Biomedical subjects

Matcheri S Keshavan

Publications and source records attributed to Matcheri S Keshavan.

At least 73 records · Page 4Linked to original sources

PubMed2004

Impairment of verbal memory and learning in antipsychotic-naïve patients with first-episode schizophrenia.

BACKGROUND: Verbal memory deficits are of interest in schizophrenia because of the potential relationship to functional and anatomic mesial temporal lobe pathology in this disorder. The goal of this study was to characterize the nature of verbal memory impairments in antipsychotic-naïve schizophrenic patients early in the course of illness. METHODS: Neuroleptic-naïve patients with schizophrenia (n=62) and healthy individuals (n=67), matched on IQ, age, sex, and parental socioeconomic status, were administered the California Verbal Learning Test (CVLT). RESULTS: Schizophrenia participants performed significantly worse than healthy individuals on measures of verbal learning, short- and long-term memory, and immediate attention. Deficits in recall were related to reduced use of organizational strategies to facilitate verbal encoding and retrieval. No group differences were found in rate of forgetting or susceptibility to proactive or retroactive interference. Memory deficits had minimal relation to positive or negative symptom severity. CONCLUSIONS: Schizophrenia is characterized by significant verbal memory dysfunction early in the course of illness prior to treatment with antipsychotic medications. Deficits in consistency of learning over several trials, as well as a strong relationship between semantic organizational strategies and reduced learning capacity, implicate prefrontal dysfunction as a contributor to verbal memory deficits in schizophrenia.

Adult↗

PubMed2004

Pretreatment and longitudinal studies of neuropsychological deficits in antipsychotic-naïve patients with schizophrenia.

The early course of neuropsychological dysfunction in schizophrenia and the impact of treatment on these deficits need to be better specified. A sample of 45 patients with schizophrenia underwent five neuropsychological evaluations from prior to treatment with antipsychotic treatment through a 2-year follow-up period. A comparison sample of 33 matched healthy individuals underwent neuropsychological evaluations at similar time points. At baseline, a generalized deficit across cognitive domains was evident for the schizophrenia sample. After 6 weeks of treatment, patients showed modest improvements in visual memory and visual perception, but a decline in verbal memory. Verbal memory performance returned to baseline levels by the 6-month follow-up while deficits in other neuropsychological domains persisted throughout the 2-year period. Relatively static and generalized neuropsychological dysfunction, evident from illness onset, is consistent with neurodevelopmental rather than neurodegenerative models of schizophrenia.

Adult↗

PubMed2004

Abnormalities in MRI-measured signal intensity in the corpus callosum in schizophrenia.

The microstructural integrity of the corpus callosum (CC) in first-episode schizophrenia patients was assessed by measuring the signal intensity (SI) in T1-weighted MRI images. Analyses revealed that compared to both healthy controls and non-schizophrenic patients, schizophrenia patients showed reductions in SI in all the callosal subregions, the genu, body, isthmus and splenium in first-episode schizophrenia. These results indicate that schizophrenia is characterized by pathology of this principal interhemispheric commissure; the abnormalities may reflect distributed (rather than localized) interhemispheric disconnectivity that extends beyond the heteromodal association cortices.

Adolescent↗

PubMed2004

Anatomic evaluation of the orbitofrontal cortex in major depressive disorder.

BACKGROUND: The orbitofrontal cortex (OFC) plays a major role in neuropsychologic functioning including exteroceptive and interoceptive information coding, reward-guided behavior, impulse control, and mood regulation. This study examined the OFC and its subdivisions in patients with MDD and matched healthy control subjects. METHODS: Magnetic resonance imaging (MRI) was performed on 31 unmedicated MDD and 34 control subjects matched for age, gender, and race. Gray matter volumes of the OFC and its lateral and medial subdivisions were measured blindly. RESULTS: The MDD patients had smaller gray matter volumes in right medial [two-way analysis of covariance F(1,60) = 4.285; p =.043] and left lateral OFC [F(1,60) = 4.252; p =.044]. Left lateral OFC volume correlated negatively with age in patients but not in control subjects. Male, but not female patients exhibited smaller left and right medial OFC volumes compared with healthy control subjects of the same gender. CONCLUSIONS: These findings suggest that patients with MDD have reduced OFC gray matter volumes. Although this reduction might be important in understanding the pathophysiology of MDD, its functional and psychopathologic consequences are as yet unclear. Future studies examining the relationship between specific symptomatic dimensions of MDD and OFC volumes could be especially informative.

Adult↗

PubMed2004

Normal pituitary volumes in children and adolescents with bipolar disorder: a magnetic resonance imaging study.

The volume of the pituitary gland in adults with bipolar disorder has previously been reported to be smaller than that of healthy controls. Such abnormalities would be consistent with the HPA dysfunction reported in this illness. We conducted a study of children and adolescents with bipolar disorder to determine whether size abnormalities in the pituitary gland are already present early in illness course. Magnetic resonance imaging (MRI) morphometric analysis of the pituitary gland was carried out in 16 DSM-IV children and adolescents with bipolar disorder (mean age+/-sd=15.5+/-3.4 years) and 21 healthy controls (mean age+/-sd=16.9+/-3.8 years). Subjects underwent a 1.5 T MRI, with 3-D Spoiled Gradient Recalled (SPGR) acquisition. There was no statistically significant difference between pituitary gland volumes of bipolar patients compared to healthy controls (ANCOVA, age, gender, and ICV as covariates; F=1.77, df=1,32, P=.19). There was a statistically significant direct relationship between age and pituitary gland volume in both groups (r=.59, df=17, P=.007 for healthy controls; r=.61, df=12, P=.008 for bipolar patients). No evidence of size abnormalities in the pituitary gland was found in child and adolescent bipolar patients, contrary to reports involving adult bipolar patients. This suggests that anatomical abnormalities in this structure may develop later in illness course as a result of continued HPA dysfunction.

Adolescent↗

PubMed2004

Approaches for adolescents with an affected family member with schizophrenia.

Prospective studies of adolescents at risk for schizophrenia (high-risk studies) can shed light on the possible premorbid precursors of schizophrenia. Recent studies have provided evidence of neurobehavioral, brain structural, physiologic, and neurochemical deficits in adolescent nonpsychotic high-risk relatives that may date back to childhood or earlier. These results are collectively providing a critical window into the inter-relationships between genetic predisposition, neurodevelopment, and premorbid indicators of risk in schizophrenia. Convergent approaches are inherently powerful in mutually informing each other in enriching the knowledge of the risk factors that predict the eventual onset of schizophrenia. Defining such reliable predictors of the onset of schizophrenia may provide us with the tools to better understand the etiology and pathophysiology of the illness, and may pave the way for innovative methods of treatment and possibly prevention. The authors review the relevant literature in this promising field of inquiry and summarize recent findings from high-risk studies.

Adolescent↗

PubMed2004

Abnormalities of the corpus callosum in nonpsychotic children with chromosome 22q11 deletion syndrome.

Chromosome 22q11 deletion syndrome (22q11DS) is associated with elevated rates of schizophrenia and other psychoses in adulthood. Childhood morphologic brain abnormalities are frequently reported, but the significance of these and their relationship to the development of schizophrenia are unclear. We sought to delineate midline neuroanatomical abnormalities in nonpsychotic children with 22q11DS and their age- and sex-matched controls and compare these to those reported in individuals with schizophrenia. On qualitative analysis, we found a high incidence of midline developmental abnormalities (cavum septum pellucidum, or CSP). On quantitative analysis, the total corpus callosum (CC) area was significantly increased in the patient group and among the subregions, the patients had a significantly larger isthmus. These findings of an increased area of the corpus callosum, specifically the isthmus, have not been reported before in individuals with 22q11DS. We also found a relative lack of the age-related increase in the size of the corpus callosum in the children with 22q11DS. There were no differences in cerebellar vermis measurements between the patient and control groups. Our findings are indicative of frequent midline brain anomalies, including dysgenesis of the corpus callosum, in nonpsychotic children with 22q11DS. Although the increased size of the corpus callosum in our 22q11DS patients is in direct contrast to the decrease seen in schizophrenia, the high frequency of structural midline abnormalities in these nonpsychotic children with 22q11DS is similar to that seen in schizophrenia. Further longitudinal studies on these children will help determine which of these structural abnormalities is/are pertinent to the development of psychosis.

Abnormalities, Multiple↗

PubMed2004

Insight and prefrontal cortex in first-episode Schizophrenia.

Few studies have investigated the neurobiological basis of impaired insight in antipsychotic-naive schizophrenia. However, the relationship between insight and specific prefrontally mediated cognitive functions suggests that insight deficits may be an expression of prefrontal cortical dysfunction. This study was designed to examine the relationship among insight, neurocognition, and dorsolateral prefrontal cortex (DLPFC) volumes in first-episode antipsychotic-naive schizophrenia subjects. DLPFC volumes were compared between 35 first-episode schizophrenia subjects with good (n = 17) and poor insight (n = 18). Morphometric measurements were based on MRI scans by trained raters blind to clinical information. First-episode schizophrenia subjects with poor insight showed decreased right DLPFC volumes relative to those with good insight. In addition, those with poor insight had higher levels of perseverative errors (PEs) on the Wisconsin Card Sort Test (WCST). No differences in other neuropsychological measures were found between the good and poor insight groups. Similarly, no differences were found between schizophrenia subjects with good versus poor insight on any of the psychopathological measures employed in this study. These findings suggest that poor insight in schizophrenia may be a function of specific prefrontally mediated neurocognitive deficits rather than a global impairment in neuropsychological functioning or different profiles of psychopathology.

Adult↗

PubMed2004

Parahippocampal gyrus in first episode psychotic disorders: a structural magnetic resonance imaging study.

Neuropathological abnormalities in schizophrenia have been demonstrated in the parahippocampal gyrus (PHG). Only a few studies on first-episode neuroleptic-naive schizophrenia patients have been done using in vivo neuroimaging techniques. The authors examined the PHG morphology using structural MRI in neuroleptic-naive subjects with first episode psychoses. Volumetric measurements of PHG and intracranial volume (ICV) were obtained on subjects with schizophrenia and schizoaffective disorders (SCZ; n = 33), nonschizophrenia psychotic disorders (NSCZ; n = 11) and matched healthy subjects (HS; n = 43). The subjects were rated on the Brief Psychiatric Rating Scale (BPRS). Group differences and clinical correlations of ICV-adjusted PHG volumes were examined. Left PHG was significantly different across the groups consisting of SCZ, NSCZ and HS. PHG was larger in NSCZ compared to SCZ but not relative to HS. Bilaterally, PHG was no different between SCZ and HS. In pooled psychotic patients, the PHG volume negatively correlated with total positive symptom, delusion and conceptual disorganization scores on BPRS. Patients with delusions had relatively smaller PHG compared to nondelusional subjects. Observed differences in PHG volume in first-episode neuroleptic-naive patients suggest that these observations are not confounded by illness chronicity or medication effects. Significant association of PHG volume with psychotic symptoms suggests that PHG pathology plays an important role in the etiopathology of psychosis and its symptoms.

Adult↗

PubMed2004

1H MRS study of dorsolateral prefrontal cortex in healthy individuals before and after lithium administration.

The mechanism of action of lithium is still largely unknown. However, recent animal and human studies suggested the possible neuroprotective effects of this medication. In particular, a recent magnetic resonance spectroscopy (MRS) study showed the increase of cortical brain levels of N-acetyl-aspartate (NAA), a putative marker of neuronal integrity/functioning, in both bipolar patients and normal controls after 4 weeks of lithium administration. We investigated the effects of lithium on NAA levels in a sample of healthy individuals using in vivo 1H MRS in dorsolateral prefrontal cortex (DLPFC), a region likely implicated in the pathophysiology of bipolar disorder. In vivo short echo-time 1H-MRS measurements of 8 cm3 single voxels placed bilaterally in the DLPFC were conducted at baseline and after 4 weeks of lithium administration on 12 healthy individuals (mean age+/-SD = 25.0+/-9.8 years; six males). After lithium administration, no significant differences in NAA, phosphocreatine plus creatine, glycerophosphocholine plus phosphocholine (or choline-containing molecules), and myo-inositol absolute levels or ratios were found in DLPFC (paired t-tests, p > 0.05). Contrary to prior MRS reports in bipolar patients, we found that lithium administration did not significantly increase NAA levels in the DLPFC of healthy individuals. Future longitudinal studies will be needed to further investigate whether chronic lithium treatment increases NAA levels in other brain regions in healthy individuals, and whether it promotes changes in these levels in specific brain regions in bipolar patients.

Adolescent↗

PubMed2004

Early treatment-induced improvement of negative symptoms predicts cognitive functioning in treatment-naive first episode schizophrenia: a 2-year followup.

Studying neuroleptic-naive first episode schizophrenia is a strategy for investigating clinical and neuropsychological abnormalities at a very early phase of the disease without confounding influences of illness duration and medication effects. We examined the clinical and neuropsychological time course over 2 years in 32 neuroleptic-naive first episode patients (20 males, 12 females) and 21 healthy individuals with similar sociodemographic characteristics. Early treatment-induced reduction of negative symptoms predicted superior cognitive performance throughout followup in the domains of verbal fluency, attention, and non-verbal learning and memory. There were no associations between psychotic or disorganized symptoms and cognitive variables. These findings suggest an important relationship between treatment efficacy of antipsychotic medication and the longer term course of cognitive deficits in schizophrenia.

Adolescent↗

PubMed2004

Reduced red blood cell membrane essential polyunsaturated fatty acids in first episode schizophrenia at neuroleptic-naive baseline.

There is emerging evidence in schizophrenia of membrane abnormalities, primarily reductions in the essential omega-3 and omega-6 series of polyunsaturated fatty acids (PUFA). Because previous studies have largely been in chronic patients, it is not known whether these membrane abnormalities also occur early in illness. In the present study, red blood cell membrane fatty acid levels were determined by capillary gas chromatography from 24 neuroleptic-naive patients with first episode schizophrenia or schizoaffective disorder and 31 age-matched normal controls. Relative to normal subjects, patients had significant reductions in total PUFA (-13%) but not in monounsaturated or saturated fatty acids. Specifically, significant reductions were found in arachidonic acid (-18%), docosapentaenoic acid (-36%), and docosahexaenoic acid (-26%) concentrations. These reductions were not related to age, gender, smoking status, or cotinine levels. These results confirm previous findings of membrane deficits in schizophrenia and show that significant PUFA reductions occur early in the illness, prior to initiation of treatment, raising the possibility that these deficits are trait related. The findings also suggest that membrane fatty acid losses are quite specific to the highly unsaturated fatty acids.

Adult↗

PubMed2004

Neuropsychological dysfunction in antipsychotic-naive first-episode unipolar psychotic depression.

OBJECTIVE: The profile of neuropsychological impairment associated with unipolar psychotic depression remains unclear. The authors used a neuropsychological test battery to characterize the neuropsychiatric profile of patients with unipolar psychotic depression, relative to that of patients with nonpsychotic unipolar depression, patients with schizophrenia, and healthy comparison subjects. METHOD: Study subjects included antipsychotic-naive patients with a first episode of psychotic unipolar depression (N=20), antipsychotic-naive and unmedicated patients with nonpsychotic unipolar depression (N=14), antipsychotic-naive patients with first-episode schizophrenia (N=86), and healthy volunteers (N=81). Groups were matched on age, sex, race, education, parental socioeconomic status, and estimated premorbid intelligence. Psychotic patients were followed clinically for 2 years to confirm diagnosis. All participants completed a standard neuropsychological battery, including tests of general intelligence, executive function, attention, verbal memory, motor skills, and visual-spatial perception. RESULTS: Patients with psychotic depression had a pattern of neuropsychological dysfunction that was similar to but less severe than that of patients with schizophrenia. In contrast, patients with nonpsychotic unipolar depression had a neuropsychological profile that was similar to that of healthy individuals but that included mild dysfunction on tests of attention. Neuropsychological test performance was generally independent of acute clinical symptoms, but some pairwise group differences were attenuated by covariation for symptom severity. CONCLUSIONS: The similar neuropsychological profiles for schizophrenia and psychotic depression suggest that these psychotic disorders may have common pathophysiological features. The dramatic differences in performance between the patients with psychotic depression and those with nonpsychotic depression point to a marked distinction in neurocognitive function associated with the expression of psychosis in depressed patients.

Adult↗

PubMed2004

The entorhinal cortex in first-episode psychotic disorders: a structural magnetic resonance imaging study.

OBJECTIVE: Neuropathological findings regarding the entorhinal cortex in schizophrenia are conflicting. The authors used structural magnetic resonance imaging to examine the entorhinal cortex volumes of healthy subjects and medication-naive patients experiencing their first episode of psychotic illness. METHOD: The study included 33 patients with schizophrenia and related disorders, 11 patients with nonschizophrenic disorders, and 43 matched healthy subjects. All subjects were rated on the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms, and volumetric measurements of the entorhinal cortex were obtained for all subjects. The authors examined differences across the groups as well as clinical correlations of entorhinal cortex volumes adjusted for intracranial volume. RESULTS: A significant diagnosis effect was seen in the left entorhinal cortex: patients with schizophrenia and related disorders and patients with nonschizophrenic psychotic disorders had smaller left entorhinal cortex volumes than healthy subjects. The mean entorhinal cortex volume of patients with schizophrenic disorders did not differ from that of patients with nonschizophrenic psychotic disorders. In patients with schizophrenic disorders, the entorhinal cortex volume positively correlated with severity of delusions. The mean entorhinal cortex volume of patients with nondelusional psychotic disorders was significantly smaller than that of patients with delusional psychotic disorders and healthy subjects. CONCLUSIONS: Smaller entorhinal cortex volume in first-episode, neuroleptic-naive psychotic disorders may not be a confound of the effects of illness chronicity or antipsychotic treatment. Entorhinal cortex pathology appears to have a significant association with positive symptoms, specifically delusions. The impairment of functions in which the entorhinal cortex participates-such as novelty detection, associative learning, and processing episodic, recognition, and autobiographical memory-could be responsible for its association with psychotic disorders and delusions.

Adult↗

PubMed2004

Relationships between cognitive and neurological performance in neuroleptic-naïve psychosis.

The authors explored relationships between neuropsychological performance and neurological exam abnormalities in 86 never-medicated patients with nonorganic psychosis (59 with schizophrenia or schizoaffective disorder) and 51 healthy subjects. Assessments include a reliable subset of the Neurological Evaluation Scale (rNES) and several neuropsychological tests of attention, executive function, memory, and current and premorbid intelligence. Principal components analysis of the rNES yielded two main factors. Of these, CogPer (consisting of more cognitively demanding perceptual tasks) showed stronger relationships than RepMot (consisting of repetitive manual motor tasks) to neuropsychological measures. Customarily, frontal neuropsychological tasks also relate more strongly to CogPer than to RepMot. Approximately one-half of the variability in these cognitive and neurological assessments is shared.

Adult↗

PubMed2004

Premorbid characterization in schizophrenia: the Pittsburgh High Risk Study.

Prospective studies of young relatives at risk for schizophrenia can shed light on the possible premorbid precursors of the disease. Ongoing studies in Pittsburgh suggest that young non-psychotic high risk relatives have neurobehavioral, brain structural, physiological, and neurochemical deficits that may date back to childhood or earlier. We summarize these data, review the relevant literature in this emerging field, and provide some new data suggesting alterations in sleep architecture in young relatives at risk for schizophrenia. Collectively, such data are likely to help us to predict the eventual emergence of schizophrenia, schizophrenia spectrum or non-spectrum psychopathology.

Journal Article↗

PubMed2003

Magnetic resonance imaging study of corpus callosum abnormalities in patients with bipolar disorder.

BACKGROUND: This study was conducted to further examine the hypothesis of abnormalities in size of corpus callosum in subjects with bipolar disorder. METHODS: Sixteen right-handed DSM-IV bipolar I patients and 27 right-handed healthy control subjects were studied. A 1.5-T GE Signa magnet was used, and three-dimensional gradient echo imaging (spoiled gradient recall acquisition) was conducted. Area measurements of corpus callosum were obtained blindly, with a semi-automated software, by a well-trained rater. RESULTS: Right-handed bipolar I patients had significantly smaller total corpus callosum, genu, posterior body, and isthmus areas compared with right-handed healthy control subjects (analysis of covariance with age, gender, and intracranial volume as covariates, p <.05). Partial correlation analyses, controlled for intracranial volumes, found a significant inverse relationship between age and total callosal, genu, anterior body, isthmus, and circularity in healthy control subjects (p <.05) but not in bipolar patients (p >.05). CONCLUSIONS: Smaller callosal areas may lead to altered inter-hemispheric communication and be involved in the pathophysiology and cognitive impairment found in bipolar disorder.

Adult↗

PubMed2003

Anatomical MRI study of basal ganglia in major depressive disorder.

The basal ganglia form a part of the brain neuroanatomic circuits that may be involved in mood regulation. Decreases in basal ganglia volumes have been previously reported in major depressive disorder patients in comparison to healthy controls. In this study, we measured caudate, putamen, and globus pallidus volumes in 25 patients with major depressive disorder (4 M; age+/-S.D.=41+/-11 years) and 48 healthy controls (29 M; age+/-S.D.=35+/-10 years), using high-resolution magnetic resonance imaging (MRI), in an attempt to replicate prior findings. Unlike most previous studies, we did not find significant differences between patient and control groups in basal ganglia volumetric measures. Nonetheless, there was a significant interaction between diagnosis and cerebral hemisphere, with MDD patients showing decreased asymmetry in globus pallidus volumes in comparison with healthy controls. Furthermore, in the patient group, left putamen volumes correlated inversely with length of illness, and left globus pallidus volume correlated directly with number of prior depressive episodes. These findings suggest that abnormalities in lateralization and possibly neurodegenerative changes in basal ganglia structures participate in the pathophysiology of major depressive disorder.

Adolescent↗