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.

No abstract

Borderline personality (BPD) and complex posttraumatic stress disorders (PTSD) are both powerfully associated with the experience of interpersonal violence during childhood and adolescence. The disorders frequently co-occur and often result in pervasive problems in, e.g., emotion regulation and altered pain perception, where the endocannabinoid system is deeply involved. We hypothesize an endocannabinoid role in both disorders. We investigated serum levels of the endocannabinoids anandamide and 2-arachidonoylglycerol and related fatty acid ethanolamides (FAEs) in BPD, PTSD, and controls. Significant alterations were found for both endocannabinoids in BPD and for the FAE oleoylethanolamide in PTSD suggesting a respective link to both disorders.

No abstract

SUMMARYLittle is known about the relation between pineal volume and insomnia. Melatonin promotes sleep processes and, administered as a drug, it is suitable to improve primary and secondary sleep disorders in humans. Recent magnetic resonance imaging studies suggest that human plasma and saliva melatonin levels are partially determined by the pineal gland volume. This study compares the pineal volume in a group of patients with primary insomnia to a group of healthy people without sleep disturbance. Pineal gland volume (PGV) was measured on the basis of high-resolution 3 Tesla MRI (T1-magnetization prepared rapid gradient echo) in 23 patients and 27 controls, matched for age, gender and educational status. Volume measurements were performed conventionally by manual delineation of the pineal borders in multi-planar reconstructed images. Pineal gland volume was significantly smaller (P < 0.001) in patients (48.9 AE 26.6 mm 3 ) than in controls (79 AE 30.2 mm 3 ). In patients PGV correlated negatively with age (r = À0.532; P = 0.026). Adjusting for the effect of age, PGV and rapid eye movement (REM) latency showed a significant positive correlation (r S = 0.711, P < 0.001) in patients. Pineal volume appears to be reduced in patients with primary insomnia compared to healthy controls. Further studies are needed to clarify whether low pineal volume is the basis or the consequence of functional sleep changes to elucidate the molecular pathology for the pineal volume loss in primary insomnia.

Schizophrenia is a complex brain disorder that may be accompanied by idiopathic inflammation. Classic central nervous system (CNS) inflammatory disorders such as viral encephalitis or multiple sclerosis can be characterized by incongruent serum and cerebrospinal fluid (CSF) IgG due in part to localized intrathecal synthesis of antibodies. The dietary antigens, wheat gluten and bovine milk casein, can induce a humoral immune response in susceptible individuals with schizophrenia, but the correlation between the food-derived serological and intrathecal IgG response is not known. Here, we measured IgG to wheat gluten and bovine milk casein in matched serum and CSF samples from 105 individuals with first-episode schizophrenia (n=75 antipsychotic-naïve), and 61 controls. We found striking correlations in the levels of IgG response to dietary proteins between serum and CSF of schizophrenia patients, but not controls (schizophrenia, R2=0.34–0.55, p≤0.0001; controls R2=0.05–0.06, p>0.33). A gauge of blood-CSF barrier permeability and CSF flow rate, the CSF-to-serum albumin ratio, was significantly elevated in cases compared to controls (p≤0.001–0.003). Indicators of intrathecal IgG production, the CSF IgG index and the specific Antibody Index, were not significantly altered in schizophrenia compared to controls. Thus, the selective diffusion of bovine milk casein and wheat gluten antibodies between serum and CSF in schizophrenia may be the function of a low-level anatomical barrier dysfunction or altered CSF flow rate, which may be transient in nature.

These findings support the hypothesis of an involvement of anandamide in cognitive processes impaired in schizophrenia and are consistent with a protective effect of elevated anandamide levels herein.

Uncalcified solid pineal tissue measured by 3D-T2-TSE and SWI is related to human saliva melatonin levels. The analysis of the sleep quality and pineal volume suggests a linkage between better sleep quality and hormonal active pineal tissue.