Early postnatal depletion of NMDA receptor development affects behaviour and NMDA receptor expression until later adulthood in rats--a possible model for schizophrenia.

There is increasing evidence that a dysfunction of the N-methyl-d-aspartate (NMDA) receptor system plays a key role in the pathophysiology of schizophrenia. Non-competitive NMDA-antagonists induce schizophrenia-like symptoms and cognitive impairment in healthy humans as well as rodents. As receptor dysfunction precedes clinical disorder manifestation, the present study investigated whether transient perinatal NMDA antagonism constitutes a suitable long-term animal model for schizophrenia. Male Wistar rats were treated from postnatal days 6-21 with the NMDA receptor antagonist MK-801, and then subjected to behavioural analysis up to an age of 180d. Alterations in cortical NMDA receptor expression and lymphocyte cAMP-response-element-binding-protein (CREB) were assessed. In comparison to controls, MK-801-treated animals showed differences in behaviour up to an age of 180d. Western blot analysis revealed that transient perinatal application of MK-801 caused a persistent increase in cortical NMDA-R1 protein in combination with a persistent disturbance of CREB phosphorylation, a downstream target of NMDA signalling. This animal model demonstrates that early postnatal NMDA receptor blockade leads to schizophrenia-like symptoms with persistent behavioural and neurochemical disturbances throughout life. Therefore, it might provide a basis for further understanding of the disease and evaluation of new therapeutic strategies.

Delay of gratification and executive performance in individuals with schizophrenia: putative role for eating behavior and body weight regulation.

OBJECTIVE: Impairment in executive functions and disturbed weight regulation are common features in individuals with schizophrenia on antipsychotics. Still, the clinical management of weight gain, including educational programs, is insufficient. Therefore, we hypothesized that distinct executive impairment is associated with the inability to self-control food intake. METHOD: In the present study we investigated the performance in a paradigm analyzing the executive subfunction "delay of gratification" in individuals with schizophrenia (n=29) compared with controls (n=23) and the interrelationship between delay of gratification, overall executive functioning, reported eating behavior and the BMI. We applied a board-game paradigm to operationalize delay of gratification: on designated fields individuals need to decide about a small amount of immediate reinforcement versus double the amount in the end. Appetite and eating behavior were assessed by self-report scales, executive functioning by BADS. RESULTS: We found that the patients performed significantly worse in our paradigm and that this is associated with lower executive functioning. However, the interrelationship between all parameters is complex: there is a significant positive correlation between the reported perceived appetite and executive functioning whereas the reported restrained eating behavior, significantly more frequent in patients, is correlated with low executive functioning and high disinhibition in eating situations. CONCLUSIONS: We conclude that executive functions are necessary to successfully manage eating behavior. Thus, better understanding of the cognitive mechanisms might help to support the patients more efficiently in their tough job to keep control.

Delta power in sleep in relation to neuropsychological performance in healthy subjects and schizophrenia patients.

Delta power in sleep is of increasing interest because of its association with waking performance in neuropsychological tests. In schizophrenia, this link might be impaired because of a decrease in delta power in sleep and pronounced cognitive deficits. The authors analyzed delta power in sleep and neuropsychological performance in 16 patients with schizophrenia on stable medication with amisulpride and 17 healthy subjects. In healthy subjects, the authors found significant positive correlations between morning performance in declarative memory, procedural learning, and attention and delta power, especially in frontal channels. The authors interpret these results in terms of dysfunctions of thalamocortical and prefrontal networks in schizophrenia.

Impairment of visuospatial memory is associated with decreased slow wave sleep in schizophrenia.

Cognitive impairments such as memory deficits and sleep disturbances are common clinical features of schizophrenia. Since sleep plays an important role in consolidation of memory, we hypothesize, that there is an interrelationship between distinct alterations in sleep and memory performance in schizophrenia. We studied 17 patients with schizophrenia on stable antipsychotic medication with amisulpride (age range 22-44 years; 7 women) and 17 healthy controls (matched for age, gender and educational level). Sleep was recorded and scored according to the standard criteria by Rechtschaffen and Kales. Immediately before polysomnography and the morning after we performed neuropsychological tasks including Rey-Osterrieth Complex Figure Test and a test for recall of spatial location for testing aspects of declarative memory and a mirror tracing skill for procedural memory. In comparison to healthy controls, the patients showed a significant increase in sleep onset latency and a significant decrease in sleep efficiency and amount of slow wave sleep (SWS). Furthermore, the patients' performance in recall of the Rey-figure and of spatial location the next morning was significantly impaired. These impairments in the tests for visuospatial memory were positively correlated with reduction in the amount of SWS and in sleep efficiency. These results point to a functional interrelationship between regulation of SWS and performance in visuospatial memory in schizophrenia. If these results of our pilot study hold true, they will allow the development of innovative treatment strategies for neuropsychological deficits in patients with schizophrenia.