Jennifer K. Johnson

Neurocognitive performance and functional disability in the psychosis prodrome

OBJECTIVE This study evaluates the pattern of neuropsychological deficits and their association with clinical symptomatology and social functioning in individuals identified as ultra-high-risk (UHR) for psychosis. METHODS A sample of 45 UHR individuals was identified using the Structured Interview for Prodromal Syndromes (SIPS) from consecutive referrals to the Staglin Music Festival Center for the Assessment and Prevention of Prodromal States (CAPPS) at UCLA. Participants were administered a neurocognitive test battery, as well as measures of global (Strauss-Carpenter Outcome Scale) and social functioning (UCLA Social Attainment Survey). RESULTS Participants showed significant deficits in speed of processing, verbal learning and memory, and motor speed. Poorer verbal learning and memory performance was significantly associated with poorer social functioning, and there was a trend for poorer performance on reasoning and problem solving to be associated with poorer global functioning. Verbal memory independently predicted social functioning over and above severity of negative symptoms. Cognitive deficits were not associated with severity of clinical symptomatology. CONCLUSIONS Despite the absence of fully psychotic symptoms, UHR individuals experience significant cognitive deficits, particularly on tasks requiring speeded information-processing and efficient recall from memory, and these deficits appear to be associated with functional disability in a manner parallel to that observed in patients with established psychotic illness.

The prodromal questionnaire (PQ): Preliminary validation of a self-report screening measure for prodromal and psychotic syndromes

This study aims to establish preliminary validity of the Prodromal Questionnaire (PQ), a 92-item self-report screening measure for prodromal and psychotic symptoms. Adolescents and young adults (N = 113) referred to a prodromal psychosis research clinic completed the PQ and the Structured Interview for Prodromal Syndromes (SIPS [Miller, T.J., McGlashan, T.H., Woods, S.W., Stein, K., Driesen, N., Corcoran, C.M., Hoffman, R., Davidson, L., 1999. Symptom assessment in schizophrenic prodromal states. Psychiatric Quarterly 70(4), 273-287]), an interview with established validity for predicting future psychosis. When maximizing selection of true positive cases, scores on a subset of PQ items that assess positive symptoms predicted a concurrent prodromal or psychotic SIPS diagnosis with 90% sensitivity and 49% specificity. The PQ shows good preliminary validity in detecting individuals with an interview-diagnosed prodromal or psychotic syndrome, but it is less sensitive to the threshold between prodromal and full-blown psychosis.

The effects of acute and chronic dexamethasone administration on insulin binding to isolated rat hepatocytes and adipocytes

In an effort to determine the possible relationship between changes in insulin-receptor binding and the glucocorticoid-induced insulin-resistant state, we studied insulin binding to specific receptors located on isolated adipocytes and hepatocytes obtained from dexamethasone (D)-treated rats. Three groups of D-treated rats were studied: (1) acute high-dose treatment (1.5 mg/kg/6 days), (2) acute low-dose treatment (0.125 mg/kg/6 days), and (3) chronic low-dose treatment (0.125 mg/kg/21 days). When insulin binding to isolated hepatocytes was studied, we found that binding to isolated hepatocytes was studied, we found that binding was only 30%-50% of control values when cells from the D-treated animals were used. This decrease in binding was greatest for cells from the acute high-dose group, indicating a dose-response effect, and least for cells from the chronic group, suggesting a tendency toward return of insulin-receptor binding during chronic treatment. When insulin binding to isolated adipocytes was studied, binding was 50%-60% of control values when cells from both acute D-treated groups were used. While the magnitude of the decrease in insulin binding was not as great as that seen with hepatocytes, the decrease was still greatest using cells from the acute high-dose group as compared to the acute low-dose group. Thus, a dose-response effect was suggested in both tissues. On the other hand, the effects of chronic D treatment on insulin binding were strikingly different in the two cell systems. After chronic D treatment, insulin binding to adipocytes returned to near-normal levels, while a 55% decrease in binding to hepatocytes persisted. Thus, the tendency toward return of insulin binding after chronic D treatment seen with hepatocytes was almost fully expressed by adipocytes. This might be related to the amelioration of the corticosteroid-induced insulin-resistant state which has been reported after chronic corticosteroid administration to humans. In conclusion, (1) a decrease in insulin binding is associated with corticosteroid excess, and it is possible that this decreased binding is related to the insulin resistance which results from corticosteroid administration; (2) the return of insulin binding toward normal after chronic D treatment could well be related to the improvement in insulin resistance seen during chronic corticosteroid administration to humans; and (3) the difference in effects of chronic D treatment on insulin binding to hepatocytes versus adipocytes indicates that changes in insulin binding can be tissue specific.

Do schizotypal symptoms mediate the relationship between genetic risk for schizophrenia and impaired neuropsychological performance in co-twins of schizophrenic patients?

BACKGROUND Neurocognitive deficits and symptoms of schizotypal personality disorder are both elevated in the first-degree relatives of schizophrenic patients, but their relationship to each other and their potential common genetic source remain unclear. METHODS Fifty unaffected co-twins of schizophrenic patients and 123 control twins were assessed with a neuropsychological battery and structured clinical interviews. RESULTS Working memory was influenced by genetic risk for schizophrenia but not schizotypal symptoms. Nearly all other domains were influenced by schizotypy symptoms but only in the co-twins of schizophrenic patients. Schizotypy symptoms in the absence of a family history did not seem to be related to impaired neurocognitive functioning. CONCLUSIONS Schizotypy symptoms in those with genetic risk for schizophrenia are associated with increased risk for cognitive deficits. Some neurocognitive deficits might covary with subpsychotic symptoms due to a shared genetic factor. Community-ascertained schizotypal individuals might not be appropriate for modeling underlying genetic risk for schizophrenia.

Comparison of 125-I-insulin binding and degradation to isolated rat hepatocytes and liver membranes.

We have compared the ability of rat liver plasma membranes and isolated hepatocytes to bind and degrade insulin. Isolated cells were prepared in two different ways: by mechanical separation of cells and by coliagenase digestion of extracellular matrix. In all studies the binding and degradative characteristics of both types of hepatocyte preparations were identical. Furthermore, with one exception, the binding characteristics of membranes and cells were also quite similar. The only exception concerned the amount of insulin bound by hepatocytes as compared to liver membranes. Thus, at concentrations of cells (1.2 × 106 cells per milliliter) and membranes (150 µg. protein per milliliter) that gave equal binding at insulin concentrations <100 ng./ml., the amount of insulin specifically bound at insulin concentrations >100 ng./ml. was greater with use of hepatocytes. Additional studies indicated that, in contrast to membranes, at the higher insulin concentration only 75 percent of the previously bound insulin could be recovered from hepatocytes. Thus, a nondissociable component exists, which probably represents intracellular radioactivity and appears to account for the higher specific insulin binding by cells at higher insulin concentrations. When insulin degradation was studied at the above hepatocyte and plasma membrane concentrations, cells degraded 30 per cent more insulin than did membranes. Kinetic analysis of these data revealed that the Km for insulin degradation (5 × 10−7 M at 37°) was the same for both systems whereas the Vmax was greater with use of hepatocytes. In conclusion: (1) Preparation of hepatocytes by coliagenase digestion does not appear to alter insulin binding or degradation; (2) studies of liver membranes and isolated hepatocytes obtained from normal rats should yield similar information about insulin-receptor interaction as long as insulin concentrations <100 ng./ml. are used; (3) at very high insulin concentrations, some of the radioactivity appears to enter the cells; (4) the kinetics of insulin degradation by hepatocytes and liver membranes are similar; and (5) insulin degradation appears to be primarily a membrane phenomenon.