purpose.MethodsWe introduce a novel, compact questionnaire, Mood Zoom (MZ), embedded in a customised smart-phone application. MZ asks participants to rate anxiety, elation, sadness, anger, irritability and energy on a 7-point Likert scale. For comparison, we used four standard clinical questionnaires administered to participants weekly to quantify mania (ASRM), depression (QIDS), anxiety (GAD-7), and quality of life (EQ-5D). We monitored 48 Bipolar Disorder (BD), 31 Borderline Personality Disorders (BPD) and 51 Healthy control (HC) participants to study longitudinal (median±iqr: 313±194 days) variation and differences of mood traits by exploring the data using diverse time-series tools.ResultsMZ correlated well (|normalR|>0.5,p<0.0001) with QIDS, GAD-7, and EQ-5D. We found statistically strong (|normalR|>0.3,p<0.0001) differences in variability in all questionnaires for the three cohorts. Compared to HC, BD and BPD participants exhibit different trends and variability, and on average had higher self-reported scores in mania, depression, and anxiety, and lower quality of life. In particular, analysis of MZ variability can differentiate BD and BPD which was not hitherto possible using the weekly questionnaires.LimitationsAll reported scores rely on self-assessment; there is a lack of ongoing clinical assessment by experts to validate the findings.ConclusionsMZ could be used for efficient, long-term, effective daily monitoring of mood instability in clinical psychiatric practice.