[Impairments in neurocognitive functions in patients with long COVID: A systematic review]. / Stoornissen in neurocognitieve functies bij patiënten met long COVID: een systematische review.

BACKGROUND: Studies have shown impairments in neurocognitive functions which persist more than 3 months after COVID-19 (long COVID). It remains unclear what these impairments entail, how long they persist and what proportion of the patients exhibit them. AIM: To define the specific neurocognitive profile and to determine the proportion of deficits in at least one cognitive domain in patients with long COVID. METHOD: We conducted a systematic search in PubMed according to PRISMA 2020 guidelines with the following inclusion criteria: peer reviewed publications in which patients were assessed more than 3 months following acute COVID-19 by means of a test battery for different domains of neurocognition. RESULTS: We found a total of 1178 papers, of which 7 cohort studies and 1 case-control study were selected. The proportion of patients having deficits in at least one domain of neurocognition ranged from 23% to 100%. Most frequent impairments were found in attention and speed of information processing, anterograde memory, working memory and executive function. Quality of the included studies was moderate. CONCLUSION: Impairments in neurocognitive functions are highly prevalent among patients with long COVID and include various cognitive domains. We encourage further research to continue studying the complex interaction of COVID-19, neurocognitive impairments and neuropsychiatric syndromes.

High unrecognized SARS-CoV-2 exposure of newly admitted and hospitalized psychiatric patients.

BACKGROUND: Patients with pre-existing mental disorders are at higher risk for SARS-CoV-2 infection and adverse outcomes, and severe mental illness, including mood and psychosis spectrum disorders, is associated with increased mortality risk. Despite their increased risk profile, patients with severe mental illness have been understudied during the pandemic, with limited estimates of exposure in inpatient settings. OBJECTIVE: The aim of this study was to describe the SARS-CoV-2 seroprevalence and antibody titers, and pro-inflammatory cytokine concentrations of newly admitted or hospitalized psychiatric inpatients without known history of COVID-19 infection, using robust quantitative multi-antigen assessments, and compare patients' exposure to that of hospital staff. METHODS: This multi-centric, cross-sectional study compared SARS-CoV-2 seroprevalence and titers of 285 patients (University Psychiatric Centre Duffel [UPCD] N = 194; Assistance-Publique-Hopitaux de Paris [AP-HP] N = 91), and 192 hospital caregivers (UPCD N = 130; AP-HP N = 62) at two large psychiatric care facilities between January 1st and the May 30th 2021. Serum levels of SARS-CoV-2 antibodies against Spike proteins (full length), spike subunit 1 (S1), spike subunit 2 (S2), spike subunit 1 receptor binding domain (S1-RBD) and Nucleocapsid proteins were quantitatively determined using an advanced capillary Western Blot technique. To assess the robustness of the between-group seroprevalence differences, we performed sensitivity analyses with stringent cut-offs for seropositivity. We also assessed peripheral concentrations of IL-6, IL-8 and TNF-a using ELLA assays. Secondary analyses included comparisons of SARS-CoV-2 seroprevalence and titers between patient diagnostic subgroups, and between newly admitted (hospitalization ≤ 7 days) and hospitalized patients (hospitalization > 7 days) and correlations between serological and cytokines. RESULTS: Patients had a significantly higher SARS-CoV-2 seroprevalence (67.85 % [95% CI 62.20-73.02]) than hospital caregivers (27.08% [95% CI 21.29-33.77]), and had significantly higher global SARS-CoV-2 titers (F = 29.40, df = 2, p < 0.0001). Moreover, patients had a 2.51-fold (95% CI 1.95-3.20) higher SARS-CoV-2 exposure risk compared to hospital caregivers (Fisher's exact test, P < 0.0001). No difference was found in SARS-CoV-2 seroprevalence and titers between patient subgroups. Patients could be differentiated most accurately from hospital caregivers by their higher Spike protein titers (OR 136.54 [95% CI 43.08-481.98], P < 0.0001), lower S1 (OR 0.06 [95% CI 0.02-0.15], P < 0.0001) titers and higher IL-6 (OR 3.41 [95% CI 1.73-7.24], P < 0.0001) and TNF-α (OR 34.29 [95% CI 5.00-258.87], P < 0.0001) and lower titers of IL-8 (OR 0.13 [95% CI 0.05-0.30], P < 0.0001). Seropositive patients had significantly higher SARS-COV-2 antibody titers compared to seropositive hospital caregivers (F = 19.53, df = 2, P < 0.0001), while titers were not different in seronegative individuals. Pro-inflammatory cytokine concentrations were not associated with serological status. CONCLUSION: Our work demonstrated a very high unrecognized exposure to SARS-CoV-2 among newly admitted and hospitalized psychiatric inpatients, which is cause for concern in the context of highly robust evidence of adverse outcomes following COVID-19 in psychiatric patients. Attention should be directed toward monitoring and mitigating exposure to infectious agents within psychiatric hospitals.

The relationship between immune and cognitive dysfunction in mood and psychotic disorder: a systematic review and a meta-analysis.

BACKGROUND: In psychotic and mood disorders, immune alterations are hypothesized to underlie cognitive symptoms, as they have been associated with elevated blood levels of inflammatory cytokines, kynurenine metabolites, and markers of microglial activation. The current meta-analysis synthesizes all available clinical evidence on the associations between immunomarkers (IMs) and cognition in these psychiatric illnesses. METHODS: Pubmed, Web of Science, and Psycinfo were searched for peer-reviewed studies on schizophrenia spectrum disorder (SZ), bipolar disorder (BD), or major depressive disorder (MDD) including an association analysis between at least one baseline neuropsychological outcome measure (NP) and one IM (PROSPERO ID:CRD42021278371). Quality assessment was performed using BIOCROSS. Correlation meta-analyses, and random effect models, were conducted in Comprehensive Meta-Analysis version 3 investigating the association between eight cognitive domains and pro-inflammatory and anti-inflammatory indices (PII and AII) as well as individual IM. RESULTS: Seventy-five studies (n = 29,104) revealed global cognitive performance (GCP) to be very weakly associated to PII (r = -0.076; p = 0.003; I2 = 77.4) or AII (r = 0.067; p = 0.334; I2 = 38.0) in the combined patient sample. Very weak associations between blood-based immune markers and global or domain-specific GCP were found, either combined or stratified by diagnostic subgroup (GCP x PII: SZ: r = -0.036, p = 0.370, I2 = 70.4; BD: r = -0.095, p = 0.013, I2 = 44.0; MDD: r = -0.133, p = 0.040, I2 = 83.5). We found evidence of publication bias. DISCUSSION: There is evidence of only a weak association between blood-based immune markers and cognition in mood and psychotic disorders. Significant publication and reporting biases were observed and most likely underlie the inflation of such associations in individual studies.

[Use of depot antipsychotics in Belgium between 1997 and 2016]. / Gebruik van depotantipsychotica in België, 1997-2016.

BACKGROUND: Antipsychotics are considered the cornerstone for the treatment of schizophrenia and are increasingly used in the treatment of mood disorders. A lack of drug adherence is a frequently occurring problem. Depot antipsychotics have been co-developed in order to deal with this problem. AIM: To map the depot antipsychotics prescription behaviour of psychiatrists and general practitioners in outpatient practice in Belgium. METHOD: Analysis of sales data of antipsychotics between 1997 and 2016. Data were supplied by Pharmanet, a database within the National Institute for Health and Disability Insurance (NIHDI). RESULTS: In the period 1997-2004, outpatient sales of depot antipsychotics decreased by 20%. The portion of depot antipsychotics in total antipsychotics sales dropped from 14.9% (1997) to 8.5% (2004). After second-generation depot antipsychotics were introduced from 2004, the sales figures of depot antipsychotics increased by 83%. In 2016, 9.8% of antipsychotic prescriptions was a depot antipsychotic prescription. As of 2012, more second-generation depot antipsychotics (52.2%) were sold than first-generation depot antipsychotics (47.8%). Psychiatrists were quicker to adopt second-generation depot antipsychotics than general practitioners, a trend similar to oral antipsychotics. CONCLUSION: Outpatient sales of depot antipsychotics in Belgium were on the rise after second-generation long-acting preparations were introduced to the market. Recent Scandinavian studies suggest that an increase in prescription of depot antipsychotics may contribute to better clinical outcomes.

Understanding personalized dynamics to inform precision medicine: a dynamic time warp analysis of 255 depressed inpatients.

BACKGROUND: Major depressive disorder (MDD) shows large heterogeneity of symptoms between patients, but within patients, particular symptom clusters may show similar trajectories. While symptom clusters and networks have mostly been studied using cross-sectional designs, temporal dynamics of symptoms within patients may yield information that facilitates personalized medicine. Here, we aim to cluster depressive symptom dynamics through dynamic time warping (DTW) analysis. METHODS: The 17-item Hamilton Rating Scale for Depression (HRSD-17) was administered every 2 weeks for a median of 11 weeks in 255 depressed inpatients. The DTW analysis modeled the temporal dynamics of each pair of individual HRSD-17 items within each patient (i.e., 69,360 calculated "DTW distances"). Subsequently, hierarchical clustering and network models were estimated based on similarities in symptom dynamics both within each patient and at the group level. RESULTS: The sample had a mean age of 51 (SD 15.4), and 64.7% were female. Clusters and networks based on symptom dynamics markedly differed across patients. At the group level, five dynamic symptom clusters emerged, which differed from a previously published cross-sectional network. Patients who showed treatment response or remission had the shortest average DTW distance, indicating denser networks with more synchronous symptom trajectories. CONCLUSIONS: Symptom dynamics over time can be clustered and visualized using DTW. DTW represents a promising new approach for studying symptom dynamics with the potential to facilitate personalized psychiatric care.

A Survey on BDSM-related Activities: BDSM Experience Correlates with Age of First Exposure, Interest Profile, and Role Identity.

BDSM is an omnibus term covering a spectrum of activities within bondage/discipline, dominance/submission, and sadism/masochism relationships. To date, BDSM practitioners experience stigma due to a general unfamiliarity with the practice and marginalization of this type of sexual behavior. Destigmatization occurs partly through knowledge expansion and identification with the stigmatized group. In this study within the Belgian population, we aimed to characterize certain aspects of socioeconomic status and specific BDSM preferences of individuals with differing BDSM experience levels. We show that individuals who perform BDSM in a community setting (BDSM clubs, events. BDSM-CP) are generally higher educated, are significantly younger when first becoming aware of their inclination toward kink-oriented sex, and have a more strict BDSM role identity (Dom vs. Sub) than individuals who engage in BDSM-related activities in a private setting (BDSM-PP). This latter group in turn display a more pronounced Dom/Sub identification than individuals who only fantasize about the practice (BDSM-F). Our data indicate BDSM interest is a sexual preference already manifesting at early age, with role identification profiles becoming gradually more pronounced based on the practitioner's contextual experience.

[Prenatal psychological stress and the development of affective disorders in children: literature review]. / Prenatale psychologische stress­factoren en de ontwikkeling van affectieve stoornissen bij het kind: literatuuroverzicht.

BACKGROUND: The prenatal period appears to be important not only for the development of somatic disorders, but also for the development of psychiatric disorders. Stress and the way people deal with this may play an important role.
AIM: To investigate to what extent prenatal maternal psychological stress is a risk factor for the development of affective disorders in the child. and to demonstrate the importance of systematic screening of the psychological well-being of pregnant mothers and mothers with a pregnancy wish.
METHOD: A systematic literature review via a search in PubMed and Web of Science for articles in English or Dutch.
RESULTS: Prenatal maternal anxiety, depression and subjectively experienced stress are important risk factors in the development of affective disorders in the child, influencing the development of both anxiety disorders and depression.
CONCLUSION: This literature research substantiates the fetal programming hypothesis in which prenatal maternal psychological stress (anxiety, depression and subjectively experienced stress) influences the development of affective disorders in the growing child.

Psychomotor assessment as a tool to differentiate schizophrenia from other psychotic disorders.

GOAL: The aim of this study is to assess to what extent psychomotor assessment can aid the clinician in differentiating between schizophrenia and other psychotic disorders. METHODS: Enrolled subjects were recent in remission patients (n=304), who all met DSM-IV (APA, 2013) criteria for either schizophrenia (Sz; n=117), schizoaffective disorder (SaD; n=36), psychotic disorder not otherwise specified (P-NOS) (n=86), substance/medication-induced psychotic disorder (SIPD; n=33) or major depressive disorder with psychotic features (MDD-p; n=32). The patients were submitted to a psychomotor test battery. RESULTS: Patients with schizophrenia generally perform worse on most tests. Using cluster analysis a combination of three tests, namely the sensory integration subscale of the Neurological Evaluation Scale (NES), a Figure Copying Task (FCT) and the finger tapping test (FTT), came out to be useful to clinically differentiate between schizophrenia and substance-induced psychotic disorder (SIPD) or psychosis not otherwise specified (P-NOS). When comparing schizophrenia only to a group of patients with SIPD, the differentiation potential becomes even greater with a 76.1% chance to correctly diagnose patients with schizophrenia and 75% chance for patients with SIPD. CONCLUSION: A combination of NES, FCT and FTT shows promising results as a clinical tool in daily practice to differentiate schizophrenia from other psychotic disorders. Future prospective studies to confirm these results are necessary.

[The effect of mood-stabilising drugs on cytokine levels in bipolar disorder: a systematic review]. / De impact van stemmingsstabiliserende geneesmiddelen op cytokineconcen-traties bij patiënten met een bipolaire stoornis: een systematisch literatuur-onderzoek1.

ACHTERGROND: Veranderde cytokineconcentraties bij personen met een bipolaire stoornis ten opzichte van controle-personen suggereren een rol van het immuunsysteem in de pathofysiologie van bipolaire stoornis. Farmacotherapie is een belangrijke verstorende factor in klinisch onderzoek naar cytokineconcentraties.
DOEL: Evalueren van cytokineconcentraties bij medicatievrije patiënten met een bipolaire stoornis en van het effect van stemmingsstabiliserende geneesmiddelen op deze concentraties.
METHODE: We doorzochten systematisch PubMed en Embase naar klinische studies die cytokineconcentraties bij medicatievrije patiënten met een bipolaire stoornis beschrijven of het effect van een individueel stemmingsstabiliserend geneesmiddel op deze concentraties evalueren.
RESULTATEN: Van de 564 gescreende artikelen werden er 17 geïncludeerd. Resultaten bij medicatievrije patiënten toonden stemmingsgerelateerde cytokineveranderingen. Hoewel geen data over de kortetermijneffecten van lithium beschikbaar waren, was lithiumgebruik langer dan 2 maanden geassocieerd met normale cytokineconcentraties. Twee studies rapporteerden geen effect van valproïnezuur. We vonden geen studies over carbamazepine, lamotrigine of antipsychotica.
CONCLUSIE: Dit systematisch literatuuroverzicht toont stemmingsgerelateerde cytokineveranderingen bij medicatievrije patiënten met een bipolaire stoornis met de meeste evidentie voor een pro-inflammatoire immuunrespons tijdens manie. Euthymie en langdurig lithiumgebruik zijn geassocieerd met normale cytokineconcentraties. Er is een belangrijke methodologische heterogeniteit en onvoldoende replicatie tussen studies. Longitudinale studies met medicatievrije beginmetingen, gerandomiseerde monotherapeutische behandelprotocollen en nauwkeurige monitoring van stemming zijn noodzakelijk.
BACKGROUND: Alterations of the cytokine level in persons with bipolar disorder - when compared to controls - suggest that the immune system plays a role in the pathophysiology of bipolar disorder. Pharmacotherapy is an important confounding factor in clinical research on cytokine levels.
AIM: To evaluate the evidence on cytokine levels in medication-free bipolar disorder and to study the effects that single mood-stabilising drugs have on these levels.
METHOD: We searched PubMed and Embase systematically in order to single out clinical studies that reported on cytokine levels in medication-free bipolar disorder or that commented on the effects of single mood-stabilising drugs on cytokine levels.
RESULTS: Of the 564 articles that we screened, we detected 17 that were particularly relevant for our investigation. Results for medication-free patients point to mood-related alterations in cytokine levels. Although we found no data relating to short-term effects of lithium, the use of lithium in euthymic populations was associated with normal cytokine levels. Two studies reported no effect of valproate. We did not find any studies relating to carbamazepine, lamotrigine or antipsychotics.
CONCLUSION: Our systematic review of the literature suggests the presence of mood-related changes in cytokine levels in medication-free patients with bipolar disorder, with the most evidence for a proinflammatory response during a manic episode. Euthymia and long-term use of lithium use are associated with normal cytokine levels. There is considerable heterogeneity in the methods used in these studies and too little replication. Future research will have to include longitudinal studies with medication-free baseline measurements. It will also be necessary to draw up single-drug treatment protocols and to conduct intensive mood-related monitoring.

Inhibitory control in euthymic bipolar disorder: Event related potentials during a Go/NoGo task.

OBJECTIVES: Patients with bipolar disorder (BD) are reported to have difficulties with inhibition, even in a euthymic state. However, the literature on cortical activity associated with response inhibition in BD remains ambiguous. This study investigates inhibition in euthymic BD using electrophysiological measures, while controlling for effects of specific medications. METHODS: Twenty patients with BD were compared with eighteen healthy controls on a Go/NoGo task while electroencephalogram was recorded. Behavioral and event-related potential (ERP) measurements were analyzed for the two groups. Medication effects were controlled for in the analysis. RESULTS: Patients with BD had marginally reduced NoGo N2 amplitudes and increased NoGo P3 amplitudes compared with healthy controls when patients using benzodiazepines were excluded from the study. No behavioral differences between the groups were found. CONCLUSIONS: Reduced NoGo N2 amplitudes in BD reflect aberrant conflict detection, an early stage of the inhibition process. In addition, increased NoGo P3 amplitudes in BD despite normal task performance reflect an overactive cortical system during a simple inhibition task. SIGNIFICANCE: Difficulties in early stages of inhibition in BD appear to have been compensated by increased cortical activation. This study extends current knowledge regarding cortical activations relating to inhibition in BD.

[Social dysfunction in schizotypy]. / Sociale disfunctie bij schizotypie.

BACKGROUND: Schizotypy is a personality organisation that is closely related to schizotypal personality disorder and schizophrenia and is characterised by deficits in social functioning. Although the dimensions of social dysfunction have not yet been fully explored certain aspects of social dysfunction are promising predictive markers for schizophrenia. AIM: To describe schizotypy and its influence on social functioning. METHOD: We reviewed the literature systematically using the online databases PubMed and PsycINFO. RESULTS: The disorder known as schizotypy lies at the basis of schizotypal personality disorder. Both disorders are characterised by an increased risk for schizophrenia. The social dysfunctioning seen in schizotypy corresponds to the social dysfunction seen in schizophrenia. Impairments in social cognition are causal factors of this social dysfunction. Both the negative and the positive dimension of schizotypy influence social cognition. CONCLUSION: More focused, objective and interactive research to the various aspects of social functioning in schizotypy is needed in order to discover potential premorbid markers for schizophrenia.

[Social cognition in bipolar disorder]. / Sociale cognitie bij bipolaire stoornis.

BACKGROUND: Bipolar disorder is characterised by disturbed mood regulation. Recently, research has focused on cognitive deficits, including social-cognitive deficits, which have a major impact on daily functioning. AIM: To review the recent literature on social cognition in both the symptomatic and the remission phases in bipolar disorder and to discuss the link between social cognition and psychosocial functioning. METHOD: We reviewed the literature systematically using the most important literature databases and cross-references. RESULTS: Deficits in social-cognitive domains such as emotion recognition and Theory of Mind become apparent during both the symptomatic and remission phases. These deficits are influenced by moderating variables such as medication use, clinical symptoms and neurocognitive deficits. Furthermore, in some recent studies these social-cognitive deficits have been linked to poorer functioning. CONCLUSION: In bipolar disorder, social-cognitive deficits are present in different areas and are to a large extent independent of the mood phase. There is an urgent need for more research into the various cognitive domains and into the effect that these have on daily functioning in all phases of bipolar disorder.

[Ethical advice regarding the relationship between psychiatrists and the pharmaceutical industry]. / Deontologisch advies inzake de omgang van psychiaters met de farmaceutische industrie.

BACKGROUND: The pharmaceutical industry is an important partner in mental health care. AIM: To provide ethical advice that will help psychiatrists build a balanced relationship with the pharmaceutical industry. METHOD: In this article we present the current advisory principles that have been developed by the Flemish Psychiatric Association (Vlaamse Vereniging voor Psychiatrie; VVP). RESULTS: Not only do we give general advice that is relevant for all psychiatrists, but we also give advice that is applicable specifically to the psychiatrist-researcher, teachers and psychiatric trainees. Finally, we explain more fully how the VVP, as an organisation, deals with these issues. CONCLUSION: It is important that the psychiatrists and the pharmaceutical industry deal with each other in a balanced and constructive manner, thereby stimulating progress in the field of psychiatry. For this purpose the VVP has formulated a number of ethical principles which, in our view, define the way in which psychiatrists should deal with the pharmaceutical industry.

[Comparison between the regions of Belgium with regard to the amounts of antipsychotics prescribed during the period 2004-2012: a national survey]. / Voorschrijven van antipsychotica; landelijke vergelijking van de Belgische gewesten, 2004-2012.

BACKGROUND: Antipsychotics are prescribed frequently to treat a wide range of psychiatric and non-psychiatric indications. Over the last few years there has been a marked increase in the use of antipsychotics. However, specific prescribing patterns seem to be determined mainly by regional and national differences. AIM: In this study we compare developments in the sales of antipsychotics in the three Belgian regions (Flanders, Wallonia and Brussels) between 2004 and 2012. METHOD: For our study we used data supplied by Pharmanet regarding the sales of their antipsychotics in Belgium. Pharmanet forms part of the National Institute for Health and Disability Insurance (RIZIV), which is the organisation responsible for collecting information about the prescription behaviour of Belgian doctors. RESULTS: Between 2004 and 2012 the sales of antipsychotics in Belgium increased by 57 %. Nevertheless, the low percentage of prescriptions for long-term use (6.6-8.7 % of the antipsychotics prescribed for a treatment period of six months or longer) suggests that several important groups of patients were being undertreated. Relative to the size of the population of Belgium as a whole, more antipsychotics were sold in Wallonia and Brussels than in Flanders, a trend that remained relatively stable over time, namely over the period 2004 and 2012. The preference for second-generation antipsychotics was more pronounced in Flanders and the shift to second-generation antipsychotics occurred faster in Flanders than in Wallonia and Brussels. CONCLUSION: In Belgium there seems a clear need for a more unified and rational policy with regards to the prescribing and use of psychotropic drugs.

EEG correlates of impaired self-other integration during joint-task performance in schizophrenia.

Deficits in a wide variety of social cognitive processes are well established in schizophrenia. However, research focusing on actual interacting individuals is surprisingly scarce. Problems in low-level processes such as self-other integration may importantly underlie often-reported higher-level deficits. The current study aimed at measuring possible disturbances in self-other integration in schizophrenia using both behavioral and event-related potential (ERP) measures. Sixteen healthy controls and fifteen schizophrenia patients performed a social Simon task in both a joint and an individual setting. Behaviorally, patients showed general slower reaction times, but comparable self-other integration as reflected in the social Simon effect. The ERP results for the healthy controls revealed increased no-go P3 amplitudes in the joint compared with the individual setting. Crucially, patients did not show this increase in no-go P3 amplitude. In line with previous research, the present ERP findings demonstrate that healthy volunteers needed more effort to inhibit their responses in the joint compared with the individual setting. Patients however, showed altered self-other integration when they had to withhold their responses while their co-actor had to act. These outcomes indicate that schizophrenia patients have deficits in low-level processes required for successful joint action.