Impaired Sensorimotor Adaption in Schizophrenia in Comparison to Age-Matched and Elderly Controls.

BACKGROUND: The "cognitive dysmetria hypothesis" of schizophrenia proposes a disrupted communication between the cerebellum and cerebral cortex, resulting in sensorimotor and cognitive symptoms. Sensorimotor adaptation relies strongly on the function of the cerebellum. OBJECTIVES: This study investigated whether sensorimotor adaptation is reduced in schizophrenia compared with age-matched and elderly healthy controls. METHODS: Twenty-nine stably treated patients with schizophrenia, 30 age-matched, and 30 elderly controls were tested in three motor adaptation tasks in which visual movement feedback was unexpectedly altered. In the "rotation adaptation task" the perturbation consisted of a rotation (30° clockwise), in the "gain adaptation task" the extent of the movement feedback was reduced (by a factor of 0.7) and in the "vertical reversal task," up- and downward pen movements were reversed by 180°. RESULTS: Patients with schizophrenia adapted to the perturbations, but their movement times and errors were substantially larger than controls. Unexpectedly, the magnitude of adaptation was significantly smaller in schizophrenia than elderly participants. The impairment already occurred during the first adaptation trials, pointing to a decline in explicit strategy use. Additionally, post-adaptation aftereffects provided strong evidence for impaired implicit adaptation learning. Both negative and positive schizophrenia symptom severities were correlated with indices of the amount of adaptation and its aftereffects. CONCLUSIONS: Both explicit and implicit components of sensorimotor adaptation learning were reduced in patients with schizophrenia, adding to the evidence for a role of the cerebellum in the pathophysiology of schizophrenia. Elderly individuals outperformed schizophrenia patients in the adaptation learning tasks.

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

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.

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

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-ß, 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-ß, 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-ß 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.

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

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.

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

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.

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

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.

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

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.

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

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.

State-associated changes in longitudinal [18F]-PBR111 TSPO PET imaging of psychosis patients: Evidence for the accelerated ageing hypothesis?

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 [18F]-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 (VT), 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 VT existed between cohorts during the psychotic state, but not at follow-up. Patients' relative change in VT over time correlated with age (cortical grey matter Pearson's r.574). PANSS positive subscale scores correlated with regional VT during psychosis (cortical grey matter r.767). Plasma CRP and quinolinic acid were independently associated with lower VT. 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.

Fifty Shades of Belgian Gray: The Prevalence of BDSM-Related Fantasies and Activities in the General Population.

BACKGROUND: Bondage and discipline, dominance and submission, and sadism and masochism (BDSM) is gaining popularity through the mainstream media. Nevertheless, very little is known about the prevalence of BDSM-related fantasies and activities in the general population. AIM: To determine the prevalence of BDSM fantasies and behavioral involvement in four different age groups of the general population in Belgium. METHODS: By use of a cross-sectional survey questionnaire, the level of interest in several BDSM-related activities was investigated in a sample representative of the general Belgian population (N = 1,027). The questionnaire evaluated interest in 54 BDSM activities and 14 fetishes. Self-identification as BDSM practitioner, situational context of BDSM practice, age at awareness of these interests, and transparency to others were queried. OUTCOMES: Individual item scores and summary scores on four BDSM categories were included in the analyses. RESULTS: A high interest in BDSM-related activities in the general population was found because 46.8% of the total sample had ever performed at least one BDSM-related activity and an additional 22% indicated having (had) fantasies about it. Interestingly, 12.5% of the total population indicated performing at least one BDSM-related activity on a regular basis. When asked whether they saw themselves as being interested in BDSM, 26% stated this to be the case and 7.6% self-identified as BDSM practitioners. Interests in dominant and submissive activities were comparable and, remarkably, were highly intercorrelated. BDSM and fetish interests were significantly higher in men than in women. The older group (48-65 years) had significantly lower BDSM scores compared with their younger peers. Of participants with a BDSM interest, 61.4% became aware of it before 25 years of age. CLINICAL IMPLICATIONS: There is a high level of interest in BDSM in the general population, which strongly argues against stigmatization and pathologic characterization of these interests. STRENGTHS AND LIMITATIONS: This is the first thorough study concerning prevalence of interest in and fantasies about a wide range of BDSM-related activities in the general population worldwide. Although our findings tend to argue against it, we cannot completely rule out participation bias introduced by non-interest in the non-completers. In addition, some topics might have been subject to interpretation by the respondents. CONCLUSION: Interest in BDSM is present in most of the general population. Further research is needed to destigmatize it by confirming BDSM as a leisurely preference rather than a psychiatric affliction. Holvoet L, Huys W, Coppens V, et al. Fifty Shades of Belgian Gray: The Prevalence of BDSM-Related Fantasies and Activities in the General Population. J Sex Med 2017;14:1152-1159.

Implicit motor sequence learning in schizophrenia and in old age: reduced performance only in the third session.

Although there still is conflicting evidence whether schizophrenia is a neurodegenerative disease, cognitive changes in schizophrenia resemble those observed during normal aging. In contrast to extensively demonstrated deficits in explicit learning, it remains unclear whether implicit sequence learning is impaired in schizophrenia and normal aging. Implicit sequence learning was investigated using a computerized drawing task, the 'implicit pattern learning task (IPLT)' in 30 stable patients with schizophrenia, 30 age-matched controls and 30 elderly subjects on two consecutive days and after 1 week (sessions 1, 2 and 3). Fixed sequence trials were intermixed with random trials, and sequence learning was assessed by subtraction of the response time in fixed sequence trials from random trials. Separate analyses of response times and movement accuracy (i.e., directional errors) were performed. Explicit sequence knowledge was assessed using three different awareness tasks. All groups learned equally during sessions 1 and 2. In session 3, control subjects showed significantly larger learning scores than patients with schizophrenia (p = .012) and elderly subjects (p = .021). This group difference is mainly expressed in movement time and directional errors. Patients with schizophrenia demonstrated less subjective sequence awareness, and both patients with schizophrenia and elderly subjects had less explicit sequence recall. Explicit recall was positively correlated with task performance in all groups. After a short 24 h interval, all subjects showed similar improvements in implicit sequence learning. However, no benefit of prior task exposure 1 week later was observed in patients with schizophrenia and elderly subjects compared to controls. As patients with schizophrenia and elderly both display less explicit sequence recall, the control group superiority after 1 week could be explained by an explicit learning component. The few patients with schizophrenia and elderly subjects who had some sequence recall could possibly utilize this explicit knowledge to improve their task performance but did this by distinct mechanisms.

IL-6-dependent proliferation of alpha cells in mice with partial pancreatic-duct ligation.

AIMS/HYPOTHESIS: IL-6 was recently shown to control alpha cell expansion. As beta cells expand following partial pancreatic-duct ligation (PDL) in adult mice, we investigated whether PDL also causes alpha cells to expand and whether IL-6 signalling is involved. As alpha cells can reprogramme to beta cells in a number of beta cell (re)generation models, we examined whether this phenomenon also exists in PDL pancreas. METHODS: Total alpha cell volume, alpha cell size and total glucagon content were evaluated in equivalent portions of PDL- and sham-operated mouse pancreases. Proliferation of glucagon(+) cells was assessed by expression of the proliferation marker Ki67. Inter-conversions between alpha and beta cells were monitored in transgenic mice with conditional cell-type-specific labelling. The role of IL-6 in regulating alpha cell proliferation was evaluated by in situ delivery of an IL-6-inactivating antibody. RESULTS: In response to PDL surgery, alpha cell volume in the ligated tissue was increased threefold, glucagon content fivefold and alpha cell size by 10%. Activation of alpha cell proliferation in PDL pancreas required IL-6 signalling. A minor fraction of alpha cells derived from beta cells, whereas no evidence for alpha to beta cell conversion was obtained. CONCLUSIONS/INTERPRETATION: In PDL-injured adult mouse pancreas, new alpha cells are generated mainly by IL-6-dependent self-duplication and seldom by reprogramming of beta cells.

Short-term overexpression of VEGF-A in mouse beta cells indirectly stimulates their proliferation and protects against diabetes.

AIMS/HYPOTHESIS: Vascular endothelial growth factor (VEGF) has been recognised by loss-of-function experiments as a pleiotropic factor with importance in embryonic pancreas development and postnatal beta cell function. Chronic, nonconditional overexpression of VEGF-A has a deleterious effect on beta cell development and function. We report, for the first time, a conditional gain-of-function study to evaluate the effect of transient VEGF-A overexpression by adult pancreatic beta cells on islet vasculature and beta cell proliferation and survival, under both normal physiological and injury conditions. METHODS: In a transgenicmouse strain, overexpressing VEGF-A in a doxycycline-inducible and beta cell-specific manner, we evaluated the ability of VEGF-A to affect islet vessel density, beta cell proliferation and protection of the adult beta cell mass from toxin-induced injury. RESULTS: Short-term VEGF-A overexpression resulted in islet hypervascularisation, increased beta cell proliferation and protection from toxin-mediated beta cell death, and thereby prevented the development of hyperglycaemia. Extended overexpression of VEGF-A led to impaired glucose tolerance, elevated fasting glycaemia and a decreased beta cell mass. CONCLUSIONS/INTERPRETATION: Overexpression of VEGF-A in beta cells time-dependently affects glycometabolic control and beta cell protection and proliferation. These data nourish further studies to examine the role of controlled VEGF delivery in (pre)clinical applications aimed at protecting and/or restoring the injured beta cell mass.

Continuous theta burst stimulation for bipolar depression: A multicenter, double-blind randomized controlled study exploring treatment efficacy and predictive potential of kynurenine metabolites.

BACKGROUND: While theta burst stimulation (TBS) shows promise in Major Depressive Disorder (MDD), its effectiveness in bipolar depression (BD-D) remains uncertain. Optimizing treatment parameters is crucial in the pursuit of rapid symptom relief. Moreover, aligning with personalized treatment strategies and increased interest in immunopsychiatry, biomarker-based stratification of patients most likely to benefit from TBS might improve remission rates. We investigated treatment effectiveness of continuous TBS (cTBS) compared to sham in BD-D, and assessed the capacity of plasma kynurenine pathway metabolites to predict treatment outcome. METHODS: Thirty-seven patients with BD-D underwent accelerated active or sham cTBS treatment in a multicenter, double-blind, randomized controlled trial. Depressive symptoms were measured with the 17-item Hamilton Depression Rating Scale (HDRS-17) before treatment (T0), 3-4 days posttreatment (T1) and 10-11 days posttreatment (T2). Plasma tryptophan, kynurenine, kynurenic acid and quinolinic acid concentrations were quantified with ELISA. Linear mixed models were used for statistical analyses. RESULTS: Although the total sample showed depressive symptom improvement, active cTBS did not demonstrate greater symptom alleviation compared to sham. However, higher baseline quinolinic acid significantly predicted symptom improvement in the active treatment group, not in sham-stimulated patients. LIMITATIONS: The modest sample size limited the power to detect significant differences with regard to treatment effect. Also, the follow-up period was 10-11 days, whereas similar studies usually follow up for at least one month. CONCLUSION: More research is required to optimize cTBS for BD-D and explore the involvement of quinolinic acid in treatment outcome.

Anti-spike antibody responses to SARS-CoV-2 mRNA vaccines in people with schizophrenia and schizoaffective disorder.

Importance: Individuals with schizophrenia are at higher risk for severe COVID-19 illness and severe breakthrough infection following vaccination. It is unclear whether immune response to vaccination differs in this population. Objective: To assess whether anti-SARS-CoV-2 spike antibody titers after vaccination differ in people with a diagnosis of schizophrenia or schizoaffective disorder (SZ) compared to controls without a psychiatric disorder. Design: This cohort study assessed antibody response following the first and second dose of mRNA vaccines at longitudinal timepoints, up to 7 weeks following the first dose of vaccine. Setting: A multi-center study including psychiatric healthcare settings in the United States and Europe. Participants: 205 adults with no history of COVID-19 infection, including 106 individuals with SZ and 99 controls without a psychiatric disorder, who received their first dose of SARS-CoV-2 mRNA vaccine between December 20, 2020 and May 27, 2021. Main outcomes and measures: Mean SARS-CoV-2 anti-Spike IgG antibody levels within 7 weeks after the first dose of vaccination. Results: A total of 205 individuals (mean [SD] age, 44.7 [12.0] years; 90 [43.9%] male) were included, of which 106 (51.7%) were diagnosed with SZ. SZ was associated with lower mean log antibody levels (-0.15; 95% CI, -0.27 to -0.03, P = 0.016) after adjusting for age, sex, body mass index, smoking, days since vaccination, and vaccine manufacturer. In secondary analyses of dose-specific responses, SZ was associated with a lower mean log antibody level after the second dose of vaccine (-0.23; 95% CI -0.39 to -0.06, P = 0.006), but not the first dose of vaccine (0.00; 95% CI -0.18- 0.19, P = 0.96). Conclusions and Relevance: In this cohort study of individuals with SZ and a control group without psychiatric disorders, SZ was associated with lower SARS-CoV-2 anti-spike antibody levels following 2 doses of SARS-CoV-2 mRNA vaccination. This highlights the need for further studies assessing vaccine immunogenicity in individuals with schizophrenia.

BDSM in North America, Europe, and Oceania: A Large-Scale International Survey Gauging BDSM Interests and Activities.

BDSM bondage and discipline, dominance and submission, and sadism and masochism is a widespread and highly prevalent yet stigmatized practice of intimacy and sexuality. In recent years, international interest in BDSM research has grown, mainly resulting in prevalence studies in various countries. To date, however, no research has investigated international and intercontinental differences in the nature of BDSM interests and fantasies, BDSM roles and practicing contexts among BDSM practitioners. In order to explore international discrepancies in BDSM identity, fantasies, and activities among self-identified BDSM practitioners, a group of FetLife (a social network website for BDSM and kink interested individuals) members (N = 1,112) originating from North America (n = 458), Europe (n = 566), Oceania (n = 46), and Other (n = 42) completed the survey. Europeans reported an earlier age of onset of fantasizing about BDSM than did North Americans. More North Americans indicated practicing BDSM in a public context than did Europeans and Oceanians. These differences could in part be explained by different cultural backgrounds, higher levels of religiosity, and current stigmas toward non-traditional sexual interests. Future research should focus on clarifying whether cultural mechanisms underlie these dissimilarities.

Kynurenine pathway abnormalities are state-specific but not diagnosis-specific in schizophrenia and bipolar disorder.

Schizophrenia (SCZ) and bipolar disorder (BD) are associated with immunological dysfunctions that have been hypothesized to lead to clinical symptomatology in particular through kynurenine pathway abnormalities. The aim of this study was thus to investigate the impact of serum kynurenine metabolite levels on diagnosis, clinical state, symptom severity and clinical course in a large French transdiagnostic cohort of SCZ and BD patients. Four patient groups (total n = 507) were included in a cross-sectional observational study: 1) hospitalized acute bipolar patients (n = 205); 2) stable bipolar outpatients (n = 116); 3) hospitalized acute schizophrenia patients (n = 111) and 4) stable schizophrenia outpatients (n = 75), in addition to healthy controls (HC) (n = 185). The quantitative determination of serum kynurenine metabolites was performed using liquid chromatography-tandem mass spectrometry. Kynurenine levels were lower in all patients combined compared to HC while ANCOVA analyses did not reveal inter-diagnostic difference between SCZ and BD. Interestingly, hospitalized patients of both diagnostic groups combined displayed significantly lower kynurenine levels than stabilized outpatients. Psychotic symptoms were associated with lower quinaldic acid (F = 9.18, p=<.001), which is KAT-driven, whereas a longer duration of illness contributed to abnormalities in tryptophan (F = 5.41, p = .023), kynurenine (F = 16.93, p=<.001), xanthurenic acid (F = 9.34, p = .002), quinolinic acid (F = 9.18, p = .003) and picolinic acid (F = 4.15, p = .043), metabolized through the KMO-branch. These data confirm illness state rather than diagnosis to drive KP alterations in SCZ and BD. Lower levels of KP metabolites can thus be viewed as a transdiagnostic feature of SCZ and BD, independently associated with acute symptomatology and a longer duration of illness. Quinaldic acid has seldomly been investigated by previous studies and appears an important state marker in SCZ and BD. As serum samples are used in this study, it is not possible to extrapolate these findings to the brain.

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

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.

Brain Versus Blood: A Systematic Review on the Concordance Between Peripheral and Central Kynurenine Pathway Measures in Psychiatric Disorders.

Objective: Disturbances in the kynurenine pathway have been implicated in the pathophysiology of psychotic and mood disorders, as well as several other psychiatric illnesses. It remains uncertain however to what extent metabolite levels detectable in plasma or serum reflect brain kynurenine metabolism and other disease-specific pathophysiological changes. The primary objective of this systematic review was to investigate the concordance between peripheral and central (CSF or brain tissue) kynurenine metabolites. As secondary aims we describe their correlation with illness course, treatment response, and neuroanatomical abnormalities in psychiatric diseases. Methods: We performed a systematic literature search until February 2021 in PubMed. We included 27 original research articles describing a correlation between peripheral and central kynurenine metabolite measures in preclinical studies and human samples from patients suffering from neuropsychiatric disorders and other conditions. We also included 32 articles reporting associations between peripheral KP markers and symptom severity, CNS pathology or treatment response in schizophrenia, bipolar disorder or major depressive disorder. Results: For kynurenine and 3-hydroxykynurenine, moderate to strong concordance was found between peripheral and central concentrations not only in psychiatric disorders, but also in other (patho)physiological conditions. Despite discordant findings for other metabolites (mainly tryptophan and kynurenic acid), blood metabolite levels were associated with clinical symptoms and treatment response in psychiatric patients, as well as with observed neuroanatomical abnormalities and glial activity. Conclusion: Only kynurenine and 3-hydroxykynurenine demonstrated a consistent and reliable concordance between peripheral and central measures. Evidence from psychiatric studies on kynurenine pathway concordance is scarce, and more research is needed to determine the validity of peripheral kynurenine metabolite assessment as proxy markers for CNS processes. Peripheral kynurenine and 3-hydroxykynurenine may nonetheless represent valuable predictive and prognostic biomarker candidates for psychiatric disorders.