First-degree Relatives Of Schizophrenic Probands Research Articles

The Stability of Inhibitory and Working Memory Deficits in Children and Adolescents Who are Children of Parents With Schizophrenia

Cognitive deficits are a central feature of schizophrenia and occur in first-degree relatives of schizophrenic probands, even in the absence of psychotic symptoms. A number of cognitive domains have been implicated including measures of response inhibition and working memory. While the stability of cognitive deficits has been demonstrated in individuals with schizophrenia, stability of deficits has not been explored in first-degree relatives. This report focuses on 25 children (ages 6-15 years), all with at least one schizophrenic parent. The children were assessed twice, utilizing inhibitory and working memory tasks, with a mean 2.6 years between visits. Stop reaction time (a measure of motor inhibition) and performance on a counting span task (a measure of verbal working memory) were borderline to mildly impaired (compared with a typically developing comparison group) at both visits with similar effect sizes (stopping task time 1, effect size = 0.46, time 2 effect size = 0.50; counting span time 1 effect size = 0.53, time 2 effect size = 0.42). For these 2 tasks, individual age-adjusted scores also correlated across both time points (r = 0.41-0.76) suggesting that individual children maintained deficits across time. As etiologically driven strategies are developed for the cognitive deficits of schizophrenia, expansion of these treatments to relatives who share the cognitive but not the psychotic symptoms may be worth exploring.

Evoked gamma band synchronization and the liability for schizophrenia

Objective: Electroencephalographic (EEG) synchronization in the gamma band is thought to represent a neuronal mechanism by which the brain integrates information processed in different cortical areas to build a coherent internal representation. Previous studies have reported abnormal gamma range (∼40 Hz) synchronization in schizophrenic patients. We tested a group of first-degree relatives of schizophrenic probands who have schizophrenia spectrum personality symptoms, and a group of schizophrenic patients, to examine whether individuals with increased liability for schizophrenia have reduced gamma synchronization. Method: A steady-state auditory evoked potential paradigm was used to evaluate the brain's capacity to sustain 20, 30, and 40 Hz EEG synchronization in 11 relatives, 24 schizophrenic patients (11 on conventional, 13 on new generation antipsychotic medications), and 17 normal controls. Results: Relatives with schizophrenic spectrum personality symptoms had reduced power at 40 Hz synchronization compared to normal controls ( p=0.022). Previous findings of reduced steady-state gamma band synchronization in schizophrenic patients were not directly replicated in this study. Patients as a group did not significantly differ from controls, but patients taking new generation antipsychotics had significantly enhanced 40 Hz synchronization compared to patients taking conventional antipsychotics ( p<0.001). There were no group differences in 20 or 30 Hz synchronization. Conclusions: Gamma band synchronization was found to be reduced in first-degree relatives with schizophrenia spectrum personality symptoms. Patients on new generation antipsychotic medications may exhibit enhanced gamma band synchronization.

Genetic heterogeneity in schizophrenia II: conditional analyses of affected schizophrenia sibling pairs provide evidence for an interaction between markers on chromosome 8p and 14q

Information from multiple genome scans and collaborative efforts suggests that schizophrenia is a heterogeneous, complex disorder with polygenic and environmental antecedents. In a previous paper we demonstrated that stratification of families on the basis of co-segregating phenotypes (psychotic affective disorders (PAD) and schizophrenia spectrum personality disorders (SSPD) in first-degree relatives of schizophrenic probands increased linkage evidence in the chromosome 8p21 region (D8S1771) among families with co-segregating SSPD. We have now applied a method of conditional analysis of sib-pairs affected with schizophrenia, examining shared alleles identical-by-descent (IBD) at multiple loci. The method yields enhanced evidence for linkage to the chromosome 8p21 region conditioned upon increased allele sharing at a chromosome 14 region. The method produces a more refined estimate of the putative disease locus on chromosome 8p21, narrowing the region from 18 cM (95% confidence interval) in our previous genome scan, to approximately 9.6 cM. We have also shown that the affected siblings sharing two alleles IBD at the chromosome 8p21 region and one allele IBD at the chromosome 14 region differ significantly in clinical symptoms from non-sharing affected siblings. Thus the analysis of allele sharing at a putative schizophrenia susceptibility locus conditioned on allele sharing at other loci provides another important method for dealing with heterogeneity.

Neuroimaging studies of the hippocampus in schizophrenia

Three neuroimaging techniques, morphometric neuroimaging, magnetic resonance spectroscopy, and functional neuroimaging, have provided evidence for abnormal hippocampal structure and function in schizophrenia. Hippocampal volume reduction is now one of the most consistent structural abnormalities found in schizophrenia: it is present at the onset of the illness and, to a lesser degree, in first-degree relatives of schizophrenic probands. Decreased levels of N-acetyl-aspartate point towards a cellular basis of such volume changes. Functional neuroimaging studies have demonstrated abnormal levels of hippocampal activity at rest, during the experience of auditory hallucinations, and during the performance of memory retrieval tasks. These results of neuroimaging studies complement evidence from post-mortem and behavioral studies, which have found regionally specific abnormalities of the hippocampus and of memory function in schizophrenia.

Family study of acute and transient psychotic disorders: comparison with schizophrenia

Acute non-organic psychoses, as often described in European and Indian literature, and categorized as 'Acute and transient psychotic disorders' in ICD-10, lack a clear nosological distinction from schizophrenia. A family study of psychiatric disorders in first-degree relatives (FDRs) of 40 ICD-10-diagnosed probands of acute and transient psychotic disorders (ATP) was carried out using a semi-structured interview schedule. The results were compared with those of 40 schizophrenic probands. FDRs of ATP probands had a higher prevalence of ATP than those of schizophrenic probands. FDRs of schizophrenic probands had significantly higher prevalence of schizophrenia than those of ATP probands. ATP subtypes with schizophrenic symptomatology (ICD-10 codes F 23.1 and F 23.2) had more family history of schizophrenia than the rest of the ATP subtypes. ATP as a group has a differential pattern of risk of illness compared to schizophrenia. Further, the subtypes subsumed under ICD-10 ATP may be genetically heterogeneous, those with schizophrenia-like symptomatology being possibly more akin to schizophrenia itself or forming an interface between ATP and schizophrenia.

39-63 - Psychiatric morbidity in first-degree relatives of schizophrenic probands

39-63 - Psychiatric morbidity in first-degree relatives of schizophrenic probands

Dopamine metabolism and deficit-related characteristics in first-degree relatives of schizophrenic probands

Dopamine metabolism and deficit-related characteristics in first-degree relatives of schizophrenic probands

"True" schizotypal personality disorder: a study of co-twins and relatives of schizophrenic probands.

The aim of the study was to investigate the type and nature of personality disorders among biological relatives of schizophrenic probands. A total of 176 nonschizophrenic co-twins and other first-degree relatives of schizophrenic probands were compared to 101 co-twins and first-degree relatives of probands with major depression. Schizotypal personality disorders were more common and histrionic personality disorders less common among the biological relatives of schizophrenic probands than among relatives of probands with major depression. A further exploration of the schizotypal criteria revealed that the so-called "negative" criteria such as odd speech, inappropriate affect, and odd behavior, as well as excessive social anxiety, were significantly more common among the relatives of schizophrenic probands. The latter criterion seems particularly important. The so-called "positive" schizotypal criteria were partly, although not statistically significantly, more common among the relatives of probands with major depression. There were only minor differences in frequencies of the negative criteria between monozygotic co-twins, dizygotic co-twins, and other first-degree relatives of schizophrenic probands. The present study suggests that DSM-III-R schizotypal disorder is defined by a set of criteria that partly describe a "true" schizophrenia-related personality disorder and partly features that are not specific for relatives of schizophrenic probands. Furthermore, the genetic relationship between schizophrenia and "true" schizotypal personality disorder seems weak. Excessive social anxiety may be a marker of a possible genetic link between the disorders.

Risk factors in schizophrenia. Season of birth, gender, and familial risk.

The risk for schizophrenia among first-degree relatives of schizophrenic probands obtained from an epidemiological sample using family history methods was examined to determine whether month of birth of the proband was associated with familial risk. The results of this study of the first-degree relatives of 106 female schizophrenics and 275 male schizophrenics suggested that the relatives of probands born in the months February to May had the highest risk, although the association between month of birth and familial risk among the male probands was present only for those relatives who had onset of schizophrenia before the age of 30.

Failure to find evidence of schizophrenia in first-degree relatives of schizophrenic probands.

The first-degree relatives (N = 199) of DSM-III schizophrenic probands (N = 39) were diagnosed from chart data by a rater who was blind to proband diagnosis. No cases of even "possible" schizophrenia were found. This augments the growing evidence that the genetic component in schizophrenia may be less than was formerly suspected.