Is vitamin D hypothesis for schizophrenia valid? Independent segregation of psychosis in a family with vitamin-D-dependent rickets type IIA.

The vitamin D hypothesis of schizophrenia is a recent concept bringing together old observations on environmental risk factors and new findings on the neurodevelopmental effects of vitamin D. Candidate genes related to the vitamin D endocrine system have not yet been fully explored for this purpose. The coexistence of vitamin-D-dependent-rickets type II with alopecia (VDDR IIA) and different forms of psychosis in the same inbred family has provided us with an opportunity to investigate the presumed relationship between vitamin D deficiency and psychosis. Psychiatric examination and molecular genetic studies were performed in this family overloaded with psychotic disorders and VDDR IIA. Forty members were evaluated in order to describe their phenotypic features. The family was tested for a linkage to the chromosome 12q12-q14 region where the vitamin D receptor (VDR) gene is located. Psychosis was the common phenotype in the 18 psychiatrically affected members. Pedigree analysis did not show a cosegregation of psychosis and rickets. Lod scores were not significant to prove a linkage between psychosis and VDR locus. The authors concluded that (1) the neurodevelopmental consequences of vitamin D deficiency do not play a causative role in psychotic disorders, (2) these two syndromes are inherited independently, and (3) vitamin D deficiency does not act as a risk factor in subjects susceptible to psychosis.

[Hunting the susceptibility gene for psychosis: a study of a family overloaded with schizophrenia and bipolar disorder]. / Sizofreni ve bipolar bozuklugun yüklülük gösterdigi genis bir ailede psikoza yatkinlik geninin arastirilmasi.

OBJECTIVE: It is a long-standing debate whether schizophrenia and bipolar disorder are separate clinical entities or different poles on a spectrum. In this paper we present a family overloaded with schizophrenia, and schizoaffective, bipolar and unipolar disorders. Common loci for bipolar affective disorder and schizophrenia were tested by linkage analysis. METHOD: The pedigree of an index family which had been followed by our department for nearly 20 years was extended. The index family members were diagnosed by two psychiatrists with two distinct structured interview schedules (SCID-I and SADS-L). A field visit was undertaken for the evaluation of the extended family (n= 40) and SADS-L was used for psychiatric assessment. Blood samples were collected for molecular studies. A linkage study has been performed for overlapping susceptibility regions for schizophrenia and affective disorders (10p13-p12, 13q32, 18p and 22q11-q13) and a locus (20p11.2-q13) to which a linkage had been shown in a bipolar family who lived in the same region. Both autosomal recessive and dominant mode of inheritance were assumed in the analysis. RESULTS: The pedigree consisted of 108 individuals of whom 23 are affected. All affected subjects presented psychotic features except for 5 unipolar patients. The pedigree was reconstructed with respect to psychosis phenotype. Further linkage and haplotype analysis excluded all five loci on chromosomes 10, 13, 18, 20 and 22 under both autosomal dominant and recessive modes of inheritance assumption. CONCLUSION: A potential linkage between the psychosis gene and reported susceptibility loci overlapping in bipolar affective disorder and schizophrenia was not demonstrated Genome-wide analysis should be performed.

Relationship between vitamin D levels and depressive symptoms in renal transplant recipients.

OBJECTIVE: Vitamin D deficiency might influence the development of depression; however, the association between vitamin D and depression in renal transplant recipients has not been evaluated. We aimed to test if there is a relation between 25-hydroxy (OH) vitamin D levels and depressive symptoms in patients with kidney transplantation. METHODS: This was a cross-sectional and descriptive study. A total of 117 renal transplant recipients (44 female, 73 male; mean age, 39.0 ± 11.7 years) were included in the study. Patients were stratified to two groups according to the cut-off point (7) of depression subscale (D) of Hospital Anxiety Depression Scale (HADS), with or without depression risk. Blood biochemistry, glomerular filtration rate (GFR), and 25-OH vitamin D levels were determined. RESULTS: Depression scores were higher than cut-off point in 33.3% (n = 39) of patients. The mean 25-OH vitamin D level was 19.6 ± 12.0 µg/L. In the group with depression risk, 25-OH vitamin D levels were significantly lower than the other group (15.2 ± 9.2 µg/L and 21.9 ± 12.7 µg/L, respectively; p = 0.004). No significant difference was observed between the two groups in terms of demographic parameters, blood biochemistry, and GFR. A negative correlation was detected between HADS-D score and vitamin D levels (r = -0.365, p < 0.0001). CONCLUSION: Lower serum 25-OH vitamin D levels are associated with higher depressive symptom levels among renal transplantation recipients. This finding should be the basis for further clinical studies and for future prospects on vitamin D supplementation for prevention and treatment of depression in these patients.

Identifying gene-environment interactions in schizophrenia: contemporary challenges for integrated, large-scale investigations.

Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype.

Platelet monoamine oxidase activity in alcoholism subtypes: relationship to personality traits and executive functions.

AIMS: The purpose of the present study was to compare alcoholic subtypes (type 1 versus type 2) with regard to platelet monoamine oxidase (MAO) activity. A possible relationship between enzyme activity, personality traits and executive functions was also investigated. METHODS: Seventeen type 1 and 16 type 2 in-patient male chronic alcoholic patients and 17 healthy male volunteers were included in the study. The personality traits were investigated by the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Executive functions were assessed by the Wisconsin Card Sorting Test (WCST). RESULTS: When compared to the healthy subjects, platelet MAO activity was reduced in both alcoholic groups. The enzyme activity of the type 2 group was significantly lower than that of type 1 patients. Both groups of alcoholic patients also displayed impairment in executive functions. The comparison of the MMPI-2 scores of the study groups revealed that type 2 alcoholics had more severe psychopathology. CONCLUSIONS: The results support previous evidence suggesting that platelet MAO activity is a useful biochemical measure for the subtyping of alcoholics.