Dissociable effects of 5-HT2C receptor antagonism and genetic inactivation on perseverance and learned non-reward in an egocentric spatial reversal task

Cognitive flexibility can be assessed in reversal learning tests, which are sensitive to modulation of 5-HT2C receptor (5-HT2CR) function. Successful performance in these tests depends on at least two dissociable cognitive mechanisms which may separately dissipate associations of previous positive and negative valence. The first is opposed by perseverance and the second by learned non-reward. The current experiments explored the effect of reducing function of the 5-HT2CR on the cognitive mechanisms underlying egocentric reversal learning in the mouse. Experiment 1 used the 5-HT2CR antagonist SB242084 (0.5 mg/kg) in a between-groups serial design and Experiment 2 used 5-HT2CR KO mice in a repeated measures design. Animals initially learned to discriminate between two egocentric turning directions, only one of which was food rewarded (denoted CS+, CS−), in a T- or Y-maze configuration. This was followed by three conditions; (1) Full reversal, where contingencies reversed; (2) Perseverance, where the previous CS+ became CS− and the previous CS− was replaced by a novel CS+; (3) Learned non-reward, where the previous CS− became CS+ and the previous CS+ was replaced by a novel CS-. SB242084 reduced perseverance, observed as a decrease in trials and incorrect responses to criterion, but increased learned non-reward, observed as an increase in trials to criterion. In contrast, 5-HT2CR KO mice showed increased perseverance. 5-HT2CR KO mice also showed retarded egocentric discrimination learning. Neither manipulation of 5-HT2CR function affected performance in the full reversal test. These results are unlikely to be accounted for by increased novelty attraction, as SB242084 failed to affect performance in an unrewarded novelty task. In conclusion, acute 5-HT2CR antagonism and constitutive loss of the 5-HT2CR have opposing effects on perseverance in egocentric reversal learning in mice. It is likely that this difference reflects the broader impact of 5HT2CR loss on the development and maintenance of cognitive function

Neurodevelopmental risk factors in schizophrenia

The authors review environmental and neurodevelopmental risk factors for schizophrenic disorders, with emphasis on minor physical anomalies, particularly craniofacial anomalies and dermatoglyphic variations. The high prevalence of these anomalies among schizophrenic subjects supports the neurodevelopmental theory of the etiology of schizophrenia, since they suggest either genetically or epigenetically controlled faulty embryonic development of structures of ectodermal origin like brain and skin. This may disturb neurodevelopment that in turn may cause these subjects to be at increased risk for the development of schizophrenia and related disorders. The precise confirmation of this theory, at least in some cases, will provide further understanding of these illnesses, allowing easy and inexpensive identification of subjects at risk and providing guidelines for the development of new pharmacological interventions for early treatment and even for primary prevention of the illness

Memory functions in geriatric chronic schizophrenic patients: a neuropsychological study

This study characterized memory functions in geriatric schizophrenic inpatients with a battery of memory tests sensitive to neuropsychological impairments in either temporal or frontal brain regions. In patients clinically rated as cognitively impaired (n = 24), nearly all of these measures showed deficits relative to less impaired patients (n = 25). Factor analysis found consistent correlations between the tests and their putative cortical localization. Discriminant analysis suggested the pattern of impairments was not consistent with a generalized deficit. These results introduce the possibility, to be directly tested with neuropathological study, that the severe cognitive deficits in elderly schizophrenic patients are due to dysfunctions in either the temporal or frontal regions of the cerebral cortex, with the specific type of dysfunction varying across cases

Cognitive impairment and negative symptoms in geriatric chronic schizophrenic patients: a follow-up study

Cognitive impairment is increasingly recognized as an important aspect of schizophrenia. Since cognitive impairment has many features in common with the negative symptoms of the illness, it is possible that some of the characteristics attributed to negative symptoms are due to an association with cognitive impairments. In order to test this hypothesis, 174 chronically hospitalized geriatric schizophrenic patients were examined twice at a 1-year follow-up with ratings of the severity of their symptoms (using the Positive and Negative Syndrome Scale: PANSS) and assessments of cognitive functions with the Mini-Mental State Examination and a brief neuropsychological battery aimed at the typical impairments seen in dementia. Positive symptoms were unassociated with any of the cognitive variables, while negative symptom severity was correlated with each of the cognitive measures. In the cross-temporal analyses, cognitive impairments were more stable over time than negative symptom scores, but cognitive impairment did not predict the severity of any negative symptom over time. At each assessment, however, cognitive impairment was strongly correlated with each of the seven negative symptoms studied. These data indicate that cognitive impairments and negative symptoms are related, but discriminable, features in schizophrenia and that the considerable overlap between some negative symptoms and estimates of cognitive function may suggest a rethinking of the definition of some of these symptoms

Age disorientation in chronically hospitalized patients with mood disorders

Age disorientation was studied in 45 geriatric patients with chronic mood disorders. In a yearly assessment of cognitive functions, subjects were questioned about their age, year of birth, and the current year. Patients who misstated their age by ≥ 5 years were considered age disoriented. Among the 45 patients, age-disorientation data were available for 32 patients, with the remainder either stating that they did not know their age or providing age-delusional responses. Six of the 32 patients were characterized as age disoriented at baseline and again at 12- to 18-month follow-up assessment. Age-disoriented patients perfomed worse overall on the Mini-Mental State Examination compared with patients who did not show age disorientation. Future studies of brain function and structure should include poor-outcome patients with mood disorders as well as patients with schizophrenia in attempts to identify the possible neurological dysfunctions that may underlie the phenomenon of age disorientation

Social-Adaptive Functioning Evaluation (SAFE): A Rating Scale for Geriatric Psychiatric Patients

Geriatric chronic psychiatric inpatients often remain in a chronic psychiatric hospital because of serious deficits in adaptive life functions. Because the addi-tional complications and adaptive changes associated with aging have not been considered in previous scales, the Social-Adaptive Functioning Evaluation (SAFE) was developed. The items in the scale measure social-interpersonal, instrumental, and life skills functioning and are designed to be rated by observation, caregiver contact, and interaction with the subject if possible. Interrater and test-retest reliability were examined (ft = 60) and convergent and discriminant validity were rated against other relevant measures ( « = 50) in separate studies, with all being found adequate. Th