Gebiologeerd

Oratie uitgesproken bij de aanvaarding van het ambt van hoogleraar in de Psychiatrie, i.h.b. Biologische Psychiatrie aan de Universiteit Leiden op vrijdag 6 december 201

The clinical and cost-effectiveness of a self-management intervention for patients with persistent depressive disorder and their partners/caregivers: study protocol of a multicenter pragmatic randomized controlled trial

Background: After regular treatment, patients with persistent depressive disorder (PDD) may remain in specialized psychiatric outpatient care without achieving remission. Lacking other options, these patients often receive long-term, non-protocolized care as usual (CAU) that does not involve the partner/caregiver of the patient. Although the revised depression treatment guidelines suggest focusing on psychiatric rehabilitation and self-management as the next treatment step for PDD, an evidence-based cost-effective self-management protocol for PDD is lacking. This study investigates the "Patient and Partner Education Program for All Chronic Illnesses" (PPEP4All) as a brief self-management protocol that could lead to lower costs, higher quality of life, and less disease burden in PDD patients and their partners/caregivers.Methods: Presented is the rationale and methods of a multicenter pragmatic randomized controlled trial to evaluate the clinical efficacy and cost-effectiveness of PPEP4All for patients with PDD and their partners/caregivers. In accordance with current recommendations, a mixed methods research approach is used with both quantitative and qualitative data. A total of 178 eligible outpatients with PDD and their partners/caregivers are recruited and randomized to either PPEP4All or CAU. Those assigned to PPEP4All receive nine weekly self-management sessions with a trained PPEP4All therapist. Primary and secondary outcome measurements are at 0, 3, 6, and 12 months.Discussion: This project will result in the implementation of a self-management intervention for patients with PDD, meeting an urgent need in mental healthcare. Using PPEP4All can optimize the quality and efficiency of care for both patients with PDD and their partners/caregivers.Stress-related psychiatric disorders across the life spa

Differential Fairness Decisions and Brain Responses After Expressed Emotions of Others in Boys with Autism Spectrum Disorders

Little is known about how emotions expressed by others influence social decisions and associated brain responses in autism spectrum disorders (ASD). We investigated the neural mechanisms underlying fairness decisions in response to explicitly expressed emotions of others in boys with ASD and typically developing (TD) boys. Participants with ASD adjusted their allocation behavior in response to the emotions but reacted less unfair than TD controls in response to happiness. We also found reduced brain responses in the precental gyrus in the ASD versus TD group when receiving happy versus angry reactions and autistic traits were positively associated with activity in the postcentral gyrus. These results provide indications for a role of precentral and postcentral gyrus in social-affective difficulties in ASD

Acute effects of caffeine on threat-selective attention: Moderation by anxiety and EEG theta/beta ratio

BackgroundSpontaneous EEG theta/beta ratio (TBR) probably marks prefrontal cortical (PFC) executive control, and its regulation of attentional threat-bias. Caffeine at moderate doses may strengthen executive control through increased PFC catecholamine action, dependent on basal PFC function.GoalTo test if caffeine affects threat-bias, moderated by baseline frontal TBR and trait-anxiety.MethodsA pictorial emotional Stroop task was used to assess threat-bias in forty female participants in a cross-over, double-blind study after placebo and 200 mg caffeine.ResultsAt baseline and after placebo, comparable relations were observed for negative pictures: high TBR was related to low threat-bias in low trait-anxious people. Caffeine had opposite effects on threat-bias in low trait-anxious people with low and high TBR.ConclusionsThis further supports TBR as a marker of executive control and highlights the importance of taking baseline executive function into consideration when studying effects of caffeine on executive functions.FSW - Self-regulation models for health behavior and psychopathology - ou

Altered neurobiological processing of unintentional social norm violations: a multiplex, multigenerational functional magnetic resonance imaging study on social anxiety endophenotypes

BACKGROUND: Patients with social anxiety disorder (SAD) fear negative evaluation in social situations. Specifically, previous work indicated that social anxiety is associated with increased medial prefrontal cortex activation in response to unintentional social norm (SN) transgressions, accompanied by increased embarrassment ratings for such SN violations. Here, we used data from the multiplex, multigenerational LFLSAD (Leiden Family Lab study on Social Anxiety Disorder), which involved two generations of families genetically enriched for SAD, and investigated whether these neurobiological and behavioral correlates of unintentional SN processing are SAD endophenotypes. Of four endophenotype criteria, we examined two: first, the cosegregation of these characteristics with social anxiety (SA) within families of SAD probands (criterion 4), and second, the heritability of the candidate endophenotypes (criterion 3).METHODS: Participants (n = 110, age range 9.0-61.5 years, eight families) performed the revised Social Norm Processing Task; functional magnetic resonance imaging data and behavioral ratings related to this paradigm were used to examine whether brain activation in response to processing unintentional SN violations and ratings of embarrassment were associated with SA levels. Next, heritability of these measurements was estimated.RESULTS: As expected, voxelwise functional magnetic resonance imaging analyses revealed positive associations between SA levels and brain activation in the medial prefrontal cortex and medial temporal gyrus, superior temporal gyrus, and superior temporal sulcus, and these brain activation levels displayed moderate to moderately high heritability. Furthermore, although SA levels correlated positively with behavioral ratings of embarrassment for SN transgressions, these behavioral characteristics were not heritable.CONCLUSIONS: These results show, for the first time, that brain responses in the medial prefrontal cortex and medial temporal gyrus, superior temporal gyrus, and superior temporal sulcus, related to processing unintentional SN violations, provide a neurobiological candidate endophenotype of SAD.Pathways through Adolescenc

Dissociable relations between amygdala subregional networks and psychopathy trait dimensions in conduct‐disordered juvenile offenders

Psychopathy is a serious psychiatric phenomenon characterized by a pathological constellation of affective (e.g., callous, unemotional), interpersonal (e.g., manipulative, egocentric), and behavioral (e.g., impulsive, irresponsible) personality traits. Though amygdala subregional defects are suggested in psychopathy, the functionality and connectivity of different amygdala subnuclei is typically disregarded in neurocircuit-level analyses of psychopathic personality. Hence, little is known of how amygdala subregional networks may contribute to psychopathy and its underlying trait assemblies in severely antisocial people. We addressed this important issue by uniquely examining the intrinsic functional connectivity of basolateral (BLA) and centromedial (CMA) amygdala networks in relation to affective, interpersonal, and behavioral traits of psychopathy, in conduct-disordered juveniles with a history of serious delinquency (N 5 50, mean age 5 16.83 6 1.32). As predicted, amygdalar connectivity profiles exhibited dissociable relations with different traits of psychopathy. Interpersonal psychopathic traits not only related to increased connectivity of BLA and CMA with a corticostriatal network formation accommodating reward processing, but also predicted stronger CMA connectivity with a network of cortical midline structures supporting sociocognitive processes. In contrast, affective psychopathic traits related to diminished CMA connectivity with a frontolimbic network serving salience processing and affective responding. Finally, behavioral psychopathic traits related to heightened BLA connectivity with a frontoparietal cluster implicated in regulatory executive functioning. We suggest that these traitspecific shifts in amygdalar connectivity could be particularly relevant to the psychopathic phenotype, as they may fuel a self-centered, emotionally cold, and behaviorally disinhibited profile. Hum Brain Mapp 37:4017–4033, 2016

Cortical thickness in Dutch police officers: an examination of factors associated with resilience

Previous neuroimaging studies on resilience have generally compared resilience and psychopathology after stress exposure, which does not allow for conclusions regarding correlates specific to resilience. The aim of the present study was to investigate resilience-specific correlates in cortical thickness and/or cortical surface area and their correlations with psychometric measurements, using a three-group design that included a non-trauma-exposed control group in order to disentangle effects related to resilience from those related to psychopathology. Structural magnetic resonance imaging scans were acquired from 82 Dutch police officers. Participants were categorized into resilient (n = 31; trauma exposure, no psychopathology), vulnerable (n = 32; trauma exposure, psychopathology), and control groups (n = 19; no trauma exposure, no psychopathology). Specific regions of interest (ROIs) were identified based on previous studies that found the rostral and caudal anterior cingulate cortex (ACC) to be implicated in trauma-related psychopathology. Cortical thickness and surface area of the ROIs-the rostral and caudal ACC-and of the whole brain were examined. No significant differences in cortical thickness or surface area were found between the resilient group and other groups in the ROI and whole-brain analyses. Thus, the results of the present study provide no evidence of an association between resilience to traumatic stress and measures of thickness and surface area in cortical regions of the brain in a sample of Dutch police officers.Stress-related psychiatric disorders across the life spa

Exploring the course of adolescent anxiety and depression: associations with white matter tract microstructure

Cross-sectional Diffusion Tensor Imaging (DTI) studies have reported alterations in white matter (WM) microstructure in adolescents with internalizing psychopathology. Yet, longitudinal studies investigating the course of WM microstructure are lacking. This study explored WM alterations and its relation to clinical symptoms over time in adolescents with internalizing disorders. DTI scans were acquired at baseline and after three months in 22 adolescents with clinical depression and comorbid anxiety (INT), and 21 healthy peers (HC) (age: 12-18). Tract-based spatial statistics was used for three voxelwise analyses: i) changes in WM microstructure between and within the INT and HC group; ii) associations between changes in symptom severity and changes in WM microstructure within youths with INT; and iii) associations between baseline WM parameters with changes in symptom severity within youths with INT. Data did not reveal changes in WM microstructure between or within groups over three months' time nor associations between changes in WM microstructure and changes in self-reported symptoms (analyses corrected for age, gender and puberty stage). Lower baseline levels of fractional anisotropy (FA) in the right posterior corona radiata (PCR) and right cingulum were associated with a higher decrease of depressive symptoms within the INT group. Post hoc analysis of additional WM parameters in the significant FA clusters showed that higher levels of baseline mean diffusivity and radial diffusivity in the PCR were associated with a lower decrease in depressive symptoms. Baseline WM microstructure characteristics were associated with a higher decrease in depressive symptoms over time. These findings increase our understanding of neurobiological mechanisms underlying the course of internalizing disorders in adolescents.Pathways through Adolescenc

Salivary markers of stress system activation and social withdrawal in humans

Social withdrawal is an early and common feature of psychiatric disorders. Hypothalamic-pituitary-adrenal (HPA)-axis activation through increased salivary cortisol (sC) and sympathetic activation through increased salivary alpha-amylase (sAA) may play a role. We aimed to study whether the link between increased sC and sAA on the one hand and depression on the other hand is mediated by social withdrawal. In this cross-sectional, observational study, sC and sAA measures were measured in seven saliva samples in 843 participants (231 psychiatric patients and 612 healthy controls). Social withdrawal was assessed through the Brief Symptom Inventory (BSI)-, the Short Form 36-, and the Dutch Dimensional Assessment of Personality Pathology social withdrawal subscales, and analyzed using linear regression and mediation analyses. On average, participants were 44.0 years old (SD = 12.8; 64.1% female). Basal and diurnal sAA were unrelated to any social withdrawal scale and depression. Certain sC measures were positively associated with the BSI social withdrawal subscale (i. e., area under the curve with respect to the increase, beta = 0.082, p = 0.02; evening sC value: beta = 0.110, p = 0.003; and mean sC value: beta = 0.097; p = 0.01). We found limited support for statistical mediation by social withdrawal (measured using a composite social withdrawal score) on the relationship between evening sC and depression. Thus, although we found no support for a role of basal and diurnal sAA in social withdrawal, HPAaxis activation may partly aggravate social withdrawal in depressive disorders.Stress-related psychiatric disorders across the life spa