Biomedical subjects

M C Wichers

Publications and source records attributed to M C Wichers.

4 recordsLinked to original sources

PubMed2005

Early increase in vegetative symptoms predicts IFN-alpha-induced cognitive-depressive changes.

BACKGROUND: The vegetative symptoms of depression resemble the symptoms of malaise associated with activation of the inflammatory response system (IRS), and can be regarded as an expression of a central motivational state that resets the organism's priorities to promote recovery from infection. Early vegetative symptoms, however, may also contribute to the high rates of depression seen later in the course of immune activation. We hypothesized that the onset of vegetative-depressive symptoms early in the treatment with the pro-inflammatory cytokine IFN-alpha in chronic hepatitis C patients would increase the risk for subsequent depressive cognitions. METHOD: Sixteen patients eligible for IFN-alpha treatment and free of psychiatric disorders were recruited. The DSM-IV, the Multidimensional Fatigue Inventory, and the Montgomery-Asberg Depression Rating Scale (MADRS) were administered at baseline and 1, 2, 4, 8, 12 and 24 weeks after treatment was initiated. Cognitive-depressive and vegetative-depressive symptom clusters were constructed. RESULTS: Fatigue and depression scores increased significantly during IFN-alpha treatment. Depression scores were highest at week 8 of treatment. First week increase in vegetative-depressive symptom score predicted cognitive-depressive symptom score at week 8 and at week 24. CONCLUSIONS: During IFN-alpha treatment, vegetative symptoms of depression appear earlier than, and are predictive of, their cognitive counterparts. This finding suggests that low mood state may in part be driven by the increase in early vegetative-depressive symptoms in the course of IFN-alpha-induced immune activation.

Adult↗

PubMed2005

IDO and interferon-alpha-induced depressive symptoms: a shift in hypothesis from tryptophan depletion to neurotoxicity.

Studies show that administration of interferon (IFN)-alpha causes a significant increase in depressive symptoms. The enzyme indoleamine 2,3-dioxygenase (IDO), which converts tryptophan (TRP) into kynurenine (KYN) and which is stimulated by proinflammatory cytokines, may be implicated in the development of IFN-alpha-induced depressive symptoms, first by decreasing the TRP availability to the brain and second by the induction of the KYN pathway resulting in the production of neurotoxic metabolites. Sixteen patients with chronic hepatitis C, free of psychiatric disorders and eligible for IFN-alpha treatment, were recruited. Depressive symptoms were measured using the Montgomery Asberg Depression Rating Scale (MADRS). Measurements of TRP, amino acids competing with TRP for entrance through the blood-brain barrier, KYN and kynurenic acid (KA), a neuroprotective metabolite, were performed using high-performance liquid chromatography. All assessments were carried out at baseline and 1, 2, 4, 8, 12 and 24 weeks after treatment was initiated. The MADRS score significantly increased during IFN-alpha treatment as did the KYN/TRP ratio, reflecting IDO activity, and the KYN/KA ratio, reflecting the neurotoxic challenge. The TRP/CAA (competing amino acids) ratio, reflecting TRP availability to the brain, did not significantly change during treatment. Total MADRS score was significantly associated over time with the KYN/KA ratio, but not with the TRP/CAA ratio. Although no support was found that IDO decreases TRP availability to the brain, this study does support a role for IDO activity in the pathophysiology of IFN-alpha-induced depressive symptoms, through its induction of neurotoxic KYN metabolites.

Adult↗

PubMed2002

Prenatal life and post-natal psychopathology: evidence for negative gene-birth weight interaction.

BACKGROUND: Many studies suggest that pregnancy and birth complications (PBCs) are environmental risk factors for child psychopathology. However, it is not known whether the effects of PBCs occur independently of genetic predisposition. The current study examined the possibility of gene-environment interaction in a twin design. METHOD: The East Flanders Prospective Twin Survey prospectively records the births of all twin pairs born in East Flanders, Belgium. The current study included 760 twin pairs aged 6-17 years. Multilevel regression analysis was used to assess the effects of several PBCs collected around the time of birth. Using structural equation modelling, ACE models assuming additive genetic (A), shared environmental (C) and unique environmental (E) influences, were compared in order to examine whether the contribution of genetic factors to parent-rated child problem behaviour varied as a function of exposure to dichotomously and continuously defined PBCs. RESULTS: A main independent effect of lower birth weight, corrected for gestational age (small for gestational age--SGA), on child problem behaviour was found. In addition, there was an interaction between genetic influence and SGA, in that being smaller for gestational age resulted in less influence of additive genetic factors on individual differences in problem behaviour. CONCLUSIONS: Results are suggestive of negative gene-birth weight interaction. Children who are SGA are less sensitive to the genetic effects, and those with high genetic vulnerability are less sensitive to the effects of being SGA in bringing about post-natal mental health effects.

Adolescent↗

PubMed2001

Associations between nonshared environment and child problem behaviour.

BACKGROUND: Twin studies suggest that environmental effects on the development of child psychopathology largely involve nonshared environmental processes. However, the influence of the nonshared environment may have been overestimated, as the relationship between environment and behaviour may be genetically mediated. A direct measure of the nonshared environment (using the Sibling Inventory of Differential Experience - SIDE) was investigated in relation to child psychopathology, and tested for possible genetic mediation. METHOD: Parent-rated versions of the Child Behaviour Checklist (CBCL) and the SIDE were collected in 760 twin pairs aged 6-17 years. Multilevel regression analysis was used to assess the influence of SIDE scores on CBCL total problem scores, internalising symptoms, externalising symptoms and depressive symptom scores. Genetic mediation was assessed by examining interaction with zygosity in the association between SIDE scores and differences in CBCL scores (absence of interaction indicating no genetic mediation). RESULTS: The results revealed significant associations between SIDE dimensions on the one hand, and degree of internalising, externalising, depression and total symptom scores on the other. However, the effects were non-linear, and especially apparent for the extremes of differential environmental experience within twin pairs. Overall, there was no strong evidence for genetic mediation of associations between nonshared environment and symptoms. CONCLUSIONS: Direct, genetically unconfounded but skewed relationships may exist between nonshared environment on the one hand and behavioural differences on the other, although longitudinal data are necessary to determine the direction of effects.

Adolescent↗