Publications by authors named "Manuel Morrens"

89 Publications

Twenty-Four-Hour Heart Rate Is a Trait but Not State Marker for Depression in a Pilot Randomized Controlled Trial With a Single Infusion of Ketamine.

Front Psychiatry 2021 29;12:696170. Epub 2021 Jul 29.

Department of Neurosciences, Psychiatry Research Group, KU Leuven-University of Leuven, Leuven, Belgium.

Abnormalities of heart rate (HR) and its variability are characteristic of major depressive disorder (MDD). However, circadian rhythm is rarely taken into account when statistically exploring state or trait markers for depression. A 4-day electrocardiogram was recorded for 16 treatment-resistant patients with MDD and 16 age- and sex-matched controls before, and for the patient group only, after a single treatment with the rapid-acting antidepressant ketamine or placebo (clinical trial registration available on https://www.clinicaltrialsregister.eu/ with EUDRACT number 2016-001715-21). Circadian rhythm differences of HR and the root mean square of successive differences (RMSSD) were compared between groups and were explored for classification purposes. Baseline HR/RMSSD were tested as predictors for treatment response, and physiological measures were assessed as state markers. Patients showed higher HR and lower RMSSD alongside marked reductions in HR amplitude and RMSSD variation throughout the day. Excellent classification accuracy was achieved using HR during the night, particularly between 2 and 3 a.m. (90.6%). A positive association between baseline HR and treatment response ( = 0.55, = 0.046) pointed toward better treatment outcome in patients with higher HR. Heart rate also decreased significantly following treatment but was not associated with improved mood after a single infusion of ketamine. Our study had a limited sample size, and patients were treated with concomitant antidepressant medication. Patients with depression show a markedly reduced amplitude for HR and dysregulated RMSSD fluctuation. Higher HR and lower RMSSD in depression remain intact throughout a 24-h day, with the highest classification accuracy during the night. Baseline HR levels show potential for treatment response prediction but did not show potential as state markers in this study. EUDRACT number 2016-001715-21.
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http://dx.doi.org/10.3389/fpsyt.2021.696170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358607PMC
July 2021

Tryptophan Catabolites in Bipolar Disorder: A Meta-Analysis.

Front Immunol 2021 19;12:667179. Epub 2021 May 19.

Faculty of Medicine and Health Sciences, Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Antwerp, Belgium.

Objective: Tryptophan catabolites (TRYCATs) are implicated in the pathophysiology of mood disorders by mediating immune-inflammation and neurodegenerative processes. We performed a meta-analysis of TRYCAT levels in bipolar disorder (BD) patients compared to healthy controls.

Methods: A systematic literature search in seven electronic databases (PubMed, Embase, Web of Science, Cochrane, Emcare, PsycINFO, Academic Search Premier) was conducted on TRYCAT levels in cerebrospinal fluid or peripheral blood according to the PRISMA statement. A minimum of three studies per TRYCAT was required for inclusion. Standardized mean differences (SMD) were computed using random effect models. Subgroup analyses were performed for BD patients in a different mood state (depressed, manic). The methodological quality of the studies was rated using the modified Newcastle-Ottawa Quality assessment Scale.

Results: Twenty-one eligible studies were identified. Peripheral levels of tryptophan (SMD = -0.44; < 0.001), kynurenine (SMD = - 0.3; = 0.001) and kynurenic acid (SMD = -.45; = < 0.001) were lower in BD patients versus healthy controls. In the only three eligible studies investigating TRP in cerebrospinal fluid, tryptophan was not significantly different between BD and healthy controls. The methodological quality of the studies was moderate. Subgroup analyses revealed no significant difference in TRP and KYN values between manic and depressed BD patients, but these results were based on a limited number of studies.

Conclusion: The TRYCAT pathway appears to be downregulated in BD patients. There is a need for more and high-quality studies of peripheral and central TRYCAT levels, preferably using longitudinal designs.
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http://dx.doi.org/10.3389/fimmu.2021.667179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170319PMC
May 2021

The Potential Use of Peripheral Blood Mononuclear Cells as Biomarkers for Treatment Response and Outcome Prediction in Psychiatry: A Systematic Review.

Mol Diagn Ther 2021 05 12;25(3):283-299. Epub 2021 May 12.

Faculty of Medicine and Health Sciences, Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, R3.22, Building R, Campus Drie Eiken, Universiteitsplein 1, 2610, Antwerp, Belgium.

Background: Psychiatric disorders have a major impact on the global burden of disease while therapeutic interventions remain insufficient to adequately treat a large number of patients. Regrettably, the efficacy of several psychopharmacological treatment regimens becomes apparent only after 4-6 weeks, and at this point, a significant number of patients present as non-responsive. As such, many patients go weeks/months without appropriate treatment or symptom management. Adequate biomarkers for treatment success and outcome prediction are thus urgently needed.

Objective: With this systematic review, we provide an overview of the use of peripheral blood mononuclear cells (PBMCs) and their signaling pathways in evaluating and/or predicting the effectiveness of different treatment regimens in the course of psychiatric illnesses. We highlight PBMC characteristics that (i) reflect treatment presence, (ii) allow differentiation of responders from non-responders, and (iii) prove predictive at baseline with regard to treatment outcome for a broad range of psychiatric intervention strategies.

Review Methods: A PubMed database search was performed to extract papers investigating the relation between any type of PBMC characteristic and treatment presence and/or outcome in patients suffering from severe mental illness. Criteria for eligibility were: written in English; psychiatric diagnosis based on DSM-III-R or newer; PBMC isolation via gradient centrifugation; comparison between treated and untreated patients via PBMC features; sample size ≥ n = 5 per experimental group. Papers not researching in vivo treatment effects between patients and healthy controls, non-clinical trials, and non-hypothesis-/data-driven (e.g., -omics designs) approaches were excluded.

Data Synthesis: Twenty-nine original articles were included and qualitatively summarized. Antidepressant and antipsychotic treatments were mostly reflected by intracellular inflammatory markers while intervention with mood stabilizers was evidenced through cell maturation pathways. Lastly, cell viability parameters mirrored predominantly non-pharmacological therapeutic strategies. As for response prediction, PBMC (subtype) counts and telomerase activity seemed most promising for antidepressant treatment outcome determination; full length brain-derived neurotrophic factor (BDNF)/truncated BDNF were shown to be most apt to prognosticate antipsychotic treatment.

Conclusions: We conclude that, although inherent limitations to and heterogeneity in study designs in combination with the scarce number of original studies hamper unambiguous identification, several PBMC characteristics-mostly related to inflammatory pathways and cell viability-indeed show promise towards establishment as clinically relevant treatment biomarkers.
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http://dx.doi.org/10.1007/s40291-021-00516-8DOI Listing
May 2021

Inflammatory Markers May Inform the Effects of Electroconvulsive Therapy on Cognition in Patients with Depression.

Neuropsychobiology 2021 Apr 28:1-9. Epub 2021 Apr 28.

Department of Psychiatry, University Psychiatric Center Duffel, Duffel, Belgium.

Introduction: The neurobiological mechanisms underlying the acute cognitive effects of electroconvulsive therapy (ECT) remain poorly understood. Prior research has shown that proinflammatory cytokines such as IL-6, TNF-α, IL1-β, and IL-10 may interfere with cognitive functioning. Interestingly, immunomodulation is one of the proposed modes of action of ECT. This study investigates whether changes of peripheral levels of IL-6, TNF-α, IL1-β, and IL-10 are related to changes in cognitive functioning following ECT.

Methods: In the week before and 1 week after an acute course of ECT, 62 patients suffering from depression underwent a neuropsychological evaluation to assess their processing speed using the Symbol Digit Substitution Test (SDST), verbal episodic memory using the Hopkins Verbal Learning Test-Revised (HVLT-R), and their retrospective autobiographic memory using the Autobiographical Memory Interview (AMI) with the peripheral inflammatory markers being measured at the same 2 time points.

Results: Patients improved drastically following ECT, while their main performance on both the HVLT-R and AMI declined and their SDST scores remained stable. The levels of IL-6 and IL1-β had both decreased, where the decrease in IL-6 was related to the decrease in HVLT-R scores. Higher baseline IL-10 levels were associated with a more limited decrease of the HVLT-R scores.

Conclusion: Our findings tentatively suggest that the effects of ECT on verbal episodic memory may be related to the treatment's immunomodulatory properties, most notably due to decreased IL-6 levels. Moreover, baseline IL-10 appears to be a potential biomarker to predict the effects of ECT on verbal episodic memory. Whilst compelling, the results of this study should be interpreted with caution as, due to its exploratory nature, no correction for multiple comparisons was made. Further, a replication in larger cohorts is warranted.
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http://dx.doi.org/10.1159/000515931DOI Listing
April 2021

Beyond Pain: A Study on the Variance of Pain Thresholds Within BDSM Interactions in Dominants and Submissives.

J Sex Med 2021 03 26;18(3):556-564. Epub 2021 Feb 26.

Collaborative Antwerp Psychiatric Research Institute (CAPRI), Faculty of Medicine and Health Sciences, Campus Drie Eiken, University of Antwerp, Antwerp, Belgium; University Department of Psychiatry, Campus Duffel, Duffel, Belgium.

Background: BDSM is an acronym describing bondage and discipline, dominance and submission, and sadism and masochism. Afflicting or receiving pain is usually an important part of the BDSM interaction.

Aim: This research will focus on better understanding the aspect of pain within a BDSM interaction.

Methods: Submissive and dominant counterparts of 35 couples were recruited to participate in a BDSM interaction, of which 34 dominants and 33 submissives were included in the analyses. A non-BDSM interested control group (n = 27) was included to control for social interaction, of which 24 were included in the analyses.

Outcomes: This research investigates the differences in (i) baseline pain thresholds, (ii) the impact of a BDSM interaction on those thresholds, and (iii) threshold moderating factors like pain cognition between submissive and dominant BDSM participants and control individuals.

Results: BDSM practitioners have a higher pain threshold overall and a BSDM interaction will result in a temporary elevation of pain thresholds for submissives. Additionally, pain thresholds in dominants will be dependent upon their fear of pain and tendency to catastrophize pain and submissives will experience less fear of pain than the control group.

Clinical Implications: By further enhancing our understanding of the mechanisms behind a BDSM interaction in this way, we aspire to relieve the stigma these practitioners still endure.

Strengths & Limitations: This is one of the first studies of its kind with a large sample size compared to similar research, which makes it a significant contribution to the field. It must be mentioned that there is a possible selection bias because recruitment was only done through the Flemish BDSM community and specifically those who visit clubs. Additionally, pain threshold remains a subjective measurement, which must be taken into account.

Conclusion: This study helps shed further light on the biological processes behind a BDSM interaction through pain threshold measurements. Wuyts E, De Neef N, Coppens V, et al. Beyond Pain: A Study on the Variance of Pain Thresholds Within BDSM Interactions in Dominants and Submissives. J Sex Med 2021;18:556-564.
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http://dx.doi.org/10.1016/j.jsxm.2021.01.001DOI Listing
March 2021

Meta-Analysis on the Effect of Contingency Management for Patients with Both Psychotic Disorders and Substance Use Disorders.

J Clin Med 2021 Feb 6;10(4). Epub 2021 Feb 6.

Faculty of Medicine and Health Sciences, Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, 2610 Antwerp, Belgium.

Background: Substance use disorders (SUD) are highly prevalent among psychotic patients and are associated with poorer clinical and functional outcomes. Effective interventions for this clinical population are scarce and challenging. Contingency management (CM) is one of the most evidence-based treatments for SUD's, however, a meta-analysis of the effect of CM in patients with a dual diagnosis of psychotic disorder and SUD has not been performed.

Methods: We searched PubMed and PsycINFO databases up to December 2020.

Results: Five controlled trials involving 892 patients were included. CM is effective on abstinence rates, measured by the number of self-reported days of using after intervention (95% CI -0.98 to -0.06) and by the number of negative breath or urine samples after intervention (OR 2.13; 95% CI 0.97 to 4.69) and follow-up (OR 1.47; 95% CI 1.04 to 2.08).

Conclusions: Our meta-analysis shows a potential effect of CM on abstinence for patients with SUD and (severe) psychotic disorders, although the number of studies is limited. Additional longitudinal studies are needed to confirm the sustained effectivity of CM and give support for a larger clinical implementation of CM within services targeting these vulnerable co-morbid patients.
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http://dx.doi.org/10.3390/jcm10040616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916027PMC
February 2021

Hospital-wide SARS-CoV-2 antibody screening of staff in a university psychiatric centre in Belgium.

BJPsych Open 2021 Jan 20;7(1):e40. Epub 2021 Jan 20.

Collaborative Antwerp Psychiatric Research Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Belgium; and Department of Psychiatry, University Psychiatric Hospital Campus Duffel, Belgium.

In this first serosurvey among psychiatric healthcare providers, only 3.2% of a sample of 431 staff members of a Belgian University Psychiatric Centre, screened 3-17 June 2020, had SARS-CoV-2 immunoglobulin G antibodies, which is considerably lower compared with both the general population and other healthcare workers in Belgium. The low seroprevalence was unexpected, given the limited availability of personal protective equipment and the high amount of COVID-19 symptoms reported by staff members. Importantly, exposure at home predicted the presence of antibodies, but exposure at work did not. Measures to prevent transmission from staff to patients are warranted in psychiatric facilities.
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http://dx.doi.org/10.1192/bjo.2020.172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844164PMC
January 2021

Images of Recovery: A PhotoVoice Study on Visual Narratives of Personal Recovery in Persons with Serious Mental Illness.

Community Ment Health J 2021 08 23;57(6):1151-1163. Epub 2020 Nov 23.

Department of Psychology, Health & Technology, University of Twente, Enschede, The Netherlands.

Personal recovery has become a guiding paradigm in mental health services. Most research on recovery is based on the exploration of personal stories of service users through verbal methods. As not everyone with psychiatric problems is able to verbally formulate a recovery narrative, the current study assesses personal recovery through PhotoVoice, with emphasis on visualisation, small stories and participation. Two ten-week groups were conducted with 18 participants living with severe mental illnesses. They participated in both the collection and analysis of visual narratives. Across the images produced by participants, four main recovery themes were found : People, Places, Activities and Finding Meaning. Compared to other frameworks, the emphasis participants put on the theme Places adds value to the understanding of recovery processes. Furthermore, participants showed that recovery is about dealing with vulnerabilities as well as aspiring a meaningful life. This study demonstrates that exploring visual narratives is powerful within recovery oriented mental health.
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http://dx.doi.org/10.1007/s10597-020-00746-wDOI Listing
August 2021

Antipsychotic Treatment Failure: A Systematic Review on Risk Factors and Interventions for Treatment Adherence in Psychosis.

Front Neurosci 2020 9;14:531763. Epub 2020 Oct 9.

Collaborative Antwerp Psychiatric Research Institute, University of Antwerp, Antwerp, Belgium.

Antipsychotic medication non-adherence has detrimental effects on patients' clinical outcome. It is unclear which risk factors affect adherence most and which interventions are effective at improving adherence to antipsychotic medication. The aim of this systematic review is to summarize evidence exploring risk factors of non-adherence to antipsychotic treatment and effectiveness of intervention to improve adherence in patients with psychotic spectrum disorders. We conducted a systematic search in PubMed from 1994 to 2019 using a structured search strategy. Studies were quality assessed, and studies reporting on possible risk factors and intervention strategies were synthesized. We reviewed 26 studies on factors related to antipsychotic medication adherence and 17 studies on interventions to improve adherence in patients with psychosis spectrum disorders. Risk factors of non-adherence included younger age, poor illness insight, cannabis abuse, and the presence of severe positive symptoms. Antipsychotic medication adherence was associated with positive attitude toward medication of both patients and their family, family involvement, and illness insight. Somewhat consistent evidence was found for interventions involving family and technology-based interventions and strategies combining depot medication with psychoeducation. However, given the wide range of heterogeneous interventions and methodological limitations, findings must be interpreted with caution. Despite much effort invested in the research area of antipsychotic medication adherence, the heterogeneity in study design and outcome, adding to confounding effects and possible biases, and methodological restraints complicate comparability of the results. Future research in this field should therefore be conducted on patient-tailored interventions, considering risk factors affecting the patient and implementing well-validated, standardized assessment methods. Accordingly, this systematic review seeks to facilitate endeavors improving adherence to antipsychotic treatment by identifying modifiable and non-modifiable risk factors, outlining effective intervention strategies, and proposing recommendations to enhance adherence strategies.
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http://dx.doi.org/10.3389/fnins.2020.531763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584050PMC
October 2020

Improvement of psychomotor retardation after electroconvulsive therapy is related to decreased IL-6 levels.

Prog Neuropsychopharmacol Biol Psychiatry 2021 03 19;105:110146. Epub 2020 Oct 19.

Department of Psychiatry, University Psychiatric Center Duffel, Stationstraat 22, Duffel 2570, Belgium; Department of Psychiatry, Collaborative Antwerp Psychiatric Research Institute (CAPRI), Faculty of Medicine and Health Sciences, University of Antwerp, Universiteitsplein 1, Antwerp 2610, Belgium.

Background: Prior studies suggest that IL-6 may be involved in the pathophysiology of psychomotor symptoms in depression. Electroconvulsive therapy (ECT), as yet the most effective biological treatment of severe depression, is known to improve psychomotor functioning, while recent studies have shown a decrease in the elevated IL-6 levels of depressed patients following ECT.

Objectives: This study investigates whether the improvement in psychomotor functions in patients with depression after ECT is related to changes in IL-6 levels.

Methods: Peripheral IL-6 was quantified and the severity of psychomotor agitation and retardation determined using the CORE assessment of psychomotor symptoms in 62 patients with a (unipolar or bipolar) depressive episode within one week before and within one week after their course of ECT.

Results: IL-6 levels had decreased significantly following ECT and both psychomotor retardation and agitation had improved. The decrease in IL-6 levels was related to the improvement of psychomotor retardation, with post-hoc analysis revealing that higher baseline IL-6 levels positively correlated with higher psychomotor retardation scores.

Conclusion: With this study, we provide the first evidence that the improvement of psychomotor retardation after ECT for depression is related to the immunomodulatory properties of the treatment, most specifically the decrease in IL-6 levels.
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http://dx.doi.org/10.1016/j.pnpbp.2020.110146DOI Listing
March 2021

Blood-based kynurenine pathway alterations in schizophrenia spectrum disorders: A meta-analysis.

Schizophr Res 2020 09 25;223:43-52. Epub 2020 Sep 25.

Faculty of Medicine and Health Sciences, Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Antwerp, Belgium; Scientific Initiative of Neuropsychiatric and Psychopharmacological Studies (SINAPS), University Psychiatric Centre Duffel, Duffel, Belgium.

Introduction: The kynurenine pathway (KP) has been proposed as indirect link between systemic immune responses and clinical symptom development in schizophrenia spectrum disorders (SSD). Empirical evidence for such immune-related KP shifts in SSD has however resulted in divergent findings.

Methods: We conducted a systematic literature search in PubMed. Thirty papers (total number of patients n = 1506; controls: n = 1432) reported on peripheral concentrations of KP metabolites in SSD patients versus controls. Six KP metabolites were included in a meta-analysis, with secondary analysis of covariate and subgroup effects of patients' symptomatic state, age and duration of illness.

Results: Tryptophan (SMD: -0.30; p = .003) and Xanthurenic Acid (SMD: -0.80; p < .001) were significantly decreased in SSD compared to controls, while Quinolinic Acid (SMD: -0.40; p = .08) and Kynurenic Acid (SMD: -0.39; p = .04) were only significantly decreased in patients with acute or highly symptomatic illness. Finally, in relatively older patient cohorts Kynurenine (SMD: -0.31; p = .02) and Kynurenic Acid (SMD: -0.40; p = .002) were found to be decreased.

Conclusion: A partial downregulation of the KP is observed in SSD patients, in particular during acute symptomatic states and in older age, effects that were independent from each other. In contrast, younger and stable or remitted patients display limited to no KP metabolite abnormalities. The current meta-analysis illustrates the dynamic nature of KP abnormalities. It should be noted that all included studies investigated peripheral KP metabolites, which do not necessarily reflect central KP metabolite abnormalities in schizophrenic patients.
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http://dx.doi.org/10.1016/j.schres.2020.09.007DOI Listing
September 2020

The Psychology of Kink: A Cross-Sectional Survey Study Investigating the Roles of Sensation Seeking and Coping Style in BDSM-Related Interests.

Arch Sex Behav 2021 04 15;50(3):1197-1206. Epub 2020 Sep 15.

Collaborative Antwerp Psychiatric Research Institute, Faculty of Medical and Health Sciences, University of Antwerp, Antwerp, Belgium.

Despite the gaining popularity in mainstream media of the phenomenon that is BDSM, empirical research on the motives and underlying psychological mechanisms driving BDSM practitioners is scarce. The current study focused on the potential driving roles of sensation seeking and coping styles in BDSM-related interests and behavior. A cross-sectional survey questionnaire was completed by 256 Dutch-speaking BDSM practitioners (110 men, 135 women, 7 gender fluid, 2 genderless, 1 other not specified), 1 missing (this participant did not answer the question regarding gender, but did answer all other survey items) and a matched control group lacking any BDSM interest recruited from the general Belgian population (N = 300; 135 men, 158 women, 4 gender fluid, 3 genderless). The questionnaire consisted of several items surveying different BDSM identities and interest levels of BDSM-related activities, an adapted version of the Dutch Sensation Seeking Scale, and items querying seven coping styles. Compared to controls, BDSM practitioners reported significantly higher levels of sensation seeking for all dimensions (experience seeking, thrill seeking, and distraction seeking), as well as the use of more active coping skills such as problem solving and taking action. Gender differentiated which specific coping skills were being used with women seeking out more emotional support and comfort and reaching out more for help and advice in both the BDSM and control group, and men taking more action and seeking distraction in leisure. About 40% of the practitioners reported using BDSM itself as a coping strategy. Further research is needed to explore the link between coping and sexuality in general, and to other psychological processes that drive BDSM interests in order to destigmatize and normalize consensual BDSM-related activities within the general population.
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http://dx.doi.org/10.1007/s10508-020-01807-7DOI Listing
April 2021

Movement disorder and sensorimotor abnormalities in schizophrenia and other psychoses - European consensus on assessment and perspectives.

Eur Neuropsychopharmacol 2020 09 23;38:25-39. Epub 2020 Jul 23.

Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Electronic address:

Over the last three decades, movement disorder as well as sensorimotor and psychomotor functioning in schizophrenia (SZ) and other psychoses has gained greater scientific and clinical relevance as an intrinsic component of the disease process of psychotic illness; this extends to early psychosis prediction, early detection of motor side effects of antipsychotic medication, clinical outcome monitoring, treatment of psychomotor syndromes (e.g. catatonia), and identification of new targets for non-invasive brain stimulation. In 2017, a systematic cooperation between working groups interested in movement disorder and sensorimotor/psychomotor functioning in psychoses was initiated across European universities. As a first step, the members of this group would like to introduce and define the theoretical aspects of the sensorimotor domain in SZ and other psychoses. This consensus paper is based on a synthesis of scientific evidence, good clinical practice and expert opinions that were discussed during recent conferences hosted by national and international psychiatric associations. While reviewing and discussing the recent theoretical and experimental work on neural mechanisms and clinical implications of sensorimotor behavior, we here seek to define the key principles and elements of research on movement disorder and sensorimotor/psychomotor functioning in psychotic illness. Finally, the members of this European group anticipate that this consensus paper will stimulate further multimodal and prospective studies on hypo- and hyperkinetic movement disorders and sensorimotor/psychomotor functioning in SZ and other psychotic disorders.
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http://dx.doi.org/10.1016/j.euroneuro.2020.07.003DOI Listing
September 2020

Meta-analysis of the Glial Marker TSPO in Psychosis Revisited: Reconciling Inconclusive Findings of Patient-Control Differences.

Biol Psychiatry 2021 02 15;89(3):e5-e8. Epub 2020 Jul 15.

Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet and Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden. Electronic address:

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http://dx.doi.org/10.1016/j.biopsych.2020.05.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899168PMC
February 2021

What Can Be Learned from Dimensional Perspectives on Psychiatry?

Neuropsychobiology 2020 8;79(4-5):249-250. Epub 2020 Jun 8.

Collaborative Antwerp Psychiatric Research Institute (CAPRI), Faculty of Medicine and Health Sciences, Campus Drie Eiken, University of Antwerp, Antwerp, Belgium.

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http://dx.doi.org/10.1159/000508762DOI Listing
April 2021

Perspective: Solving the Heterogeneity Conundrum of TSPO PET Imaging in Psychosis.

Front Psychiatry 2020 1;11:362. Epub 2020 May 1.

Collaborative Antwerp Psychiatric Research Institute, University of Antwerp, Antwerp, Belgium.

Positron emission tomography using ligands targeting translocator protein 18 kDa (TSPO PET) is an innovative method to visualize and quantify glial inflammatory responses in the central nervous system . Compared to some other neuropsychiatric disorders, findings of TSPO PET in schizophrenia and related psychotic disorders have been considerably more heterogeneous. Two conflicting meta-analyses have been published on the topic within the last year: one asserting evidence for decreased TSPO uptake, while the other observed increased TSPO uptake in a selection of studies. In this paper, we review and discuss five hypotheses which may explain the observed variability of TSPO PET findings in psychotic illness, namely that (1) an inflammatory phenotype is only present in a subgroup of psychosis patients; (2) heterogeneity is caused by interference of antipsychotic medication; (3) interference of other clinical confounders in the study populations (such as age, sex, BMI, smoking, and substance use); or (4) methodological variability between studies (such as choice of tracer and kinetic model, genotyping, study power, and diurnal effects); and (5) the glial responses underlying changes in TSPO expression are themselves heterogeneous and dynamic. Finally, we propose four key recommendations for future research proposals to mitigate these different causes of heterogeneity.
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http://dx.doi.org/10.3389/fpsyt.2020.00362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206714PMC
May 2020

Profiling of the Peripheral Blood Mononuclear Cell Proteome in Schizophrenia and Mood Disorders for the Discovery of Discriminatory Biomarkers: A Proof-of-Concept Study.

Neuropsychobiology 2020 11;79(4-5):324-334. Epub 2020 May 11.

Scientific Initiative for Neuropsychiatric and Psychopharmacological Studies (SINAPS), Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Antwerp, Belgium.

Introduction: Current diagnoses in psychiatry are solely based on the evaluation of clinical presentation by the treating psychiatrist. This results in a high percentage of misdiagnosis and consequential inefficient treatment; especially regarding major depressive disorder (MDD), depression in the context of bipolar disorder (BD-D), bipolar disorder with manic symptoms (BD-M), and psychosis in the context of schizophrenia (SZ). Objective biomarkers allowing for accurate discriminatory diagnostics are therefore urgently needed.

Methods: Peripheral blood mononuclear cell (PBMC) proteomes of patients with MDD (n = 5) , BD-D (n = 3), BD-M (n = 4), and SZ (n = 4), and also of healthy controls (HC; n = 6) were analyzed by state-of-the-art mass spectrometry. Proteins with a differential expression of a >2 standard deviation (SD) expression fold change from that of the HC and between either MDD versus BD-D or BD-M versus SZ were subsequently identified as potential discriminatory biomarkers.

Results: In total, 4,271 individual proteins were retrieved from the HC. Of these, about 2,800 were detected in all patient and HC samples. For objective discrimination between MDD and BD-D, 66 candidate biomarkers were found. In parallel, 72 proteins might harbor a biomarker capacity for differential diagnostics of BD-M and SZ. A single biomarker was contraregulated versus HC in each pair of comparisons.

Discussion: With this work, we provide a register of candidate biomarkers with the potential to objectively discriminate MDD from BD-D, and BD-M from SZ. Although concerning a proof-of-concept study with limited sample size, these data provide a stepping-stone for follow-up research on the validation of the true discriminatory potential and feasibility of clinical implementation of the discovered biomarker candidates.
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http://dx.doi.org/10.1159/000507631DOI Listing
April 2021

Inflammation, Hippocampal Volume, and Therapeutic Outcome following Electroconvulsive Therapy in Depressive Patients: A Pilot Study.

Neuropsychobiology 2020 28;79(3):222-232. Epub 2020 Feb 28.

Department of Psychiatry, Radboud University, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.

Introduction: Electroconvulsive therapy (ECT) influences the concentration of peripheral inflammatory markers, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). In which way this immune effect contributes to the impact of ECT on the central nervous system in depression remains unknown.

Objective: The aim of this study was to examine whether the hippocampal volumetric increase in depressed patients treated with ECT is related to changes in peripheral IL-6 and TNF-α levels.

Methods: IL-6 and TNF-α plasma levels were measured in 62 patients 1 week before and after an acute course of ECT. Hippocampal volumes were analyzed in a magnetic resonance imaging (MRI) subsample of 13 patients at the same time points.

Results: A significant decrease in IL-6 levels was observed in the total sample and a significant increase in hippocampal volume in the MRI subsample. The reduction of peripheral IL-6 correlated with an increase in total hippocampal volume. A more limited decrease of TNF-α correlated with a more limited increase of both the total and left hippocampus volumes.

Conclusion: This pilot study is the first to highlight the link between peripheral immune changes and hippocampal volume increase following ECT. Further research is required to conclude whether ECT indeed exerts its central effect on the brain via changes of peripheral inflammatory markers.
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http://dx.doi.org/10.1159/000506133DOI Listing
January 2021

Between Pleasure and Pain: A Pilot Study on the Biological Mechanisms Associated With BDSM Interactions in Dominants and Submissives.

J Sex Med 2020 04 7;17(4):784-792. Epub 2020 Feb 7.

Collaborative Antwerp Psychiatric Research Institute (CAPRI), Faculty of Medicine and Health Sciences, Campus Drie Eiken, University of Antwerp, Antwerp, Belgium; University Department of Psychiatry, University Psychiatric Centre Duffel, Duffel, Belgium.

Background: BDSM is an abbreviation used to reference the concepts of bondage and discipline, dominance and submission, sadism, and masochism, enacted by power exchanges between consensual partners.

Aim: To shed light upon the rewarding biological mechanisms associated with BDSM interactions.

Methods: A group of 35 BDSM couples (dominant and submissive counterparts) were recruited and tested during a BDSM interaction, with an additional control group of 27 non-BDSM interested people tested in a normal social interaction.

Outcomes: We compared the evolution of the stress and reward hormone levels of cortisol, beta-endorphins, and endocannabinoids (2AG and anandamide) in a group of BDSM practitioners before and after an active BDSM interaction with the levels in control individuals.

Results: We showed that submissives showed increases in cortisol and endocannabinoid levels due to the BDSM interaction, with dominants only showing increased endocannabinoid levels when the BDSM interaction was associated with power play.

Clinical Implications: This study effectively provides a link between behavior that many think of as aberrant on one hand, and biological pleasure experience on the other, in the hope that it may relieve some of the stigma these practitioners still endure.

Strengths & Limitations: It is one of the first and largest studies of its kind, but is still limited in sample size and only represents a specific population of Flemish BDSM practitioners.

Conclusion: Even though this is one of the first studies of its kind, we can conclude that there is a clear indication for increased pleasure in submissives when looking at biological effects of a BDSM interaction, which was related to the increases in experienced stress. Wuyts E, De Neef N, Coppens V, et al. Between Pleasure and Pain: A Pilot Study on the Biological Mechanisms Associated With BDSM Interactions in Dominants and Submissives. J Sex Med 2020;17:784-792.
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http://dx.doi.org/10.1016/j.jsxm.2020.01.001DOI Listing
April 2020

Immune and Neuroendocrine Trait and State Markers in Psychotic Illness: Decreased Kynurenines Marking Psychotic Exacerbations.

Front Immunol 2019 17;10:2971. Epub 2020 Jan 17.

Faculty of Medicine and Health Sciences, Collaborative Antwerp Psychiatric Research Institute, University of Antwerp, Antwerp, Belgium.

Different patterns of immune system upregulation are present in the acute vs. post-treatment states of psychotic illness. We explored the existence of state and trait markers in the peripheral immune system and two immune-associated neuroendocrine pathways (IDO and GTP-CH1 pathway) in a longitudinal sample of psychosis patients. We also evaluated the association of these markers with neuropsychiatric symptomatology. Plasma concentrations of peripheral blood markers were measured in a transdiagnostic group of 49 inpatients with acute psychosis and 52 matched healthy control subjects. Samples were obtained in patients within 48 h after hospital admission for an acute psychotic episode (before initiation of antipsychotics), after 1-2 weeks and again after 8 weeks of treatment. Kynurenine, kynurenic acid (KA), 3-hydroxykynurenine (3-HK), quinolinic acid (QA), phenylalanine, tyrosine, nitrite, and neopterin were measured using HPLC and LC-MS/MS analysis. Concentrations of CRP, CCL2 (MCP1) and cytokines were determined with multiplex immunoassay. PANSS interviews and cognitive tests were performed at baseline and follow-up. Mixed model analyses were used to identify trait and state markers. Patients had significantly higher plasma concentrations of CRP, CCL2, IL1RA, and lower concentrations of KA and KA/Kyn at all time points (F7.5-17.5, all < 0.001). Increased concentrations of IL6, IL8, IL1RA, TNFα, and CCL2 and decreased QA and 3-HK (F8.7-21.0, all < 0.005) were found in the acute psychotic state and normalized after treatment. Low nitrite concentrations at admission rose sharply after initiation of antipsychotic medication (F42.4, < 0.001). PANSS positive scale scores during the acute episode correlated with pro-inflammatory immune markers ( ≥ |0.5|), while negative scale scores correlated inversely with IDO pathway markers ( ≥ |0.4|). Normalization of KA and 3-HK levels between admission and follow-up corresponded to a larger improvement of negative symptoms ( = 0.5, < 0.030) A reverse association was found between relative improvement of SDST scores and decreasing KA levels ( = 0.5, < 0.010). The acute psychotic state is marked by state-specific increases of immune markers and decreases in peripheral IDO pathway markers. Increased CRP, CCL2, and IL1RA, and decreased KA and KA/Kyn are trait markers of psychotic illness.
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http://dx.doi.org/10.3389/fimmu.2019.02971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978914PMC
December 2020

Neuroendocrine and Inflammatory Effects of Childhood Trauma Following Psychosocial and Inflammatory Stress in Women with Remitted Major Depressive Disorder.

Brain Sci 2019 Dec 13;9(12). Epub 2019 Dec 13.

Collaborative Antwerp Psychiatric Research Institute, University of Antwerp, Wilrijk 2610, Belgium.

The dysregulation of the inflammatory and neuroendocrine systems seen in major depressive disorder (MDD) may persist after remission and this is associated with a higher risk of relapse. This vulnerable subgroup may be characterized by a history of childhood trauma. In a single-blind randomized placebo-controlled crossover study, 21 women with remitted recurrent MDD and 18 healthy controls were exposed to psychosocial stress (Trier social stress test) or inflammatory stress (typhoid vaccine), or both, to investigate the effects of childhood trauma on the neuroendocrine and inflammatory responses. Childhood trauma was assessed using the Childhood Trauma Questionnaire and participants were dichotomized into a traumatized and non-traumatized group. Serum adrenocorticotropic hormone (ACTH), cortisol, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were measured at regular intervals after each intervention. The effects of trauma, time, and intervention on these parameters were modeled by fitting linear mixed models. Childhood trauma in itself did not have a main effect on the outcome measurements. However, an interactional effect of trauma with stressor type was found in the remitted MDD group: trauma was associated with higher cortisol levels only after adding immunological to psychosocial stress, and with lower TNF-α levels in response to vaccination. This suggests the existence of a vulnerable trauma-associated MDD endophenotype.
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http://dx.doi.org/10.3390/brainsci9120375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956125PMC
December 2019

The Interplay of Inflammatory Processes and Cognition in Alcohol Use Disorders-A Systematic Review.

Front Psychiatry 2019 12;10:632. Epub 2019 Sep 12.

Faculty of Medicine and Health Sciences, Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Antwerp, Belgium.

Of late, evidence emerges that the pathophysiology of psychiatric diseases and their affiliated symptomatologies are at least partly contributable to inflammatory processes. Also in alcohol use disorders (AUD), this interaction is strongly apparent, with severely immunogenic liver cirrhosis being one of the most critical sequelae of chronic abusive drinking. This somatic immune system activation negatively impacts brain functioning, and additionally, alcohol abuse appears to have a direct detrimental effect on the brain by actively stimulating its immune cells and responses. As cognitive decline majorly contributes to AUD's debility, it is important to know to what extent impairment of cognitive functioning is due to these (neuro-)inflammatory aberrations. We hereby summarize the current existing literature on the interplay between AUD, inflammation, and cognition in a systematic review according to the PRISMA-P guidelines for the systematic review. Although literature on the role of inflammation in alcohol use-related cognitive deficiency remains scarce, current findings indicate that pro-inflammatory processes indeed result in exacerbation of several domains of cognitive deterioration. Interestingly, microglia, the immune cells of the brain, appear to exert initial compensatory neuroprotective functionalities upon acute ethanol exposure while chronic alcohol intake seems to attenuate these responses and overall microglial activity. As these results indicate inflammation to be of importance in cognitive impairment following alcohol consumption and might as such provide alternate therapeutic avenues, a considerable increase in research efforts in this domain is urgently required.
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http://dx.doi.org/10.3389/fpsyt.2019.00632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751886PMC
September 2019

A mood state-specific interaction between kynurenine metabolism and inflammation is present in bipolar disorder.

Bipolar Disord 2020 02 30;22(1):59-69. Epub 2019 Aug 30.

Collaborative Antwerp Psychiatric Research Institute (CAPRI), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.

Objectives: Cytokines are thought to contribute to the pathogenesis of psychiatric symptoms by kynurenine pathway activation. Kynurenine metabolites affect neurotransmission and can cause neurotoxicity. We measured inflammatory markers in patients with bipolar disorder (BD) and studied their relation to kynurenine metabolites and mood.

Methods: Patients with BD suffering from an acute mood episode were assigned to the depressive (n = 35) or (hypo)manic (n = 32) subgroup. Plasma levels of inflammatory markers [cytokines, C-reactive protein] and kynurenine metabolites [tryptophan (TRP), kynurenine (KYN), 3-hydroxykynurenine (3-HK), quinolinic acid (QA), kynurenic acid (KYNA)] were measured on 6 time points during 8 months follow-up. Biological marker levels in patients were compared to controls (n = 35) and correlated to scores on mood scales. Spearman correlations and linear mixed models were used for statistical analysis.

Results: Twenty patients of the manic subgroup, 29 of the depressive subgroup, and 30 controls completed the study. The manic subgroup had a rapid remission of mood symptoms, but in the depressive subgroup subsyndromal symptoms persisted. No differences in inflammation were found between groups. A strong correlation between tumor necrosis factor-α and KYN, KYN/TRP, 3-HK and QA (ρ > 0.60) was specific for the manic group, but only at baseline (during mania). The depressive subgroup had a lower neuroprotective ratio (KYNA/3-HK, P = .0004) and a strong association between interferon-y and kynurenine pathway activation (P < .0001). KYNA was low in both patient groups versus controls throughout the whole follow-up (P = .0008).

Conclusions: Mania and chronic depressive symptoms in BD are accompanied by a strong interaction between inflammation and a potentially neurotoxic kynurenine metabolism.
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http://dx.doi.org/10.1111/bdi.12814DOI Listing
February 2020

Enhanced Molecular Appreciation of Psychiatric Disorders Through High-Dimensionality Data Acquisition and Analytics.

Methods Mol Biol 2019 ;2011:671-723

Receptor Biology Lab, Department of Biomedical Research, University of Antwerp, Antwerp, Belgium.

The initial diagnosis, molecular investigation, treatment, and posttreatment care of major psychiatric disorders (schizophrenia and bipolar depression) are all still significantly hindered by the current inability to define these disorders in an explicit molecular signaling manner. High-dimensionality data analytics, using large datastreams from transcriptomic, proteomic, or metabolomic investigations, will likely advance both the appreciation of the molecular nature of major psychiatric disorders and simultaneously enhance our ability to more efficiently diagnose and treat these debilitating conditions. High-dimensionality data analysis in psychiatric research has been heterogeneous in aims and methods and limited by insufficient sample sizes, poorly defined case definitions, methodological inhomogeneity, and confounding results. All of these issues combine to constrain the conclusions that can be extracted from them. Here, we discuss possibilities for overcoming methodological challenges through the implementation of transcriptomic, proteomic, or metabolomics signatures in psychiatric diagnosis and offer an outlook for future investigations. To fulfill the promise of intelligent high-dimensionality data-based differential diagnosis in mental disease diagnosis and treatment, future research will need large, well-defined cohorts in combination with state-of-the-art technologies.
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http://dx.doi.org/10.1007/978-1-4939-9554-7_39DOI Listing
March 2020

Addiction, Anhedonia, and Comorbid Mood Disorder. A Narrative Review.

Front Psychiatry 2019 22;10:311. Epub 2019 May 22.

Collaborative Antwerp Psychiatric Research Institute (CAPRI), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.

Recently, anhedonia has been recognized as an important Research Domain Criterion (RDoC) by the National Institute of Mental Health. Anhedonia is proposed to play an essential role in the pathogenies of both addictive and mood disorders, and possibly their co-occurrence with a single individual. However, up to now, comprehensive information about anhedonia concerning its underlying neurobiological circuitries, the neurocognitive correlates, and their role in addiction, mood disorder, and comorbidity remains scarce. In this literature review of human studies, we bring together the current state of knowledge with respect to anhedonia in its relationship with disorders in the use of substances (DUS) and the comorbidity with mood disorders. A PubMed search was conducted using the following search terms: (Anhedonia OR Reward Deficiency) AND ((Drug Dependence OR Abuse) OR Alcohol OR Nicotine OR Addiction OR Gambling OR (Internet Gaming)). Thirty-two articles were included in the review. Anhedonia is associated with substance use disorders, and their severity is especially prominent in DUS with comorbid depression. Anhedonia may be both a trait and a state dimension in its relation to DUS and tends to impact DUS treatment outcome negatively.
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http://dx.doi.org/10.3389/fpsyt.2019.00311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538808PMC
May 2019

Aberrant fronto-striatal connectivity and fine motor function in schizophrenia.

Psychiatry Res Neuroimaging 2019 06 30;288:44-50. Epub 2019 Apr 30.

Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Antwerp, Belgium; University Psychiatric Hospital Antwerp, Campus Duffel, Belgium.

Abnormal fine motor function is a frequent finding in schizophrenia and has been linked to structural and functional brain alterations. However, whether fine motor function is related to functional alterations within the motor system remains unclear. The aim of this study was to assess whether abnormalities in resting-state functional connectivity are present in schizophrenia patients and to investigate how these abnormalities may be related to fine motor function. We examined 19 schizophrenia patients and 16 healthy controls using resting-state functional connectivity for 11 bilateral regions of interest. Fine motor function was assessed on a set of copying tasks and the Symbol-Digit-Substitution Test. We found significantly reduced functional connectivity between the left caudate nucleus and bilateral dorsolateral prefrontal cortex (DLPFC) and between the left putamen and bilateral supplementary motor area (SMA) proper in patients compared to controls. Altered connectivity from DLPFC to caudate nucleus was related to fine motor tasks, which are sensitive to psychomotor speed, whereas aberrant connectivity between the SMA proper and putamen was associated to both, fine motor task, which are sensitive to psychomotor speed and to speed of information processing. Our findings emphasize the role of fronto-striatal connections in the pathogenesis of fine motor impairments in schizophrenia.
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http://dx.doi.org/10.1016/j.pscychresns.2019.04.010DOI Listing
June 2019

Do Immune Dysregulations and Oxidative Damage Drive Mood and Psychotic Disorders?

Neuropsychobiology 2020 16;79(4-5):251-254. Epub 2019 Apr 16.

Translational Research Center, University Hospital of Psychiatry, University of Bern, Bern, Switzerland.

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http://dx.doi.org/10.1159/000496622DOI Listing
April 2021

Bondage-Discipline, Dominance-Submission and Sadomasochism (BDSM) From an Integrative Biopsychosocial Perspective: A Systematic Review.

Sex Med 2019 Jun 5;7(2):129-144. Epub 2019 Apr 5.

Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Antwerp, Belgium; University Psychiatric Hospital Antwerp, Campus Duffel, Duffel, Antwerp, Belgium. Electronic address:

Introduction: BDSM (bondage and discipline, dominance and submission, and sadism and masochism) increasingly receives attention from the scientific community. Where earlier research efforts mainly focused on epidemiologic characteristics, psychological and biologic factors driving BDSM preferences have recently gained interest as well.

Aim: To bring together all the existing scientific literature on BDSM from a biopsychosocial perspective.

Methods: Based on the PRISMA guidelines, the current systematic review brings together all the existing literature on BDSM from a biopsychosocial perspective.

Main Outcome Measure: Prevalence rates of BDSM interests were investigated in the literature, as well as the associations between BDSM interests on one hand and personality traits, adverse childhood experiences, education levels, sexual orientations and biological markers on the other.

Results: Biologic factors such as gender identity, sex hormone levels, and the neurologic constitution of the brain's pain and reward systems influence BDSM orientation. With regard to psychological factors, both personality traits (eg, higher levels of openness or extraversion) and the presence of a personality disorder have been associated with a heightened interest in BDSM, although only limited supporting evidence is available. Additionally, sensation-seeking levels and impulsivity seem to contribute, because they presumably guide one's drive to explore new or more-intense kinks. Whereas attachment styles impact couple dynamics, they also influence willingness to explore limits in a BDSM context. Lastly, education levels impact relational and sexual dynamics.

Strengths And Limitations: The limitations of the current review reflect those of the topical scientific literature. Although the number of studies focused on all aspects of BDSM is exponentially growing, most of these are only descriptive, and very few focus on underlying driving processes.

Conclusion: From this biopsychosocial perspective, we offer a dimensional approach while integrating the factors driving the onset and evolution of BDSM interests. De Neef N, Coppens V, Huys W, et al. Bondage-Discipline, Dominance-Submission and Sadomasochism (BDSM) From an Integrative Biopsychosocial Perspective: A Systematic Review. Sex Med 2019;7:129-144.
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http://dx.doi.org/10.1016/j.esxm.2019.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525106PMC
June 2019

Problem behaviours and Major Depressive Disorder in adults with intellectual disability and autism.

Psychiatry Res 2018 12 15;270:769-774. Epub 2018 Oct 15.

CREA (Research and Clinical Centre), San Sebastiano Foundation, Florence Italy. Electronic address:

The high prevalence of Problem Behaviours (PB) in persons with intellectual disability (ID) and Autism Spectrum Disorder (ASD) has been associated by some researchers to a proportionate frequency of Major Depressive Disorder (MDD), which have a different presentation in persons with ID and ASD than in the general population, mostly as behavioural changes. Nevertheless, evidence on this behavioural equivalency is still scarce. The present study aims at evaluating the rate of MDD in persons with ID and ASD presenting PB. Two groups of persons with mild-to-moderate ID and ASD, with and without PB underwent a complex clinical (Diagnostic Manual - Intellectual Disability) and instrumental (Reiss Screen for Maladaptive Behaviour; Mini Psychiatric Assessment Schedule for Adults with Developmental Disabilities). The prevalence of MDD was found to be significantly higher in the group with PB. The severity of depressive symptoms resulted to have a strong correlation with the scores of instrumental assessment of PB. Our findings support previous literature on a high association between PB and MDD in persons with ID and ASD. The level of the equivalency between specific MDD symptoms and different PB deserves further investigations.
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http://dx.doi.org/10.1016/j.psychres.2018.10.039DOI Listing
December 2018

State-associated changes in longitudinal [F]-PBR111 TSPO PET imaging of psychosis patients: Evidence for the accelerated ageing hypothesis?

Brain Behav Immun 2019 03 29;77:46-54. Epub 2018 Nov 29.

Collaborative Antwerp Psychiatric Research Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium; University Psychiatric Hospital Antwerp, Campus Duffel, Duffel, Belgium.

Objective: To determine whether state-associated changes in microglial activity, measured with translocator-protein positron emission tomography (TSPO PET), can be identified in psychosis patients through longitudinal evaluation of their regional tracer uptake over the clinical course from acute psychosis to post-treatment follow-up, and comparison to healthy controls. We also evaluated the relation between tracer uptake, clinical symptoms and peripheral immunological markers.

Method: Second-generation radioligand [F]-PBR111 TSPO PET-CT was used for longitudinal dynamic imaging in 14 male psychosis patients and 17 male age-matched healthy control subjects. Patients were first scanned during an acute psychotic episode followed by a second scan after treatment. Prior genotyping of subjects for the rs6917 polymorphism distinguished high- and mixed-affinity binders. The main outcome was regional volume of distribution (V), representing TSPO binding. Plasma concentrations of CRP, cytokines and kynurenines were measured at each timepoint.

Results: We found a significant three-way interaction between time of scan, age and cohort (cortical grey matter F6.50, p.020). Age-dependent differences in V existed between cohorts during the psychotic state, but not at follow-up. Patients' relative change in V over time correlated with age (cortical grey matter Pearson's r.574). PANSS positive subscale scores correlated with regional V during psychosis (cortical grey matter r.767). Plasma CRP and quinolinic acid were independently associated with lower V.

Conclusions: We identified a differential age-dependent pattern of TSPO binding from psychosis to follow-up in our cohort of male psychosis patients. We recommend future TSPO PET studies in psychosis patients to differentiate between clinical states and consider potential age-related effects.
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http://dx.doi.org/10.1016/j.bbi.2018.11.318DOI Listing
March 2019
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