Common and distinct patterns of grey-matter volume alteration in major depression and bipolar disorder: evidence from voxel-based meta-analysis.

Finding robust brain substrates of mood disorders is an important target for research. The degree to which major depression (MDD) and bipolar disorder (BD) are associated with common and/or distinct patterns of volumetric changes is nevertheless unclear. Furthermore, the extant literature is heterogeneous with respect to the nature of these changes. We report a meta-analysis of voxel-based morphometry (VBM) studies in MDD and BD. We identified studies published up to January 2015 that compared grey matter in MDD (50 data sets including 4101 individuals) and BD (36 data sets including 2407 individuals) using whole-brain VBM. We used statistical maps from the studies included where available and reported peak coordinates otherwise. Group comparisons and conjunction analyses identified regions in which the disorders showed common and distinct patterns of volumetric alteration. Both disorders were associated with lower grey-matter volume relative to healthy individuals in a number of areas. Conjunction analysis showed smaller volumes in both disorders in clusters in the dorsomedial and ventromedial prefrontal cortex, including the anterior cingulate cortex and bilateral insula. Group comparisons indicated that findings of smaller grey-matter volumes relative to controls in the right dorsolateral prefrontal cortex and left hippocampus, along with cerebellar, temporal and parietal regions were more substantial in major depression. These results suggest that MDD and BD are characterised by both common and distinct patterns of grey-matter volume changes. This combination of differences and similarities has the potential to inform the development of diagnostic biomarkers for these conditions.

Psychological processes underlying the association between childhood trauma and psychosis in daily life: an experience sampling study.

BACKGROUND: Evidence has accumulated that implicates childhood trauma in the aetiology of psychosis, but our understanding of the putative psychological processes and mechanisms through which childhood trauma impacts on individuals and contributes to the development of psychosis remains limited. We aimed to investigate whether stress sensitivity and threat anticipation underlie the association between childhood abuse and psychosis. METHOD: We used the Experience Sampling Method to measure stress, threat anticipation, negative affect, and psychotic experiences in 50 first-episode psychosis (FEP) patients, 44 At-Risk Mental State (ARMS) participants, and 52 controls. Childhood abuse was assessed using the Childhood Trauma Questionnaire. RESULTS: Associations of minor socio-environmental stress in daily life with negative affect and psychotic experiences were modified by sexual abuse and group (all p FWE < 0.05). While there was strong evidence that these associations were greater in FEP exposed to high levels of sexual abuse, and some evidence of greater associations in ARMS exposed to high levels of sexual abuse, controls exposed to high levels of sexual abuse were more resilient and reported less intense negative emotional reactions to socio-environmental stress. A similar pattern was evident for threat anticipation. CONCLUSIONS: Elevated sensitivity and lack of resilience to socio-environmental stress and enhanced threat anticipation in daily life may be important psychological processes underlying the association between childhood sexual abuse and psychosis.

Has analytical flexibility increased in imaging studies of bipolar disorder and major depression?

There has been extensive discussion of problems of reproducibility of research. Analytical flexibility may contribute to this, by increasing the likelihood that a reported finding represents a chance result. We explored whether analytical flexibility has increased over time, using human imaging studies of bipolar disorder and major depression. Our results indicate that the number of measures collected per study has increased over time for studies of bipolar disorder, but not for studies of major depression.

A structural MRI study of motor conversion disorder: evidence of reduction in thalamic volume.

OBJECTIVE: To investigate potential abnormalities in subcortical brain structures in conversion disorder (CD) compared with controls using a region of interest (ROI) approach. METHODS: Fourteen patients with motor CD were compared with 31 healthy controls using high-resolution MRI scans with an ROI approach focusing on the basal ganglia, thalamus and amygdala. Brain volumes were measured using Freesurfer, a validated segmentation algorithm. RESULTS: Significantly smaller left thalamic volumes were found in patients compared with controls when corrected for intracranial volume. These reductions did not vary with handedness, laterality, duration or severity of symptoms. CONCLUSIONS: These differences may reflect a primary disease process in this area or be secondary effects of the disorder, for example, resulting from limb disuse. Larger, longitudinal structural imaging studies will be required to confirm the findings and explore whether they are primary or secondary to CD.

Late-life obesity is associated with smaller global and regional gray matter volumes: a voxel-based morphometric study.

OBJECTIVE: Obesity adversely affects frontal lobe brain structure and function. Here we sought to show that people who are obese versus those who are of normal weight over a 5-year period have differential global and regional brain volumes. DESIGN: Using voxel-based morphometry, contrasts were done between those who were recorded as being either obese or of normal weight over two time points in the 5 years prior to the brain scan. In a post-hoc preliminary analysis, we compared scores for obese and normal weight people who completed the trail-making task. SUBJECTS: A total of 292 subjects were examined following exclusions (for example, owing to dementia, stroke and cortical infarcts) from the Prospective Investigation of the Vasculature in Uppsala Seniors cohort with a body mass index of normal weight (<25 kg m(-2)) or obese (30 kg m(-2)). RESULTS: People who were obese had significantly smaller total brain volumes and specifically, significantly reduced total gray matter (GM) volume (GMV) (with no difference in white matter or cerebrospinal fluid). Initial exploratory whole brain uncorrected analysis revealed that people who were obese had significantly smaller GMV in the bilateral supplementary motor area, bilateral dorsolateral prefrontal cortex (DLPFC), left inferior frontal gyrus and left postcentral gyrus. Secondary more stringent corrected analyses revealed a surviving cluster of GMV difference in the left DLPFC. Finally, post-hoc contrasts of scores on the trail-making task, which is linked to DLPFC function, revealed that obese people were significantly slower than those of normal weight. CONCLUSION: These findings suggest that in comparison with normal weight, people who are obese have smaller GMV, particularly in the left DLPFC. Our results may provide evidence for a potential working memory mechanism for the cognitive suppression of appetite that may lower the risk of developing obesity in later life.

The impact of the Val158Met catechol-O-methyltransferase genotype on neural correlates of sad facial affect processing in patients with bipolar disorder and their relatives.

BACKGROUND: The Met allele of the catechol-O-methyltransferase (COMT) valine-to-methionine (Val158Met) polymorphism is known to affect dopamine-dependent affective regulation within amygdala-prefrontal cortical (PFC) networks. It is also thought to increase the risk of a number of disorders characterized by affective morbidity including bipolar disorder (BD), major depressive disorder (MDD) and anxiety disorders. The disease risk conferred is small, suggesting that this polymorphism represents a modifier locus. Therefore our aim was to investigate how the COMT Val158Met may contribute to phenotypic variation in clinical diagnosis using sad facial affect processing as a probe for its neural action. METHOD: We employed functional magnetic resonance imaging to measure activation in the amygdala, ventromedial PFC (vmPFC) and ventrolateral PFC (vlPFC) during sad facial affect processing in family members with BD (n=40), MDD and anxiety disorders (n=22) or no psychiatric diagnosis (n=25) and 50 healthy controls. RESULTS: Irrespective of clinical phenotype, the Val158 allele was associated with greater amygdala activation and the Met158 allele with greater signal change in the vmPFC and vlPFC. Signal changes in the amygdala and vmPFC were not associated with disease expression. However, in the right vlPFC the Met158 allele was associated with greater activation in all family members with affective morbidity compared with relatives without a psychiatric diagnosis and healthy controls. CONCLUSIONS: Our results suggest that the COMT Val158Met polymorphism has a pleiotropic effect within the neural networks subserving emotional processing. Furthermore the Met158 allele further reduces cortical efficiency in the vlPFC in individuals with affective morbidity.

Neural correlates of emotional processing in psychosis risk and onset - A systematic review and meta-analysis of fMRI studies.

Aberrant emotion processing is a well-established component of psychotic disorders and is already present at the first episode of psychosis (FEP). However, the role of emotion processing abnormalities in the emergence of psychosis and the underlying neurobiology remain unclear. Here, we systematically reviewed functional magnetic resonance studies that used emotion processing task paradigms in FEP patients, and in people at clinical high-risk for psychosis (CHRp). Image-based meta-analyses with Seed-based d Mapping on available studies (n = 6) were also performed. Compared to controls, FEP patients showed decreased neural responses to emotion, particularly in the amygdala and anterior cingulate cortex. There were no significant differences between CHRp subjects and controls, but a high degree of heterogeneity was identified across studies. The role of altered emotion processing in the early phase of psychosis may be clarified through more homogenous experimental designs, particularly in the CHRp population.

The effects of lithium and anticonvulsants on brain structure in bipolar disorder.

OBJECTIVE: To investigate the effect of lithium, anticonvulsants and antipsychotics on brain structure in bipolar disorder (BD). METHOD: A cross-sectional structural brain magnetic resonance imaging study of 74 remitted patients with BD, aged 18-65, who were receiving long-term prophylactic treatment with lithium or anticonvulsants or antipsychotics. Global and regional grey matter, white matter, and cerebrospinal fluid volumes were compared between treatment groups. RESULTS: Grey matter in the subgenual anterior cingulate gyrus on the right (extending into the hypothalamus) and in the postcentral gyrus, the hippocampus/amygdale complex and the insula on the left was greater in BD patients on lithium treatment compared to all other treatment groups. CONCLUSION: Lithium treatment in BD has a significant effect on brain structure particularly in limbic/paralimbic regions associated with emotional processing.

Neural activation during cognitive reappraisal in girls at high risk for depression.

OBJECTIVE: Although emotion dysregulation, one of the core features of depression, has long been thought to be a vulnerability factor for major depressive disorder (MDD), surprisingly few functional magnetic resonance imaging (fMRI) studies have investigated neural correlates of emotion regulation strategies in unaffected high risk individuals. METHOD: Sixteen high risk (RSK) young women and fifteen matched low risk controls (CTL) were scanned using fMRI while performing an emotion regulation task. During this task, participants were instructed to reappraise their negative emotions elicited by International Affective Picture System images (IAPS). In addition, Difficulties in Emotion Regulation Strategies Scale (DERS) was used to assess participants' emotion dysregulation levels. RESULTS: Both RSK and CTL individuals show increased amygdala activation in response to negative emotional stimuli, however no difference was found between groups in using cognitive reappraisal strategies and functions of brain regions implicated in cognitive reappraisal. Interestingly, our psychometric test results indicate that high risk individuals are characterised by lower perceived emotional clarity (EC). CONCLUSION: Results of the current study suggest depression vulnerability may not be linked to the effectiveness of cognitive reappraisal. Alternatively, lower EC may be a vulnerability factor for depression.

Whole-Brain Atrophy Rate in Idiopathic Parkinson's Disease, Multiple System Atrophy, and Progressive Supranuclear Palsy.

In multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), the absence of surrogate endpoints makes clinical trials long and expensive. We aim to determine annualized whole-brain atrophy rates (a-WBAR) in idiopathic Parkinson's disease (IPD), MSA, and PSP. Ten healthy controls, 20 IPD, 12 PSP, and 8 MSA patients were studied using a volumetric MRI technique (SIENA). In controls, the a-WBAR was 0.37% ± 0.28 (CI 95% 0.17-0.57), while in IPD a-WBAR was 0.54% ± 0.38 (CI 95% 0.32-0.68). The IPD patients did not differ from the controls. In PSP, the a-WBAR was 1.26% ± 0.51 (CI 95%: 0.95-1.58). In MSA, a-WBAR was 1.65% ± 1.12 (CI 95%: 0.71-2.59). MSA did not differ from PSP. The a-WBAR in PSP and MSA were significantly higher than in the IPD group (p = 0.004 and p < 0.001, resp.). In PSP, the use of a-WBAR required one-half of the patients needed for clinical scales to detect a 50% reduction in their progression. In MSA, one-quarter of the patients would be needed to detect the same effect. a-WBAR is a reasonable candidate to consider as a surrogate endpoint in short clinical trials using smaller sample sizes. The confidence intervals for a-WBAR may add a potential retrospective application for a-WBAR to improve the diagnostic accuracy of MSA and PSP versus IPD.

Progressive brain changes in schizophrenia related to antipsychotic treatment? A meta-analysis of longitudinal MRI studies.

CONTEXT: Antipsychotic treatment is the first-line treatment option for schizophrenia. Individual studies suggested they can significantly affect brain structure and account for progressive brain changes observed during the illness. OBJECTIVES: To quantitatively examine the effect of antipsychotics as compared to illness related factors on progressive brain changes in schizophrenia. DATA SOURCES: Electronic databases were searched until April 2012. All magnetic resonance imaging studies reporting progressive brain changes in schizophrenia subjects and antipsychotic exposure were retrieved. STUDY SELECTION: 30 longitudinal MRI studies with antipsychotic administration in schizophrenia patients met the inclusion criteria. DATA EXTRACTION: Brain volumes before and after antipsychotic exposure, duration of illness, severity of psychotic symptoms as well as demographic, clinical, and methodological variables were extracted from each publication, or obtained directly from its authors. DATA SYNTHESIS: The overall sample was of 1046 schizophrenia patients and 780 controls for a median duration of follow-up of 72.4 weeks. At baseline, patients showed significant whole brain volume reductions and enlarged lateral ventricle (LV) volumes compared to controls. No baseline volumetric abnormalities were detected in the gray matter volumes (GMV), white matter volumes, cerebrospinal fluid and caudate nucleus. Longitudinally, there were progressive GMV decreases and LV enlargements in patients but not in controls. The GMV decreases were inversely correlated with cumulative exposure to antipsychotic treatments, while no effects were observed for duration of illness or illness severity. CONCLUSIONS: Schizophrenia is characterized by progressive gray matter volume decreases and lateral ventricular volume increases. Some of these neuroanatomical alterations may be associated with antipsychotic treatment.