Biomedical subjects

Jim van Os

Publications and source records attributed to Jim van Os.

At least 19 recordsLinked to original sources

PubMed2007

Stress-reactivity in psychosis: evidence for an affective pathway to psychosis.

This paper will review a series of studies using the Experience Sampling Method that suggest that altered sensitivity to stress is an endophenotype for psychosis. The Experience Sampling Method is a structured diary technique allowing the assessment of emotional reactivity to stressors occurring in normal daily life. Elevated emotional reactivity to stress was found in subjects vulnerable to psychosis, suggesting that affective responses to stressors in the flow of daily life are an indicator of genetic and/or environmental liability to psychosis. Indeed, the small stressors in daily life associated with affective responses also predict more intense moment-to-moment variation of subtle positive psychotic experiences. Increased emotional reactivity was found to be independent from cognitive impairments, and argued to constitute evidence of an affective pathway to psychosis that may underlie a more episodic, reactive, good-outcome type of psychosis. Evidence for this hypothesis was found in data suggesting that the experience of stressful life events and early trauma were associated with increased stress-sensitivity, and that women were more likely to display elevated stress-reactivity. These findings are discussed in the light of recent biological and psychological mechanisms.

Affect↗

PubMed2006

Instability in self-esteem and paranoia in a general population sample.

BACKGROUND: Research on the association between paranoia and self-esteem has yielded inconsistent findings. Some studies have indicated an association between paranoia and low self-esteem, while other studies have shown an association with high self-esteem. A plausible explanation for these inconsistencies is that self-esteem is unstable in paranoid individuals. METHOD: The association between instability in self-esteem and paranoia was assessed in a general population risk set of 4636 individuals using logistic regression analysis. RESULTS: Self-esteem instability was significantly associated with the presence of paranoid symptoms (OR 1.27 95% CI 1.12-1.45) and not with other positive psychotic symptoms (OR 1.09 95% CI 0.96-1.23), adjusted for a range of a priori selected confounders. CONCLUSION: The finding of a specific association between unstable self-esteem and paranoia is in line with a recent psychological model suggesting that paranoid beliefs arise partly as a consequence of dysfunctional efforts to regulate self-esteem.

Adolescent↗

PubMed2006

The impact of subclinical psychosis on the transition from subclinicial mania to bipolar disorder.

BACKGROUND: In the general population, symptoms of mania and psychosis are more broadly distributed than their associated clinical syndromes. Little is known, however, about how these subclinical population phenotypes co-vary with and impact on each other. METHOD: In a representative population cohort of 7076 adults, prevalence of mania and psychosis symptoms and syndromes were assessed with the CIDI at baseline, at one (T1) and two years later (T2). The degree of comorbidity between subclinical mania and subclinical psychosis was examined, as well as the impact of subclinical comorbidity on social impairment and transition from subclinical mania to onset of bipolar disorder. RESULTS: The lifetime prevalence of at least one manic and one psychotic symptom was 4.1% and 4.2% respectively. Excluding individuals with any lifetime DSM-III-R bipolar or psychotic disorder (n=218), these prevalences were 2.3% (subclinical mania) and 2.8% (subclinical psychosis). Individuals with subclinical mania had a 17% risk of subclinical psychosis, compared with 2.3% in those without (P<0.000). Comorbid subclinical psychosis in individuals with subclinical mania was much more predictive of a future diagnosis of bipolar disorder (positive predictive values of 3% versus 10% respectively). CONCLUSION: Subclinical phenotypes of mania and psychosis are more prevalent than their clinical counterparts and cluster together. The risk factors for psychosis may facilitate the formation of more "toxic" combinations of subclinical mania and subclinical psychosis with a higher probability of transition to bipolar disorder. A better understanding of this pathway is crucial for the development of early interventions.

Adult↗

PubMed2006

An experimental study of catechol-o-methyltransferase Val158Met moderation of delta-9-tetrahydrocannabinol-induced effects on psychosis and cognition.

Observational studies have suggested that psychometric psychosis liability and a functional polymorphism in the catechol-O-methyltransferase (COMT Val(158)Met) gene moderate the psychosis-inducing effect of cannabis. To replicate and extend this finding, a double-blind, placebo-controlled cross-over design was used in which patients with a psychotic disorder (n=30), relatives of patients with a psychotic disorder (n=12), and healthy controls (n=32) were exposed to Delta-9-tetrahydrocannabinol (Delta-9-THC, the principal component of cannabis) or placebo, followed by cognitive assessment and assessment of current psychotic experiences. Previous expression of psychometric psychosis liability was also assessed. Models of current psychotic experiences and cognition were examined with multilevel random regression analyses to assess (i) main effects of genotype and condition, (ii) interactions between condition and genotype, and (iii) three-way interactions between condition, genotype, and psychometric psychosis liability. Carriers of the Val allele were most sensitive to Delta-9-THC-induced psychotic experiences, but this was conditional on prior evidence of psychometric psychosis liability. Delta-9-THC impacted negatively on cognitive measures. Carriers of the Val allele were also more sensitive to Delta-9-THC-induced memory and attention impairments compared to carriers of the Met allele. Experimental effects of Delta-9-THC on cognition and psychosis are moderated by COMT Val(158)Met genotype, but the effects may in part be conditional on the additional presence of pre-existing psychosis liability. The association between cannabis and psychosis may represent higher order gene-environment and gene-gene interactions.

Adolescent↗

PubMed2006

Premorbid IQ as a predictor for the course of IQ in first onset patients with schizophrenia: a 10-year follow-up study.

The aim of the present study was to examine the longitudinal course of IQ and its heterogeneity in patients with schizophrenia, from the perspective of the two main "subtypes" of schizophrenia described in the literature: progressive cognitive deficit versus cognitive stabilisation or recovery. Premorbid IQ scores and WAIS IQ scores of 100 first onset patients were obtained at first hospitalization (T1) and after 10 years (T2). Significant changes in IQ over time were found, representing (i) at T1, a deterioration compared to premorbid intelligence (B=-6.3, 95% CI -9.5 to -3.0, p<0.0001), followed by (ii) a recovery at T2 where IQ matched premorbid intelligence again (B=0.5, 95% CI -3.1 to 4.0, p=0.79). In addition, a significant interaction was found between course of IQ over time and estimated premorbid IQ, demonstrating that subjects with lower premorbid IQ levels remained stable over time whereas in individuals with higher premorbid IQ levels a pattern of deterioration was evident at T1, followed by a recovery up to premorbid level at T2. The data confirm the importance of estimated premorbid IQ as an indicator of the longitudinal course of cognitive functioning in patients with schizophrenia and add evidence to the hypothesis of heterogeneity or "subtypes" of schizophrenia. The data, however, do not confirm the existence of progressive deterioration of cognitive functioning. Rather, catching up of cognitive function later in the course of the illness may take place in those whose deficits become apparent in the early phases of illness, whereas those with the most severe premorbid impairments remain stable.

Adult↗

PubMed2006

Evidence that the urban environment specifically impacts on the psychotic but not the affective dimension of bipolar disorder.

OBJECTIVES: High rates of psychotic disorders and psychotic symptoms have been found in urban environments but reports for bipolar affective illness have been inconsistent, possibly due to failure to stratify for comorbid psychotic symptoms. It was hypothesised, therefore, that any effect of urbanicity on the bipolar phenotype would be moderated by comorbid psychotic symptoms. METHODS: In a random, representative population cohort of 7049 adults with no history of non-affective psychotic disorder, the cumulative incidence of bipolar and psychotic symptoms and syndromes, assessed with the CIDI, was examined over five levels of population density of place of residence. Similarly, the degree of comorbidity between broadly and narrowly defined bipolar phenotypes on the one hand, and the dichotomous presence of broadly (17.2%) and narrowly defined (3.8%) psychotic symptoms on the other, was examined as a function of population density of place of residence. RESULTS: The rate of bipolar disorder, however defined, was progressively higher in more urbanised areas. However, in models of bipolar phenotypes, a strong interaction between comorbid psychosis and level of urbanicity was apparent, indicating that the greater the degree of psychotic comorbidity, the greater the effect size of the urban environmental factor. For bipolar disorder without psychosis, no effect of urbanicity was apparent. CONCLUSIONS: The results suggest differential environmental causal effects on affective and cognitive dimensions of bipolar psychopathology that are nevertheless strongly comorbid within the same categorically defined disorder, possibly due to the effect of shared genetic risk factors.

Adolescent↗

PubMed2006

Evidence that brain tissue volumes are associated with HVA reactivity to metabolic stress in schizophrenia.

BACKGROUND: Although liability to psychosis is thought to have its origins in cerebral alterations, expressed as cerebral grey and white matter loss, less is known about the degree to which such vulnerabilities impact on functional parameters, in particular altered stress reactivity. Breier et al. [Breier, A., Davis, O.R., Buchanan, R.W., Moricle, L.A., Munson, R.C., 1993b. Effects of metabolic perturbation on plasma homovanillic acid in schizophrenia. Relationship to prefrontal cortex volume. Arch. Gen. Psychiatry 50(7), 541-550] reported that lower prefrontal cortex volume was associated with altered metabolic stress response, but this finding has never been replicated. METHODS: Thirty-one patients with psychosis underwent structural magnetic resonance imaging scanning and a metabolic stress paradigm (glucoprivic 2-deoxyglucose (2DG) condition versus placebo condition) that yielded information on plasma homovanillic acid (HVA) reactivity. Total cerebral tissue volumes were derived from automated segmentation procedures. Associations between metabolic stress and tissue volumes (as well as their interactions) on the one hand, and plasma HVA level on the other, were investigated using multilevel random regression techniques. RESULTS: Analysis revealed a significant increase in plasma HVA over time in the 2DG condition. The increase in HVA in the stress condition was stronger in patients with lower grey and white matter volumes. There was no significant interaction between metabolic stress and CSF volume. CONCLUSION: Lower grey and white matter volumes in schizophrenia are associated with a dysregulated dopaminergic/noradrenergic mediated stress response. These findings may support the hypothesis that alterations in cortico-subcortical connections affect psychosis susceptibility through an altered stress response.

Adolescent↗

PubMed2006

Cannabis use and expression of mania in the general population.

BACKGROUND: Cannabis use is common in patients with bipolar disorder, however little is known about cannabis as a risk factor for mania. In order to investigate the association between exposure to cannabis and subsequent development of manic symptoms whilst controlling for psychotic symptoms, a longitudinal population-based study was carried out. METHODS: 4815 individuals aged 18 to 64 years were interviewed using the Composite International Diagnostic Interview at baseline, 1 year follow up and 3 year follow up, including assessment of substance use, manic symptoms and psychotic symptoms. RESULTS: Use of cannabis at baseline increased the risk for manic symptoms during follow-up (adjusted OR 2.70, 95% CI: 1.54, 4.75), adjusted for age, sex, educational level, ethnicity, single marital status, neuroticism, use of other drugs, use of alcohol, depressive symptoms and manic symptoms at baseline. The association between cannabis use and mania was independent of the prevalence and the incidence of psychotic symptoms. There was no evidence for reverse causality, as manic symptoms at baseline did not predict the onset of cannabis use during follow-up (OR = 0.35, 95% CI: 0.03, 3.49). LIMITATIONS: As 3 years is a relative short period of follow-up, long-term effects of cannabis use on mania outcomes could not be detected. CONCLUSION: The results suggest that cannabis use may affect population expression of manic symptoms (and subsequent risk to develop bipolar disorder [Regeer, E.J., Krabbendam, L., R, DE Graaf, Ten Have, M., Nolen, W.A., Van Os, J., 2006. A prospective study of the transition rates of subthreshold (hypo)mania and depression in the general population. Psychol Med, 1-9.]). These findings may not be due to the emergence of psychotic symptoms or the effects of self-medication.

Adolescent↗

PubMed2006

Associations between delusion proneness and personality structure in non-clinical participants: comparison between young and elderly samples.

BACKGROUND: Few studies have explored the prevalence of delusions in the non-clinical, elderly population. In addition, the association between personality structure and delusions remains poorly investigated. The aims of the present study were, first, to explore the relation between age and the prevalence of delusion proneness and, second, to examine the association between personality and delusion proneness in young and elderly participants. SAMPLING AND METHODS: A sample of young (n = 343; aged 18-30 years) and elderly (n = 183; aged 60-75 years) non-clinical participants completed the 21-item version of the Peters et al. Delusions Inventory (PDI-21), an elaborated and validated version of the Launay-Slade Hallucinations Scale, and the revised version of the NEO Personality Inventory (NEO-PI-R). RESULTS: Mean scores on the PDI-21 for the young and elderly participants were compared. An independent t test revealed that the total mean scores were significantly higher for young participants compared to elderly participants. PDI-21 items were then re-grouped into previously validated factors. Independent t tests revealed that young participants had significantly higher scores for items related to suspiciousness and persecutory ideas, thought disturbances and jealousy, grandiose ideas, paranormal beliefs and apocalyptic ideas. In contrast, elderly participants scored significantly higher than young participants on the religious ideation factor. Associations between scores on the NEO-PI-R and the PDI-21 were then examined for the two groups. For the young sample, correlational analyses revealed a significant relationship between the total score on the PDI-21 and scores on the openness, neuroticism and agreeability facets of the NEO-PI-R. For the elderly sample, correlational analyses revealed a significant relationship between the total score on the PDI-21 and the openness facet of the NEO-PI-R. DISCUSSION: Results from the study reveal that delusional ideation is a relatively common experience for both young and elderly non-clinical participants. In addition, findings are in line with studies suggesting that neuroticism and aspects related to neuroticism increase the risk for the development of psychotic symptoms such as delusions. However, it is important to mention that, because the present study includes non-clinical subjects and is a cross-sectional study, more research is needed.

Adolescent↗

PubMed2006

Social disadvantage and schizophrenia. A combined neighbourhood and individual-level analysis.

OBJECTIVE: To study, in a geographically defined area, associations between the neighbourhood social environment and individual socioeconomic status on the one hand, and treated incidence of schizophrenia and level of subsequent service use on the other. METHOD: A combined data set of (i) patients with a case register diagnosis of schizophrenia and (ii) population controls was subjected to multilevel analyses, including neighbourhood exposures (neighbourhood socioeconomic disadvantage and social capital) and individual level confounders. Separate analyses were conducted for inpatient and outpatient psychiatric service consumption as indexed by the case register. RESULTS: Neighbourhood socioeconomic disadvantage and neighbourhood social capital did not impact on the treated incidence of schizophrenia, but quantity of inpatient service consumption was higher in neighbourhoods with higher level of social control (i.e. where it is more likely that neighbours intervene in neighbourhood-threatening situations). In addition, most indicators of lower individual socioeconomic status were associated with higher treated incidence, while treated incidence was lower when individual educational status was low. CONCLUSION: Residents of high social control neighbourhoods may seek greater levels of resolution of psychiatric disorder in patient-residents, and by consequence may induce greater levels of inpatient service consumption in patients diagnosed with schizophrenia. Individual-level indicators of social disadvantage are associated with higher risk of treated psychotic disorder, with the exception of lower educational status, which may confer a lower probability of treatment given the presence of psychotic disorder.

Adult↗

PubMed2006

The wider social environment and changes in self-reported quality of life in the transition from late childhood to early adolescence: a cohort study.

BACKGROUND: Neighbourhood socioeconomic disadvantage and social capital have been associated with adolescent well-being, but the majority of studies were cross-sectional, and the time window over which the neighbourhood may impact on development is unknown. Therefore, the contribution of the neighbourhood environment to adolescents' quality of life and the course of these effects during the period of transition from childhood to early adolescence was examined. METHODS: A cohort of adolescents living in Maastricht (The Netherlands), with a mean age of 11.2 years at baseline and of 13.5 years at follow-up was followed. Adolescents who responded both at baseline and at follow-up were included in the analysis (n = 475). Multilevel regression analyses estimated neighbourhood effects while controlling for individual-level effects. Neighbourhood-level socioeconomic and social capital variables, individual-level confounders, and baseline values of the outcome measures were included in the models. RESULTS: None of the neighbourhood factors was associated with changes in general health or mental health over the two-year period. However, two-year exposure to greater disparity between individual level socioeconomic status on the one hand and neighbourhood level of socioeconomic status on the other (e.g. high socioeconomic status adolescents living in deprived neighbourhoods and vice versa) negatively impacted on self-esteem and satisfaction. CONCLUSION: The neighbourhood environment per se does not contribute to change in quality of life during the transition to early adolescence. However, adolescents living in families whose socioeconomic status deviates from the mean level of neighbourhood socioeconomic deprivation may be negatively affected.

Adolescent↗

PubMed2006

Hearing impairment and psychosis: a replication in a cohort of young adults.

Previous work has demonstrated an association between hearing impairment and psychosis. In the current study, this association was studied in a cohort of young people. In addition, it was studied to what degree duration of hearing problems (i.e. onset earlier in life) impacted on risk. Data were derived from the Greek National Perinatal Survey, a prospective birth cohort study of 11,048 neonates at baseline, 6594 seven-year olds at T1 and 3500 nineteen-year olds at T2. A significant association was found at age 19 years between the presence of hearing impairment and the presence of self-reported positive psychotic-like experiences (beta = 0.18, S.E. = 0.02, p < 0.000). In addition, this association was conditional on the duration of hearing problems, in that the association at age 19 years was stronger if hearing impairment had already been reported at age 7 years (test for interaction: p = 0.022). These results replicate previous findings of an association between hearing impairment and psychosis, extend it to the age range of late adolescence, and suggest that longer duration is associated with stronger risk.

Adolescent↗

PubMed2006

Gene regulation by hypoxia and the neurodevelopmental origin of schizophrenia.

Neurodevelopmental changes may underlie the brain dysfunction seen in schizophrenia. While advances have been made in our understanding of the genetics of schizophrenia, little is known about how non-genetic factors interact with genes for schizophrenia. The present analysis of genes potentially associated with schizophrenia is based on the observation that hypoxia prevails in the embryonic and fetal brain, and that interactions between neuronal genes, molecular regulators of hypoxia, such as hypoxia-inducible factor 1 (HIF-1), and intrinsic hypoxia occur in the developing brain and may create the conditions for complex changes in neurodevelopment. Consequently, we searched the literature for currently hypothesized candidate genes for susceptibility to schizophrenia that may be subject to ischemia-hypoxia regulation and/or associated with vascular expression. Genes were considered when at least two independent reports of a significant association with schizophrenia had appeared in the literature. The analysis showed that more than 50% of these genes, particularly AKT1, BDNF, CAPON, CCKAR, CHRNA7, CNR1, COMT, DNTBP1, GAD1, GRM3, IL10, MLC1, NOTCH4, NRG1, NR4A2/NURR1, PRODH, RELN, RGS4, RTN4/NOGO and TNF, are subject to regulation by hypoxia and/or are expressed in the vasculature. Future studies of genes proposed as candidates for susceptibility to schizophrenia should include their possible regulation by physiological or pathological hypoxia during development as well as their potential role in cerebral vascular function.

Animals↗

PubMed2006

Childhood victimisation and developmental expression of non-clinical delusional ideation and hallucinatory experiences: victimisation and non-clinical psychotic experiences.

BACKGROUND: Victimisation in childhood may be associated with adult psychosis. The current study examined this association in the crucial developmental period of early adolescence and investigated whether (1) unwanted sexual experiences, and (2) being bullied, were associated with non-clinical delusional ideation and hallucinatory experiences in a general population sample of 14 year olds. METHODS: Data were derived from standard health screenings of the Youth Health Care Divisions of the Municipal Health Services in Maastricht, the Netherlands. A self-report questionnaire was filled out by a total of 1290 adolescents to assess non-clinical psychotic experiences, as well as experiences of being bullied and sexual trauma. RESULTS: Non-clinical psychotic experiences were strongly and independently associated with both bullying (OR=2.9, 95% CI 1.8-4.8) and sexual trauma (OR=4.8, 95% CI 2.3-10.1). CONCLUSIONS: The results suggest that reported associations between childhood victimisation and adult psychosis can be understood in a developmental framework of onset of at-risk mental states in early adolescence. In addition, the data suggest that the traumatic experience of being bullied may also feed the cognitive and biological mechanisms underlying formation of psychotic ideation.

Adolescent↗

PubMed2006

Antipsychotic-induced tardive dyskinesia and the Ser9Gly polymorphism in the DRD3 gene: a meta analysis.

BACKGROUND: A polymorphic site in the gene encoding the dopamine 3 receptor (DRD3) resulting in a serine (Ser) into glycine (Gly) substitution has been shown to affect dopamine binding affinity, and may contribute to individual differences in susceptibility to antipsychotic-induced tardive dyskinesia (TD). METHODS: A Medline, EMBASE and PsychINFO search of literature published between 1976 and March 2005 yielded 11 studies from which data were extracted for calculation of pooled estimates using meta-analytic techniques. RESULTS: The Gly allele increased the risk relative to the Ser allele (OR=1.17; 95% CI: 1.01-1.37) with evidence of publication bias. No significant genotype effects were apparent. CONCLUSIONS: TD may be associated with functional variation in the DRD3 allele. However, caution is required in interpreting this finding, as there is evidence of publication bias, genetic methodology has shortcomings, and the relation between antipsychotics, schizophrenia and TD is complex.

Alleles↗

PubMed2006

Tardive dyskinesia in schizophrenia is associated with prolactin-related sexual disturbances.

Tardive dyskinesia (TD) may occur in never-medicated patients with psychotic illness, indicating the existence of non-medication, possibly disease-related, causes. We tested the hypothesis that, independent of the antipsychotic-induced rise in prolactin, the incidence of TD would be associated with the incidence of prolactin-related sexual disturbances (PRSD), which would be suggestive of a common pathology involving multiple dopamine tracts. Simple, global measures of TD and PRSD (loss of libido, amenorrhea, gynaecomastia, impotence, and galactorrhea) were rated in a prospective, observational European Health Outcomes Study (SOHO). New onset of TD and new onset of PRSD at 3, 6, and 12 months was analyzed in a risk set of 4263 patients using a Cox proportional hazard model yielding adjusted hazard ratios (aHR). Incidence of TD was significantly and linearly comorbid with the incidence of PRSD in both men and women. Compared to those with no PRSD, the risk for TD was 2.0 (95% CI: 1.1, 3.7) with one PRSD, 2.4 (95% CI: 1.3, 4.5) with two PRSD, and 3.6 (95% CI: 1.1, 11.8) with three PRSD. Associations were stronger in those who only had received prolactin-sparing medications (aHR per unit PRSD increase=2.0, 95% CI: 1.2, 3.3) than in those who only had received prolactin-raising medications (aHR=1.3, 95% CI: 0.9, 1.9). In people with schizophrenia, TD and PRSD show comorbidities that are independent of antipsychotic-induced alterations in plasma prolactin. This may suggest a shared, pandopaminergic pathological mechanism associated with schizophrenia itself, rather than only a medication effect.

Adult↗

PubMed2006

Evidence that the outcome of developmental expression of psychosis is worse for adolescents growing up in an urban environment.

BACKGROUND: The urban environment may increase the risk for psychotic disorder in interaction with pre-existing risk for psychosis, but direct confirmation has been lacking. The hypothesis was examined that the outcome of subclinical expression of psychosis during adolescence, as an indicator of psychosis-proneness, would be worse for those growing up in an urban environment, in terms of having a greater probability of psychosis persistence over a 3.5-year period. METHOD: A cohort of 918 adolescents from the Early Developmental Stages of Psychopathology Study (EDSP), aged 14-17 years (mean 15.1 years), growing up in contrasting urban and non-urban environments, completed a self-report measure of psychotic symptoms at baseline (Baseline Psychosis) and at first follow-up around 1 year post-baseline (T1). They were again interviewed by trained psychologists for the presence of psychotic symptoms at the second follow-up on average 3.5 years post-baseline (T2). RESULTS: The rate of T2 psychotic symptoms was 14.2% in those exposed to neither Baseline Psychosis nor Urbanicity, 12.1% in those exposed to Urbanicity alone, 14.9% in those exposed to Baseline Psychosis alone and 29.0% in those exposed to both Baseline Psychosis and Urbanicity. The odds ratio (OR) for the combined exposure was 2.46 [95% confidence interval (CI) 1.46-4.14], significantly greater than that expected if Urbanicity and Baseline Psychosis acted independently. CONCLUSION: These findings support the suggestion that the outcome of the developmental expression of psychosis is worse in urban environments. The environment may impact on risk for psychotic disorder by causing an abnormal persistence of a developmentally common expression of psychotic experiences.

Adolescent↗

PubMed2006

Stress-related negative affectivity and genetically altered serotonin transporter function: evidence of synergism in shaping risk of depression.

CONTEXT: Genetic moderation of the depression-inducing effects of stressful life events (SLEs) has been reported, but findings suggest that genes may not moderate the effects of SLEs per se but instead may moderate the risk of depression associated with the stable tendency to develop negative emotions in response to minor environmental experiences. OBJECTIVE: To examine whether a functional polymorphism of the serotonin transporter gene (5-HTTLPR) moderates the association between negative affectivity (neuroticism) and depression and to what degree this can explain previous findings involving SLEs. DESIGN: A prospective cohort study involving 1 baseline and 4 follow-up measurements in 15 months analyzing change in self-reported depressive symptoms across time as a function of negatively attributed SLEs, neuroticism, 5-HTTLPR, and their interactions. SETTING: General community. PARTICIPANTS: A population-based sample of 374 ethnically homogeneous young adult female twins. MAIN OUTCOME MEASURE: A continuous score of self-reported depressive symptoms. RESULTS: The depressogenic effect of SLEs in the 3 months before interview was significantly greater in women with 2 short (S) alleles compared with women with 1 or none. However, this effect disappeared after accounting for the effect of SLEs conditional on neuroticism. Similarly, the depressogenic effect of neuroticism was progressively greater with number of S alleles, and this was unchanged after accounting for the effect of neuroticism conditional on SLEs. CONCLUSIONS: Genotype x environment interactions in depression may be more productively interpreted by involving mechanisms more proximal to psychological experience itself. The probability that stress-related cognitive vulnerabilities for depression result in symptom formation may be moderated by a neurobiologic phenotype characterized by altered processing of negative emotions associated with variation in 5-HTTLPR.

Adolescent↗