Marieke Wichers

Early adversity and 5-HTT-BDNF genes: new evidences of gene-environment interactions on depressive symptoms in a general population

BACKGROUNDnAdverse childhood experiences have been described as one of the major environmental risk factors for depressive disorder. Similarly, the deleterious impact of early traumatic experiences on depression seems to be moderated by individual genetic variability. Serotonin transporter (5-HTT) and brain-derived neurotrophic factor (BDNF) modulate the effect of childhood adversity on adult depression, although inconsistencies across studies have been found. Moreover, the gene x environment (GxE) interaction concerning the different types of childhood adversity remains poorly understood. The aim of this study was to analyse the putative interaction between the 5-HTT gene (5-HTTLPR polymorphism), the BDNF gene (Val66Met polymorphism) and childhood adversity in accounting for adult depressive symptoms.nnnMETHODnA sample of 534 healthy individuals filled in self-report questionnaires of depressive symptomatology [the Symptom Check List 90 Revised (SCL-90-R)] and different types of childhood adversities [the Childhood Trauma Questionnaire (CTQ)]. The 5-HTTLPR polymorphism (5-HTT gene) and the Val66Met polymorphism (BDNF gene) were genotyped in the whole sample.nnnRESULTSnTotal childhood adversity (beta=0.27, p<0.001), childhood sexual abuse (CSA; beta=0.17, p<0.001), childhood emotional abuse (beta=0.27, p<0.001) and childhood emotional neglect (beta=0.22, p<0.001) had an impact on adult depressive symptoms. CSA had a greater impact on depressive symptoms in Met allele carriers of the BDNF gene than in the Val/Val group (F=5.87, p<0.0001), and in S carriers of the 5-HTTLPR polymorphism (5-HTT gene) (F=5.80, p<0.0001).nnnCONCLUSIONSnChildhood adversity per se predicted higher levels of adult depressive symptoms. In addition, BDNF Val66Met and 5-HTTLPR polymorphisms seemed to moderate the effect of CSA on adult depressive symptoms.

A prospective twin study of birth weight discordance and child problem behavior

BACKGROUNDnWe investigated whether low birth weight constitutes a causal risk factor for child problem behavior, using a variation of the co-twin control method.nnnMETHODSnIn a representative sample of 745 twin pairs (monozygotic: 324 pairs), birth weight was recorded at birth and child problem behavior at mean age 10 years was measured with the Child Behaviour Checklist (CBCL).nnnRESULTSnLower birth weight was a continuous risk factor for later child problem behavior (adjusted regression coefficient over units of 500 g: beta = -.15, p =.046), and greater levels of within-pair CBCL discordance did not result in a reduced effect size. Greater within-pair birth weight discordance was associated with greater within-pair CBCL score discordance (beta =.35, p <.001). This latter effect was similar in monozygotic (beta =.34, p =.005) and dizygotic twins (beta =.37, p =.003).nnnCONCLUSIONSnThe fact that (1) the effect size of the association between low birth weight and child problem behavior was not reduced in pairs with greater levels of CBCL discordance, and (2) similar effect sizes were found in monozygotic and dizygotic twins for the within-pair association between birth weight discordance and CBCL score discordance, suggests that the observed relationship between low birth weight and child problem behavior is not due to a shared environmental or genetic variable that influences both characteristics. Lower birth weight is a causal risk factor for child problem behavior, the effects of which may well extend into adulthood.

The dynamic interplay between negative and positive emotions in daily life predicts response to treatment in depression: A momentary assessment study

OBJECTIVESnAlthough the treatment of depressive illness aims to restore the imbalance between an excess of negative affect (NA) and a shortage of positive affect (PA), no study has examined how NA and PA may influence each other in depression. This study examines how NA and PA dynamically influence each other in depression and how this may impact on treatment response.nnnDESIGNnDepressed help-seeking individuals participated in the Experience Sampling Method (ESM), which enables visualization of subtle dynamic alterations of momentary affective states over time. Thereafter, participants received a combination of antidepressant treatment and psychotherapy, and were followed up each month.nnnMETHODSnNA and PA were assessed during ESM at 10 random moments per day for 6 days. Depressive symptoms were assessed at baseline and at monthly intervals during treatment.nnnRESULTSnFuture response to treatment was associated with altered baseline NA-PA dynamics in individuals with previous depressive episodes. Their daily life boosts of PA were followed by a stronger suppression of NA over subsequent hours than in other depressed groups or controls.nnnCONCLUSIONSnSubtle individual differences in daily life emotional dynamics predict future treatment outcome in depression.

No major role for X-inactivation in variations of intelligence and behavioral problems at middle childhood.

Although members of monozygotic (MZ) twin pairs are identical in genomic sequence, epigenetic mechanisms may occasion difference in gene expression and, consequently, twin discordance in complex traits. Recent work suggests that the epigenetic process of X‐inactivation in female individuals may impact on intelligence and child behavioral problems. The timing of X‐inactivation has been linked to chorionic splitting in MZ twins. Dichorionic monozygotic (DC‐MZ) twinning, unlike monochorionic monozygotic (MC‐MZ) twinning, occurs prior to the time of X‐inactivation in female organisms. Therefore, the hypothesis of a causal role of X‐inactivation in intelligence and behavioral problems can be analyzed by modeling the statistical interaction between sex and chorion type for within‐pair differences in these traits in MZ twins. In this study, the effect of X‐inactivation on childhood behavioral problems, measured with the CBCL, was studied in a sample of 324 MZ twin pairs from the EFPTS and the effect of X‐inactivation on IQ was studied in a sample of 272 twin pairs from the same twin survey. Information on chorion type, gestational age, and birth weight was additionally collated. No significant statistical interaction was found between sex and chorion type, indicating that X‐inactivation is not likely involved in variations in intelligence or behavioral problems in middle childhood. Further studies are required to replicate these findings and may explore the role of X‐inactivation at different ages or at the extreme scores in the spectrum of intelligence and behavioral problems or may focus on other epigenetic mechanisms.