Cortical surface characteristics among offspring of schizophrenia subjects.

BACKGROUND: A systematic study of cortical surface parameters in adolescent offspring of schizophrenia subjects before clinical manifestation could clarify neurodevelopmental antecedents of increased genetic risk. We examined these measures obtained on structural magnetic resonance imaging (MRI) scans at baseline and one year on a series of offspring of schizophrenia parents and healthy subjects. METHODS: We measured cortical surface area, curvature and thickness using BRAINS2 on structural MRI scans acquired using 1.5 T GE whole body scanner on all subjects. We examined the differences between study groups at baseline using mixed-effects models, and longitudinal trajectory of these measures using linear mixed-effects models. RESULTS: At baseline, offspring of schizophrenia parents showed reduced gyral surface area in the fronto-parietal lobes along with increased sulcal curvature and parietal gyral cortical thinning compared to healthy subjects. Prospective follow up of these subjects for one year showed shrinking of the total surface area, especially in the bilateral frontal and occipital regions along with preservation of cortical thickness among offspring of schizophrenia parents whereas healthy subjects showed preserved or increased surface area and cortical thinning. Correlation of these measures with lobar volumes was not observed at baseline cross-sectional comparisons but was observed in longitudinal examinations. DISCUSSION: Our observations suggest that adolescents with genetically elevated risk for schizophrenia show altered cortical surface measures affecting cortical surface area and thickness differentially suggesting a divergent trajectory of neurodevelopment. Cortical surface measures appear to be more sensitive to genetic liability to schizophrenia compared to volumetric measures.

Grey matter volume reductions in the emotion network of patients with depression and coronary artery disease.

Coronary Artery Disease (CAD) and Major Depressive Disorder (MDD) commonly co-occur and may be linked by a network of brain regions involved in emotion regulation, including the orbitofrontal cortex, amygdala/parahippocamal region and insula. We hypothesized structural differences in this emotion network more prominently in CAD+MDD versus CAD and healthy control (CTRL) groups that do not involve depression-related emotion circuitry. In contrast, we hypothesized structural similarities between CAD+MDD and MDD groups, both involving depression-related circuitry. We obtained structural magnetic resonance imaging scans from age-matched consenting subjects (CAD+MDD, n = 12; CAD, n = 12; MDD, n = 19; CTRL, n = 17) and performed a region of interest analysis. We found decreased grey matter volumes in the bilateral orbitofrontal cortex, bilateral amygdala/parahippocampal gyrus and right insula in CAD+MDD versus CTRL subjects and decreased grey matter volumes in the bilateral amygdala/parahippocampal regions in CAD+MDD versus CAD subjects. We found grey matter reductions in the right orbitofrontal cortex of CAD+MDD versus MDD subjects, and reductions in right insula of CAD versus CRTL subjects. Our results support that the network of brain regions involved in emotion regulation may be relevant to the relationship between CAD and MDD.

Untreated illness duration correlates with gray matter loss in first-episode psychoses.

Frontolimbic neural circuit dysfunction has been thought to underlie schizophrenia. Prolonged duration of untreated illness (DUI) is associated with frontolimbic structural changes. We present data addressing this question in minimally treated first-episode patients with psychoses. To determine the relationship between DUI and gray matter changes in schizophrenia, we analyzed the structural magnetic resonance images of 82 minimally treated first-episode patients with psychotic disorder by using optimized voxel-based morphometry. DUI inversely correlated with gray matter in the left fusiform gyrus extending into the lingual gyrus, cerebellum, and the parahippocampal gyrus. The observed inverse relationship between DUI and temporal gray matter density is consistent with a progressive process during the early course of schizophrenia.

Structural brain abnormalities in borderline personality disorder: a voxel-based morphometry study.

Imaging studies using region-of-interest morphometry and positron emission tomography have contributed to our understanding of structural and functional abnormalities in borderline personality disorder (BPD); however, both methods have practical limitations to their usefulness for exploratory studies of brain-behavior relationships. We used voxel-based morphometry (VBM) in 34 subjects with BPD and 30 healthy control (HC) subjects to study effects of diagnosis, gender, childhood sexual abuse, depressed mood, impulsivity and aggression on group differences. VBM is a computer-based method for whole brain analysis that combines the advantages of a functional study with a structural method. The BPD subjects, diagnosed with the Diagnostic Interview for Borderline Patients and the International Personality Disorders Examination, were compared with 30 HC subjects, with age and gender covaried. Analyses were repeated separately by gender and, in women, by histories of childhood sexual abuse. Depressed mood, impulsivity, and aggression were covaried in separate analyses. Compared with HC, BPD subjects had significant bilateral reductions in gray matter concentrations in ventral cingulate gyrus and several regions of the medial temporal lobe, including the hippocampus, amygdala, parahippocampal gyrus, and uncus. BPD women (and abused BPD women), but not BPD men, had significant reductions in medial temporal lobe, including the amygdala. BPD men, but not BPD women, showed diminished gray matter concentrations in the anterior cingulate gyrus compared with findings in HC subjects. Covarying for depressed mood rendered group differences non-significant in the ventral cingulate but had little effect on differences in medial temporal cortex. Covarying for aggression (LHA) had relatively little effect on group differences, while covarying for impulsivity, as determined by the Barratt Impulsiveness Scale, rendered all previously noted voxel-level group differences non-significant. Diminished gray matter in the prefrontal cortex and the medial temporal cortex may mediate the dysregulation of impulse and affect in BPD. Group differences varied greatly by gender, levels of depression, and impulsivity. VBM is an efficient method for exploratory study of brain-behavior relationships.

Brain structure and symptom dimension relationships in obsessive-compulsive disorder: a voxel-based morphometry study.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a clinically heterogenous disorder characterized by temporally stable symptom dimensions. Past inconsistent results from structural neuroimaging studies of OCD may have resulted from the effects of these specific symptom dimensions as well as other socio-demographic and clinical variables upon gray matter (GM) volume. METHODS: GM volume was measured in 25 adult OCD patients and 20 adult healthy controls using voxel-based morphometry (VBM), controlling for age and total brain GM volume. Univariate and multivariate regression analyses were carried out between regions of GM difference and age, age of onset, medication load, OCD severity, depression severity, and separate symptom dimension scores. RESULTS: Significant GM volumetric differences in OCD patients relative to controls were found in dorsal cortical regions, including bilateral BA6, BA46, BA9 and right BA8 (controls>patients), and bilateral midbrain (patients>controls). Stepwise regression analyses revealed highly significant relationships between greater total OCD symptom severity and smaller GM volumes in dorsal cortical regions and larger GM volumes in bilateral midbrain. Greater age was independently associated with smaller GM volumes in right BA6, left BA9, left BA46 and larger GM volumes in right midbrain. Greater washing symptom severity was independently associated with smaller GM volume in right BA6, while there was a trend association between greater hoarding symptom severity and lower GM volume in left BA6. LIMITATIONS: The sample was relatively small to examine the relationship between symptom scores and GM volumes. Multiple patients were taking medication and had comorbid disorders. CONCLUSIONS: These analyses suggest dorsal prefrontal cortical and bilateral midbrain GM abnormalities in OCD that appear to be primarily driven by the effects of total OCD symptom severity. The results regarding the relationship between GM volumes and symptom dimension scores require examination in larger samples.

Gray matter differences between pediatric obsessive-compulsive disorder patients and high-risk siblings: a preliminary voxel-based morphometry study.

Neuroimaging studies have identified alterations in frontostriatal circuitry in obsessive-compulsive disorder (OCD). Voxel-based morphometry (VBM) allows for the assessment of differences in gray matter density across the whole brain. VBM has not previously been used to examine regional gray matter density in pediatric OCD patients and the siblings of pediatric OCD patients. Volumetric magnetic resonance imaging (MRI) studies were conducted in 10 psychotropic naïve pediatric patients with OCD, 10 unaffected siblings of pediatric patients with OCD, and 10 healthy controls. VBM analysis was conducted using SPM2. Statistical comparisons were performed with the general linear model, implementing small volume random field corrections for a priori regions of interest (anterior cingulate cortex or ACC, striatum and thalamus). VBM analysis revealed significantly lower gray matter density in OCD patients compared to healthy in the left ACC and bilateral medial superior frontal gyrus (SFG). Furthermore, a small volume correction was used to identify a significantly greater gray matter density in the right putamen in OCD patients as compared to unaffected siblings of OCD patients. These findings in patients, siblings, and healthy controls, although preliminary, suggest the presence of gray matter structural differences between affected subjects and healthy controls as well as between affected subjects and individuals at risk for OCD.

Reduced N-acetyl-aspartate levels in schizophrenia patients with a younger onset age: a single-voxel 1H spectroscopy study.

Schizophrenia is widely considered a neurodevelopmental disorder. The timing of psychosis onset may determine the degree of functional and biological deficits. In this study, the association between age of onset of psychosis and in vivo biochemical levels was assessed in first-episode, antipsychotic-naive (FEAN) schizophrenia subjects. We hypothesized greater biochemical deficits in the younger-onset FEAN subjects. In vivo, (1)H spectroscopy measurements of the left dorsolateral prefrontal cortex (DLPFC) were conducted on FEAN subjects (15 schizophrenia and 3 schizoaffective subjects) and healthy comparison subjects of comparable age and gender distribution (N=61). N-acetyl-aspartate was significantly lower in the left DLPFC of FEAN subjects as compared to healthy comparison subjects. However, there was a significant subject group-by-age interaction for N-acetyl-aspartate. Early-onset FEAN subjects showed lower N-acetyl-aspartate levels compared to the younger healthy comparison subjects, while adult-onset FEAN and older healthy comparison subjects did not differ. The lower N-acetyl-aspartate levels in the DLPFC of early-onset subjects suggest a reduction in functioning neurons or specifically a reduction in the proliferation of dendrites and synaptic connections, which is not apparent in the adult-onset schizophrenia subjects.

Effect of antipsychotics on pituitary gland volume in treatment-naïve first-episode schizophrenia: a pilot study.

The objective of this study was to examine the effect of antipsychotics on pituitary volume in schizophrenic subjects. Pituitary volumes were measured in 16 patients with schizophrenia at baseline and 12 months after treatment with an antipsychotic medication using magnetic resonance imaging (MRI). A group of 12 healthy controls was evaluated at baseline and after 12 months. Pituitary volume significantly increased in the schizophrenic subjects after treatment (12% increase). This appeared to be specific to the prolactin-elevating drugs. In controls, pituitary volume did not change significantly (3% decrease). Pituitary volume may be a useful biomarker for treatments that affect neuroendocrine function.

Cerebellar volume in offspring from multiplex alcohol dependence families.

BACKGROUND: Increased susceptibility for developing alcohol dependence (AD) might be related to structural differences in brain circuits that influence the salience of rewards and/or modify the efficiency of information processing. The role of the cerebellum in regulating cognitive functions is being increasingly recognized along with its well-known influence on motor performance. Additionally, developmental changes in cerebellar volume during adolescence have been reported. METHODS: Magnetic resonance imaging was used to measure the cerebellum in 17 high-risk adolescent and young adult offspring from multiplex alcohol dependence families and 16 control subjects matched for gender, age, and IQ. RESULTS: High-risk (HR) adolescents/young adults showed increased total cerebellum volume and total grey in comparison with control subjects. Age-related decreases in total grey volume were seen with age, a pattern that was not seen in HR offspring. CONCLUSIONS: Offspring from multiplex families for AD manifest genetic susceptibility by having larger cerebellar volume, which seems to be related to lesser grey matter pruning for age. Larger cerebellar volumes in adult obsessive compulsive disorder (OCD) patients have been reported. This suggests a possible similarity in structural underpinnings for alcohol dependence and OCD.

Volumetric alterations of the orbitofrontal cortex in autism.

Recent evidence has implicated the orbitofrontal cortex (OFC) in the pathophysiology of social deficits in autism. An MRI-based morphometric study of the OFC was conducted involving 11 children with autism (age range 8.1-12.7 years) and 18 healthy, age-matched controls (age range 8.9-12.8 years). Decreased grey matter volume in the right lateral OFC in the patient group was found, and correlations were observed between social deficits and white, but not grey, matter structures of the OFC. These findings support the role of OFC in autism and warrant further investigations of this structure using structural and functional methodologies.

Risperidone in first-episode psychosis: a longitudinal, exploratory voxel-based morphometric study.

Previous studies have provided evidence supporting a neuroplastic effect of atypical antipsychotics. The present investigation explores the short-term effects of risperidone on brain parenchyma by performing voxel-based morphometry on baseline and 6-week follow-up MRI scans obtained from 15 neuroleptic-naïve individuals with first-episode psychosis treated with risperidone and 15 healthy controls. The risperidone-treated subjects demonstrated changes in grey matter and white matter in several brain regions, including superior temporal gyrus. No areas of change were found in controls. The results of this exploratory investigation support the possibility that risperidone has short-term effects on brain parenchyma in individuals with first-episode psychosis.