Biomedical subjects

M S Keshavan

Publications and source records attributed to M S Keshavan.

131 records · Page 8Linked to original sources

PubMedDate not supplied

Is schizophrenia due to excessive synaptic pruning in the prefrontal cortex? The Feinberg hypothesis revisited.

Several lines of evidence support the notion that a substantial reorganization of cortical connections, involving a programmed synaptic pruning, takes place during adolescence in humans. A review of neurobiological abnormalities in schizophrenia indicates that the neurobiological parameters that undergo peripubertal regressive changes may be abnormal in this disorder. An excessive pruning of the prefrontal corticocortical, and corticosubcortical synapses, perhaps involving the excitatory glutamatergic inputs to pyramidal neurons, may underlie schizophrenia. A reciprocal failure of pruning in certain subcortical structures, such as lenticular nuclei, may also occur. Several developmental trajectories, related to early brain insults as well as genetic factors affecting postnatal neurodevelopment, could lead to the illness. These models would have heuristic value and may be consistent with several known facts of the schizophrenic illness, such as its onset in adolescence and the gender differences in its onset and natural course. The relationship between these models and other etiological models of schizophrenia are summarized and approaches to test relevant hypotheses are discussed.

Age of Onset↗

PubMedDate not supplied

Slow-wave sleep and symptomatology in schizophrenia and related psychotic disorders.

Deficits in slow-wave sleep (SWS), or delta sleep, are frequently seen in schizophrenia, but their relationship with schizophrenic symptomatology remains unclear. We examined the association between visually scored and automated measures of SWS and positive and negative symptoms in a series of unmedicated patients with schizophrenia and related psychotic disorders. Total and average automated delta wave counts were significantly inversely associated with negative symptoms overall, and the psychomotor poverty syndrome in particular. Total delta counts were also inversely related to the disorganization syndrome. No relation was seen between reality distortion or the Brief Psychiatric Rating Scale (BPRS) positive symptoms and SWS. These findings support the view that SWS deficits may be related to negative symptoms of schizophrenia and may perhaps be mediated by impaired functioning of frontothalamic neural circuits.

Adult↗

PubMedDate not supplied

MRI study of posterior fossa structures and brain ventricles in bipolar patients.

Previous brain imaging studies have suggested anatomical abnormalities in posterior fossa structures and brain ventricles in bipolar patients. Such abnormalities could possibly be implicated in the pathophysiology of bipolar disorder. Twenty-two DSM-IV bipolar outpatients (mean age+/-S.D.=36+/-10 years) and 22 healthy controls (mean age+/-S.D.=38+/-10 years) underwent an 1.5T MRI (3D-gradient echo-imaging SPGR), performed in the coronal plane (TR=25 ms, TE=5 ms, slice thickness=1.5 mm). The brain structures of interest were traced blindly with a semi-automated software. No significant differences were found between bipolar patients and healthy controls for any posterior fossa measures, or for measures of third or lateral ventricles (MANOVA, age covariate, P>0.05). Age was directly correlated with 3rd ventricle volumes in bipolar patients (Pearson correlation coefficient=0.458, P=0.032), but not in healthy controls (Pearson correlation coefficient=0.313, P=0.155). There was a significant direct correlation between the number of prior illness episodes and right lateral ventricle volumes (Partial correlation coefficient=0.658, P=0.011). Familial patients had smaller left and right cerebellar hemispheres and total vermis volumes, and larger left lateral ventricle volumes compared with non-familial ones (MANOVA, age covariate, P<0.05). In this preliminary study, we were not able to replicate previous findings of abnormalities in cerebellum or brain ventricles in bipolar individuals. However, there were suggestions that abnormalities in cerebellum, vermis, and lateral ventricle sizes may be present in familial cases of the disorder, which should be further examined in future studies with larger patient samples.

Adult↗

PubMedDate not supplied

Superior temporal gyrus and the course of early schizophrenia: progressive, static, or reversible?

Accumulating evidence suggests alterations in brain structure, especially in the prefrontal and temporal cortex, in schizophrenia. Previous studies examining the progression of brain structural alterations in schizophrenia have led to conflicting results. Morphometric studies of the superior temporal gyrus (STG) volumes were conducted in a series of neuroleptic-naive first-episode schizophrenic patients, non-schizophrenic first-episode psychotic patients, and matched healthy controls. Three-dimensional MRI scans were carried out in these subjects before and after one year of treatment. Volume reductions were seen at baseline in the left superior temporal gyrus (adjusted for intracranial volume) in both of the patient groups. Pretreatment illness duration was inversely related to the volume of the left superior temporal gyrus; this relation was confined to males. One-year follow-up MRI investigations in a smaller subset of patients suggested that the STG volume reductions may be reversible. No significant changes were noted in the STG volumes in matched healthy controls who were also scanned at baseline as well as at one-year follow-up. These findings have implications for understanding the nature of the neuropathological processes in early schizophrenia, as well as the potential impact of early treatment.

Adult↗

PubMedDate not supplied

Development, disease and degeneration in schizophrenia: a unitary pathophysiological model.

In recent years, several pathophysiological models of schizophrenia, i.e. the early and late brain neurodevelopmental and post-illness onset neurodegenerative models, have been proposed and theorists have often argued as if these explanations are mutually exclusive. We propose that all these mechanisms may interact cumulatively during successive critical 'windows of vulnerability' during brain development and during the early course of the illness to lead to the clinical manifestations of the illness. Early brain insults may lead to dysplasia of selective neural networks that account for the premorbid cognitive and psychosocial dysfunction seen in many patients. The onset of psychosis in adolescence may be related to an excessive elimination of synapses and secondarily, phasic dopaminergic overactivity. Following illness onset, these neurochemical alterations in relation to continuing untreated psychosis may lead to further neurodegenerative processes. A reduction in tonic glutamatergic neurotransmission and a phasic glutamatergic excess can potentially predispose to these processes and may have considerable explanatory power. This hypothesis is consistent with central characteristics of schizophrenia such as premorbid manifestations, adolescent onset, functional decline early in this illness, cognitive impairments, the role of dopamine and the role of genes and environment in pathophysiology. This 'three hit' model extends similar integrative conceptualization by other investigators and generates testable predictions of relevance to future pathophysiology and treatment research in schizophrenia.

Adolescent↗