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.

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.

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.

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.

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.

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.

Background: 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. Methods: 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. Results: 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 (r = 0.55, p = 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. Limitations: Our study had a limited sample size, and patients were treated with concomitant antidepressant medication. Conclusion: 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. Clinical trial registration: EUDRACT number 2016-001715-21.

Tryptophan Catabolites in Bipolar Disorder: A Meta-Analysis.

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; p < 0.001), kynurenine (SMD = - 0.3; p = 0.001) and kynurenic acid (SMD = -.45; p = < 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.

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.

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.

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.

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

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.

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

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.

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

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.

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.

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.