Wayne Su

The Association of Elevated Body Mass Index with Reduced Brain Volumes in First-Episode Mania

BACKGROUND Compared with normal-weight patients, obese patients with bipolar I disorder (BD) suffer more manic and depressive episodes and make more suicide attempts. In the general population, obesity is associated with reduced total brain volume (TBV) and gray matter volume (GMV), but the neurobiology of obesity in BD has not been investigated. METHODS We used magnetic resonance imaging to examine TBV, GMV, white matter volume (WMV), as well as frontal, parietal, occipital, and temporal lobe volumes, in 55 healthy subjects (17 overweight/obese and 38 normal weight) and 57 patients with BD following their first manic episode (20 overweight/obese and 37 normal weight). RESULTS Linear regression analyses demonstrated that when other predictors of brain volume were accounted for, increased body mass index (BMI) in healthy subjects was significantly associated with decreased TBV and GMV. In contrast, increased BMI in patients with BD was significantly associated with decreased WMV and temporal lobe volume, areas of known vulnerability in early BD. CONCLUSIONS This is the first published report to show a relationship between elevated BMI and reduced brain volumes in BD, or any psychiatric illness. Our results suggest that obesity is associated with unique neurobiological changes in BD. They further imply a possible biological mechanism underlying the association between obesity and a more severe illness course in BD.

Body Mass Index–Related Regional Gray and White Matter Volume Reductions in First-Episode Mania Patients

BACKGROUND We previously reported that overweight/obese first-episode mania patients had reduced white matter (WM) and temporal lobe volumes compared with normal-weight patients. WM reductions are characteristic of early-stage bipolar disorder (BD), whereas temporal lobe reductions are frequently reported later in the illness. These findings thus suggested a testable hypothesis: that the neuropathology of BD is exacerbated with elevated body mass index (BMI). METHODS We used voxel-based morphometry to examine the relationship between BMI and regional gray matter (GM) and WM volumes in our sample of 57 euthymic first-episode mania patients and 55 healthy subjects. We hypothesized that elevated BMI in patients, but not healthy subjects, would be associated with volume reductions in frontal, temporal, and subcortical limbic brain regions implicated in the pathophysiology of BD. RESULTS At recovery from their first manic episode, patients with higher BMI had GM and WM reductions in the predicted emotion-generating and -regulating regions. In contrast, healthy subjects with higher BMI had reduced occipital lobe GM only. Factorial analyses confirmed significant BMI × diagnosis interactions for the WM reductions. Approximately three-quarters of patients with elevated BMI were overweight rather than obese; thus, weight-related volume reductions were detectable in patients with modestly elevated BMI. CONCLUSIONS This is the first hypothesis-driven test of, and supporting evidence for, our theory that elevated BMI is associated with unique brain changes in BD that have a negative impact on regions believed to be vulnerable in the illness. Our results suggest a neurobiological mechanism to explain the well-validated link between obesity and illness severity in BD.

Effects of eight weeks of atypical antipsychotic treatment on middle frontal thickness in drug-naïve first-episode psychosis patients

Atypical antipsychotic medications generally maintain or increase gray matter amount and functioning. First-episode psychosis patients have lower gray matter volume in the middle frontal gyrus, as well as worse performance on spatial working memory tasks compared to controls. This study investigated the effects of short-term four- and eight-week atypical treatment on middle frontal thickness and spatial working memory in first-episode psychosis patients. Nineteen drug-naïve first-episode psychosis patients treated with risperidone or quetiapine and 26 controls completed structural magnetic resonance imaging, a spatial working memory task, and clinical assessment at three intervals (baseline, four weeks, and eight weeks; all patients and 23 controls completed all three assessments). Caudal and rostral middle frontal thicknesses were measured using the automated program Freesurfer. Positive, negative, and general symptoms of the Positive and Negative Syndrome Scale (PANSS) decreased significantly in patients, with most of the change occurring in the first four weeks of treatment. Patients demonstrated an increase in rostral middle frontal thickness over eight weeks of treatment compared to controls. There was a medium effect size relationship between reduction in negative symptoms at four and eight weeks, and a change in rostral middle frontal thickness over eight weeks. No changes were found in spatial working memory ability. Short-term atypical treatment with risperidone or quetiapine can increase prefrontal cortical thickness in psychosis. These findings are notable given the role of the rostral middle frontal region in cognition and the relationship between better cognitive functioning and better functional outcome in psychosis.

White matter tract abnormalities in first-episode psychosis

Fibers connecting fronto-temporal and fronto-medial structures that pass through the anterior limb of the internal capsule (ALIC) subserve executive and psychomotor functioning. Both of these functions are adversely affected in schizophrenia, and may be abnormal at illness onset. In a study of first-episode psychosis, we used diffusion tensor imaging (DTI) and cognitive testing to examine ALIC integrity. Fourteen early psychosis patients and 29 healthy volunteers were included. Symptoms were assessed with the Positive and Negative Syndromes Scale (PANSS). All structural and diffusion scans were acquired on a GE Signa 1.5T scanner. A T1-weighted 3D FSPGR Inversion Recovery imaging series was acquired for manual seeding in structural space. Diffusion tensor imaging (DTI) was performed, and all DTI images were co-registered to structural space. Seeds were manually drawn bilaterally on the coronal plane at a specified location. Diffusion images were post-processed for subsequent Tract-based Spatial Statistics (TBSS) analysis. First-episode psychosis patients had significantly smaller fronto-medial and fronto-temporal AIC tract volumes compared to healthy volunteers on the left and the right (p-values<0.04). No differences in mean fractional anisotropy (FA) were seen within either left or right tracts (p-values>0.05), nor did TBSS reveal any other differences in FA values between groups in other regions. Relationships between tract volumes and symptom severity were not observed in this study.

Childhood maltreatment and corpus callosum volume in recently diagnosed patients with bipolar I disorder: data from the Systematic Treatment Optimization Program for Early Mania (STOP-EM).

Childhood trauma (CT) has been associated with abnormalities in the corpus callosum (CC). Decreased CC volumes have been reported in children and adolescents with trauma as well as adults with CT compared to healthy controls. CC morphology is potentially susceptible to the effects of Bipolar Disorder (BD) itself. Therefore, we evaluated the relationship between CT and CC morphology in BD. We using magnetic resonance imaging in 53 adults with BD recently recovered from their first manic episode, with (n = 23) and without (n = 30) CT, defined using the Childhood Trauma Questionnaire (CTQ) and 16 healthy controls without trauma. ANCOVA was performed with age, gender and intracranial volume as covariates in order to evaluate group differences in CC volume. The total CC volume was found to be smaller in BD patients with trauma compared to BD patients without trauma (p < .05). The differences were more pronounced in the anterior region of the CC. There was a significant negative correlation between CTQ scores and total CC volume in BD patients with trauma (p = .01). We did not find significant differences in the CC volume of patients with/without trauma compared to the healthy subjects. Our sample consists of patients recovered from a first episode of mania and are early in the course of illness and reductions in CC volume may occur late in the course of BD. It might mean there may be two sources of CC volume reduction in these patients: the reduction due to trauma, and the further reduction due to the illness.

Characterization of white matter integrity deficits in cocaine-dependent individuals with substance-induced psychosis compared with non-psychotic cocaine users

With sufficient drug exposure, some individuals develop transient psychotic symptoms referred to as ‘substance‐induced psychosis’ (SIP), which closely resemble the symptoms observed in schizophrenia spectrum disorders. The comparability in psychotic presentation between SIP and the schizophrenias suggests that similar underlying neural deficits may contribute to the emergence of psychosis across these disorders. Only a small number of studies have investigated structural alterations in SIP, and all have been limited to volumetric imaging methods, with none controlling for the effects of chronic drug exposure. To investigate white matter abnormalities associated with SIP, diffusion tensor imaging was employed in a group of individuals with cocaine‐associated psychosis (CAP; n = 24) and a cocaine‐dependent non‐psychotic (CDN) group (n = 43). Tract‐based spatial statistics was used to investigate group differences in white matter diffusion parameters. The CAP group showed significantly lower fractional anisotropy values than the CDN group (p < 0.05) in voxels within white matter tracts of fronto‐temporal, fronto‐thalamic and interhemispheric pathways. The greatest differences in white matter integrity were present in the corpus callosum, corona radiata, bilateral superior longitudinal fasciculi and bilateral inferior longitudinal fasciculi. Additionally, the CAP group had voxels of significantly higher radial diffusivity in a subset of the previously mentioned pathways. These results are the first description of white matter integrity abnormalities in a SIP sample and indicate that differences in these pathways may be a shared factor in the expression of different forms of psychosis.

Relationship between body mass index and hippocampal glutamate/glutamine in bipolar disorder

BACKGROUND We previously reported that patients with early-stage bipolar disorder, but not healthy comparison controls, had body mass index (BMI)-related volume reductions in limbic brain areas, suggesting that the structural brain changes characteristic of bipolar disorder were more pronounced with increased weight. AIMS To determine whether the most consistently reported neurochemical abnormality in bipolar disorder, increased glutamate/glutamine (Glx), was also more prominent with higher BMI. METHOD We used single-voxel proton magnetic resonance spectroscopy to measure hippocampal Glx in 51 patients with first-episode mania (mean BMI = 24.1) and 28 healthy controls (mean BMI = 23.3). RESULTS In patients, but not healthy controls, linear regression demonstrated that higher BMI predicted greater Glx. Factorial ANCOVA showed a significant BMI × diagnosis interaction, confirming a distinct effect of weight on Glx in patients. CONCLUSIONS Together with our volumetric studies, these results suggest that higher BMI is associated with more pronounced structural and neurochemical limbic brain changes in bipolar disorder, even in early-stage patients with low obesity rates.

THE IMPACTS OF YOGA AND AEROBIC EXERCISE ON NEURO-COGNITION AND BRAIN STRUCTURE IN EARLY PSYCHOSIS – A PRELIMINARY ANALYSIS OF THE RANDOMIZED CONTROLLED CLINICAL TRIAL

This journal suppl. entitled: Abstracts of the 3rd Biennial Schizophrenia International Research Conference

Structural brain markers are differentially associated with neurocognitive profiles in socially marginalized people with multimorbid illness

Objective: The authors examined associations between complementary fronto-temporal structural brain measures (gyrification, cortical thickness) and neurocognitive profiles in a multimorbid, socially marginalized sample. Method: Participants were recruited from single-room occupancy hotels and a downtown community courthouse (N = 299) and grouped on multiple neurocognitive domains using cluster analysis. Subsequently, the authors evaluated whether the fronto-temporal brain indices, and proxy measures of neurodevelopment and acquired brain insult/risk exposure differentiated members of the 3 distinct neurocognitive clusters. Results: Greater frontal and temporal gyrification and more proxies of aberrant neurodevelopment were associated with the lowest functioning neurocognitive cluster (Cluster 3). Further, for older participants (50+ years), increased cortical thickness in frontal regions was associated with the higher functioning neurocognitive cluster (Cluster 1). Finally, the greatest acquired brain insult/risk exposure was associated with the cluster characterized by selective decision-making impairment (Cluster 2). Conclusions: Fronto-temporal structural brain indices, and proxies of neurodevelopment and acquired brain insult/risk exposure were differentially associated with neurocognitive profiles in socially marginalized persons. These findings highlight the unique pathways to neurocognitive impairment in a heterogeneous population and help to clarify the vulnerabilities confronted by different subgroups.

MAG Gene Variation and Cortical Gray Matter Volume in First Episode Schizophrenia

Evidence implicating myelin related genes in the pathophysiology of schizophrenia is accumulating. Abnormalities of brain structure at the onset of psychosis may be related to variation in genes such as myelin associated glycoprotein (MAG). Subjects with first episode schizophrenia (n = 30) or schizoaffective disorder (n = 11), and healthy comparison subjects (n = 43) participated in an MRI scan. Two single nucleotide polymorphisms (rs720309, rs720308) in the MAG gene were genotyped. MAG genotype variation predicted cortical gray matter volume in first episode schizophrenia patients (p = 0.039), but not in controls (p = 0.827). Cortical gray matter, total gray matter, total white matter, and ventricular cerebrospinal fluid volumes did not differ between groups. Genetic variation in the MAG gene may predict cortical gray matter volume differences in patients in the first episode of schizophrenia or schizoaffective disorder.