Even though schizophrenia has a strong hereditary component, departures from simple genetic transmission are prominent. DNA methylation has emerged as an epigenetic explanatory candidate of schizophrenia's nonmendelian characteristics. To investigate this assumption, we examined genome-wide (global) and gene-specific DNA methylation levels, which are associated with genomic stability and gene expression activity, respectively. Analyses were conducted using DNA from leukocytes of patients with schizophrenia and controls. Global methylation results revealed a highly significant hypomethylation in patients with schizophrenia (P<2.0×10(-6)) and linear regression among patients generated a model in which antipsychotic treatment and disease onset explained 11% of the global methylation variance (adjusted R(2)=0.11, ANOVA P<0.001). Specifically, haloperidol was associated with higher ("control-like") methylation (P=0.001), and early onset (a putative marker of schizophrenia severity) was associated with lower methylation (P=0.002). With regard to the gene-specific methylation analyses, and in accordance with the dopamine hypothesis of psychosis, we found that the analyzed region of S-COMT was hypermethylated in patients with schizophrenia (P=0.004). In summary, these data support the notion of a dysregulated epigenome in schizophrenia, which, at least globally, is more pronounced in early-onset patients and can be partly rescued by antipsychotic medication. In addition, blood DNA-methylation signatures show promise of serving as a schizophrenia biomarker in the future.-Melas, P. A., Rogdaki, M., Ösby, U., Schalling, M., Lavebratt, C., Ekström, T. J. Epigenetic aberrations in leukocytes of patients with schizophrenia: association of global DNA methylation with antipsychotic drug treatment and disease onset.

Neuropeptide Y (NPY) is known to influence emotional processing and decreased NPY levels have been associated with mood and anxiety disorders. Alternative splicing of pre-messenger RNA is a cellular mechanism that allows for transcriptome diversity, yet there is limited knowledge in this respect with regard to Npy. Since the hippocampus and the prefrontal cortex play an important role in affective disorders, we investigated alternative splicing of Npy in these regions of a rat model of depression (Flinders Sensitive Line, FSL) and its controls (Flinders Resistant Line, FRL). The existence of different Npy messenger RNA (mRNA) variants was examined using 5' and 3' RACE. In addition to the Npy mRNA species annotated in GenBank and Ensembl, we identified a novel "short" mRNA splice variant. Immunoblotting results argued against a putative translation of this "short" mRNA into protein in brain tissue. Compared to the FRL, the FSL had reduced "short"Npy mRNA levels in the HIP (P=0.00014) and the PFC (P=0.016). Gene expression analyses in five brain regions of an outbred rat strain supported the presence of the "short"Npy transcript in all examined regions and showed that it is expressed in ∼2.4-fold lower levels than the "long"Npy mRNA. Finally, sequencing of the 5' RACE products revealed a transcription start site of Npy that is different from the currently annotated position. These data add to the characterization of the rat Npy mRNA and demonstrate the presence of a novel transcript with a so far unknown function.

Being raised in the genomic era may not only increase knowledge of available genetic testing but may also have an impact on how genetic information is perceived. However, little is known about how current adolescents react to the language commonly used by health care professionals providing prenatal counseling. In addition, as risk communication is related to numbers and figures, having different educational backgrounds may be associated with variability in risk perceptions. In order to investigate these issues, a previously developed questionnaire studying different ways of being told about hypothetical anomalies in a baby and corresponding risks (Abramsky and Fletcher Prenatal Diagnosis 22(13):1188-1194, 2002) was administered to high-school students in Sweden. A total of 344 questionnaires were completed by students belonging to a natural science or a social science program. The data show that teenage participants found technical jargon and words such as rare and abnormal more worrying than the presented comparison terms. Negative framing effects and perception differences related to numeric risk formats were also present. Additionally, participants' gender and educational program did not seem to have an effect on risk assessment. In addition to reporting the questionnaire results, we discuss the ethical implications of the data based on the norm of non-directiveness and make some recommendations for practice. In general, genetic counselors should be aware that the language used within clinical services can be influential on this group of upcoming counselees.

P11 (S100A10) has been associated with the pathophysiology of depression both in human and rodent models. Different types of antidepressants have been shown to increase P11 levels in distinct brain regions and P11 gene therapy was recently proven effective in reversing depressive-like behaviours in mice. However, the molecular mechanisms that govern P11 gene expression in response to antidepressants still remain elusive. In this study we report decreased levels of P11, associated with higher DNA methylation in the promoter region, in the prefrontal cortex of the Flinders Sensitive Line (FSL) genetic rodent model of depression. This hypermethylated pattern was reversed to normal, as indicated by the control line, after chronic administration of escitalopram (a selective serotonin reuptake inhibitor; SSRI). The escitalopram-induced hypomethylation was associated with both an increase in P11 gene expression and a reduction in mRNA levels of two DNA methyltransferases that have been shown to maintain DNA methylation in adult forebrain neurons (Dnmt1 and Dnmt3a). In conclusion, our data further support a role for P11 in depression-like states and suggest that this gene is controlled by epigenetic mechanisms that can be affected by antidepressant treatment.

The XVII World Congress of Psychiatric Genetics, sponsored by The International Society of Psychiatric Genetics (ISPG) took place in San Diego, California from 4 to 8 November 2009. Approximately 550 participants gathered to discuss the latest molecular genetic findings relevant to serious mental illness, including schizophrenia, mood disorders, substance abuse, autism, and attention deficit disorder. Recent advances in the field were discussed, including the genome-wide association studies results, copy number variation (CNV) in the genome, genomic imaging, and large multicenter collaborations. The following report, written by junior travel awardees who were assigned sessions as rapporteurs represents some of the areas covered in oral presentation during the conference, and reports on some of the notable major new findings described at this 2009 World Congress of Psychiatric Genetics.

Objectives To investigate empirically the motivations for not consenting to DNA biobanking in a Swedish population-based study and to discuss the implications. Design Structured questionnaires and semistructured interviews. Setting A longitudinal epidemiological project (PART) ongoing since 1998 in Stockholm, Sweden. The DNA-collection wave took place during 2006-7. Participants 903 individuals completed the questionnaire (participation rate 36%) and 23 were interviewed. All individuals had participated in both non-genetic waves of the project, but refused to contribute saliva samples during the DNA-collection wave. Main outcome measures Motivations behind refusing to consent to DNA biobanking, with subsequent focus on participants' explanations regarding this unwillingness. Results Public refusal to consent to DNA biobanking, as revealed by the questionnaire, was mainly explained by a lack of personal relevance of DNA contribution and feelings of discomfort related to the DNA being used for purposes other than the respective study. Interviews of individuals representing the second motivation, revealed a significant mistrust of DNA biobank studies. The underlying beliefs and attitudes were associated with concerns about integrity, privacy, suspiciousness and insecurity. However, most interviewees were supportive of genetic research per se and interpreted their mistrust in the light of distressing environmental influences. Conclusion The results suggest a need for guidelines on benefit sharing, as well as trustworthy and stable measures to maintain privacy, as a means for increasing personal relevance and trust among potential participants in genetic research. Measures taken from biobanks seem insufficient in maintaining and increasing trust, suggesting that broader societal measures should be taken.

BACKGROUND: There is extensive evidence, from both clinical cases and rodent models, for reduced levels of the widely expressed neuropeptide Y (NPY) in anxiety and depressive disorders. The rare allele of the Leu7Pro polymorphism in the signal peptide of preproNPY has been associated with higher processing into mature NPY, and higher NPY levels in plasma and cerebrospinal fluid. The Pro7 allele was proposed to protect against depression in a small Swedish clinical sample (Heilig M., Zachrisson O., Thorsell A., Ehnvall A., Mottagui-Tabar S., Sjögren M., Asberg M., Ekman R., Wahlestedt C., Agren H., 2004. Decreased cerebrospinal fluid neuropeptide Y (NPY) in patients with treatment refractory unipolar major depression: preliminary evidence for association with preproNPY gene polymorphism. J. Psychiatr. Res. 38, 113-121). METHOD: Leu7Pro was analyzed in a large well-characterized longitudinal population-based sample of adult Swedes with data on life situation and life history, including 461 with depression diagnosis, 157 with anxiety diagnosis and 1514 healthy individuals with no symptom of psychopathology. RESULTS: Pro7 was rarer in depression cases than in healthy individuals (OR=2.7; P=0.0004). The protective effect of Pro7 was similar despite exposure to known environmental vulnerability factors. Pro7 appeared with similar effect size in those with an anxiety diagnosis, but this was not statistically significant (OR=2.3; P=0.06). LIMITATION: The size of the anxiety sample and possibly some recall bias of childhood conditions. CONCLUSION: Pro7 allele of preproNPY protected against depression among Swedes. Pro7 is not common, but was found to exert its protective effect also in an environment-induced vulnerable state. This supports a protective effect of NPY in line with previous reports suggesting anxiolytic-like and antidepressant-like effects of NPY.