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.

The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA’s first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.

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.

Bipolar disorder (BD) is characterized by recurrent mood episodes ranging from severe depression to acute full-blown mania. Both states of this severe psychiatric disorder have been associated with alterations of reward processing in the brain. Here, we present results of a functional magnetic resonance imaging (fMRI) study on the neural correlates and functional interactions underlying reward gain processing and reward dismissal in favor of a long-term goal in bipolar patients. Sixteen medicated patients diagnosed with bipolar I disorder, euthymic to mildly depressed, and sixteen matched healthy controls performed the 'desire-reason dilemma' (DRD) paradigm demanding rejection of priorly conditioned reward stimuli to successfully pursue a superordinate goal. Both groups exhibited significant activations in reward-related brain regions, particularly in the mesolimbic reward system. However, bipolar patients showed reduced neural responses of the ventral striatum (vStr) when exploiting a reward stimulus, and exhibited a decreased suppression of the rewardrelated activation of the mesolimbic reward system while having to reject immediate reward in favor of the long-term goal. Further, functional interaction between the anteroventral prefrontal cortex and the vStr in the 'DRD' was significantly impaired in the bipolar group. These findings provide evidence for a reduced responsivity of the vStr to reward stimuli in BD, possibly related to clinical features like anhedonia. The disturbed top-down control of mesolimbic reward signals by prefrontal brain regions in BD can be interpreted in terms of a disease-related enhanced impulsivity, a trait marker of BD.

In a laboratory smoking experiment, 25 couples in which 1 or both partners continued to smoke despite 1 of them having heart or lung disease discussed a health-related disagreement before and during a period of smoking. Immediately afterward, the partners used independent joysticks to recall their continuous emotional experience during the interaction while watching themselves on video. Participants in dual-smoker couples reported increased positive emotion contingent upon lighting up, whereas those in single-smoker couples reported the opposite. The results highlight the role of smoking in close relationships, particularly in regulating emotional closeness when both partners smoke. Attention to this fit between symptom and system may be useful in helping couples achieve stable cessation.

Schizophrenia and depression are prevalent psychiatric disorders, but their underlying neural bases remains poorly understood. Neuroimaging evidence has pointed towards the relevance of functional connectivity aberrations in default mode network (DMN) hubs, dorso-medial prefrontal cortex and precuneus, in both disorders, but commonalities and differences in resting state functional connectivity of those two regions across disorders has not been formally assessed. Here, we took a transdiagnostic approach to investigate resting state functional connectivity of those two regions in 75 patients with schizophrenia and 82 controls from 4 scanning sites and 102 patients with depression and 106 controls from 3 sites. Our results demonstrate common dysconnectivity patterns as indexed by a significant reduction of functional connectivity between precuneus and bilateral superior parietal lobe in schizophrenia and depression. Furthermore, our findings highlight diagnosis-specific connectivity reductions of the parietal operculum in schizophrenia relative to depression. In light of evidence that points towards the importance of the DMN for social cognitive abilities and well documented impairments of social interaction in both patient groups, it is conceivable that the observed transdiagnostic connectivity alterations may contribute to interpersonal difficulties, but this could not be assessed directly in our study as measures of social behavior were not available. Given the operculum's role in somatosensory integration, diagnosis-specific connectivity reductions may indicate a pathophysiological mechanism for basic self-disturbances that is characteristic of schizophrenia, but not depression.

Although spousal support predicts the success of a smoker's cessation efforts, "social-support" interventions based on teaching partners better support skills have had consistently disappointing results. We examined the potential utility of a family consultation (FAMCON) intervention based on family-systems principles in a treatment-development project involving 20 couples in which one partner (the primary smoker) continued to smoke despite having or being at significant risk for heart or lung disease. The 50% rate of stable abstinence achieved by primary smokers over at least 6 months exceeds benchmark success rates reported in the literature for other comparably intensive interventions, suggesting that a couple-focused intervention different in concept and format from social-support interventions tested in the past may hold promise for health-compromised smokers. The FAMCON approach appeared particularly well suited to female smokers and smokers whose partner also smoked--two subgroups at high risk for relapse.

Unipolar and bipolar groups displaying similar symptomatology could be clearly distinguished by characteristic changes in large-scale networks, encouraging further investigation of network fingerprints for clinical use. Hum Brain Mapp 37:808-818, 2016. © 2015 Wiley Periodicals, Inc.