Ron Mengelers

The effects of FreeSurfer Version, workstation type, and Macintosh Operating System Version on anatomical volume and cortical thickness measurements.

FreeSurfer is a popular software package to measure cortical thickness and volume of neuroanatomical structures. However, little if any is known about measurement reliability across various data processing conditions. Using a set of 30 anatomical T1-weighted 3T MRI scans, we investigated the effects of data processing variables such as FreeSurfer version (v4.3.1, v4.5.0, and v5.0.0), workstation (Macintosh and Hewlett-Packard), and Macintosh operating system version (OSX 10.5 and OSX 10.6). Significant differences were revealed between FreeSurfer version v5.0.0 and the two earlier versions. These differences were on average 8.8±6.6% (range 1.3–64.0%) (volume) and 2.8±1.3% (1.1–7.7%) (cortical thickness). About a factor two smaller differences were detected between Macintosh and Hewlett-Packard workstations and between OSX 10.5 and OSX 10.6. The observed differences are similar in magnitude as effect sizes reported in accuracy evaluations and neurodegenerative studies. The main conclusion is that in the context of an ongoing study, users are discouraged to update to a new major release of either FreeSurfer or operating system or to switch to a different type of workstation without repeating the analysis; results thus give a quantitative support to successive recommendations stated by FreeSurfer developers over the years. Moreover, in view of the large and significant cross-version differences, it is concluded that formal assessment of the accuracy of FreeSurfer is desirable.

Childhood trauma and increased stress sensitivity in psychosis

Lardinois M, Lataster T, Mengelers R, van Os J, Myin‐Germeys I. Childhood trauma and increased stress sensitivity in psychosis.

The BDNF Val(66)Met x 5-HTTLPR x child adversity interaction and depressive symptoms: An attempt at replication.

Kaufman et al. [ 2006 ] reported a higher order interaction effect between specific genetic and environmental factors in a model of depressive symptoms, requiring independent replication. BDNF Val66Met and 5‐HTTLPR genotypes were determined in female participants pertaining to a large ongoing twin study. Participants also filled in questionnaires on childhood adversity and depressive symptoms. Two‐ and three‐way interactions between genetic polymorphisms and early adversity were examined in models of depressive symptoms. BDNF Met allele(s) moderated the effect of early adversity on depressive symptoms (two‐way interaction), and this BDNF Met × childhood adversity interaction in turn was moderated by 5‐HTTLPR genotype (three‐way interaction). However, a main effect of BDNF Met on childhood adversity was also observed, possibly indicating confounding by gene–environment correlation. Higher order interaction effects involving BDNF Val66Met, 5‐HTTLPR and childhood adversity may contribute to the etiology of depressive illness.

Social cognition and neurocognition as independent domains in psychosis

Patients with psychosis display alterations in social cognition as well as in the realm of neurocognition. It is unclear, however, to what degree these cognitive domains represent two separate dimensions of liability or the pleiotropic expression of a single deficit. The purpose of the present study was to investigate (i) to what extent alterations in social cognition represent an independent area of vulnerability to psychosis, separate from neurocognitive deficits and (ii) whether social cognition is one construct or can be divided into several subcomponents. Five social cognition and three neurocognitive tasks were completed by 186 participants with different levels of vulnerability for psychosis: 44 patients with psychotic disorder; 47 subjects at familial risk; 41 subjects at psychometric risk and 54 control subjects. The social cognition tasks covered important basic subcomponents of social cognition, i.e. mentalisation (or theory of mind), data gathering bias (jumping to conclusions), source monitoring and attribution style. Neurocognitive tasks assessed speed of information processing, inhibition, cognitive shifting and strategy-driven retrieval from semantic memory. The results of factor analysis suggested that neurocognition and social cognition are two separate areas of vulnerability in psychosis. Furthermore, the social cognition measures lacked significant overlap, suggesting a multidimensional construct. Cognitive liabilities to psychosis are manifold, and include key processes underlying basic person-environment interactions in daily life, independent of cognition quantified by neuropsychological tests.

Reduced Stress-Sensitivity or Increased Reward Experience: The Psychological Mechanism of Response to Antidepressant Medication

Depression has often been associated with increased negative affect reactivity to stress (Stress-Sensitivity) and reduced capacity to experience pleasure or positive affect (Reward Experience). To date, no studies have prospectively examined changes in Stress-Sensitivity and Reward Experience following antidepressant treatment. The sample included 83 depressed patients and 22 healthy controls. A randomized controlled trial was carried out with patients receiving either imipramine or placebo for 6 weeks. At baseline and 6 weeks, patients and controls participated in an Experience Sampling procedure, prospectively measuring ecologically valid daily life appraisals of activities and mood states. The course of depression was assessed with the Hamilton Depression Rating Scale (HDRS). Multilevel linear regression analyses showed that patients had higher negative and lower positive appraisals of activities than controls. In addition, patients showed increased Stress-Sensitivity (negative affect reactivity to negatively appraised activities). Treatment with imipramine decreased Stress-Sensitivity and increased Reward Experience (positive affect reactivity to positively appraised activities). Changes in Stress-Sensitivity and Reward Experience were in part reducible to changes in the process of activity appraisal itself. However, increase in Reward Experience, but not decrease in Stress-Sensitivity, discriminated between patients who responded and those who did not, independent of changes in the process of activity appraisal itself. Response to treatment in depression may be conditional on restoration of hedonic capacity, the cerebral substrate of which requires further study in relation to antidepressant response. A search for (synergistic) antidepressant therapies specifically targeting ability to experience reward may be warranted.

Prediction of transition from common adolescent bipolar experiences to bipolar disorder: 10-year study

BACKGROUND Although (hypo)manic symptoms are common in adolescence, transition to adult bipolar disorder is infrequent. AIMS To examine whether the risk of transition to bipolar disorder is conditional on the extent of persistence of subthreshold affective phenotypes. METHOD In a 10-year prospective community cohort study of 3021 adolescents and young adults, the association between persistence of affective symptoms over 3 years and the 10-year clinical outcomes of incident DSM-IV (hypo)manic episodes and incident use of mental healthcare was assessed. RESULTS Transition to clinical outcome was associated with persistence of symptoms in a dose-dependent manner. Around 30-40% of clinical outcomes could be traced to prior persistence of affective symptoms. CONCLUSIONS In a substantial proportion of individuals, onset of clinical bipolar disorder may be seen as the poor outcome of a developmentally common and usually transitory non-clinical bipolar phenotype.

Does reactivity to stress cosegregate with subclinical psychosis? A general population twin study

Objective:  This study assessed the relationship between stress reactivity (trait 1) and psychosis (trait 2) across genetically related persons (cross‐twin, cross‐trait design) to examine whether stress reactivity is an uncontaminated and unconfounded familial marker of psychosis risk.

The Catechol-O-Methyl Transferase Val158Met Polymorphism and Experience of Reward in the Flow of Daily Life

Genetic moderation of experience of reward in response to environmental stimuli is relevant for the study of many psychiatric disorders. Experience of reward, however, is difficult to capture, as it involves small fluctuations in affect in response to small events in the flow of daily life. This study examined a momentary assessment reward phenotype in relation to the catechol-O-methyl transferase (COMT) Val158Met polymorphism. A total of 351 participants from a twin study participated in an Experience Sampling Method procedure to collect daily life experiences concerning events, event appraisals, and affect. Reward experience was operationalized, as the effect of event appraisal on positive affect (PA). Associations between COMT Val158Met genotype and event appraisal on the one hand and PA on the other were examined using multilevel random regression analysis. Ability to experience reward increased with the number of ‘Met’ alleles of the subject, and this differential effect of genotype was greater for events that were experienced as more pleasant. The effect size of genotypic moderation was quite large: subjects with the Val/Val genotype generated almost similar amounts of PA from a ‘very pleasant event’ as Met/Met subjects did from a ‘bit pleasant event’. Genetic variation with functional impact on cortical dopamine tone has a strong influence on reward experience in the flow of daily life. Genetic moderation of ecological measures of reward experience is hypothesized to be of major relevance to the development of various behavioral disorders, including depression and addiction.

A community study of psychosocial functioning and weight in young children and adolescents

BACKGROUND Children with either underweight or overweight may be at risk for mental health problems and require mental health service use. The present study investigated the relationship between weight status and psychosocial dysfunctioning in children of two different age groups (5-6 and 13-14 years). METHODS Using height and weight measurements collected during routine medical examinations of all children in a circumscribed geographical region, measures of underweight and overweight were calculated in young children (aged 5-6 years; n=797) and in adolescents (13-14 years; n=614). In addition, parent-reported questionnaires (young children) and adolescent-reported questionnaires (adolescents), including the Strengths and Difficulties Questionnaire (SDQ), provided information on psychopathology subscales including emotional symptoms, conduct problems, hyperactivity-inattention, peer problems and prosocial behaviour. RESULTS Few associations were apparent after controlling for confounding variables. Young children who were underweight (but not severely underweight) less frequently displayed conduct problems, while adolescents who were overweight or obese reported more peer problems and less prosocial behaviour than did children of normal weight. Children who were underweight and children who were overweight did not score higher on any of the other psychopathology scales than did children of normal weight in either age group. CONCLUSION Our findings suggest that the domains of weight problems and psychopathology do not display strong associations. However, there are indications that some areas of psychopathology may be differentially associated with weight problems. Further longitudinal research is warranted.

Susceptibility to Depression Expressed as Alterations in Cortisol Day Curve: A Cross-Twin, Cross-Trait Study

Objective: To examine, using a cross-twin cross-trait design, the hypotheses 1) that the genetic and environmental susceptibility to depression is expressed, in part, as alterations in cortisol day curves and 2) that cortisol abnormalities are not merely the consequence of depressive states or the stressors associated with its onset. Alteration of diurnal secretion of cortisol is a possible endophenotype of depression, as depressed patients show alterations in cortisol dynamics over the day. Methods: Salivary cortisol measurements were obtained in a sample of 279 twin pairs at 10 random times a day for 5 days. A structured clinical interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) axis I mood disorder (SCID) was administered. Using multilevel regression analysis, the moderating influence of a lifetime diagnosis of depression in the co-twin on the association between time of day and cortisol concentrations in the proband twin was examined. Results: Diurnal variation in cortisol in the proband twin differed as a function of lifetime diagnosis of depression in the co-twin. In addition, this moderating effect was significantly stronger for dizygotic than for monozygotic twins. Conclusions: Probands of co-twins with lifetime depression have a different diurnal cortisol profile than those without, suggesting that altered hypothalamic-pituitary-adrenal axis functioning is an indicator of depression susceptibility. DZ = dizygotic; ESM = experience sampling method; FDR = first-degree relative; GR = glucocorticoid receptor; HPA = hypothalamic-pituitary-adrenal; MDD = major depressive disorder; MZ = monozygotic; SCID = structured clinical interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) disorders.