Biomedical subjects

Matcheri S Keshavan

Publications and source records attributed to Matcheri S Keshavan.

At least 37 records · Page 2Linked to original sources

PubMed2006

An MRI study of increased cortical thickness in autism.

OBJECTIVE: The purpose of this study was to examine cortical thickness in autism in light of the postmortem evidence of cortical abnormalities of the disorder. METHOD: Magnetic resonance imaging (MRI) scans were acquired from 17 children with autism and 14 healthy comparison subjects, and sulcal and gyral thickness were measured for the total brain and for all lobes. RESULTS: Increases in total cerebral sulcal and gyral thickness were observed in children with autism relative to comparison subjects. Similar findings were noted in the temporal and parietal lobes but not in the frontal and occipital lobes. CONCLUSIONS: These preliminary findings indicate that increased cortical thickness may contribute to the increased gray matter volume and total brain size that have been observed in autism and may also be related to anomalies in cortical connectivity.

Autistic Disorder↗

PubMed2006

Pathways to care for African Americans with early psychosis.

Research examining pathways to care among African Americans with recent-onset psychosis is limited but suggests that African Americans have more complex and less desirable routes into care compared with whites. Delays in treatment of psychotic illness contribute to increasing rates of hospitalization, lengths of stay, long-term functional disability, and poor outcomes. African Americans may be less likely to seek help than whites, which may be due partly to stigma and beliefs in the African-American community about causes of mental illness as well as to external obstacles, such as involuntary civil commitment. Because African Americans are more likely than whites to seek assistance in primary care, the general practitioner or family physician has a potentially greater role in the identification of psychotic illnesses among African Americans. Further research is necessary to evaluate the role of ethnicity in treatment delays among patients with recent-onset psychotic illnesses.

Black People↗

PubMed2006

Magnetic resonance imaging study of the orbitofrontal cortex in autism.

The orbitofrontal cortex is involved in multiple psychologic functions, such as emotional and cognitive processing, learning, and social behavior. These functions are variably impaired in individuals with autism. The present study examined the size of the orbitofrontal cortex, and its medial and lateral subdivisions, using magnetic resonance imaging (MRI) scans obtained from 40 non-mentally retarded individuals with autism and 41 healthy controls. No differences were observed between the two groups on any of the orbitofrontal cortex measurements. However, when compared with controls, a smaller right lateral orbitofrontal cortex was observed in children and adolescents with autism, whereas a larger right lateral orbitofrontal cortex was found in adult patients. Interestingly, a positive relationship was found in the patient group between circumscribed interests and all orbitofrontal cortex structures. The present study suggests the absence of global volumetric abnormalities in the orbitofrontal cortex in autism and indicates that the functional disturbances in this structure might not be related to anatomic alterations.

Adolescent↗

PubMed2005

Prefrontal subregions and dimensions of insight in first-episode schizophrenia--a pilot study.

Deficits in insight are multidimensional, and include symptom unawareness and misattribution. We and others have observed that these deficits may be related to a prefrontal dysfunction. However, few studies have examined the relationship between specific prefrontal sub-regions and the awareness and attributional dimensions of insight in schizophrenia. This study examined the correlation between insight dimensions of awareness and attribution of symptoms and dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) volume in 14 subjects with first-episode, antipsychotic-naïve (FEAN) schizophrenia. In addition, 21 healthy subjects provided control data for volumetric assessments. Insight was assessed with Scale to Assess Unawareness of Mental Disorders. Morphometric assessments were adjusted for intra-cranial volume and were conducted by trained raters blind to clinical information using BRAINS-2. Average scores on current awareness of symptoms (1=aware; 5=unaware) were negatively correlated with right DLPFC volume and average scores on current attribution of symptoms (1=attribute; 5=misattribute) with right medial OFC volume. Unawareness and misattribution of symptoms in FEAN schizophrenia may have distinct neuroanatomical bases. DLPFC deficits may have resulted in illness unawareness by interfering with self-monitoring, while OFC abnormalities may have mediated symptom misattribution by conferring aberrant salience to perceived symptomatology.

Adult↗

PubMed2005

Decreased coherence in higher frequency ranges (beta and gamma) between central and frontal EEG in patients with schizophrenia: A preliminary report.

Schizophrenia is associated with a dysfunction of cognitive integration that may be due to abnormalities in inhibitory neural circuitry. A previous study found a failure of gamma band (25-45 Hz) synchronization in patients with schizophrenia compared to controls. Another recent study also stressed the importance of investigating high frequencies in the scalp-recorded sleep electroencephalogram (EEG). In this study, we compared coherence between first episode drug-naïve patients with schizophrenia (n=8) and age- and sex-matched normal controls (n=8) using two 32-s epochs of C4 and F4 EEG. The coherence was obtained using 4096 data points (128 Hz signal) using cross-spectral analysis with Blackman-Tukey window in beta (15.25-24.75 Hz) and gamma (25-44.75 Hz) frequency bands. We used wake, non-rapid eye movement (NREM) and rapid eye movement (REM) sleep periods for the analyses. Our results show a significant decrease in coherence in both beta and gamma frequency bands in patients. Post-hoc 't' tests revealed a significantly lower coherence only during the wake stage in patients with schizophrenia in beta as well as gamma frequency bands. These results further support the importance of the analyses of high-frequency bands in the EEG and support previous findings of abnormal neural synchrony in patients with schizophrenia. These results have been discussed further in relation to wake and sleep stages.

Adult↗

PubMed2005

Genetically predisposed offspring with schizotypal features: an ultra high-risk group for schizophrenia?

Biomarkers proposed in the schizophrenia diathesis have included neurocognitive deficits in domains such as working memory that implicate prefrontal systems. However, the relationship between these biomarkers and psychopathological markers such as schizotypy has not been systematically assessed, particularly in adolescent offspring of schizophrenia patients. Convergence between these markers may identify individuals at especially high risk for schizophrenia. In the current study the authors assessed whether functional deficits in working memory assessed using the oculomotor delayed response task (ODR) and executive function assessed using the Wisconsin Card Sort task (WCST), and structural deficits in prefrontal cortex, in the adolescent offspring of patients were predictive of schizotypy. Schizotypal offspring made more perseverative errors on the WCST (p<.002) and showed age-related deficits on the ODR task (p<.02) compared to their non-schizotypal counterparts or healthy controls. Reduced gray matter concentration in prefrontal cortex (p<.001) was also associated with schizotypy. Schizotypy in offspring of schizophrenia patients appears to be highly associated with known biomarkers of the illness such as executive function impairment and reductions in cortical gray matter. Furthermore, schizotypy appears to interact with development leading to greater impairment in working memory in schizotypal offspring closer to the typical age of onset of schizophrenia than non-schizotypal offspring. Thus, clinical and neurocognitive biomarkers of the illness appear to be highly interrelated in this sample of at-risk offspring. We propose that schizotypy may define a hyper vulnerable sub-sample among individuals genetically predisposed to schizophrenia and that future studies that attempt to assess risk may benefit from such a convergent approach.

Adolescent↗

PubMed2005

Premorbid indicators and risk for schizophrenia: a selective review and update.

Prospective studies of young relatives at risk for schizophrenia (high-risk studies, HR) can shed light on premorbid precursors of schizophrenia. Early HR studies pointed to a wide prevalence of schizophrenia spectrum psychopathology among young relatives at increased genetic risk. Recent studies suggest that young HR relatives have neurobehavioral deficits and structural, physiological, and neurochemical brain abnormalities that may date back to childhood or earlier. In this paper, we provide a selected overview of the lessons and limitations of early "first generation" studies and the beginning insights from recent "second generation" studies. We also provide an interim summary of data from the ongoing studies of young relatives at risk for schizophrenia in Pittsburgh. Collectively, such data may help us to predict the eventual emergence of schizophrenia, and schizophrenia spectrum or non-spectrum psychopathology.

Adolescent↗

PubMed2005

Dorsolateral prefrontal cortex morphology and short-term outcome in first-episode schizophrenia.

Several clinical predictors of outcome in schizophrenia have been described; however, very few studies have examined neurobiological factors that predict outcome. The objective of this study was to examine the value of the morphology of the dorsolateral prefrontal cortex (DLPFC) determined by magnetic resonance imaging (MRI) as a predictor of short-term functional outcome in antipsychotic-naive patients with first-episode schizophrenia or schizoaffective disorder. Twenty-seven consecutive patients with first-episode schizophrenia or schizoaffective disorder underwent structural MRI at baseline. Functional outcome - a composite measure of social and employment subscales of the Strauss-Carpenter Scale - was assessed at 1 and 2 years. Volume of the left DLPFC at baseline predicted functional outcome in schizophrenia at 1 but not at 2 years. Specific cognitive functions regulated by the left DLPFC may be critical for functional outcome.

Adult↗

PubMed2005

Pituitary volume in pediatric obsessive-compulsive disorder.

BACKGROUND: Abnormalities in the limbic-hypothalamic-pituitary-adrenal (LHPA) axis have been implicated in the pathogenesis of obsessive-compulsive disorder (OCD). To our knowledge, however, no prior study has measured pituitary gland volume in OCD. METHODS: Volumetric magnetic resonance imaging studies were conducted in 31 psychotropic drug-naïve children (10 boys, 21 girls) aged 8-17 years and 31 case-matched healthy comparison subjects. RESULTS: Pituitary volume was significantly smaller in patients with OCD as compared with healthy control subjects (11% smaller). Smaller pituitary volume in patients with OCD was associated with increased compulsive but not obsessive symptom severity. Boys with OCD had smaller pituitary gland volumes compared with control boys (20% smaller). No significant differences in pituitary volume were observed between girls with OCD and control girls. Boys with OCD had significantly smaller pituitary volumes than girls with OCD (31% smaller), whereas control boys also had smaller pituitary gland volumes compared with control girls (21% smaller). CONCLUSIONS: These findings provide new evidence of reduced pituitary volume in pediatric OCD that seems to be more prominent in male patients. The observed alterations in pituitary volume are consistent with neuroendocrine studies that have reported abnormalities in the LHPA axis in OCD.

Adolescent↗

PubMed2005

Investigation of corpus callosum in schizophrenia with diffusion imaging.

BACKGROUND: Corpus callosum (CC) is the main white matter commissure between the two cerebral hemispheres. Abnormalities of CC have been shown in schizophrenia patients by magnetic resonance imaging (MRI) studies. We here further investigated CC organization with diffusion imaging (DWI) in a sample of schizophrenia patients recruited from the epidemiologically defined catchment area of South Verona, Italy. METHODS: Sixty-seven patients with schizophrenia and 70 normal controls were studied. Regions of interests (ROIs), standardized at 5 pixels, were placed in CC on the non-diffusion weighted echoplanar images (b = 0) and were then automatically transferred to the corresponding maps to obtain the apparent diffusion coefficient (ADC) of water molecules. RESULTS: ADC measures for all callosal subregions in schizophrenia patients were significantly greater compared to normal controls (ANCOVA, p < 0.05). Positive symptoms significantly correlated with anterior callosal ADC measures (partial correlation analyses, p < 0.05). CONCLUSIONS: These findings support the existence of widespread microstructure disruption of CC in schizophrenia, which may ultimately lead to inter-hemispheric misconnection, and also suggest a specific role of anterior transcallosal disconnectivity in underlying positive symptoms. Future longitudinal MRI studies in high risk and first-episode patients together with neurophysiological tests are indicated to further examine CC anatomical abnormalities and inter-hemispheric transmission in schizophrenia.

Adult↗

PubMed2005

The effects of antipsychotic medication on factor and cluster structure of neurologic examination abnormalities in schizophrenia.

This study extends a previous study of the factor structure of the neurologic examination in unmedicated schizophrenia, utilizing cluster analysis and adding a medicated condition. We administered a modified version of the Neurologic Evaluation Scale (NES) on two occasions to 80 patients with schizophrenia or schizoaffective disorder, once while on antipsychotic medications and once while off medication. Data were distilled by combining right- and left-side scores, and by excluding rarely abnormal and unreliable items from the analysis. Principal components analysis yielded an intuitive four-factor solution in the unmedicated condition, but an inscrutable five-factor solution during medication. Cluster analysis revealed three groups: normal, cognitively impaired, and diffusely impaired. These results were also less interpretable with data from the medicated condition. Neurologic performance was better in the medicated than in the unmedicated condition. As is the case with other domains of symptoms and performance in schizophrenia, relationships among neurologic exam variables are altered by the presence of antipsychotic medication.

Adult↗

PubMed2005

Urinary pH in panic disorder.

Urinary pH was evaluated in panic disorder (PD) patients compared with both psychiatric and healthy control subjects. Fourteen PD patients, eight major depressive disorder (MDD) patients, and 14 healthy control (HC) subjects were examined. All patients were drug-free and met DSM-IV diagnostic criteria. The PD patients had lower urinary pH and higher levels of anxiety than both MDD and HC subjects. Additionally, urinary pH inversely correlated with anxiety levels. Although preliminary, these findings suggest that PD patients have lower urinary pH than MDD and HC subjects. Future studies that simultaneously examine both urinary and blood pH in larger numbers of PD patients and patients with other anxiety disorders, before and after treatment, need to be conducted.

Anxiety↗

PubMed2005

Optimized voxel-based morphometry of gray matter volume in first-episode, antipsychotic-naive schizophrenia.

This study examined gray matter (GM) volume abnormalities in first-episode, antipsychotic-naïve Indian schizophrenia patients. Magnetic resonance images of 18 schizophrenia patients and 18 matched healthy comparison subjects were analyzed by optimized voxel-based morphometry. Schizophrenia patients had significantly smaller global GM and greater global CSF volumes and smaller regional GM volume in superior frontal, inferior frontal, cingulate, post-central, superior temporal and parahippocampal gyri, inferior parietal lobule, insula, caudate nuclei, thalamus and cerebellum. Findings suggest limbic, heteromodal cortical, striatal, thalamic and cerebellar abnormalities in schizophrenia.

Adult↗

PubMed2005

1H Magnetic resonance spectroscopy study of dorsolateral prefrontal cortex in unipolar mood disorder patients.

Neuroimaging and postmortem studies have suggested the involvement of the dorsolateral prefrontal cortex (DLPFC) in the pathophysioloy of unipolar disorder. We examined with in vivo 1H magnetic resonance spectroscopy (MRS) the levels of specific metabolites in the DLPFC of adult unipolar patients and the role of illness chronicity on DLPFC abnormalities. Nineteen unmedicated unipolar mood disorder patients and 19 age- and gender-matched healthy controls underwent a short echo-time 1H MRS examination localized to an 8-cm3 single voxel placed in the left DLPFC. There were no significant differences in metabolite levels, including N-acetylaspartate (NAA), phosphocreatine plus creatine (PCr+Cr) and choline-containing-compounds (GPC+PC), between the two groups. However, NAA/PCr+Cr ratios were significantly lower in the chronic than in the less chronically ill patients and healthy controls. The low levels of NAA/PCr+Cr ratios in the left DLPFC of unipolar patients who had been more chronically ill suggest a potential role for illness chronicity in neuronal abnormalities in the DLPFC in unipolar disorder. This could possibly be accounted for by neurodegenerative processes arising with the progression of the illness. Future 1H MRS investigations should longitudinally examine the role of illness chronicity on DLPFC abnormalities and their relationship with the symptoms of unipolar disorder.

Adult↗

PubMed2005

Insular volumes in first-episode schizophrenia: gender effect.

Insula is a multimodal sensory integration region that acts as a gateway between somatosensory areas and limbic structures such as amygdala. Only a handful of region of interest (ROI) studies have suggested insular volume reduction in patients with schizophrenia but none have documented a gender effect on the volume of this structure. The authors used magnetic resonance images to measure insular volumes in previously untreated patients with first-episode schizophrenia (N=30) relative to those of healthy comparison subjects (N=30). Correlations with symptom severity were carried out. Intracranial volume was used as a covariate in the analysis. Female patients (N=15) had significantly reduced right insular volume relative to healthy female comparison subjects (p<0.05). On preliminary analysis, the right and left insular volumes in female patients had significant negative correlations with the positive symptoms scores (p<0.05), but not on correcting for multiple comparisons. Insula is developmentally and phylogenetically a watershed region where the more primitive allocortex transitions into the more developed isocortex. Thus its role as a substrate of neurodevelopmental hypothesis in schizophrenia and the interplay with gender deserves more attention.

Adult↗

PubMed2005

Subgenual prefrontal cortex of child and adolescent bipolar patients: a morphometric magnetic resonance imaging study.

The subgenual prefrontal cortex (SGPFC) plays an important role in emotional processing. We carried out a magnetic resonance imaging (MRI) study comparing the volume of the SGPFC in child and adolescent bipolar patients and healthy controls. The sample consisted of 15 children and adolescents who met DSM-IV criteria for bipolar disorder (mean age +/- S.D.=15.5 +/- 3.5 years) and 21 healthy adolescents (mean age +/- S.D.=16.9 +/- 3.8 years). MR images were obtained with a 1.5 T GE Signa Imaging System with Signa 5.4.3 software. SGPFC volumes were measured with the semi-automated software MedX (Sensor Systems, Sterling, VA, USA). ANCOVA was performed to compare SGPFC volumes between groups, using age, gender and intra-cranial volume (ICV) as covariates. The volumes (mean +/- S.D.) of the right and left SGPFC for bipolar patients were 291.27 +/- 88.70 mm(3) and 284.86 +/- 83.98 mm(3), respectively. For healthy controls, the right and left SGPFC volumes were 284.95 +/- 73.33 mm(3) and 307.55 +/- 73.67 mm(3), respectively. There were no statistically significant differences between groups regarding right or left SGPFC volumes. We found no evidence of volumetric abnormalities in the SGPFC of bipolar children and adolescents.

Adolescent↗

PubMed2005

Confirmatory factor analysis of the Neurological Evaluation Scale in unmedicated schizophrenia.

Factor structure of the Neurological Evaluation Scale (NES) was evaluated in 95 unmedicated patients with schizophrenia using confirmatory factor analysis (CFA). CFA was used to test four competing models that were based on prior empirical work examining the factor structure of the NES, as well as on theoretical considerations. A three-factor solution composed of "repetitive motor," "cognitive-perceptual," and "balance-tandem" factors best accounted for the data. These findings are consistent with prior exploratory studies that have suggested the NES is a multidimensional procedure that assesses diverse neurological domains. The current results contribute to the development of empirical subscales for neurological assessment procedures to be used in psychiatric conditions.

Adult↗

PubMed2005

Abnormalities in visually guided saccades suggest corticofugal dysregulation in never-treated schizophrenia.

BACKGROUND: Previous studies have reported intact visually guided saccades in schizophrenia, but these are limited by potential acute and long-term pharmacological treatment effects, small sample sizes, and a failure to follow patients over time. METHODS: Visually guided saccades were examined in 44 antipsychotic-naive patients experiencing their first episode of schizophrenia prior to treatment and again after 6, 26, and 52 weeks of antipsychotic treatment. Thirty-nine matched healthy individuals were followed over the same period. RESULTS: Before treatment, patients showed faster saccade latencies to unpredictable visual targets, suggesting reduced inhibitory regulation of brainstem saccade generators by neocortical attentional systems. Risperidone treatment reduced this deficit, suggesting a facilitation of attentional function, but haloperidol treatment did not. However, there was also a modest decline in saccade accuracy after risperidone treatment. The ability to sustain fixation of static central and peripheral targets was unimpaired before and after treatment. CONCLUSIONS: These findings provide evidence for impairments in neocortical attentional systems that cause reduced corticofugal regulation of brainstem systems in schizophrenia. This dysfunction appears to be minimized by the atypical antipsychotic risperidone but at the cost of a subtle reduction in saccade accuracy, possibly mediated via adverse effects on cerebellar vermis function.

Adult↗