David B. Schnur

Prefrontal cortex glucose metabolism and startle eyeblink modification abnormalities in unmedicated schizophrenia patients

Attentional modulation of the startle reflex was studied in 16 unmedicated schizophrenia patients and 15 control individuals during the 18F-2-deoxyglucose uptake period for positron emission tomography. In a task involving attended, ignored, and novel tones that served as prepulses, control individuals showed greater prepulse inhibition (PPI) at 120 ms and greater prepulse facilitation at 4,500 ms during attended than during ignored prepulses; the amount of PPI and facilitation during novel prepulses was intermediate. In contrast, patients failed to show differential PPI at 120 ms and tended to show greater facilitation at 4,500 ms during novel prepulses. For control individuals, greater PPI was associated with higher relative metabolic activity rates in prefrontal (Brodmann Areas 8, 9, and 10 bilaterally) and lower in visual cortex. Patients showed this relationship only for Area 10 on the left. Patients also had low metabolism in superior, middle, and inferior prefrontal cortex. Consistent with animal models, our results demonstrate the importance of the functional integrity of prefrontal cortex to PPI modulation.

Regional cerebral blood flow in mood disorders : IV. Comparison of mania and depression

Cortical regional cerebral blood flow (rCBF) was assessed in minimally medicated, relatively young adults in episodes of either acute mania (n = 11) or major depression (n = 11) and in matched normal control subjects (n = 11), using the 133xenon inhalation method, under eyes-closed, resting conditions. The three groups were equivalent in global CBF. Both patient groups showed significant reductions of rCBF in anterior cortical areas and reduction of the normal anteroposterior gradient. In addition, there was evidence of abnormal, albeit similar, patterns of flow lateralization on a regional basis in both clinical groups compared with normal subjects. An exploratory analysis revealed preliminary evidence of rCBF differences between the clinical groups, localized to the inferior frontal cortex. Otherwise, the evidence in this study suggests that young adult manic and depressed patients are predominantly similar in cortical rCBF parameters.

Attention and Clinical Symptoms in Schizophrenia

Attentional deficits, long established to characterize patients with schizophrenia spectrum disorders, have traditionally been regarded as part of the disorders clinical syndrome. In this paper we provide evidence to indicate that: a) impaired attention is a dimension of schizophrenia that is independent of clinical state, and b) that attention does not appear to respond to the medication (i.e. standard neuroleptics) most typically used to treat clinical symptoms. Since intact attention and other cognitive processes appear critical to successful functioning in the community after hospital discharge, these findings have major implications for treatment.

Persistent tardive dyskinesia and neuroleptic effects on glucose tolerance

The relations of persistent tardive dyskinesia (TD) to glucose tolerance and family history of type 2 diabetes mellitus (FH-NIDDM) were examined in 22 schizophrenic patients. All patients underwent a standard oral glucose tolerance test (GTT) while receiving haloperidol, and 15 patients also underwent a GTT when drug free. Fasting blood glucose (FBS) was significantly higher in the TD group than in the non-TD group in the medicated condition, but not in the drug-free state. TD and non-TD groups did not differ significantly in postload glucose levels either in the drug-free or in the medicated condition. However, relative to the drug-free state, haloperidol-treated TD patients showed decreased glucose tolerance while non-TD patients showed increased glucose tolerance. Seven (32%) of the 22 patients had an FH-NIDDM. A positive FH-NIDDM was significantly associated with the presence of TD and with higher drug-free FBS. A possible role of melatonin in mediating the TD-augmenting effects of FH-NIDDM and the neuroleptic-induced decrease in glucose tolerance has been proposed.

Serum antibodies to nicotinic acetylcholine receptors in schizophrenic patients

Although elevated serum levels of antibodies to the nicotinic acetylcholine receptor (nAChR) have been reported in neuroleptic treated patients with tardive dyskinesia, such antibodies have not been determined in comparable nondyskinetic patients. Using a toxin-binding inhibition assay, we examined serum anti-nAChR antibody levels in 17 DSM-III-R chronic schizophrenic patients, seven of whom had persistent tardive dyskinesia, and 10 normal controls. On the average, anti-nAChR antibody levels were significantly higher in schizophrenic patients than in normal controls, but but not differ between patients with and without tardive dyskinesia and was not related to age, sex, or duration of illness in patients.

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-

Decreased adhesiveness and altered cellular distribution of fibronectin in fibroblasts from schizophrenic patients

Relative to those from normal subjects, cultured skin fibroblasts from schizophrenic patients have been found to show abnormal growth characteristics and morphology. This study compared skin fibroblasts from 10 drug-free schizophrenic patients and 10 normal control subjects on cell adhesiveness to the substratum. Relative to fibroblasts from normal controls, those from patients showed significantly decreased cell adhesiveness, with no overlap in distribution between the groups. Since fibronectin, a major cell surface molecule, is known to be involved in the fibroblast adhesion to substratum, its extracellular and intracellular distribution was determined by immunocytochemical analysis. Both extracellular and intracellular levels of fibronectin were significantly lower, and the distribution was altered in fibroblasts from the patients.

The Impact of Successfully Completed Suicides on Psychiatric Residents

The authors report the results of unstructured interviews with five psychiatric residents who treated patients who successfully committed suicide. The residents demonstrated feelings of guilt and anger which the authors argue were indicators of narcissistic injury occurring during a narcissistically vulnerable period in their careers.This insult to the residents’ self-esteem could engender countertransference hatred toward subsequent suicidal patients. Residents whose patients have suicided, therefore, must be provided with an opportunity to ventillate their feelings in a supervisory setting. The authors also report that the experience with suicide results in the resident becoming a more cautious and independent clinician.

Abnormal growth of cultured skin fibroblasts associated with poor premorbid history in schizophrenic patients

The relations of abnormal growth of cultured skin fibroblasts, as manifest in prolonged doubling time, and a history of impaired childhood premorbid functioning, separately for social and school (instrumental) functioning were examined in 22 schizophrenic patients. Prolonged doubling time (> 2 weeks) was significantly associated with poorer childhood social functioning, even after controlling for variance due to age, sex, race, and age at onset of illness. Doubling time was not associated with school performance scores. The findings indicate that the cellular or molecular process(es) underlying abnormal growth of skin fibroblasts may be involved in, or associated with, aberrant biological processes that contribute to early dyssocial behavior in schizophrenic patients.

Comparison of negative symptoms in schizophrenic and poor outcome bipolar patients.

Using the Scale for the Assessment of Negative Symptoms (SANS), affective blunting, alogia, and attentional impairment were assessed in 30 manic patients with chronic impairment of inter-episode instrumental functioning and 85 chronic schizophrenic patients. The schizophrenic patients had markedly higher ratings on all three negative symptom dimensions. When negative symptoms were examined categorically, no manic patient was rated to show prominent affective flattening or alogia. This relative specificity may not apply to attentional impairment which was rated as prominent in 17% of the manic patients and in 55% of the schizophrenic patients.