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Biomedical subjects

Matcheri S Keshavan

Publications and source records attributed to Matcheri S Keshavan.

At least 19 recordsLinked to original sources
PubMed2026

Effect of cognitive enhancement therapy for early course schizophrenia on gray matter volume: A confirmatory multisite randomized clinical trial.

BACKGROUND: Cognitive Enhancement Therapy (CET) is an evidence-based cognitive remediation intervention for early course schizophrenia with established benefits for cognition. CET may protect against broad temporolimbic gray matter volume loss associated with cognitive improvement, but this finding has yet to be replicated. This research reexamined if CET protects against temporolimbic gray matter volume loss in an independent and larger multisite early course sample, and if this neuroprotective effect predicts cognitive and social adjustment improvement. METHODS: Ninety-nine participants with early course schizophrenia completed MRI, cognitive, and social adjustment assessments at baseline, 9 (mid-treatment), and 18 (end of treatment) months. Linear mixed-effects models examined the differential impact of CET (n = 56) compared to Enriched Supportive Therapy (n = 43) on temporolimbic gray matter volume in regions-of-interest (ROIs) that previously demonstrated CET-related neuroprotection (primary ROIs), as well as frontotemporal ROIs outlined in the first trial (secondary ROIs). RESULTS: The right rostral anterior cingulate was the only primary ROI to demonstrate a significant group × time interaction, but was unrelated to cognitive and social adjustment change. No secondary ROIs exhibited a differential treatment effect. CONCLUSION: This confirmatory trial did not recapitulate the observed broad pattern of CET-related temporolimbic gray matter volume neuroprotection. Consistent with the larger literature demonstrating limited evidence of cognitive remediation effects on the brain in schizophrenia, these findings underscore the need for continued investigation of CET-related changes with other neuroimaging modalities, especially given its established cognitive benefits. Such information is critical for cognitive remediation optimization based on validated therapeutic mechanisms.

Humans↗
PubMed2006

Pituitary volume in neuroleptic-naïve schizophrenia: a structural MRI study.

Abnormalities in the hypothalamic-pituitary-adrenal axis (HPA) have been implicated in psychosis. To our knowledge, no prior study has measured pituitary volume in a neuroleptic-naïve schizophrenic population. Herein, we present data exploring the volumetric differences in a sample of antipsychotic-naïve patients with a DSM-IV diagnosis of schizophrenia versus appropriately matched healthy controls. Pituitary volumes were measured in 51 patients with schizophrenia (36 males, 15 females, mean age+/-S.D.: 25.2+/-7.4 years) and 55 healthy controls (30 males, 25 females; mean age+/-S.D.: 25.2+/-6.6 years) Measurements were conducted on 1.5 mm thick T1-weighted coronal images from a 1.5T scanner by two trained raters. Patients with schizophrenia had significantly smaller pituitary volumes than healthy control subjects (mean volume+/-S.D.=0.58+/-0.14 cm(3) and 0.66+/-0.17 cm(3) respectively; ANCOVA (using intracranial volume, gender and age as covariates), F=6.81, df=1, 101; p=0.01). These findings provide new evidence of a smaller pituitary volume in neuroleptic-naïve patients with schizophrenia. The observed alterations in pituitary volume are consistent with neuroendocrine studies that have reported abnormalities in the HPA axis in psychosis. Similar volume reductions have been seen in other neuropsychiatric populations and may cut across diagnostic boundaries.

Adolescent↗
PubMed2006

Emotional words induce enhanced brain activity in schizophrenic patients with auditory hallucinations.

Neuroimaging studies of emotional response in schizophrenia have mainly used visual (faces) paradigms and shown globally reduced brain activity. None of these studies have used an auditory paradigm. Our principal aim is to evaluate the emotional response of patients with schizophrenia to neutral and emotional words. An auditory emotional paradigm based on the most frequent words heard by psychotic patients with auditory hallucinations was designed. This paradigm was applied to evaluate cerebral activation with functional magnetic resonance imaging (fMRI) in 11 patients with schizophrenia with persistent hallucinations and 10 healthy subjects. We found a clear enhanced activity of the frontal lobe, temporal cortex, insula, cingulate, and amygdala (mainly right side) in patients when hearing emotional words in comparison with controls. Our findings are consistent with other studies suggesting a relevant role for emotional response in the pathogenesis and treatment of auditory hallucinations.

Adult↗
PubMed2006

Regionally specific alterations in membrane phospholipids in children with ADHD: An in vivo 31P spectroscopy study.

This multi-voxel, phosphorus magnetic resonance spectroscopy ((31)P MRS) study examined the prefrontal cortex (PFC), basal ganglia (BG) and superior temporal (ST) region in 10 children with attention-deficit/hyperactivity disorder (ADHD) and 15 healthy controls. ADHD patients had lower PFC and BG phosphomonoester (PME) levels compared to healthy children. No differences were noted in the ST. These deficits in membrane phospholipid (MPL) precursor levels suggest reduced mass of cellular MPLs due to a possible underdevelopment of neuronal processes and synapses in ADHD.

Attention Deficit Disorder with Hyperactivity↗
PubMed2006

Cognitive enhancement therapy improves emotional intelligence in early course schizophrenia: preliminary effects.

This research examined the preliminary effects of Cognitive Enhancement Therapy (CET) on social cognition in early course schizophrenia, using an objective, performance-based measure of emotional intelligence. Individuals in the early course of schizophrenia were randomly assigned to either CET (n=18) or Enriched Supportive Therapy (n=20), and assessed at baseline and after 1 year of treatment with the Mayer-Salovey-Caruso Emotional Intelligence Test. A series of analyses of covariance showed highly significant (p=.005) and large (Cohen's d=.96) effects favoring CET for improving emotional intelligence, with the most pronounced improvements occurring in patients' ability to understand and manage their own and others' emotions. These findings lend preliminary support to the previously documented benefits of CET on social cognition in schizophrenia, and suggest that such benefits can be extended to patients in the early course of the illness.

Adaptation, Psychological↗
PubMed2006

Abnormal brain size effect on the thalamus in autism.

This study was conducted to examine the volume of the thalamus in autism and to investigate the effect of brain size on this structure in an attempt to replicate, in a larger sample, findings from a previous study reporting the existence of a relationship between brain volume and thalamus in healthy controls but not in individuals with autism. Additionally, the relationships between thalamic volumes and clinical features were examined. Volumetric measurements of the right and left thalamic nuclei were performed on MRI scans obtained from 40 high-functioning individuals with autism (age range: 8-45 years) and 41 healthy controls (age range: 9-43 years). No differences were observed between the two groups for unadjusted thalamic volumes. However, the expected linear relationship between TBV and thalamic volume was not observed in individuals with autism. Furthermore, no correlations were observed between thalamic volumes and clinical features. Findings from this larger study are consistent with the previous report of an abnormal brain size effect on the thalamus in autism and support the possibility of abnormal connections between cortical and subcortical structures in this disorder.

Adolescent↗
PubMed2006

Pituitary volume in treatment-naïve pediatric major depressive disorder.

BACKGROUND: Prior pilot investigation identified a larger pituitary gland volume (PGV) in pediatric patients with major depressive disorder (MDD) compared with healthy pediatric control subjects that was most prominent in boys with MDD. In this independent sample, we focus on gender differences in pituitary volume in a larger sample of pediatric patients with MDD. METHODS: Volumetric magnetic resonance imaging studies were conducted in 35 psychotropic drug-naïve children (15 boys, 20 girls), ages 8-17 years, and 35 case-matched healthy control subjects. RESULTS: The MDD boys had larger PGV (19%) compared with male control subjects. No significant diagnostic group differences in pituitary volume were observed in girls. Healthy boys had significantly smaller PGV (27%) than healthy girls, whereas MDD boys did not differ from girls with MDD. Nonfamilial (without a family history of mood disorder) boys with MDD had significantly larger PGV (35%) than male healthy control subjects and tended to have a larger PGV (27%) than familial (at least one first-degree relative with MDD) boys with MDD. Boys with familial MDD did not differ from control subjects. CONCLUSIONS: These findings provide new evidence of increased pituitary volume in psychotropic-naïve pediatric patients with MDD that seems to be more prominent in male patients with nonfamilial MDD.

Adolescent↗
PubMed2006

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.

Autistic Disorder↗
PubMed2006

Insight and frontal cortical function in schizophrenia: a review.

Insight into illness has been identified as a clinically important phenomenon, in no small part due to an association with treatment-adherence. An increasing number of studies, but not all, have observed poor insight to be a reflection of cognitive dysfunction in schizophrenia. A review of 34 published English-language studies found a significant number (i.e., 21) reporting a relationship between insight deficits and impaired performance on cognitive tasks primarily mediated by frontal cortex. A significant number of reviewed studies examined insight function in more than one psychiatric population, including bipolar and schizoaffective disorder. The most replicated findings from these studies were the correlations between insight deficits and impaired performance on the Wisconsin Card Sorting Test (WCST). More specifically, WCST perseverative errors correlated positively and the number of categories completed correlated negatively with poor insight, suggesting that impaired insight may be mediated by deficiencies in conceptual organization and flexibility in abstract thinking. Since the WCST requires the ability to demonstrate conceptual flexibility through the generation, maintenance and switching of mental sets along with the capacity to use verbal feedback to correct errors, it would appear that such 'executive' functions are most related to insight. In addition, recently identified structural correlates of poor insight in schizophrenia show some association with anosognosia in neurological patients. This review will discuss the implications of these findings and directions for future research.

Databases, Factual↗
PubMed2006

Developmental reflexes and 31P Magnetic Resonance Spectroscopy of basal ganglia in antipsychotic-naive schizophrenia.

The study examined the high energy-phosphate metabolism of basal ganglia in antipsychotic-naive schizophrenia patients with and without developmental reflexes in comparison to healthy subjects. Nineteen antipsychotic-naive schizophrenics of whom 11 had developmental reflexes and 26 age-sex-matched healthy subjects without developmental reflexes underwent in-vivo 2-D 31P Magnetic Resonance Spectroscopy of basal ganglia on a 1.5-T scanner. Mean age-at-onset of psychosis was significantly lower in patients with developmental reflexes. Mean PCr/Total ATP ratio in bilateral basal ganglia was lower in patients than healthy subjects. The ratio was the least in patients with developmental reflexes (F=10.7; df=2, 42; p<0.001). Schizophrenia patients with developmental reflexes had the lowest PCr/Total ATP ratio in basal ganglia indicating more severe metabolic abnormality. These patients had younger age-at-onset of psychosis. Together, this suggests neurodevelopmental etiopathogenesis in schizophrenia.

Adenosine Triphosphate↗
PubMed2006

Smaller cingulate volumes in unipolar depressed patients.

BACKGROUND: The anterior cingulate cortex is a key structure in brain networks involved in mood regulation. Abnormalities in this brain region are possibly implicated in the pathophysiology of depression. This anatomical magnetic resonance imaging (MRI) study compared cingulate cortex volumes in unipolar depressed patients and age- and gender-matched healthy control subjects. METHODS: Thirty-one unmedicated DSM-IV unipolar patients (24 female, aged 39.2 +/- 11.9 years [mean +/- SD]) and 31 healthy control subjects (24 female, aged 36.7 +/- 10.7 years) were studied in a 1.5-T GE Signa magnet (General Electric Medical Systems, Milwaukee, Wisconsin). Cingulate volumes were compared by analysis of covariance with intracranial volume as the covariate. RESULTS: The unipolar patients had significantly smaller anterior and posterior cingulate volumes bilaterally compared with healthy control subjects. When patients were divided into currently depressed (n = 21) and remitted (n = 10) subgroups, currently depressed patients had significantly smaller anterior and posterior cingulate volumes bilaterally compared with healthy control subjects, whereas remitted patients had significantly smaller left anterior cingulate volumes compared with healthy individuals. CONCLUSIONS: Gray matter abnormalities in the cingulate cortex are implicated in the pathophysiology of unipolar depression. Smaller cingulate volumes in currently depressed patients support the hypothesis that cingulate cortex abnormalities are state dependent, whereas changes in left anterior cingulate might be trait related.

Adolescent↗
PubMed2006

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.

Adolescent↗
PubMed2006

Longitudinal studies of antisaccades in antipsychotic-naive first-episode schizophrenia.

BACKGROUND: Prefrontal cortical dysfunctions, including disturbances in adaptive context-specific behavior, have been reported in neuropsychological and brain imaging studies of schizophrenia. Some data suggest that treatment with antipsychotic medications may ameliorate these deficits. METHOD: We investigated antisaccade performance in 39 antipsychotic-naive, first-episode schizophrenia patients who were re-evaluated 6 weeks after treatment initiation. A group of matched healthy subjects were examined at similar time-points. Patients and healthy individuals available for longer-term testing were re-assessed 26 and 52 weeks after initial testing. RESULTS: Before treatment, patients showed elevated rates of response suppression errors and prolonged latencies of correct antisaccades. Increased rates of antisaccade errors were associated with faster response latencies during a separate, visually guided saccade task, but only prior to treatment. Throughout the 1-year follow-up, patients progressively improved in their ability to voluntarily suppress context-inappropriate behavior. Although treatment assignment was by clinician choice, results of exploratory analyses revealed that patients treated with risperidone progressively planned and initiated correct antisaccades more quickly than patients receiving haloperidol. CONCLUSIONS: Deficits in the voluntary control of spatial attention are exaggerated during acute episodes of illness, but remain an enduring aspect of prefrontal dysfunction in schizophrenia even after treatment. During acute illness, speeded sensorimotor transformations may compound these deficits and contribute to the heightened distractibility associated with acute psychosis. Continued improvement in task performance throughout the 1-year follow-up suggests that partial normalization of prefrontal cognitive functions resulting from antipsychotic treatment may have a longer and more gradual time course than the reduction of acute psychotic symptoms.

Adolescent↗
PubMed2006

Adverse effects of risperidone on spatial working memory in first-episode schizophrenia.

CONTEXT: Working memory impairments are a central neurocognitive feature of schizophrenia. The nature of these impairments early in the course of illness and the impact of antipsychotic drug treatment on these deficits are not well understood. The oculomotor delayed response task is a translational spatial working memory paradigm used to characterize the neurophysiologic and neurochemical aspects of working memory in the primate brain. OBJECTIVE: To examine oculomotor delayed response task performance in patients with first-episode schizophrenia before and after antipsychotic drug treatment. DESIGN, SETTING, AND PARTICIPANTS: Twenty-five antipsychotic drug-naive, acutely ill patients with first-episode schizophrenia performed an oculomotor delayed response task at baseline before any drug treatment and again after 6 weeks of risperidone treatment. Twenty-five matched healthy controls were studied in parallel. MAIN OUTCOME MEASURE: Accuracy for remembered spatial locations on an oculomotor delayed response task. RESULTS: Before treatment, patients demonstrated baseline impairment in the ability to maintain spatial location information in working memory at longer delay-period durations (8 seconds), when maintenance demands on working memory were greatest. After 6 weeks of risperidone treatment and significant clinical improvement, this pretreatment impairment worsened such that patients were uniformly impaired across all delay period durations (1-8 seconds). This occurred in the absence of any generalized adverse effect on oculomotor systems or significant extrapyramidal adverse effects. CONCLUSIONS: Deficits in the maintenance of spatial information in working memory are present early in the course of illness. Risperidone treatment exacerbated these deficits, perhaps by impairing the encoding of information into working memory. Studies with nonhuman primates performing oculomotor delayed response tasks suggest that the apparent adverse effect of risperidone might result from treatment-related changes in modulatory functions of prefrontal D1 receptor systems.

Acute Disease↗
PubMed2006

An MRI study of minor physical anomalies in autism.

The objective of this investigation was to examine the existence of minor physical anomalies (MPA) in autism. The interorbital and interlens distances were measured on MRI scans obtained from a sample of 40 non-mentally retarded individuals with autism and 41 healthy controls. No differences were observed between the two groups on any measurements. However, when the analysis was conducted using a split median procedure, individuals with autism and either low FSIQ, PIQ, or VIQ had shorter interorbital distances when compared to controls. Hypotelorism is a MPA that may be present in a subgroup of individuals with autism. Additional research is warranted using large sample sizes with a wide range of intellectual functioning.

Adolescent↗
PubMed2006

Guidelines for clinical treatment of early course schizophrenia.

Several practice guidelines have been developed for the management of schizophrenia based on the current evidence base, but only a few have focused on the early course of this illness. In this article, we review the current literature on the approaches to management of early schizophrenia (ie, the prodromal, psychotic, and recovery phases of this illness). The efficacy of psychosocial and antipsychotic agents in the prodromal phase is an area of active research. Atypical antipsychotics are the mainstay of treatment for stabilization of the acute psychotic phase. Effective approaches in the recovery phase include combining medications with individual and family interventions, supported employment, assertive community treatment, cognitive remediation, and social skills training. Although evidence-based interventions have generated new optimism among those with the illness, more efforts are needed to increase access to care in community settings.

Antipsychotic Agents↗