ABSTRACT
Recent molecular studies have implicated common alleles of small to moderate effect and rare alleles with larger effect sizes in the genetic architecture of schizophrenia (SCZ). It is expected that the reliable detection of risk variants with very small effect sizes can only be achieved through the recruitment of very large samples of patients and controls (that is tens of thousands), or large, potentially more homogeneous samples that have been recruited from confined geographical areas using identical diagnostic criteria. Applying the latter strategy, we performed a genome-wide association study (GWAS) of 1169 clinically well characterized and ethnically homogeneous SCZ patients from a confined area of Western Europe (464 from Germany, 705 from The Netherlands) and 3714 ethnically matched controls (1272 and 2442, respectively). In a subsequent follow-up study of our top GWAS results, we included an additional 2569 SCZ patients and 4088 controls (from Germany, The Netherlands and Denmark). Genetic variation in a region on chromosome 11 that contains the candidate genes AMBRA1, DGKZ, CHRM4 and MDK was significantly associated with SCZ in the combined sample (n=11 540; P=3.89 × 10(-9), odds ratio (OR)=1.25). This finding was replicated in 23 206 independent samples of European ancestry (P=0.0029, OR=1.11). In a subsequent imaging genetics study, healthy carriers of the risk allele exhibited altered activation in the cingulate cortex during a cognitive control task. The area of interest is a critical interface between emotion regulation and cognition that is structurally and functionally abnormal in SCZ and bipolar disorder.
Subject(s)
Chromosomes, Human, Pair 11/genetics , Functional Neuroimaging/psychology , Genetic Predisposition to Disease/genetics , Psychomotor Performance/physiology , Schizophrenia/genetics , Schizophrenic Psychology , White People/genetics , Case-Control Studies , Europe , Female , Functional Neuroimaging/methods , Genome-Wide Association Study/methods , Genome-Wide Association Study/statistics & numerical data , Gyrus Cinguli/physiology , Humans , Male , Polymorphism, Single Nucleotide , Schizophrenia/physiopathologyABSTRACT
Health care professionals tend to advise alcohol dependent patients to quit tobacco consumption only after longer periods of alcohol abstinence. This recommendation reflects concerns that smoking intervention programs may adversely interfere with the outcome of ongoing alcohol detoxification and rehabilitation treatment. However, the issue of appropriate time windows for initiating changes of smoking behaviour in alcoholic patients is still in need of empirical evaluation. Thus the aim of the present study is to investigate whether alcohol dependent smokers may be able to reduce cigarette consumption very early during alcohol detoxification and rehabilitation treatment. We performed a non-randomized controlled clinical pilot trial with 56 female and male alcohol dependent smokers in an inpatient setting providing a 3-weeks alcohol detoxification program. 28 individuals received a smoking reduction program consisting of a 6-sessions approach in a group format following behavioural principles. For the control group of 28 individuals the program was not available. Tobacco consumption was assessed daily by staff members. Alcohol dependent patients participating in the smoking reduction program reduced their daily cigarette consumption rates significantly, whereas the control group showed a tendency to increase tobacco consumption. According to the tentative findings of this pilot study early smoking interventions already during alcohol detoxification appear to be a feasible approach.
