Sukdeb Mukherjee

Enzymes of the antioxidant defense system in chronic schizophrenic patients

Potentially toxic levels of oxyradicals (superoxide and hydroxyl radicals) are formed in vivo during many metabolic reactions, including oxidation of catecholamines (reviewed in Halliwell and Gutteridge 1984; 1989). In cell membranes, hydroxyl radical:~ can initiate lipid peroxidation resulting in altered membrane structure and function. Under physiological conditions, cells are protected against oxyradical-mediated damage primarily by the cooperative and sequential actions of the enzymes superoxide dismutase (SODL glutathione peroxidase (GSHPx), and catalase (CAT), which are critical components of the antioxidant defence system (AODS). There has been limited investigation of oxyradical metabolism in schizophrenia. Most investigators (Michelson et M 1977; Golse et a! 1978; Abdalla et al 1986), bat no;. all (Stnet et al 1983), have reported increased red blood cell (RBC) SOD activity m schizo-

Cigarette smoking and neuroleptic-induced parkinsonism

Several studies have reported an apparent protective effect of cigarette smoking for the risk of idiopathic Parkinsons disease (IPD). These observations are supported by neurochemical studies demonstrating enhancement of central dopaminergic neurotransmission by nicotine. We studied the prevalence and severity of neuroleptic-induced parkinsonism (NIP) in relation to cigarette smoking in a homogeneous sample of 130 psychiatric inpatients receiving long-term neuroleptic treatment. Despite the fact that smokers had significantly higher dosage of neuroleptics during the month prior to evaluation and longer exposure to medication, they presented with significantly less prevalence and severity of NIP than nonsmokers. These findings suggest that the inverse association between smoking and IPD may apply to NIP.

Neuropsychological deterioration and CT scan findings in chronic schizophrenia.

Structural abnormalities of the brain, particularly ventricular enlargement and prominence of cortical sulci, have been documented reliably in CT scan investigations of chronic schizophrenic patients. Although the clinical significance of these findings is still obscure, neuropsychological (NP) deficits have emerged as relatively robust correlates of the structural anomalies. Unfortunately, it remains unknown whether the previous findings of NP impairment in association with CT scan abnormalities reflect poor premorbid abilities or deterioration from previously higher levels. This study involved administration of an extensive NP battery and CT scans in a chronic schizophrenic sample. In addition to global and specific scales of NP functions, indices of premorbid ability and deterioration were also employed. The results are consistent with the hypothesis that CT scan findings are associated more with deterioration of functioning than with global measures of NP dysfunction or poor premorbid ability. Conversely, the findings suggest that in patients with normal scans, NP morbidity may be a consequence of failure in the acquisition of a normal cognitive repertoire.

The neuropsychology of schizophrenic speech

Recent interest in the biological basis of schizophrenia has led to a reexamination of many symptomatic aspects of the disorder in terms of brain-behavioral models. Schizophrenic speech disturbances have traditionally been described in terms of a model of acquired aphasia. We review some of the limitations of this model and provide an alternative model for the study of some characteristics of schizophrenic speech based on neuropsychological theories of frontal lobe dysfunction in schizophrenia. The emphasis is placed on the study of productive errors noted in schizophrenic speech, most notably verbal perseverations. In a study of errors observed during a sample of 15 schizophrenics performance on a confrontation naming test, we were able to reliably identify and classify hierarchic categories of verbal perseverations occurring at both semantic and phonemic levels. These perseverations constituted 20% of the total errors. We argue that these perseverations represent a special case of executive dysfunction resulting from a disturbance of language monitoring mechanisms. We examine the implications of these findings for a hypothesis of schizophrenic speech disturbances in terms of frontal lobe dysfunction and the developmental neuropathological processes involved in the illness.

Abnormal growth of skin fibroblasts from schizophrenic patients

Fibroblast cultures were established from skin biopsies of 18 schizophrenic patients (14 on drug and 4 off drug) and 13 normal subjects, and growth parameters (initial growth and rate of growth) and morphology were studied. Fibroblasts from patients took significantly longer to grow than did normal fibroblasts. Cell lines were established within 2 weeks for all normal controls, but for only 6 (33%) of 18 schizophrenic patients. The rate of growth (doubling time) was also significantly longer for fibroblasts from patients than from normals. Neither time to establishment of initial growth nor doubling time was related to age, sex, age at onset, duration of illness, or medication status in the patients. Fibroblasts from normals showed uniform, long (slender), characteristic spindle-like, bipolar appearance, with unidirectional orientation, both while growing from explant as well as after subculturing. By contrast, fibroblasts from patients generally showed random size (shorter and flatter), mostly spiny, multipolar cells with short stubby projections, and an irregular orientation resulting in a criss-cross pattern, and often exhibited poor attachment. Fibroblasts from skin biopsies of patients who were drug free at the time of biopsy showed similar initial growth, doubling time, and morphology to those from patients who were receiving neuroleptic treatment. In vitro challenge of skin biopsies of normal subjects with haloperidol in culture resulted in slight delay in initial growth and marginal increase in doubling time. However, the morphology remained normal. Possible molecular mechanisms that may be associated with abnormal growth of fibroblasts in schizophrenia are discussed.

Specificity of smooth pursuit eye movement and visual fixation abnormalities in schizophrenia : comparison to mania and normal controls

Smooth pursuit eye movements (SPEM) were assessed in 30 schizophrenic patients, 12 lithium-free manic patients, and 20 normal controls. Compared to schizophrenic patients, manic patients evidenced less SPEM impairment in an attention enhancing, sinusoidal target motion condition and had superior performance during a visual fixation condition. SPEM and visual fixation dysfunctions may be more common in schizophrenic than in acutely manic patients, even when the latter are characterized by marked attentional dysfunction, poor interepisode psychosocial functioning, and psychosis.

Season of birth and CT scan findings in schizophrenic patients

Studies of season of birth in schizophrenic patients show a peak incidence during the winter and early spring months, with the lowest incidence during the late summer and early fall months. The majority of well-controlled studies have found an 8%-10% excess frequency of winter births relative to the general population. Many sources of error have been suggested (see Boyd et al. 1986 and Bradbury and Miller 1985 for reviews) to explain the phenomenon, but it remains one of the most consistently replicated findings in schizophrenia research. It has been suggested that winter-born schizophrenic patients contain an excess of those in whom “environmental” rather than genetic events play an etiological role (Boyd et al. 1986; Hare 1986). It has also been proposed that envitonrnental events influence ventricular size. In support of this view, Reveley et al. ( 1984) have reported that lateral ventricular enlargement is associated with a his-

Schizophrenic symptoms and deterioration. Relation to computed tomographic findings.

Thirty-two patients with a research diagnosis of chronic schizophrenia were studied using structured clinical scales for premorbid adjustment, clinical symptomatology, and social deterioration. By computed axial tomography (CAT), ventricle-brain ratio (VBR) and cortical atrophy were assessed. The relation between the clinical variables and CAT findings was assessed using linear correlation. CAT-based subgroups were compared using univariate analysis of variance. Previous findings of ventricular enlargement and cortical atrophy in some schizophrenics were replicated. Premorbid asociality and social deterioration were found to have a modest, positive relation with CAT findings but formal thought disorder had a negative relation to ventricle size. There was no relation between the negative symptoms and CAT measures. Within the CAT-positive group the presence of cortical atrophy appeared to be associated with a more severe illness compared with those with ventricular enlargment but the sample sizes were too small to obtain any significant differences.

History of obstetric complications, family history, and CT scan findings in schizophrenic patients

It has been proposed that obstetric complications (OCs) are more common in patients with nonfamilial schizophrenia, and associated with lateral ventricular enlargement in such patients. We examined the relations among OCs, family history of schizophrenia or bipolar mood disorder, and lateral ventricular size and cortical sulcal prominence in 44 schizophrenic patients. A history of OCs was not related to an absence of a family history of schizophrenia, ventricle-brain ratio, or cortical sulcal prominence. None of the CT findings was related to family history.

The autonomic orienting response and CT scan findings in schizophrenia

CT scan measures of prefrontal sulcal prominence, parieto-occipital sulcal prominence, ventricle-brain ratio (VBR), and third ventricle width (TVW) were examined in 24 schizophrenic patients who were grouped on the basis of their autonomic orienting response (OR) status. A two-component definition of the OR was used that required concordance across both electrodermal and finger pulse volume components for response status assignment. The nine OR responders had significantly greater TVW than the 15 OR nonresponders. Although OR responders had higher values also on the other CT scan measures, these differences were not significant. These findings are consistent with the possibility that OR responsiveness and nonresponsiveness are related to different pathological dimensions of schizophrenia.