The impact of PLA2G4A and PTGS2 gene polymorphisms, and red blood cell PUFAs deficit on niacin skin flush response in schizophrenia patients.

We investigated the etiology of the attenuated niacin skin flush response in schizophrenia patients. Skin response to topical niacin of 0.1M, 0.01 M, 0.001 M, and 0.0001 M concentrations was rated using method of volumetric niacin response (VNR) and correlated to two functional A/G polymorphisms in genes: phospholipase A2 group IVA (BanI of the PLA2G4A), and rs689466 of the prostaglandin synthase-2 (PTGS2). We further tested the possible correlation between niacin response and fatty acid (FA) content of red blood cells (RBCs). We detected statistically significant but weak impact of both polymorphisms on niacin flush response in schizophrenia patients. The dosage of the G alleles of both polymorphisms was associated with higher VNR values, although each polymorphic variant accounted for only 1% of the overall flush response variability. Regarding FA content, both n-3 and n-6 polyunsaturated FAs (PUFAs) were significantly reduced in the patient group, but an association with niacin sensitivity was not detected.

Craniofacial morphologic and anthropometric features of Croatian schizophrenia patients and non-psychiatric controls--a pilot study.

AIM: to evaluate differences in craniofacial morphologic features and several anthropometric measures between schizophrenia patients and non-psychiatric controls, and to find the best-fit model to differentiate between two groups. METHODS: 40 morphologic features of the head and face, and 5 craniofacial anthropometric measures were evaluated using the Lane Dysmorphology Scale in 58 patients and 46 controls. Total MPA score and subscores for different craniofacial regions were calculated. Individual items were examined using logistic regression analyses to define a model that can discriminate between patient vs. control status. RESULTS: total MPA score, and several subscores (general asymmetry, nasal, lip, ear and tongue) were significantly higher in the patient group. Patients were distinguished by significantly higher measures of maxillary and mandibular facial arcs, general and subtle facial asymmetries presented as deviation of facial landmarks from the vertical facial midline and horizontals, more variable vermilion of the upper lip, tongue surface, frenulum and anterior hair margin, and more adherent and underdeveloped earlobes. A final regression model including maxillary are, facial asymmetry, and adherent earlobes as independent predictors proved useful to efficiently recognize schizophrenia patients (specificity and positive prediction value of 100% when all the three items were present in an individual) or to exclude risk for schizophrenia (sensitivity and negative prediction value of 96.6% and 84.6%, respectively, in cases no one of the three items was present). CONCLUSIONS: schizophrenia patients evidenced significantly more craniofacial dysmorphology than controls. The model revealed in the study needs to be verified in larger samples and other populations.

HFE mutations and transferrin C1/C2 polymorphism among Croatian patients with schizophrenia and schizoaffective disorder.

The aim of this study was to investigate the possible influence of hemochromatosis gene mutations (HFE-C282Y and H63D) and transferrin gene C2 variant (TF-C2) on susceptibility to schizophrenia and schizoaffective disorder and/or age at first hospital admission. Genotyping was performed in 176 Croatian patients and 171 non-psychiatric Croatian controls using PCR-RFLP analyses. Regarding the H63D mutation, allele and genotype frequencies reached boundary statistical significance. Other allele and genotype distributions were not significantly different between two groups. We also analyzed age at first hospital admission as a continuous variable using the non-parametric Mann-Whitney U-test and Kruskal-Wallis test, and multiple regression analysis. The results of these tests were negative. We concluded that investigated HFE mutations and TF-C2 variant are not high-risk genetic variants for schizophrenia/schizoaffective disorder in our population. Also our data do not support their impact on age at onset of the first psychotic symptoms.

Niacin skin flush test: a research tool for studying schizophrenia.

BACKGROUND: A body of biochemical evidence suggests that abnormal phospholipid metabolism may play a role in the etiology of schizophrenia, and possibly, other psychiatric and neurological diseases. Niacin, a B-complex vitamin, induces prostaglandin synthesis, vasodilatation, and skin flushing when applied as a solution on the skin or taken orally. In schizophrenia, diminished or absent skin response to niacin represents a robust finding. RESULTS: Attenuated niacin skin-flush response has been analysed as a potential biochemical marker of impaired prostaglandin signaling in schizophrenia. Diminished skin redness after topical application of niacin might be caused by a reduced level of the precursor arachidonic acid in the peripheral membranes, increased activity of the enzyme phospholipase A2, abnormal expression of niacin or prostaglandin receptors, or poor vasomotor activity of cutaneous capillary walls. Heritability estimates established in several studies support niacin skin flush response as a vulnerability trait for the development of psychosis. However, the exact mechanism of a reduced skin flush, the possible influence of the long-term use of antipsychotics, and the usefulness of the test for diagnostic purpose are not clear yet. CONCLUSIONS: Niacin skin flush test is a simple, non-invasive and easily replicable method in the research of schizophrenia. The studies investigating niacin flushing in schizophrenia are numerous but incoherent regarding methods of niacin application and evaluation of the results. New studies, controlling adequately for age, sex, drug abuse, diet, as well as genetic factors that may influence the intensity and reaction time, are necessary to clarify the usefulness of niacin testing in psychiatry.

Human genome variation in health and in neuropsychiatric disorders.

OBJECTIVES: Variation in the human genome may explain genetic contributions to complex traits and common diseases. FINDINGS: Until recently, single nucleotide polymorphisms were thought to be the most prevalent form of interindividual genetic variation. However, structural genomic rearrangements such as deletions, duplications, and inversions lead to variation in gene copy number and contribute even more to genomic diversity. Other sources of genomic variation include noncoding genes, pseudogenes, and mobile genetic elements (transposons). CONCLUSIONS: Genome dynamics, including changes in gene number and position as well as epigenetic modifications of coding and noncoding sequences, can affect regulation of gene expression and may contribute to the variability of complex phenotypes.

Phospholipid membrane abnormalities and reduced niacin skin flush response in schizophrenia.

OBJECTIVES: Reduced n-3 and n-6 polyunsaturated fatty acids (PUFAs) content in red blood cell (RBC) membranes and abnormal membrane phospholipid metabolism were repeatedly implicated in the etiology of schizophrenia. FINDINGS: Prenatal and perinatal depletion of PUFAs interferes with normal brain development and function. The lack of docosahexaenoic acid - DHA in the brain is reflected in lower membrane DHA/AA (AA - arachidonic acid) ratio, increased activity of AA-metabolizing enzymes, and disturbance of downstream metabolic pathways involved in signaling, growth modulation, brain glucose uptake, immune functions, neurotransmission, synaptogenesis and neurogenesis. Preliminary high-throughput metabolomic studies revealed abnormal biochemical profile in patients with schizophrenia or brief psychotic disorder when compared to healthy controls. The results of both metabolomic and proteomic studies pointed to energy metabolism and lipid biosynthesis being impaired in schizophrenia. The usefulness of antipsychotic medication and supplementation with PUFAs in reverting to the normal metabolic state has been suggested in early treatment of the first psychotic episode. Abnormalities of phospholipid metabolism can be also detected as attenuated niacin skin flush response in the variety of neuropsychiatric disorders. CONCLUSIONS: Disturbances of lipid homeostasis could represent biochemical markers in the preclinical phase of neuropsychiatric illnesses and could serve as triggers in genetically vulnerable individuals. The assessment of patients' lipid status may also help in monitoring the course of the disease and treatment response. In this regard, simple, cheap and fast niacin skin flush test might be valuable. It might help in diagnosis of adolescents and young adults with psychotic behaviour, or in defining the necessity for long-term antipsychotic therapy. Along with antipsychotic medication schizophrenic patients need specific medical nutrition therapies.