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T Sharma

Publications and source records attributed to T Sharma.

At least 55 records · Page 3Linked to original sources
PubMed2000

Exploring the social brain in schizophrenia: left prefrontal underactivation during mental state attribution.

OBJECTIVE: Evidence suggests that patients with schizophrenia have a deficit in "theory of mind," i.e., interpretation of the mental state of others. The authors used functional magnetic resonance imaging (MRI) to investigate the hypothesis that patients with schizophrenia have a dysfunction in brain regions responsible for mental state attribution. METHOD: Mean brain activation in five male patients with schizophrenia was compared to that in seven comparison subjects during performance of a task involving attribution of mental state. RESULTS: During performance of the mental state attribution task, the patients made more errors and showed less blood-oxygen-level-dependent signal in the left inferior frontal gyrus. CONCLUSIONS: To the authors' knowledge, this is the first functional MRI study to show a deficit in the left prefrontal cortex in schizophrenia during a socioemotional task.

Adult↗
PubMed2000

Sex differences in inferior parietal lobule volume in schizophrenia.

OBJECTIVE: The inferior parietal lobule is a heteromodal association cortical region that has been implicated in the pathophysiology of schizophrenia. Inferior parietal lobule gray matter volumes have been shown to differ between healthy male and female subjects, with male subjects having larger left volumes. The authors sought to determine whether these volumetric sex differences also exist in patients with schizophrenia. METHOD: The authors used magnetic resonance imaging to measure inferior parietal lobule volumes of 15 pairs of male and female schizophrenic subjects who were individually matched to each other and to 15 pairs of healthy male and female subjects. RESULTS: Male schizophrenic patients exhibited a reversal of the normal left-greater-than-right male asymmetry in this region and had left inferior parietal lobule gray matter volumes that were significantly smaller than those of healthy male subjects. Female schizophrenic patients did not differ significantly from healthy female subjects in left or right inferior parietal lobule volume or in asymmetry. CONCLUSIONS: This study provides further evidence of brain morphology sex differences in schizophrenia that possibly contribute to the differential clinical disease expression in men and women.

Age Factors↗
PubMed2000

Functional anatomy of verbal fluency in people with schizophrenia and those at genetic risk. Focal dysfunction and distributed disconnectivity reappraised.

BACKGROUND: PET studies of verbal fluency in schizophrenia report a failure of 'deactivation' of left superior temporal gyrus (STG) in the presence of activation of left dorsolateral prefrontal cortex (DLPFC), which deficit has been attributed to underlying 'functional disconnectivity'. AIM: To test whether these findings provide trait-markers for schizophrenia. METHOD: We used H2(15)O PET to examine verbal fluency in 10 obligate carriers of the predisposition to schizophrenia, 10 stable patients and 10 normal controls. RESULTS: We found no evidence of a failure of left STG deactivation in carriers or patients. Instead, patients failed to deactivate the precuneus relative to other groups. We found no differences in functional connectivity between left DLPFC and left STG but patients exhibited significant disconnectivity between left DLPFC and anterior cingulate cortex. CONCLUSIONS: Failure of left STG 'deactivation' and left fronto-temporal disconnectivity are not consistent findings in schizophrenia; neither are they trait-markers for genetic risk. Prefrontal functional disconnectivity here may characterise the schizophrenic phenotype.

Heterozygote↗
PubMed2000

Third ventricle enlargement and developmental delay in first-episode psychosis: preliminary findings.

BACKGROUND: Third rather than lateral ventriculomegaly may be a more specific finding in psychosis. The relevance of ventricular abnormality remains unclear. AIMS: To investigate the developmental correlates of ventricular enlargement. METHOD: Information on childhood development and magnetic resonance images in 1.5-mm contiguous sections were collected on 21 patients experiencing a first episode of psychosis. RESULTS: Patients (n = 21) had significantly less whole brain volume and enlarged third and lateral ventricles compared to controls (n = 25). Third ventricle (r = 0.48, P < 0.03) and lateral ventricle (r = 0.65, P < 0.01) volumes correlated with developmental score. Patients with developmental delay had significantly larger third and lateral ventricles than those without. CONCLUSIONS: Enlargement of both third and lateral ventricles is found in first-episode psychosis and is related to developmental delay in childhood. Insult to periventricular areas is relevant to the neurobiology of the disease. These findings support the view that schizophrenia involves disturbance of neurodevelopmental processes in some patients.

Adolescent↗
PubMed2000

Experience of caregiving: relatives of people experiencing a first episode of psychosis.

BACKGROUND: There has been relatively little research on caregivers of people experiencing their first episode of psychosis. AIMS: To investigate dimensions of caregiving and morbidity in caregivers of people with first-episode psychosis. METHOD: Caregivers of 40 people with first-episode psychosis were interviewed at home about their experience of caregiving, coping strategies and distress. RESULTS: Caregivers used emotional and practical strategies to cope with participants' negative symptoms and difficult behaviours and experienced more worry about these problems. They increased supervision when the participants displayed difficult behaviours. Twelve per cent of caregivers were suffering from psychiatric morbidity as defined by the General Health Questionnaire. Those living with the participant had more frequent visits to their general practitioner. CONCLUSIONS: At first-episode psychosis, caregivers are already having to cope with a wide range of problems and are developing coping strategies. Caregivers worried most about difficult behaviours and negative symptoms in participants.

Adaptation, Psychological↗
PubMed2000

The relevance of ethnic influences on pharmacogenetics to the treatment of psychosis.

Interethnic variation amongst the drug metabolising enzymes relevant to the treatment of psychosis is reviewed. The frequency of genetically determined variants at the extremes of enzyme activity is seen to vary considerably between different ethnic groups; in addition, a shift in the frequency distribution giving an overall lower population mean activity may occur. The role of dietary and other environmental influences in the generation of interethnic variation in cytochrome activity is also discussed. Clinical studies pertinent to this variation are reviewed. It is suggested that the reason for conflicting data from some clinical studies is the existence of overlapping substrate specificity, so that one cytochrome is able to substitute for another. Individuals deficient for more than one cytochrome would be likely to show much more pronounced clinical effects than those showing single cytochrome deficiency.

Antipsychotic Agents↗
PubMed2000

Surgery for stage 5 retinopathy of prematurity: the learning curve and evolving technique.

PURPOSE: To describe our experience with management of eyes with stage 5 retinopathy of prematurity (ROP). METHODS: Closed vitreoretinal surgery was done on 96 eyes of patients with stage 5 ROP. Lens was sacrificed in all but one eye. Surgery involved an attempt to clear all preretinal tissue and open the peripheral trough all round. In most instances bimanual surgery under viscoelastic was performed. RESULTS: At last follow up, anatomical success (defined as attached posterior pole) was achieved in 22.5% cases. Significant postoperative problems included reproliferation and secondary glaucoma. Only two infants obtained mobile vision. CONCLUSION: Late identification of disease, lack of prior treatment such as laser or cryo, and higher incidence of narrow-narrow funnel configuration were responsible for the poor surgical results noted in this series. The poor surgical and functional results reemphasize the need for prompt screening and management of infants at risk.

Clinical Competence↗
PubMed2000

Albendazole therapy for a recurrent orbital hydatid cyst.

Till recently, the treatment of a multiloculated hydatid cyst in the confines of the orbit was every ophthalmologist's nightmare. Over the last decade, two benzimidazole compounds, mebendazole and albendazole, have been tested clinically for use in the chemotherapy of hydatid disease.

Adolescent↗
PubMed2000

Intraocular cilia associated with perforating injury.

PURPOSE: To report a case series of penetrating injury complicated by occurrence of intraocular cilia. METHODS: Retrospective analysis of charts of 11 eyes of 11 patients with penetrating injury and intraocular cilia, presenting between September 1978 and November 1998. Ten eyes underwent surgery for trauma-related problems such as cataract, vitritis, retinal detachment etc., at which time intraocular cilia were removed. One eye did not have surgery and continues to harbour cilia at the posterior perforation site. RESULTS: Metallic wire was responsible for injury in 6 of 11 eyes with intraocular cilia. Five eyes had significant intraocular inflammation. The cilia were located in the anterior segment in 4 eyes; in the posterior segment in 6 eyes and in both in one eye. At the last follow up, 72.7% had 6/18 or better vision. Poor vision in the rest was due to recurrent retinal detachment (2 eyes) and macular scarring (1 eye). CONCLUSION: Intraocular cilia are more commonly associated with injury by a metallic wire. The presentation and management of an injured eye does not seem to be influenced by the presence of cilia in the eye.

Adolescent↗
PubMed2000

Recent developments in vitreoretinal surgery.

In the past three decades, a great improvement has occurred in microsurgical techniques used in the management of various eye diseases involving retina and vitreous. Advances in instrumentation has made the surgery easier and refined. The instruments used are narrated widely in this article. Various vitreous substitutes have been developed and are required in vitreoretinal surgery. These are gases, silicone oil, perfluorocarbon liquids and fluorosilicone oil. Anterior segment indications for vitreous surgery are: Vitreous loss during cataract surgery, thick after cataracts that can't be managed with Nd: YAG capsulotomy, vitreocorneal touch, updrawn pupils, incarcerated vitreous in the wound causing cystoid macular oedema, malignant glaucoma, penetrating keratoplasty in aphakic patients, congenital cataracts and filtering procedures in aphakic eyes. In posterior segment indications, vitrectomy is useful in penetrating trauma, haemorrhage, retinal deetachment, intra-ocular foreign bodies and infection endophthalmitis Macular surgery involves peeling of epimacular membrane or proliferation, treating vitreomacular traction syndrome, idiopathic macular holes, retinal detachment associated with optic pit, evacuation of submacular haemorrhage and excision of choroidal neovascular membranes. Available options to treat retinal detachments are pneumatic retinopexy, scleral buckling and vitreous surgery. Proliferative vitreoretinopathy remains the important cause of failure and occurs in about 8-10% cases after retinal detachment. Vitreous surgery for ocular trauma, vitrectomy for proliferative diabetic retinopathy, macular hole surgery, submacular surgery are also discussed in detail.

Diabetic Retinopathy↗
PubMed1999

Lack of normal pattern of cerebral asymmetry in familial schizophrenic patients and their relatives--The Maudsley Family Study.

Lack of the normal cerebral asymmetry has been reported in schizophrenia. We wished to test the hypothesis that this lack of the normal pattern of asymmetry is familial and that it can be found in both schizophrenic and non-schizophrenic family members. In particular, we wanted to know whether those relatives who appear to be transmitting liability to the illness also demonstrate the loss of normal asymmetry. We studied families with several members affected with schizophrenia. We carried out volumetric measurements of prefrontal, premotor, sensorimotor and occipitoparietal regions in each hemisphere using 3D reconstructed MRI images in 29 schizophrenic patients, 55 of their first degree relatives, and 39 unrelated control subjects on contiguous thin slices of the brain. Nine of the unaffected relatives appeared to be transmitting the liability for schizophrenia (e.g. the mother of a schizophrenic patient who, although not psychotic herself, had a schizophrenic parent or sibling). We termed them presumed obligate carriers and the remaining 46 relatives presumed non-obligate carriers. The healthy control subjects showed larger right than left prefrontal regions and larger left than right sensorimotor and occipitoparietal regions. The schizophrenic patients showed lack of this normal brain asymmetry in the prefrontal, sensorimotor and occipitoparietal cortical regions. The presumed obligate carriers were similar to the schizophrenic patients in exhibiting lack of asymmetries in these cortical regions, while the presumed non-obligate relatives showed lack of asymmetry only in the occipitoparietal region. There was no overall reduction in total or regional brain volumes among the groups. Our findings indicate that lack of the normal pattern of frontal and occipital asymmetry is a marker for genetic liability to schizophrenia in families multiply affected with schizophrenia.

Adult↗
PubMed1999

Differences in frontal cortical activation by a working memory task after substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia.

Antipsychotic drug treatment of schizophrenia may be complicated by side effects of widespread dopaminergic antagonism, including exacerbation of negative and cognitive symptoms due to frontal cortical hypodopaminergia. Atypical antipsychotics have been shown to enhance frontal dopaminergic activity in animal models. We predicted that substitution of risperidone for typical antipsychotic drugs in the treatment of schizophrenia would be associated with enhanced functional activation of frontal cortex. We measured cerebral blood oxygenation changes during periodic performance of a verbal working memory task, using functional MRI, on two occasions (baseline and 6 weeks later) in two cohorts of schizophrenic patients. One cohort (n = 10) was treated with typical antipsychotic drugs throughout the study. Risperidone was substituted for typical antipsychotics after baseline assessment in the second cohort (n = 10). A matched group of healthy volunteers (n = 10) was also studied on a single occasion. A network comprising bilateral dorsolateral prefrontal and lateral premotor cortex, the supplementary motor area, and posterior parietal cortex was activated by working memory task performance in both the patients and comparison subjects. A two-way analysis of covariance was used to estimate the effect of substituting risperidone for typical antipsychotics on power of functional response in the patient group. Substitution of risperidone increased functional activation in right prefrontal cortex, supplementary motor area, and posterior parietal cortex at both voxel and regional levels of analysis. This study provides direct evidence for significantly enhanced frontal function in schizophrenic patients after substitution of risperidone for typical antipsychotic drugs, and it indicates the potential value of functional MRI as a tool for longitudinal assessment of psychopharmacological effects on cerebral physiology.

Adult↗
PubMed1999

Hippocampal volume reduction in schizophrenia: effects of genetic risk and pregnancy and birth complications.

BACKGROUND: Hippocampal volume reduction has been repeatedly demonstrated in schizophrenia. The relative contribution of genetic and environmental factors to this is unclear. METHODS: To address this question, we compared volumetric measurements of the left and right hippocampus, obtained using stereological methods from brain MRI scans, from two groups of patients with schizophrenia as well as healthy controls (n = 26). Patients (n = 27) in the first group, had no family history of schizophrenia and had experienced severe pregnancy and birth complications (PBCs). The second group comprised of patients (n = 21) without a history of severe PBCs from families multiply affected with schizophrenia. RESULTS: Reduction of the left hippocampal volume was associated with the diagnosis of schizophrenia but was present only in patients with a history of severe PBCs; in this group the smaller hippocampal volume, the earlier the onset of psychosis. CONCLUSIONS: Our findings suggest that environmental factors, in this case severe PBCs, make a significant contribution to hippocampal abnormalities in schizophrenia.

Adult↗
PubMed1999

Attenuated frontal activation in schizophrenia may be task dependent.

UNLABELLED: Functional magnetic resonance imaging was used to examine the neural correlates of two linguistic tasks in schizophrenia. METHOD: Five dextral male schizophrenic patients and five volunteers matched for demographic variables and task performance participated. Echoplanar images were acquired over 5 min at 1.5 T while subjects performed two paced, covert tasks; (1) verbal fluency: silent generation of words beginning with an aurally presented cue letter, contrasted with silent repetition of the aurally presented word 'rest'; (2) semantic decision: deciding whether a visually presented cue word was 'living or non-living' and silently articulating the response, contrasted with rest. Both tasks entailed language processing; only verbal fluency requires the intrinsic generation of verbal material. Between-group differences in the mean power of experimental response to the semantic decision task were identified by a one-way analysis of covariance (ANCOVA), with a measure of stimulus-correlated motion as a covariate. Voxels demonstrating a significant interaction between task and group were identified using a two-way ANCOVA. RESULTS: In controls, both tasks were associated with activation of prefrontal cortex. In patients with schizophrenia there was a significantly reduced power of response in several prefrontal regions during verbal fluency relative to controls, a difference that was not evident for the semantic decision task. There was a significant group x task interaction in the left inferior frontal gyrus, left dorsolateral prefrontal cortex and the supplementary motor area at voxel and regional levels of analysis. CONCLUSIONS: Attenuation of frontal activation during cognitive task performance in schizophrenia does not represent a fixed deficit in frontal function, but may depend on the specific cognitive demands of the experimental task employed.

Adult↗
PubMed1999

Mapping of grey matter changes in schizophrenia.

Studies of brain changes in schizophrenia have suggested that the disorder is associated with reductions in both global and regional grey matter. In this study, we used structural neuroimaging to differentiate between these two types of change and to examine regional grey matter throughout the whole brain. Grey matter from magnetic resonance images was segmented and transformed into stereotactic space, and patients with schizophrenia and controls were compared with respect to regional grey matter (after compensating for global grey matter differences). In two preliminary analyses to test our methodology, we demonstrated that: (1) in the transformed grey matter maps, voxel values at the location of the caudate nuclei were correlated with region-of-interest measurements of caudate area in native image space, and (2) the technique detected regional grey matter changes resulting from artificial lesions created in the native images. We then used a factorial design to examine data from two studies, comprising a total of 42 schizophrenics and 52 controls. Analysis of the main effect of schizophrenia on regional grey matter revealed significant reductions in (a) the right temporal pole, insula and amygdala, (b) the left temporal pole, insula and dorsolateral prefrontal cortex.

Adult↗
PubMed1999

Supra-regional brain systems and the neuropathology of schizophrenia.

At what levels of brain organization might pathological change in schizophrenia be anatomically expressed: global, regional or supraregional? We hypothesised that brain structure reflects a set of supra-regional anatomical systems with common developmental influences. We conducted an exploratory analysis to identify supraregional brain systems and to investigate whether abnormal brain architecture in schizophrenia is manifested within one or more of these systems. Magnetic resonance (MR) images were acquired from 27 patients with schizophrenia and 37 control subjects. After segmentation and registration of each individual MRI dataset in the standard space of Talairach and Tournoux, grey matter and ventricular-cerebrospinal fluid (CSF) maps were automatically parcellated into 104 regions. We used principal components analysis of the multiple regional grey matter and ventricular-CSF measurements, on all 64 subjects, to extract the five main normative supra-regional systems. The first two of these components represented global variation in grey matter and ventricular-CSF regional measures. We interpreted the other three components as representing supra-regional systems comprising: a frontal-parietal system, a frontal-temporal system and a frontal-basal ganglia system. Schizophrenic group mean scores on the first component (global grey matter-ventricular contrast) and fourth component (frontal-temporal system) were significantly reduced compared to controls. These results suggest that pathological change in schizophrenia may be expressed at two mutually independent levels of anatomical organization: global change in a grey matter/ventricular system and supra-regional change in a frontal-temporal system.

Adult↗