Genetic investigations offer one approach at evaluating the validity of Kraepelin's division of the functional psychoses into two major groups, schizophrenia and affective illness. In this study, DSM-III criteria for major depressive disorder (MDD) were blindly applied to the interviews with relatives from the Copenhagen sample of the Danish Adoption Study of Schizophrenia. No significant difference was found in the prevalence of MDD in the biological relatives of the control adoptees and the biological relatives of all the schizophrenic or only the chronic schizophrenic adoptees. Furthermore, no difference in the prevalence of MDD was found in the adoptive relatives of the schizophrenics and control subjects. These results support neither a genetic nor a familial-environmental link between schizophrenia and MDD and support the validity of the diagnostic division between them established by Kraepelin.
Research Unit of Clinical Neuroscience, Department of Psychiatry, University of Oulu, Oulu, Finland; Center for Life Course Health Research, University of Oulu, Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland. Electronic address: firstname.lastname@example.org.
We investigated the association of family history of mental disorders, especially psychosis, with occupational and clinical outcome in psychotic disorders in a longitudinal population-based cohort. The Northern Finland Birth Cohort 1986 (n?=?9432) was used to gather the data. In total 189 individuals with psychosis were identified by age of 28. The outcome was assessed by using register information regarding occupational activity, disability pension and hospital treatments due to psychiatric cause. Parental psychosis and any psychiatric disorder were used as predictors of outcome. The results showed that presence of any parental psychiatric disorder was associated with higher number of days spent at hospital and higher number of hospitalizations in psychotic disorders, but was not associated with occupational outcome or disability pension. The presence of parental psychosis was not associated with outcome. These findings suggest that the presence of any psychiatric disorder among parents may increase the risk of poorer outcome in psychoses in terms of need of hospitalisations. Based on this study the presence of parental psychosis is not associated with outcome, but the result should be interpreted with caution due to the small sample size and conflict with the results of earlier studies.
Chromosome 1q42 is among several genomic regions showing replicated evidence of linkage with schizophrenia, but the specific susceptibility mechanisms underlying this relationship remain to be identified.
To examine a series of haplotype blocks of single-nucleotide polymorphic markers from a segment of 1q42 spanning the disrupted-in-schizophrenia 1 (DISC1) and translin-associated factor X (TRAX) genes for association with schizophrenia and several endophenotypic traits thought to be involved in disease pathogenesis.
Population-based twin cohort study.
Two hundred thirty-six subjects, consisting of 7 twin pairs concordant for schizophrenia (6 monozygotic [MZ] and 1 dizygotic [DZ]), 52 pairs discordant for schizophrenia (20 MZ and 32 DZ), and 59 demographically balanced normal pairs (28 MZ and 31 DZ), were drawn from a twin cohort consisting of all of the same-sex twins born in Finland from 1940 through 1957.
Psychiatric diagnosis, performance on neurocognitive tests of short- and long-term memory, and gray matter volume measurements taken from high-resolution magnetic resonance images.
A common haplotype incorporating 3 single-nucleotide polymorphic markers near the translocation break point of DISC1 (odds ratio, 2.6 [P = .02]) and a rare haplotype incorporating 4 markers from the DISC1 and TRAX genes (odds ratio, 13.0 [P = .001]) were significantly overrepresented among individuals with schizophrenia. These haplotypes were also associated with several quantitative endophenotypic traits previously observed to covary with schizophrenia and genetic liability to schizophrenia, including impairments in short- and long-term memory functioning and reduced gray matter density in the prefrontal cortex, as demonstrated using a population-based brain atlas method, with a trend toward association with reduced hippocampal volume.
Specific alleles of the DISC1 and TRAX genes on 1q42 appear to contribute to genetic risk for schizophrenia through disruptive effects on the structure and function of the prefrontal cortex, medial temporal lobe, and other brain regions. These effects are consistent with their production of proteins that play roles in neuritic outgrowth, neuronal migration, synaptogenesis, and glutamatergic neurotransmission.
Polymorphisms in the dopamine D2 receptor gene (DRD2) have repeatedly been associated with schizophrenia. Recently, the C957T polymorphism (rs6277), which alters mRNA stability and dopamine-induced upregulation of DRD2 expression in cell cultures and DRD2 mRNA translation in vitro, was tested for an association with the disease. Frequency of the C allele, corresponding to a normal wild-type level of expression, was higher in patients compared to controls, and that of the T allele was lower. To replicate and extend previous findings, we conducted an association study of the C957T polymorphism and two additional SNPs (C939T and TaqIA) in 311 patients with a DSM-IV diagnosis of schizophrenia and 364 mentally healthy people from the Russian population as controls. The results of our study confirmed the association between the C957T polymorphism and schizophrenia. Consistent with previous findings, frequency of the C allele and the CC genotype were higher in patients compared to the control group (p=0.002). Meta-analysis of total 5 samples also suggests significant allelic association. The distribution of C939T genotypes in the case sample was significantly different from that of the controls: in the case sample, the TT genotype frequency was higher compared to the combined frequency of CT and CC genotypes (p=0.002). Though no association was found between the TaqIA polymorphism and schizophrenia, a haplotype-wise analysis revealed a lower frequency of the T-C (C957T-TaqIA) haplotype in patients (p=0.02). In conclusion, our findings provide additional evidence for an association between the C957T polymorphism and schizophrenia.
Schizophrenia is a debilitating psychiatric disorder, affecting approximately 1% of the human population. Mostly genetic factors contribute to schizophrenia, but the genetics are complex and various aspects of brain functioning and structure, from development to synapse plasticity, seem to be involved in the pathogenesis. The goal of the study was to look for novel mutations in genes, implicated in molecular networks, important in schizophrenia. In the study four candidate genes taking part in the WNT signaling pathway were analyzed by sequencing in a cohort of 87 schizophrenia patients from Saint Petersburg, Russia. The gene list included CTNNB1 (beta-catenin), GSK3B, WNT2B and WNT7B. The impact of discovered variants on the protein function was analyzed in silico. We found three variants in the genes CTNNB1 and WNT7B, absent in healthy controls, including 212 controls from the same geographic area. The novel mutation c.1943A>G (p.N648S) in CTNNB1 seems to be the best candidate for disease-associated mutation in this study, as it damages the protein product in silico. This is the first study reporting mutations in CTNNB1 in schizophrenia.
The Helsinki High-Risk (HR) Study is a follow-up study of offspring (born between 1960 and 1964) of all females treated for schizophrenia spectrum disorders in mental hospitals in Helsinki before 1975, and controls.
To compare childhood growth among HR and control children, and to determine if any patterns in childhood growth predict later development of psychotic disorders within the HR group.
We accessed growth information from childhood health cards, which we obtained for 114 HR and 53 control offspring. The growth of HR children was compared with that of control children. Within the HR group, we investigated whether any association existed between childhood growth patterns and morbidity from psychotic disorders using logistic regression models.
The HR girls were shorter than controls at birth (p=0.030), but this disparity vanished by age 7. In contrast, HR boys were only slightly shorter at birth than controls, but the height difference increased with age, being statistically significant at 10 years (p=0.020). Among HR children, the combination of being in the lowest tertile for ponderal index at birth but in the highest tertile for BMI at 7 years predicted later development of schizophrenia (OR 22.8, 95% CI 2.0, >100, p=0.040).
Catch-up growth increases the risk of schizophrenia among offspring of mothers with psychotic disorder. Whether this is an independent risk factor or merely a reflection of some other risk factors needs further research.
Since 1962 we have followed a sample of 207 children at high risk for schizophrenia as well as 104 control children. For these individuals, the following factors and their interaction are related to an increased risk for schizophrenic breakdown: (1) greater schizophrenia family backgrounds, (2) perinatal trauma, and (3) unstable parenting and public institutional child care. The perinatal difficulties are positively related to adult periventricular atrophy. Results of a subsequent study tentatively suggest that part of the neurological deviance in schizophrenia may be produced by disruption occurring in the second trimester of fetal development.
The Copenhagen longitudinal high-risk study of offspring of 129 schizophrenic mothers commenced in 1962. At that time, the mothers were diagnosed according to contemporary Danish criteria. We have re-examined all of the hospital records of these mothers: 108 (84%) fulfil present-day DSM-III criteria for schizophrenia and 95 (74%) were diagnosed as paranoid schizophrenic according to ICD-8 criteria. In a follow-up at mean age 24, the offspring of the paranoid schizophrenic mothers were themselves found to be less frequently schizophrenic (5%) than were the offspring of non-paranoid schizophrenic mothers (29%).