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01 april 2023, Item does not contain fulltext, Polyunsaturated fatty acids (PUFAs) have important electrochemical properties and have been implicated in the pathophysiology of major depressive disorder (MDD) and its treatment. However, the relation of PUFAs with electroconvulsive therapy (ECT) has never been investigated. Therefore, we aimed to explore the associations between PUFA concentrations and response to ECT in patients with MDD. We included 45 patients with unipolar MDD in a multicentre study. To determine PUFA concentrations, we collected blood samples at the first (T0) and twelfth (T12) ECT-session. We assessed depression severity using the Hamilton Rating Scale for Depression (HAM-D) at T0, T12 and at the end of the ECT-course. ECT-response was defined as 'early response' (at T12), 'late response' (after ECT-course) and 'no' response (after the ECT-course). The PUFA chain length index (CLI), unsaturation index (UI) and peroxidation index (PI) and three individual PUFAs (eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA] and nervonic acid [NA]) were associated with response to ECT using linear mixed models. Results showed a significant higher CLI in 'late responders' compared to 'non responders'. For NA, 'late responders' showed significantly higher concentrations compared to 'early'- and 'non responders'. In conclusion, this study provides the first indication that PUFAs are associated with the efficacy of ECT. This indicates that PUFAs' influence on neuronal electrochemical properties and neurogenesis may affect ECT outcomes. Thereby, PUFAs form a potentially modifiable factor predicting ECT outcomes, that warrants further investigation in other ECT-cohorts.

Item does not contain fulltext, Purpose: Problematic substance use and Substance Use Disorders (SUD) are common in all layers of the population. Several studies suggest higher prevalence rates of problematic substance use among physicians compared to the general population, which is harmful for themselves and potentially impairs quality of care. However, nationwide comparison with a highly educated reference group is lacking. Using nationwide register data, this study compared the prevalence of clinical SUD diagnoses and alcohol consumption patterns between physicians and a highly educated reference population. Methods: A retrospective study was performed using registry data from 2011 up to and including 2019, provided by Statistics Netherlands. From the data, a highly educated reference group was selected and those with an active medical doctor registration were identified as "physicians". Clinical SUD diagnoses were identified by DSM-IV codes in mental healthcare registries. Benchmark analyses were performed, without statistical testing, to compare the prevalence of SUD diagnoses and alcohol consumption patterns between physicians and the reference population. Results: Clinical SUD diagnoses were found among 0.3% of the physicians and 0.5% of the reference population, with higher proportions of sedative use disorder among physician patients. Among drinkers, the prevalence rates of heavy and excessive drinking were respectively 4.0% and 4.3% for physicians and 7.7% and 6.4% for the reference population. Conclusion: Prevalence rates of SUD diagnoses were fairly comparable between physicians and the highly educated reference population, but physicians displayed more favorable alcohol consumption patterns. The use of sedatives by physicians might deserve attention, given the relatively higher prevalence of sedative use disorder among physicians. Overall, we observed relatively low prevalence rates of SUD diagnoses and problematic alcohol use, which may reflect a treatment gap and social desirable an

Contains fulltext : 234352pub.pdf (Publisher’s version ) (Closed access) Contains fulltext : 234352.pdf (Author’s version preprint ) (Open Access) Contains fulltext : 234352appendix.pdf (Author’s version preprint ) (Open Access), Cognitive theories of depression hold that negative contextual triggers (e.g., stressful events) induce more negative and less positive mood, in turn instigating negatively biased memories. However, context-related variability in mood and emotional memory has received insufficient attention, while the dynamic interaction between these factors plays a crucial role in the kindling of new depressive episodes. Experience Sampling Method (ESM) for repeated, daily life measures of context, mood, and autobiographic emotional memory was used in 46 currently depressed, 90 remitted-depressed, and 55 never-depressed individuals. Currently depressed individuals showed strongest negative processing style and never-depressed most positive, with remitted-depressed patients scoring intermediate. The moderated mediation model indicated that context appraisal had a direct effect on the appraisal of the recalled event (i.e., our operationalization of emotional memory), which was mediated by positive (but hardly by negative) mood and was independent of depression status. This mediation strength was relatively similar to the strength of the direct effect of context on memory. Results are in line with cognitive theories of depression. Especially context seems important for emotional memory. The association between context, mood, and memory, however, may be independent of depression status. Yet, the "level" of mood, context, and event appraisal does depend on depression status.

06 september 2023, Contains fulltext : 296242.pdf (Publisher’s version ) (Open Access), Recurrence in major depressive disorder (MDD) is common, but neurobiological models capturing vulnerability for recurrences are scarce. Disturbances in multiple resting-state networks have been linked to MDD, but most approaches focus on stable (vs. dynamic) network characteristics. We investigated how the brain's dynamical repertoire changes after patients transition from remission to recurrence of a new depressive episode. Sixty two drug-free, MDD-patients with ≥2 episodes underwent a baseline resting-state fMRI scan when in remission. Over 30-months follow-up, 11 patients with a recurrence and 17 matched-remitted MDD-patients without a recurrence underwent a second fMRI scan. Recurrent patterns of functional connectivity were characterized by applying Leading Eigenvector Dynamics Analysis (LEiDA). Differences between baseline and follow-up were identified for the 11 non-remitted patients, while data from the 17 matched-remitted patients was used as a validation dataset. After the transition into a depressive state, basal ganglia-anterior cingulate cortex (ACC) and visuo-attentional networks were detected significantly more often, whereas default mode network activity was found to have a longer duration. Additionally, the fMRI signal in the basal ganglia-ACC areas underlying the reward network, were significantly less synchronized with the rest of the brain after recurrence (compared to a state of remission). No significant changes were observed in the matched-remitted patients who were scanned twice while in remission. These findings characterize changes that may be associated with the transition from remission to recurrence and provide initial evidence of altered dynamical exploration of the brain's repertoire of functional networks when a recurrent depressive episode occurs.

Item does not contain fulltext, In line with the Research Domain Criteria (RDoC), we set out to investigate the brain basis of psychopathology within a transdiagnostic, dimensional framework. We performed an integrative structural-functional linked independent component analysis, to study the relationship between brain measures and a broad set of biobehavioral measures in a sample (n = 295) with both mentally healthy participants and patients with diverse non-psychotic psychiatric disorders (i.e. mood, anxiety, addiction, and neurodevelopmental disorders). To get a more complete understanding of the underlying brain mechanisms, we used gray and white matter measures for brain structure and both resting-state and stress scans for brain function. The results emphasize the importance of the executive control network (ECN) during the functional scans, for the understanding of transdiagnostic symptom dimensions. The connectivity between the ECN and the frontoparietal network in the aftermath of stress, was correlated with symptom dimensions across both the cognitive and negative valence domains, and also with various other health related biological and behavioral measures. Finally, we identified a multimodal component that was specifically associated with the diagnosis of autism spectrum disorder (ASD). The involvement of the default mode network, precentral gyrus and thalamus across the different modalities of this component, may reflect the broad functional domains that may be affected in ASD, like theory of mind, motor problems and sensitivity to sensory stimuli respectively. Taken together, the findings from our extentensive, exploratory analyses emphasize the importance of a dimensional and more integrative approach for getting a better understanding of the brain basis of psychopathology.

Item does not contain fulltext, Patients with attention-deficit/hyperactivity disorder (ADHD) often develop early onset substance use disorder (SUD) and show poor treatment outcomes. Both disorders show similar reward-processing alterations, but it is unclear whether these are associated with familial vulnerability to SUD. Our aim was to investigate effects of family history of SUD (FH) on reward processing in individuals with and without ADHD, without substance misuse. Behavioural and functional magnetic resonance imaging (fMRI) data from a modified monetary incentive delay task were compared between participants with and without FH (FH positive [FH+]: n = 76 and FH negative [FH-]: n = 69; 76 with ADHD, aged 16.74 ± 3.14, 82 males), while accounting for continuous ADHD scores. The main analysis showed distinct positive association between ADHD scores and reaction times during neutral versus reward condition. ADHD scores were also positively associated with anticipatory responses of dorsolateral prefrontal cortex, independent of FH. There were no main FH effects on brain activation. Yet, FH+ participants showed distinct neural alterations in ventrolateral prefrontal cortex (VLPFC), dependent on ADHD. This was driven by positive association between ADHD scores and VLPFC activation during reward outcome, only in FH+. Sensitivity analysis with stricter SUD index showed hyperactivation of anterior cingulate cortex for FH+, independent of ADHD, during reward anticipation. There were no FH or ADHD effects on activation of ventral striatum in any analysis. Findings suggest both FH and ADHD effects in circuits of reward and attention/memory during reward processing. Future studies should examine whether these relate to early substance use initiation in ADHD and explore the need for adjusted SUD prevention strategies.

Item does not contain fulltext, Patients with attention-deficit/hyperactivity disorder (ADHD) are often diagnosed with comorbid substance misuse (SM), which is associated with poor treatment efficacy. Although literature indicates similar inhibitory control deficits in both conditions, it is unclear whether SM in ADHD exaggerates pre-existing deficits, with additive or distinct impairments in patients. Our aim was to examine SM effects on inhibitory control in ADHD. Behavioural and functional magnetic resonance imaging (fMRI) data from a stop-signal task were compared across ADHD patients with and without SM (ADHD + SM and ADHD-only, respectively) and controls (n = 33/group; 79 males, mean age 18.02 ± 2.45). To limit substance use disorder (SUD) trait effects, groups were matched for parental SUD. Overall, we found worse performance for ADHD-only and/or ADHD + SM compared with controls but no difference between the ADHD groups. Moreover, the ADHD groups showed decreased frontostriatal and frontoparietal activity during successful and failed stop trials. There were no differences between the ADHD groups in superior frontal nodes, but there was more decreased activation in temporal/parietal nodes in ADHD-only compared with ADHD + SM. During go-trials, ADHD + SM showed decreased activation in inferior frontal nodes compared with ADHD-only and controls. Findings during response inhibition showed deficits in inhibition and attentional processes for ADHD patients with and without SM. Despite no evidence for SM effects during response inhibition, results during go-trials suggest distinct effects on nodes that are associated with several executive functions. Future studies should investigate whether distinct deficits in ADHD + SM relate to poor treatment results and can direct development of distinct ADHD treatment strategies for these patients.

Contains fulltext : 219704.pdf (Publisher’s version ) (Open Access), Background: Classic theories posit that depression is driven by a negative learning bias. Most studies supporting this proposition used small and selected samples, excluding patients with comorbidities. However, comorbidity between psychiatric disorders occurs in up to 70% of the population. Therefore, the generalizability of the negative bias hypothesis to a naturalistic psychiatric sample as well as the specificity of the bias to depression, remain unclear. In the present study, we tested the negative learning bias hypothesis in a large naturalistic sample of psychiatric patients, including depression, anxiety, addiction, attention-deficit/hyperactivity disorder, and/or autism. First, we assessed whether the negative bias hypothesis of depression generalized to a heterogeneous (and hence more naturalistic) depression sample compared with controls. Second, we assessed whether negative bias extends to other psychiatric disorders. Third, we adopted a dimensional approach, by using symptom severity as a way to assess associations across the sample. Methods: We administered a probabilistic reversal learning task to 217 patients and 81 healthy controls. According to the negative bias hypothesis, participants with depression should exhibit enhanced learning and flexibility based on punishment v. reward. We combined analyses of traditional measures with more sensitive computational modeling. Results: In contrast to previous findings, this sample of depressed patients with psychiatric comorbidities did not show a negative learning bias. Conclusions: These results speak against the generalizability of the negative learning bias hypothesis to depressed patients with comorbidities. This study highlights the importance of investigating unselected samples of psychiatric patients, which represent the vast majority of the psychiatric population.

Item does not contain fulltext, Introduction: Substance use disorders (SUDs) among physicians affect their health, quality of life, but potentially also their quality of care. Despite the availability of effective specific Physician Health Programs (PHPs), physicians with SUD often experience barriers when seeking professional help. Therefore, we studied barriers and facilitators when seeking help for SUD among physicians from a multiple perspective approach. Methods: A qualitative design was adopted for 2 sub-studies. First, answers of 2 open-ended questions (about anticipated barriers and facilitators) of an existing questionnaire were analyzed. This questionnaire was filled out by 1,685 general physicians (response rate = 47%). The answers of these open-ended questions were coded inductively. Second, 21 semi-structured interviews (about experienced barriers and facilitators) were performed with physician SUD-patients, significant others, and PHP employees. Themes identified in the first sub-study were used to deductively code the interview transcripts. Results were reported in accordance with the Consolidated Criteria for Reporting Qualitative Research guidelines. Results: Barriers were found at the level of the individual physician (negative feelings and lack of disease awareness), whereas facilitators were found at the level of social relationships (confrontation with SUD and social support) and health services (supportive approach, good accessibility, and positive image of services). The interviews emphasized the importance of nonjudgmental confrontation by social relationships in the process of seeking help for SUD. Conclusion: Physicians with SUD face barriers when seeking help for SUD mostly at the level of the individual physician. Health services and people around physicians with SUD could facilitate the help-seeking process by offering confidential and nonpunitive support. Future studies should explore whether the barriers and facilitators identified in this study also hold for other m

29 maart 2022, Item does not contain fulltext, Background: Anhedonia is apparent in different mental disorders and is suggested to be related to dysfunctions in the reward system and/or affect regulation. It may hence be a common underlying feature associated with symptom severity of mental disorders. Methods: We constructed a cross-sectional graphical Least Absolute Shrinkage and Selection Operator (LASSO) network and a relative importance network to estimate the relationships between anhedonia severity and the severity of symptom clusters of major depressive disorder (MDD), anxiety sensitivity (AS), attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD) in a sample of Dutch adult psychiatric patients (N = 557). Results: Both these networks revealed anhedonia severity and depression symptom severity as central to the network. Results suggest that anhedonia severity may be predictive of the severity of symptom clusters of MDD, AS, ADHD, and ASD. MDD symptom severity may be predictive of AS and ADHD symptom severity. Conclusions: The results suggest that anhedonia may serve as a common underlying transdiagnostic psychopathology feature, predictive of the severity of symptom clusters of depression, AS, ADHD, and ASD. Thus, anhedonia may be associated with the high comorbidity between these symptom clusters and disorders. If our results will be replicated in future studies, it is recommended for clinicians to be more vigilant about screening for anhedonia and/or depression severity in individuals diagnosed with an anxiety disorder, ADHD and/or ASD.

Contains fulltext : 247568.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext, Background: It is widely acknowledged that comorbidity between psychiatric disorders is common. Shared and diverse underpinnings of psychiatric disorders cannot be systematically understood based on symptom-based categories of mental disorders, which map poorly onto pathophysiological mechanisms. In the Measuring Integrated Novel Dimensions in Neurodevelopmental and Stress-Related Mental Disorders (MIND-SET) study, we make use of current concepts of comorbidity that transcend the current diagnostic categories. We test this approach to psychiatric problems in patients with frequently occurring psychiatric disorders and their comorbidities (excluding psychosis). Objective: The main aim of the MIND-SET project is to determine the shared and specific mechanisms of neurodevelopmental and stress-related psychiatric disorders at different observational levels. Methods: This is an observational cross-sectional study. Data from different observational levels as defined in the Research Domain Criteria (genetics, physiology, neuropsychology, system-level neuroimaging, behavior, self-report, and experimental neurocognitive paradigms) are collected over four time points. Included are adult (aged >= 18 years), nonpsychotic, psychiatric patients with a clinical diagnosis of a stress-related disorder (mood disorder, anxiety disorder, or substance use disorder) or a neurodevelopmental disorder (autism spectrum disorder or attention-deficit/hyperactivity disorder). Individuals with no current or past psychiatric diagnosis are included as neurotypical controls. Data collection started in June 2016 with the aim to include a total of 650 patients and 150 neurotypical controls by 2021. The data collection procedure includes online questionnaires and three subsequent sessions with (1) standardized clinical examination, physical examination, and blood sampling; (2) psychological constructs, neuropsychological tests, and biological marker sampling; and (3) neuroimaging measures. Results: We

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Radboud University, 21 juni 2022, Promotores : Schellekens, A.F.A., Buitelaar, J.K., Schene, A.H. Co-promotor : Rooij, D. van, Contains fulltext : 250093.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 247600.pdf (Publisher’s version ) (Open Access), Objectives: Depression and ADHD often co-occur and are both characterized by altered attentional processing. Differences and overlap in the profile of attention to emotional information may help explain the co-occurence. We examined negative attention bias in ADHD as neurocognitive marker for comorbid depression. Methods: Patients with depression (n = 63), ADHD (n = 43), ADHD and depression (n = 25), and non-psychiatric controls (n = 68) were compared on attention allocation toward emotional faces. The following eye-tracking indices were used: gaze duration, number of revisits, and location and duration of first fixation. Results: Controls revisited the happy faces more than the other facial expressions. Both the depression and the comorbid group showed significantly less revisits of the happy faces compared to the ADHD and the control group. Interestingly, after controlling for depressive symptoms, the groups no longer differed on the number of revisits. Conclusion: ADHD patients show a relative positive attention bias, while negative attention bias in ADHD likely indicates (sub)clinical comorbid depression.

Contains fulltext : 252011.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 251161.pdf (Publisher’s version ) (Open Access), Tricyclic antidepressants (TCAs) are frequently prescribed in case of non-response to first-line antidepressants in Major Depressive Disorder (MDD). Treatment of MDD often entails a trial-and-error process of finding a suitable antidepressant and its appropriate dose. Nowadays, a shift is seen towards a more personalized treatment strategy in MDD to increase treatment efficacy. One of these strategies involves the use of biomarkers for the prediction of antidepressant treatment response. We aimed to summarize biomarkers for prediction of TCA specific (i.e. per agent, not for the TCA as a drug class) treatment response in unipolar nonpsychotic MDD. We performed a systematic search in PubMed and MEDLINE. After full-text screening, 36 papers were included. Seven genetic biomarkers were identified for nortriptyline treatment response. For desipramine, we identified two biomarkers; one genetic and one nongenetic. Three nongenetic biomarkers were identified for imipramine. None of these biomarkers were replicated. Quality assessment demonstrated that biomarker studies vary in endpoint definitions and frequently lack power calculations. None of the biomarkers can be confirmed as a predictor for TCA treatment response. Despite the necessity for TCA treatment optimization, biomarker studies reporting drug-specific results for TCAs are limited and adequate replication studies are lacking. Moreover, biomarker studies generally use small sample sizes. To move forward, larger cohorts, pooled data or biomarkers combined with other clinical characteristics should be used to improve predictive power.

Item does not contain fulltext, Background: It is widely acknowledged that comorbidity between psychiatric disorders is common. Shared and diverse underpinnings of psychiatric disorders cannot be systematically understood based on symptom-based categories of mental disorders, which map poorly onto pathophysiological mechanisms. In the Measuring Integrated Novel Dimensions in Neurodevelopmental and Stress-Related Mental Disorders (MIND-SET) study, we make use of current concepts of comorbidity that transcend the current diagnostic categories. We test this approach to psychiatric problems in patients with frequently occurring psychiatric disorders and their comorbidities (excluding psychosis). Objective: The main aim of the MIND-SET project is to determine the shared and specific mechanisms of neurodevelopmental and stress-related psychiatric disorders at different observational levels. Methods: This is an observational cross-sectional study. Data from different observational levels as defined in the Research Domain Criteria (genetics, physiology, neuropsychology, system-level neuroimaging, behavior, self-report, and experimental neurocognitive paradigms) are collected over four time points. Included are adult (aged >= 18 years), nonpsychotic, psychiatric patients with a clinical diagnosis of a stress-related disorder (mood disorder, anxiety disorder, or substance use disorder) or a neurodevelopmental disorder (autism spectrum disorder or attention-deficit/hyperactivity disorder). Individuals with no current or past psychiatric diagnosis are included as neurotypical controls. Data collection started in June 2016 with the aim to include a total of 650 patients and 150 neurotypical controls by 2021. The data collection procedure includes online questionnaires and three subsequent sessions with (1) standardized clinical examination, physical examination, and blood sampling; (2) psychological constructs, neuropsychological tests, and biological marker sampling; and (3) neuroimaging measures. Results: We

Contains fulltext : 252781.pdf (Publisher’s version ) (Open Access), Repetitive negative thinking (RNT) captures an important transdiagnostic factor that predisposes to a maladaptive stress response and contributes to diverse psychiatric disorders. Although RNT can best be seen as a continuous symptom dimension that cuts across boundaries from health to various psychiatric disorders, the neural mechanisms underlying RNT have almost exclusively been studied in health and stress-related disorders, such as depression and anxiety disorders. We set out to study RNT from a large-scale brain network perspective in a diverse population consisting of healthy subjects and patients with a broader range of psychiatric disorders. We studied 46 healthy subjects along with 153 patients with a stress-related and/or neurodevelopmental disorder. We focused on three networks, that are associated with RNT and diverse psychiatric disorders: the salience network, default mode network (DMN) and frontoparietal network (FPN). We investigated the relationship of RNT with both network connectivity strength at rest and with the stress-induced changes in connectivity. Across our whole sample, the level of RNT was positively associated with the connectivity strength of the left FPN at rest, but negatively associated with stress-induced changes in DMN connectivity. These findings may reflect an upregulation of the FPN in an attempt to divert attention away from RNT, while the DMN result may reflect a less flexible adaptation to stress, related to RNT. Additionally, we discuss how our findings fit into the non-invasive neurostimulation literature. Taken together, our results provide initial insight in the neural mechanisms of RNT across the spectrum from health to diverse psychiatric disorders.

Contains fulltext : 252169.pdf (Publisher’s version ) (Open Access), The hippocampus consists of anatomically and functionally distinct subfields that may be differentially involved in the pathophysiology of bipolar disorder (BD). Here we, the Enhancing NeuroImaging Genetics through Meta-Analysis Bipolar Disorder workinggroup, study hippocampal subfield volumetry in BD. T1-weighted magnetic resonance imaging scans from 4,698 individuals (BD = 1,472, healthy controls [HC] = 3,226) from 23 sites worldwide were processed with FreeSurfer. We used linear mixed-effects models and mega-analysis to investigate differences in hippocampal subfield volumes between BD and HC, followed by analyses of clinical characteristics and medication use. BD showed significantly smaller volumes of the whole hippocampus (Cohen's d = -0.20), cornu ammonis (CA)1 (d = -0.18), CA2/3 (d = -0.11), CA4 (d = -0.19), molecular layer (d = -0.21), granule cell layer of dentate gyrus (d = -0.21), hippocampal tail (d = -0.10), subiculum (d = -0.15), presubiculum (d = -0.18), and hippocampal amygdala transition area (d = -0.17) compared to HC. Lithium users did not show volume differences compared to HC, while non-users did. Antipsychotics or antiepileptic use was associated with smaller volumes. In this largest study of hippocampal subfields in BD to date, we show widespread reductions in nine of 12 subfields studied. The associations were modulated by medication use and specifically the lack of differences between lithium users and HC supports a possible protective role of lithium in BD.

Contains fulltext : 252204.pdf (Publisher’s version ) (Open Access), MRI-derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis-driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large-scale meta- and mega-analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large-scale, collaborative studies of mental illness.

Contains fulltext : 284920.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 241605.pdf (Publisher’s version ) (Open Access), With an annual incidence of about 1.5 million new infections, HIV is an ongoing public health concern. Sexual transmission risk behavior (STRB) is a main driver of the HIV epidemic in most Western countries, particularly among specific populations such as men who have sex with men (MSM). This quasi-experimental pilot study examined the effectiveness of a ten-session group intervention, aiming to reduce STRB among a high-risk subpopulation of MSM living with HIV. Self-reported STRB, impulsivity, mental health symptoms, and functional impairment were compared between the intervention group (n = 12) and a control group (n = 16). At baseline, participants in the intervention group had higher levels of STRB, impulsivity, mental health problems, and functional impairment, compared to the control group. A significant time-by-group interaction effect revealed that after the intervention, STRB, impulsivity, and functional impairment reduced in the intervention group to levels comparable to the control group. These findings suggest that a targeted behavioral intervention might be an effective strategy to reduce persistent STRB and related factors in MSM living with HIV. Future studies should confirm these findings in larger samples, using randomized designs.

Item does not contain fulltext, Self-referent negative memory bias is a known risk factor for depression, but recent evidence suggests its function as a transdiagnostic cognitive depressotypic marker. The amygdala's sensitivity for negative information is considered a neurobiological depressotypic marker. However, their relationship remains unknown. We transdiagnostically investigated the association between the amygdala's sensitivity, self-referent negative memory bias and its two components: negative endorsement bias and negative recall bias. Patients (n= 125) with (multimorbid) stress-related and neurodevelopmental psychiatric disorders and healthy controls (n= 78) performed an fMRI task to assess the amygdala's sensitivity for negative information and a task outside the scanner for the biases. Linear regression models assessed their associations. The left amygdala's sensitivity for negative information was significantly positively associated with negative recall bias in patients, but not controls. There were no significant associations with self-referent negative memory bias or negative endorsement bias or between the two depressotypic markers. Thus, the left amygdala's sensitivity for negative information may be considered a neural marker of negative memory bias across psychiatric diagnoses. Further research on the interactons with known determinants such as genetic predisposition is required to fully understand the relationship between the amygdala's sensitivity for negative information and these biases.

Radboud University, 04 november 2022, Promotores : Schellekens, A.F.A., Schene, A.H. Co-promotor : Atsma, F., Contains fulltext : 283414.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext, Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted "brain age" and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen's d = 0.14, 95% CI: 0.08-0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates.

01 december 2021, Item does not contain fulltext, With an annual incidence of about 1.5 million new infections, HIV is an ongoing public health concern. Sexual transmission risk behavior (STRB) is a main driver of the HIV epidemic in most Western countries, particularly among specific populations such as men who have sex with men (MSM). This quasi-experimental pilot study examined the effectiveness of a ten-session group intervention, aiming to reduce STRB among a high-risk subpopulation of MSM living with HIV. Self-reported STRB, impulsivity, mental health symptoms, and functional impairment were compared between the intervention group (n = 12) and a control group (n = 16). At baseline, participants in the intervention group had higher levels of STRB, impulsivity, mental health problems, and functional impairment, compared to the control group. A significant time-by-group interaction effect revealed that after the intervention, STRB, impulsivity, and functional impairment reduced in the intervention group to levels comparable to the control group. These findings suggest that a targeted behavioral intervention might be an effective strategy to reduce persistent STRB and related factors in MSM living with HIV. Future studies should confirm these findings in larger samples, using randomized designs.

Contains fulltext : 221798.pdf (Publisher’s version ) (Open Access), Background: Prior work has proposed that major depressive disorder (MDD) is associated with a specific cognitive bias: Depressed patients seem to learn more from punishment than reward. This learning bias has been associated with blunting of reward-related neural responses in the striatum. A key question is whether negative learning bias is also present in MDD patients with comorbid disorders, and whether this bias is specific to depression, or shared across disorders. Methods: We employed a transdiagnostic approach, assessing a heterogenous group of (non-psychotic) psychiatric patients from the MIND-Set cohort (Radboudumc, the Netherlands), with and without MDD but also suffering from anxiety, ADHD and/or autism (n=66) and healthy controls (n=24). To investigate reward and punishment learning, we employed a deterministic reversal learning task with functional MRI. Results: In contrast to previous studies, MDD patients did not exhibit impaired reward learning or reduced reward-related neural activity anywhere in the brain. Interestingly, we observed consistently increased neural responses in bilateral lateral prefrontal cortex of patients when they received a surprising reward. This increase was not specific to MDD, but generalized to anxiety, ADHD and autism. Critically, increased prefrontal activity to surprising reward scaled with transdiagnostic symptom severity, particularly those associated with concentration and attention, as well as the number of diagnoses; patients with more comorbidities showed a stronger prefrontal response to surprising reward. Conclusions: Prefrontal enhancement may reflect compensatory working-memory recruitment, possibly to counteract the inability to swiftly update reward expectations. This neural mechanism may provide a candidate transdiagnostic index of psychiatric severity.

Contains fulltext : 226697.pdf (publisher's version ) (Closed access), Attention-Deficit/Hyperactivity Disorder (ADHD) and Substance Use Disorder (SUD) often co-occur and are associated with treatment resistance. Both disorders are characterized by similar reward-processing deficits with decreased striatal responses to reward anticipation, though literature is inconsistent. It is unclear whether substance misuse exaggerates reward-processing deficits observed in ADHD. The aim of this study was to examine substance misuse effects on reward-processing in ADHD. Functional MRI data in a Monetary Incentive Delay (MID) task from a multi-site study were compared across ADHD groups with and without substance misuse (ADHD + SM and ADHD-only, respectively) and healthy controls (n = 40/group, 74 males and 46 females, aged 13.7-25.9 years). Substance misuse was defined as misuse of alcohol, nicotine, or drugs. Groups were matched with presence/absence of parental SUD to avoid interference with SUD trait effects. Compared to ADHD-only and controls, ADHD + SM showed hyperactivation in putamen during reward anticipation. Compared to controls, the ADHD groups showed hypoactivation in motor/sensory cortices and hyperactivation in frontal pole and OFC during reward outcome. ADHD + SM also showed hyperactivation in frontal pole during neutral outcome. Moreover, ADHD + SM patients showed higher callous-unemotional (CU) traits that were positively correlated with putamen responses to reward anticipation. Our results show distinct condition-independent neural activation profile for ADHD + SM compared to ADHD-only and controls. Effects of comorbid substance misuse and variability of its prevalence across ADHD studies might have contributed to inconsistencies in ADHD literature. Contrasted with findings for reward-processing in SUD literature, results potentially suggest distinct underlying mechanisms for SUD subgroups with different characteristics, like antisocial/psychopathic traits.

Radboud University, 09 november 2021, Promotores : Tendolkar, I., Schene, A.H., Fernandez, G.S.E. Co-promotor : Eijndhoven, P.F.P. van, Contains fulltext : 238969.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 230860.pdf (publisher's version ) (Open Access), Alexithymia - reflecting deficits in cognitive emotion processing - is highly prevalent in individuals with depressive disorders. Subsequently, mixed evidence for attentional bias is found in these individuals. Alexithymia may be a potential influencing factor for attentional bias in depression. In the current study, 83 currently depressed (CD) and 76 never-depressed (ND) controls completed an eye-tracker task consisting of valenced (non)-social pictures. Alexithymia scores were also included as a moderator as both a continuous and categorical measure (so high vs. low alexithymia). No group difference or moderating effect of alexithymia was found on attentional bias. Thus, alexithymic symptoms, included both dimensionally and categorically, may not influence biased attentional processing in depression compared to ND individuals. Thus, it is important to explore other potential explaining factors for the equivocal results found on biased attentional processing of emotional information in depression.

Radboud University, 11 november 2021, Promotores : Schellekens, A.F.A., Ven, A.J.A.M. van der, Schene, A.H., Contains fulltext : 239216.pdf (Publisher’s version ) (Open Access)

Radboud University, 16 april 2021, Promotores : Schene, A.H., Cools, R. Co-promotores : Vassena, E., Vrijsen, J.N., Contains fulltext : 231206.pdf (publisher's version ) (Open Access)

Contains fulltext : 237248.pdf (Publisher’s version ) (Open Access), Background: Alterations in brain structure in attention-deficit/hyperactivity disorder (ADHD) show considerable overlap with those observed in substance use disorder (SUD). These overlapping structural alterations in ADHD and SUD might be explained by family history (FH-trait) effects of SUD, and/or substance misuse (state) effects. Our aim was to investigate effects of 1) current parental SUD (SUD-FH) and 2) recent substance misuse (SM) on brain structure in a cohort of ADHD patients and controls. Design: Cortical thickness and subcortical volumes were measured using structural MRI. We compared ADHD subjects and controls with or without SUD-FH (aim 1) and additionally explored differences between SUD-FH- and SUD-FH + subjects with one versus two parents with SUD. We also compared ADHD groups with and without SM (ADHD + SM and ADHD-only, respectively) and controls (aim 2). Findings: There was no association between SUD-FH and brain structure. Exploratory analysis on SUD-FH showed decreased IFG thickness (p = 0.032) and nucleus accumbens (NAcc) volume (p = 0.017) in subjects with two versus one SUD parent, regardless of ADHD. ADHD + SM showed decreased inferior frontal gyrus (IFG) thickness compared to controls (pars opercularis p = 0.025, pars orbitalis p = 0.010, pars triangularis p = 0.049), while no difference was found between ADHD-only and either ADHD + SM or controls. Conclusions: Despite negative findings in the primary trait-analysis, exploratory trait-analysis on SUD-FH loading suggested potential SUD trait-effects on IFG thickness and NAcc volume. Substance misuse state effects in ADHD were linked to lower IFG thickness. Future studies should confirm these findings and investigate their clinical relevance, including the functional consequences of decreased IFG thickness.

Contains fulltext : 228501.pdf (publisher's version ) (Open Access), In the past decades, monitoring programs have been developed for healthcare professionals with substance use disorders. We aimed to explore estimates of abstinence and work retention rates after participation in such monitoring programs. A literature search was performed using PubMed, Embase, PsycINFO, and CINAHL. Twenty-nine observational studies reporting on success rates (abstinence and work retention) of monitoring for healthcare professionals with a substance use disorder were included in the meta-analysis. Quality-effects models calculated pooled success rates and corresponding 95%-Confidence Intervals (CI), with subgroup analyses on monitoring elements and patient characteristics. Pooled success rates were 72% for abstinence (95%-CI = 63-80%) and 77% for work retention (95%-CI = 61-90%). Heterogeneity across studies was partly explained by the starting moment of monitoring, showing higher abstinence rates for studies that started monitoring after treatment completion (79%; 95%-CI = 72-85%) compared to studies that started monitoring with treatment initiation (61%; 95%-CI = 50-72%). About three-quarters of healthcare professionals with substance use disorders participating in monitoring programs are abstinent during follow-up and working at the end of the follow-up period. Due to selection and publication bias, no firm conclusions can be drawn about the effectiveness of monitoring for healthcare professionals with SUD.

Radboud University, 16 september 2021, Promotores : Schene, A.H., Vissers, C.T.W.M. Co-promotor : Vrijsen, J.N., Contains fulltext : 236409.pdf (Publisher’s version ) (Open Access), The majority of individuals with depression also have a concomitant diagnosis (comorbidity) of, for instance, an anxiety disorder, ADHD and/or autism spectrum disorder (ASD). This high comorbidity may indicate overlapping underlying cognitive mechanisms. One such possible vulnerability factor can be negative attentional bias: individuals with depression have a stronger preference for negative than neutral or positive information. Studies have demonstrated that the presence of a negative bias in depressed individuals could make them more prone for developing additional depressive episodes and could act as a maintaining factor for depressive symptoms in currently depressed individuals. Recent studies have found evidence for the presence of biased processing of information in other disorders such as emotional disorders and neurodevelopmental disorders as well. Therefore, to study this more in depth, this dissertation investigated whether attentional bias is also present in individuals with other (comorbid) psychiatric disorders besides depression, and if so, biased attention processing could be an overlapping cognitive marker in these disorders. Results demonstrated the presence of negative attentional bias in depression, but not in ASD without depression. Moreover, no evidence was found for associations of negative attentional bias with symptoms of ASD, depression, and anxiety sensitivity. However, evidence has been found that there is an association of symptoms of ADHD and negative attentional bias in individuals with depression and/or anxiety disorder(s). These results suggest, that negative attentional bias is potentially only a cognitive marker of depression. However, and interestingly, this negative attentional bias was also present despite additional comorbidity of for instance ASD and ADHD. For future studies, more uniformity in the way attentional bias is measured as well as assessing (comorbid) psychiatric disorders and/or symptoms is of key importance.

Item does not contain fulltext, Objective: Perseverative cognition (PC) is the repeated or long-term activation of the cognitive representation of psychological stressors and is associated with prolonged stress including somatic and mental consequences. Hence, PC might represent a cognitive process linking mental and somatic pathology, but current research on this link is limited by investigating healthy samples, markers of somatic disease, and single disorders. The present study explored the importance of PC for different mental and somatic disorders in psychiatric patients. Methods: Data from 260 naturalistic psychiatric outpatients were used. Psychiatric diagnoses were based on structured clinical interviews. Somatic diseases were assessed using a well-validated questionnaire and were clustered into (cardio)vascular and immune-/endocrine diseases. PC was operationalized using the perseverative thinking questionnaire (PTQ). Results: Multiple regression complemented with relative importance analyses showed that the PTQ total and subscale scores were associated with the presence of mood disorders, addiction, and anxiety. Unexpectedly, no relatively important associations were found between the PTQ and autism spectrum disorder, attention-deficit/hyperactivity disorder, or somatic disease. Conclusions: Our data complement previous work linking PC to stress-related mental disorders but question its immediate role in neurodevelopmental- and somatic disorders. Targeting PC in the treatment of mood disorders and perhaps also in addiction appears promising.

Radboud University, 30 september 2021, Promotores : Fernandez, G., Schene, A.H. Co-promotor : Kohn, N., Contains fulltext : 236417.pdf (Publisher’s version ) (Open Access)