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Biomedical subjects

P Sachdev

Publications and source records attributed to P Sachdev.

At least 19 recordsLinked to original sources

Reliability and validity of ratings of signal hyperintensities on MRI by visual inspection and computerised measurement.

Brain magnetic resonance imaging (MRI) scans on 98 elderly subjects, 62 with a diagnosis of schizophrenia and 36 healthy controls, were independently and blindly rated by two investigators using the visual rating methods of Fazekas et al. (Fazekas, F., Chawluk, J.B., Alavi, A., Hurtig, H.I., Zimmerman, R.A., 1987. MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. American Journal of Neuroradiology 8, 421-426) and Victoroff et al. (Victoroff, J., Mack, W.J., Grafton, S.T., Schreiber, S.S., Chui, H.C., 1994. A method to improve interrater reliability of visual inspection of brain MRI scans in dementia. Neurology 44, 2267-2276) for periventricular, deep white matter and subcortical gray matter signal hyperintensities (SHs) on T2-weighted images. The hyperintense signal volumes were measured by manual delineation of the signals on a workstation using Analyze software (computerised method). The subjects also underwent a detailed neuropsychological assessment. There was a high correlation between two experienced raters for both visual ratings, and the correspondence between the two methods was high. The inter-rater reliability for the computerised method was modest but significant, and the association between the visual and computerised methods was good except for ratings for SHs in subcortical nuclei. The Fazekas and computerised methods, and to a lesser degree the Victoroff method, had modest but significant correlations with some neuropsychological test measures. In conclusion, we did not demonstrate a clear superiority in reliability or validity for one demanding computerised method of rating SHs. Visual ratings should therefore be considered adequate for most clinical and research purposes, but such ratings should be accompanied by adequate training and the provision of standard reference images.

Aged↗

The preventative role of antioxidants (selegiline and vitamin E) in a rat model of tardive dyskinesia.

BACKGROUND: We examined the potential protective effects of two potent antioxidants, selegiline and vitamin E, in a rodent model of tardive dyskinesia (TD), viz. neuroleptic-induced spontaneous orofacial movements. METHODS: Rats were treated with fortnightly injections of fluphenazine decanoate for 12 weeks, and examined at baseline and at fortnightly intervals for vacuous chewing movements, mouth tremors and tongue protrusions. RESULTS: The administration of fluphenazine led to a progressive increase of all three types of orofacial movements. In the first study, the impact of the concomitant administration of selegiline on orofacial movements was examined. Selegiline led to a reduction in orofacial movements in neuroleptic-treated rats to the level of control rats not being administered a neuroleptic drug. In the second study, rats were fed diets either high or low in their vitamin E content. High and low vitamin E diets did not significantly affect neuroleptic-induced orofacial movements. CONCLUSIONS: Our studies provide some support for the hypothesis that oxidative injury may play a role in the genesis of neuroleptic-induced movement disorder, and prompt further examination of this hypothesis in both animals and humans.

Animals↗

An electroencephalographic investigation of late-onset schizophrenia.

We performed awake and resting electroencephalograms (EEGs) on 22 subjects with DSM-III-R schizophrenic disorder of late onset (at or after age 50 years), and compared them with the EEGs of 33 healthy community controls matched for age and gender. The EEGs were rated qualitatively and a 2-minute, artifact-free tracing from each subject was quantified manually by an experienced neurophysiologist unaware of the identity of the subject group. The only significant difference was the presence of more generalized slowing in the EEGs of schizophrenia patients, which was at least partially accounted for by the effect of neuroleptic drugs. The schizophrenic subjects did not have a greater prevalence of epileptiform disturbances or abnormal asymmetry of the EEG compared to the control group. Our study does not suggest the presence of underlying dementia in schizophrenia of late onset.

Age of Onset↗

Quantitative study of signal hyperintensities on T2-weighted magnetic resonance imaging in late-onset schizophrenia.

OBJECTIVE: The authors investigated the extent and distribution of signal hyperintensities on T2-weighted magnetic resonance imaging (MRI) of the brains of subjects with late-onset schizophrenia. METHOD: The study group consisted of 25 subjects with DSM-III-R schizophrenia and onset at age 50 or more years (late-onset schizophrenia) matched group-wise with 24 subjects with early-onset schizophrenia and 30 psychiatrically healthy volunteers. The subjects underwent clinical and neuropsychological assessments and MRI scans. Transaxial T2-weighted and proton-density images were analyzed manually for signal hyperintensities in cerebral and cerebellar white matter, the basal ganglia, thalamus, and brainstem, and quantitative measures were obtained. RESULTS: Subjects with late-onset schizophrenia had greater periventricular hyperintensities measured as widths of periventricular rims and frontal and occipital caps than the two comparison groups. Hyperintense signals elsewhere in the white matter and in the basal ganglia and brainstem did not differ between groups, but the late-onset schizophrenia group had more signal hyperintensities in the thalamus than the normal comparison group. Signal hyperintensities in the frontal-subcortical circuit regions, when considered together, did not differ between groups. Periventricular hyperintensities had significant negative correlations with intelligence, memory, and frontal-executive functioning in the total group. CONCLUSIONS: The finding of increased periventricular hyperintensities and thalamic signal hyperintensities in late-onset schizophrenia suggests the possibility that cerebrovascular disease, in an interaction with some incompletely understood vulnerability factors, may play a role in the pathogenesis of schizophrenia with onset in advanced age.

Adult↗

Double-blind controlled investigation of transcranial magnetic stimulation for the treatment of resistant major depression.

OBJECTIVE: The efficacy and safety of left prefrontal repetitive transcranial magnetic stimulation (rTMS) for treating resistant major depression were examined in a double-blind, controlled study. METHOD: Eighteen medication-resistant depressed subjects were randomly assigned to 2 weeks of real or sham rTMS, then permitted up to 4 weeks of real rTMS. Effects on mood, neuropsychological function, EEG, and hearing were assessed. RESULTS: The groups receiving real and sham rTMS improved in mood significantly over the 2-week double-blind period, but there was no significant difference between groups. CONCLUSIONS: Repetitive transcranial magnetic stimulation did not provide significantly greater improvement than did sham treatment. A 4-week course of rTMS, as administered in this study, was safe.

Affect↗

Schizophrenia with onset after age 50 years. I: Phenomenology and risk factors.

BACKGROUND: Schizophrenia occurring for the first time in late life may be a distinct entity or part of a continuum. AIMS: Can late-onset schizophrenia (LOS) and early-onset schizophrenia (EOS) be differentiated by their phenomenology and risk factors to their development? METHOD: Convenience samples of 27 DSM-III-R defined LOS subjects, 30 EOS subjects and 34 control subjects were systematically assessed. RESULTS: Premorbidly, both groups of subjects with schizophrenia had personality traits that were different from controls but not from each other. The EOS subjects had more family members with a history of psychiatric illness or schizophrenia and less hearing impairment than the other two groups, which did not differ from each other. Clinically, LOS and EOS subjects were similar, except that EOS subjects had more negative symptom scores, tended to have more delusions of guilt/sin and of being controlled and more formal thought disorder, and had significantly poorer instrumental activities of daily living. CONCLUSIONS: Phenomenology and risk factors do not distinguish discrete LOS.

Age of Onset↗

Schizophrenia with onset after age 50 years. 2: Neurological, neuropsychological and MRI investigation.

BACKGROUND: Late-onset schizophrenia (LOS) may have a basis in age-related coarse brain disease, but empirical support for this is conflicting. AIMS: Is LOS characterised by more neurological disease than early-onset schizophrenia (EOS)? METHODS: DSM-III-R-defined LOS subjects (n = 27) were compared with 30 EOS and 34 volunteer control subjects on neurological status, neuropsychological test performance and brain magnetic resonance imaging (MRI). RESULTS: LOS and EOS groups had more 'soft' neurological signs and drug-induced movement abnormalities, and performed more poorly on tests assessing speed of information processing, memory and frontal executive functioning. On MRI, the LOS and EOS groups had greater lateral ventricular size than the control group. The LOS subjects also had more signal hyperintensities in periventricular white matter and subcortical nuclei than controls. CONCLUSIONS: LOS and EOS subjects were very similar on neuropsychological, neurological and structural neuroimaging parameters, except that there were more MRI periventricular hyperintensities in LOS subjects.

Age of Onset↗

Tardive blepharospasm.

I report on five patients with tardive blepharospasm seen in a movement disorders clinic, out of 25 tardive dystonia patients. They were young (aged 25-50 yrs); four were men and three had a schizophrenic disorder. The onset was gradual while on maintenance neuroleptics in four and on withdrawal in the fifth. There were no significant antecedent events precipitating the disorder. The disorder was bilateral but asymmetric in two cases. Dyskinetic blinking was often an initial feature and tended to persist after the resolution of the blepharospasm. Orolingual dyskinesia was present in one case and tardive akathisia in two other cases. The symptoms fluctuated in severity with a number of exacerbating and relieving factors. Reduction of neuroleptic dose led to improvement with complete reversal in one of two patients who could be withdrawn off neuroleptic medication. These reports suggest that TB, although uncommon, can be a disabling disorder that may improve considerably with the cessation or dose reduction of the neuroleptic drugs. Its treatment and longitudinal course should be further examined.

Adult↗

Sex on campus: a preliminary study of knowledge, attitudes and behaviour of university students in Delhi, India.

Eight hundred and eighty-seven students from two major universities in Delhi, India, were surveyed, using a self-administered questionnaire, about their sexual knowledge, attitudes and behaviour. The data show that female students seem to be rejecting traditional Indian repressive sexual standards of premarital and non-procreative sex and the gender differences are beginning to narrow. Despite their sexual awareness, the students were highly ignorant of the facts of life. Being male and married did not make them more knowledgeable.

Adult↗

Schizophrenia-like psychosis and epilepsy: the status of the association.

OBJECTIVE: Current knowledge of the relationship between epilepsy and schizophrenia-like psychosis is examined, and the proposed pathogenetic mechanisms are evaluated. METHOD: The author provides an overview of the published literature on epilepsy and schizophrenia-like psychosis. RESULTS: The schizophrenia-like psychoses of epilepsy are inadequately categorized by the current classifications. Their categorization into ictal, postictal, and interictal psychoses is clinically useful, but it does not imply distinct pathophysiology for each. The recent interest in postictal psychoses has opened an important avenue for research. Brief interictal psychoses, involving alternation between epilepsy and psychosis and accompanied by forced normalization, are uncommon. Many aspects of the relationship with chronic interictal psychosis remain controversial. The majority of investigators support a special but not exclusive relationship with mediobasal temporal lobe epilepsy, and left temporal bias receives only limited support. The chronic psychosis resembles schizophrenia phenomenologically. Some suggested risk factors are severe and intractable epilepsy, epilepsy of early onset, secondary generalization of seizures, certain anticonvulsant drugs, and temporal lobectomy. Different neuropathological studies suggest the presence of cortical dysgenesis or diffuse brain damage. CONCLUSIONS: There are many mechanisms by which epilepsy may be associated with schizophrenia-like psychosis. It is likely that structural brain abnormalities, e.g., cortical dysgenesis or diffuse brain lesions, underlie both epilepsy and psychosis, and that the seizures modify the presentation of the psychosis, and vice versa, thus producing a clinical picture of both an affinity and an antagonism between the two disorders.

Age of Onset↗

AIDS/HIV and university students in Delhi, India: knowledge, beliefs, attitudes and behaviors.

Eight hundred eighty-seven students in social work, nursing, and humanities from two major universities in Delhi were compared regarding their knowledge about AIDS/HIV and attitudes toward PWAs and homosexuals. Their scores on the 20-item knowledge test indicate fair degree of knowledge; however, they lacked information in crucial areas of AIDS prevention and human sexual anatomy. Unmarried, female and older students and those in social work and nursing disciplines scored significantly higher on correct answers. Social work students were likely to be more positive in their attitudes toward AIDS victims than those in nursing or humanities. Knowledge was positively related to attitudes and perception of risk. Despite their awareness of personal risks only four in ten used condoms sometimes during intercourse. Educational strategies to increase cognitive and affective understanding of AIDS and its victims are discussed.

Acquired Immunodeficiency Syndrome↗

Regional cerebral blood flow in late-onset schizophrenia: a SPECT study using 99mTc-HMPAO.

Functional neuroimaging studies have been performed in many young patients with schizophrenia, but late-onset schizophrenia (LOS) remains largely unexamined by these techniques. We predicted that LOS would demonstrate regional cerebral blood flow (rCBF) abnormalities similar to those seen in early-onset schizophrenia (EOS), but with a basis in demonstrable coarse brain disease. The subjects were 15 LOS and 7 EOS patients and 27 healthy controls. Each was given a detailed clinical and neuropsychological assessment and underwent MRI and Tc99m-HMPAO single photon emission computed tomography (SPECT) scans. The LOS subjects had a significantly lower cerebral hemispheric perfusion than controls, with a lower perfusion in the frontal and temporal lobes bilaterally. The LOS group also had significantly lower left-to-right hemisphere blood flow ratios. EOS subjects had a lower frontal perfusion than the controls, which was significant in the left frontal region. The temporal perfusion in the EOS subjects was greater than in the LOS group, and not different from the control subjects. Left temporal perfusion was the most discriminating variable between LOS and control subjects on logistic regression. Correlations of perfusion with MRI were generally low with the exception that the asymmetry indices were significantly correlated, and basal ganglia perfusion correlated with basal ganglia hyperintensities on MRI. The total cerebral perfusion index correlated significantly with the mini-mental state examination (MMSE) score, and the temporal lobe perfusion correlated with MMSE scores and some verbal memory measures. In the schizophrenic groups, perfusion correlated nonsignificantly with symptom profiles. We conclude that our findings of temporal and frontal rCBF abnormalities, especially on the left side, in LOS are similar to those reported in schizophrenia in general. The results do not provide evidence for coarse brain disease underlying the rCBF abnormalities in LOS, or support the specificity of these abnormalities for particular subsyndromes of schizophrenia.

Age of Onset↗