The neurodevelopmental hypothesis of schizophrenia suggests that adverse genetic loading in conjunction with environmental factors early in fetal life causes a disruption of neural development, decades before the symptomatic manifestation of the disease. Neurocognitive deficits have been observed early on the course of schizophrenia, and their association with an early developmental brain lesion has been postulated. Dermatoglyphics have been analyzed in schizophrenia as markers of prenatal brain injury because of their early fetal ontogenesis and susceptibility to the same environmental factors that can also affect cerebral development. The aim of our study was to conduct a comparative examination of neurocognitive functions and dermatoglyphic variables in 89 sibling pairs discordant for schizophrenia spectrum disorders. Therefore, we investigated the association between these two markers to explore the prenatal origin of cognitive deficits in schizophrenia. The affected siblings were significantly impaired on all the cognitive variables assessed (Wisconsin Card Sorting Test, Trail Making Test and Continuous Performance Test) and had a greater number of dermatoglyphic anomalies. These results suggest the influence of intrauterine environmental factors in the siblings affected with schizophrenia. However, we did not detect a significant association between these two vulnerability markers in the schizophrenic patients, suggesting the role of genetic or late environmental factors in the origin of the neurocognitive deficits found in these patients.

Objective: Using a sample of sibling pairs discordant for psychosis, the authors attempted to replicate the findings of previous studies suggesting that the functional genetic polymorphism Val158Met in the catechol O-methyltransferase (COMT) gene influences prefrontal cognitive function and increases the risk for schizophrenia.Method: Eighty-nine sibling pairs discordant for psychosis were genotyped for this polymorphism and were assessed with the Wisconsin Card Sorting Test, a measure of prefrontal function. Additionally, the preferential transmission of alleles for this polymorphism was analyzed in a sample of 89 nuclear families in order to examine the genetic association.Results: In the healthy siblings, a linear relationship was seen in which performance on the Wisconsin Card Sorting Test was associated in an allele dosage fashion with COMT genotype (i.e., fewer perseverative errors with higher number of methionine alleles). However, this association was not observed in patients. Furthermore, no evidence of genetic association with psychosis was detected.Conclusions: These results seem to confirm the role of COMT genotype in the modulation of executive functions related to frontal lobe function in healthy individuals but not in schizophrenia patients.

Interleukin-1beta (IL-1beta), as well as other cytokines, has been classically implicated in the pathophysiology of major psychiatric disorders such as schizophrenia and major depression, and recent studies have implicated the IL-1beta gene and schizophrenia. Nevertheless, new approaches to this complex phenotype are necessary to clarify the risk conferred by this gene, either to the disorder or to its clinical manifestations. The aim of the present study was to explore the effect of a genetic polymorphism of the promoter region of the IL-1beta gene, in schizophrenia defined with: (i) a categorical diagnosis and (ii) a multidimensional symptom approach. We studied 356 individuals from 89 nuclear families consisting of one affected individual and the unaffected father, mother, and sib, in a family-based association study design. We find a trend for biased transmission of allele 2 from heterozygous parents to affected offspring, categorically defined (P = 0.07). This tendency was not observed in the healthy offspring. Using a multidimensional symptom approach to the diagnosis, the association was confirmed in psychotic patients showing the depressive symptom-dimension (P = 0.02).

It is well established that psychotic patients obtain higher scores on neurological soft-sign (NSS) examinations than normal controls, and also that their cognitive performance is poorer. The aims of the present study were to find threshold criteria that distinguish between normal individuals and patients suffering from psychosis, and to investigate the predictive power of NSS for cognitive impairment. The sample was composed of 56 patients suffering from psychosis and 26 normal controls. Neurological assessment was carried out by means of the Neurological Evaluation Scale (NES), and neuropsychological assessment comprised executive, memory, visuospatial abilities, and attention tests. Receiver operating characteristic analysis was used to assess the diagnostic and predictive efficiency of NSS.A total score of 3 or over on the NES scale, or presence of three or more NSS, proved to be good threshold points for defining 'abnormality' in psychosis patients in comparison with normal controls. NSS presented greater predictive power for cognitive impairment than psychopathological dimensions. Moreover, an NES total score of 8 or higher or, to a lesser extent, the presence of six or more NSS in this scale seemed to be valid cut-off points for predicting severe cognitive impairment in individuals with psychosis.NSS were highly efficient predictors of the presence of severe cognitive impairment related to psychosis. However, their ability to discriminate between individuals with psychosis and normal controls was modest.

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There is much evidence that neurological soft signs (NSS) are highly prevalent in both adults and children with schizophrenia. In addition, they have been detected as early precursors of a schizophrenic outcome in at-risk subjects. Such findings point to the possible value of NSS as neurointegrative markers in schizophrenia which has been hypothesized to be a neurodevelopmental disease. In our study we used a biobehavioral criterion to select the 'at-risk' group, a sustained attentional deficit as measured by the continuous performance test (CPT). We compared 140 normal adolescents with 162 'CPT-linked vulnerable' adolescents (index subjects) on a battery for the assessment of NSS (including laterality), IQ, frontal lobe function and schizotypy. An association was found between NSS and attentional deficit. Furthermore, index subjects with NSS were characterized by lower IQ scores, poorer performance on frontal lobe tests and greater problems with social interaction. There was also a trend for an association between male sex and both left-handedness and NSS.

The main goal of this study was to examine the performance on frontal lobe tests of normal adolescent subjects and subjects psychometrically defined as schizotypics using double criteria: (1) a CPT-linked attention deficit vulnerability and (2) a psychosis proneness measured with the Chapman's perceptual aberration scale (PAS) and the social anhedonia scale (SAS). Frontal lobe performance was assessed with the Wisconsin card sorting test (WCST), the trail-making test (TMT) and a word generation test.Overall, results show that subjects with both a CPT-linked vulnerability and a psychosis proneness did worse than the rest of subjects in most frontal lobe tests, suggesting the existence of a subtle frontal-lobe dysfunction in 'normal' adolescents that are at increased risk for schizophrenia. Our results agree with current theories that hypothesize a possible frontal-limbic dysfunction latent in schizophrenia spectrum disorders. The importance of an accurate definition of schizotypy, the specificity of the instruments and new approaches to the study of schizotypy are discussed. (C) 1997 Elsevier Science Ltd.