Cortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group.

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.

What determines continuing grey matter changes in first-episode schizophrenia and affective psychosis?

BACKGROUND: Magnetic resonance imaging (MRI) studies have shown that brain abnormalities in psychosis might be progressive during the first years of illness. We sought to determine whether first-episode psychosis (FEP) subjects show progressive regional grey matter (GM) changes compared with controls, and whether those changes are associated with diagnosis, illness course or antipsychotic (AP) use. METHOD: Thirty-two subjects with first-episode schizophrenia-spectrum disorders (FESZ), 24 patients with first-episode affective psychoses (FEAP) and 34 controls recruited using a population-based design underwent structural MRI scanning at baseline and at a 5-year follow-up. Regional GM volumes were assessed with voxel-based morphometry (VBM). Patients were treated at community settings, and about half of them remained mainly untreated. RESULTS: No significant progressive changes in GM regional volumes were observed in either the FESZ or FEAP group overall. However, FESZ subjects with a non-remitting course showed GM decrements in the left superior temporal gyrus (STG) and insula relative to remitted FESZ subjects. Non-remitted FEAP subjects exhibited a GM decrease in the dorsolateral prefrontal cortex (DLPFC) bilaterally in comparison to remitted FEAP subjects. Among FESZ subjects, AP use was associated with regional GM decrements in the right insula and increments in the cerebellum. CONCLUSIONS: Our results suggest that the progression of brain abnormalities in FEP subjects is restricted to those with a poor outcome and differs between diagnosis subgroups. AP intake is associated with a different pattern of GM reductions over time.

Longitudinal follow-up of cavum septum pellucidum and adhesio interthalamica alterations in first-episode psychosis: a population-based MRI study.

BACKGROUND: Neurodevelopmental alterations have been described inconsistently in psychosis probably because of lack of standardization among studies. The aim of this study was to conduct the first longitudinal and population-based magnetic resonance imaging (MRI) evaluation of the presence and size of the cavum septum pellucidum (CSP) and adhesio interthalamica (AI) in a large sample of patients with first-episode psychosis (FEP). METHOD: FEP patients (n=122) were subdivided into schizophrenia (n=62), mood disorders (n=46) and other psychosis (n=14) groups and compared to 94 healthy next-door neighbour controls. After 13 months, 80 FEP patients and 52 controls underwent a second MRI examination. RESULTS: We found significant reductions in the AI length in schizophrenia FEP in comparison with the mood disorders and control subgroups (longer length) at the baseline assessment, and no differences in any measure of the CSP. By contrast, there was a diagnosis×time interaction for the CSP length, with a more prominent increase for this measure in the psychosis group. There was an involution of the AI length over time for all groups but no diagnosis×time interaction. CONCLUSIONS: Our findings suggest that the CSP per se may not be linked to the neurobiology of emerging psychotic disorders, although it might be related to the progression of the disease. However, the fact that the AI length was shown to be shorter at the onset of the disorder supports the neurodevelopmental model of schizophrenia and indicates that an alteration in this grey matter junction may be a risk factor for developing psychosis.

Lack of progression of brain abnormalities in first-episode psychosis: a longitudinal magnetic resonance imaging study.

BACKGROUND: Some neuroimaging studies have supported the hypothesis of progressive brain changes after a first episode of psychosis. We aimed to determine whether (i) first-episode psychosis patients would exhibit more pronounced brain volumetric changes than controls over time and (ii) illness course/treatment would relate to those changes. METHOD: Longitudinal regional grey matter volume and ventricle:brain ratio differences between 39 patients with first-episode psychosis (including schizophrenia and schizophreniform disorder) and 52 non-psychotic controls enrolled in a population-based case-control study. RESULTS: While there was no longitudinal difference in ventricle:brain ratios between first-episode psychosis subjects and controls, patients exhibited grey matter volume changes, indicating a reversible course in the superior temporal cortex and hippocampus compared with controls. A remitting course was related to reversal of baseline temporal grey matter deficits. CONCLUSIONS: Our findings do not support the hypothesis of brain changes indicating a progressive course in the initial phase of psychosis. Rather, some brain volume abnormalities may be reversible, possibly associated with a better illness course.