Gene-environment interactions and depression.

JAMA The Journal of the American Medical Association (Impact Factor: 29.98). 11/2009; 302(17):1860-1; author reply 1861-2. DOI: 10.1001/jama.2009.1577
Source: PubMed
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    ABSTRACT: Obstetric complications and developmental delay are well-established risk factors for schizophrenia. The authors investigated whether these risk factors interact in an additive manner to further increase risk for schizophrenia. The study population encompassed all individuals born in Helsinki between 1962 and 1969 who had developmental records archived in the Helsinki City Archives. Through linkage between the Finnish Population Register, the Finnish Hospital Discharge Register, and the Child Health Archives, child health cards were traced for 189 individuals who had received a diagnosis of schizophrenia and 189 healthy comparison subjects, individually matched to case subjects on gender and year of birth. Child health cards from the Child Health Archives contain detailed prospective developmental data from birth as well as an indicator of fetal distress, as measured by the Apgar score. Detailed developmental data from the first year of life were extracted. Delayed attainment of milestones in infancy significantly increased the risk of later development of schizophrenia in a dose-response manner. There was no significant main effect of obstetric complications on risk for schizophrenia and no significant association between obstetric complications and subsequent developmental delay. However, the additive effect of obstetric complications and delayed attainment of developmental milestones significantly increased the risk of schizophrenia beyond that associated with each factor independently (odds ratio=4.6, 95% confidence interval=1.3-17.2). These data provide evidence that underlying neurodevelopmental vulnerability, as indexed by delayed attainment of milestones, combined with obstetric adversity significantly increases the risk of schizophrenia in adulthood.
    American Journal of Psychiatry 09/2011; 168(12):1295-302. · 14.72 Impact Factor
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    ABSTRACT: The serotonin transporter gene (SLC6A4) promoter polymorphism (5HTTLPR) has been associated with individual stress responses such that individuals with childhood abuse history have higher rates of depression in later life if they are homozygous short (s/s) of the gene. It is hypothesized that these findings could be explained by an integrated model of a role of the glial cell transporter and a functional difference of 5HTTLPR in the capacity of absorbing serotonin from the synapse. A hypothetical integrated model of the SLC6A4 function and the role of glial cells are put forward to explain accumulating results of recent investigations exploring the relationship between the gene and the diverse mental activities including depression and stress response. A model based on SLC6A4 variation is proposed to explain individual differences in stress vulnerability/resilience. The role of the glial cell transporter surrounding the synapse is integrated in the model to understand the modulation of the neurotransmission. It is hypothesized that a synapse with less serotonin transporter contributes to unstable processing in neurotransmission as compared to a synapse with more serotonin transporter. As such, based on functional differences of 5HTTLPR in the expression of the serotonin transporter, it is asserted that individuals with the s/s genotype process neurotransmission differently and in a reactive way. This integrated model of 5HTTLPR and glial cells suggests that the efficacy of serotonin reuptake in the synapse may play a crucial role in variability of neurotransmission, which can lead to differences in the stress response and the pathophysiology of depression.
    Medical Hypotheses 03/2012; 78(3):410-4. · 1.15 Impact Factor
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    ABSTRACT: Variations within the catechol-O-methyltransferase (COMT) gene have been associated with pain severity in temporomandibular disorders (TMDs). Psychological factors such as personal conflicts, life stress and depression, are well known to be associated with onset, severity and chronicity of pain disorders. We hypothesized that the relationship between the COMT gene and TMD pain is modified by depressive symptoms. Cross-sectional data from the population-based Study of Health in Pomerania (SHIP) in Germany were used to estimate additive interactions between depressive symptoms and 22 single-nucleotide polymorphisms (SNPs) of the COMT gene and the neighbouring thioredoxin reductase 2 (TXNRD2) gene on TMD pain. All participants were Caucasian subjects from a rural area in Northeast Germany. After exclusion of 79 subjects with antidepressant medication, 29.9% of the remaining 3904 subjects reported lifetime depressive symptoms. TMD pain was assessed by a standardized clinical examination. Among various TMD signs, only those that assessed muscle or joint pain on palpation were used as recommended. Six SNPs from the first of three COMT/TXNRD2 haploblocks interacted with depressive symptoms on TMD pain (smallest p-value: 2.7 × 10(-10) ). In subjects without depressive symptoms, rs5993882 was identified as the SNP most likely to be related to TMD pain. In subjects with symptoms of depression, rs1544325 was the corresponding top COMT SNP. Our results indicate that variants within the COMT gene are associated with pain perception. However, this association is highly moderated by the absence or presence of lifetime depressive symptoms.
    European journal of pain (London, England) 12/2011; 16(6):878-89. · 3.37 Impact Factor