Motor learning and performance in schizophrenia and aging: two different patterns of decline.

Psychomotor slowing has consistently been observed in schizophrenia, however research on motor learning in schizophrenia is limited. Additionally, motor learning in schizophrenia has never been compared with the waning of motor learning abilities in the elderly. Therefore, in an extensive study, 30 individuals with schizophrenia, 30 healthy age-matched controls and 30 elderly participants were compared on sensorimotor learning tasks including sequence learning and adaptation (both explicit and implicit), as well as tracking and aiming. This paper presents new findings on an explicit motor sequence learning task, an explicit verbal learning task and a simple aiming task and summarizes all previously published findings of this large investigation. Individuals with schizophrenia and elderly had slower Movement Time (MT)s compared with controls in all tasks, however both groups improved over time. Elderly participants learned slower on tracking and explicit sequence learning while individuals with schizophrenia adapted slower and to a lesser extent to movement perturbations in adaptation tasks and performed less well on cognitive tests including the verbal learning task. Results suggest that motor slowing is present in schizophrenia and the elderly, however both groups show significant but different motor skill learning. Cognitive deficits seem to interfere with motor learning and performance in schizophrenia while task complexity and decreased movement precision interferes with motor learning in the elderly, reflecting different underlying patterns of decline in these conditions. In addition, evidence for motor slowing together with impaired implicit adaptation supports the influence of cerebellum and the cerebello-thalamo-cortical-cerebellar (CTCC) circuits in schizophrenia, important for further understanding the pathophysiology of the disorder.

Case report: Psychosis with catatonia in an adult man: a presentation of neurosarcoidosis.

Introduction: Sarcoidosis is a multisystem non-caseous granulomatous disease of unknown origin with predominant lung involvement and a variable clinical course. Although rare, neuropsychiatric manifestations such as confusion, problems in orientation, memory dysfunction, delusions, hallucinations and catatonia can be presenting features of sarcoidosis with nervous system involvement, also known as neurosarcoidosis. Case description: We present a 39-year-old man with acute-onset vertigo, balance problems and confusion quickly developing delusions, hallucinations, catatonic symptoms and suicidal behaviour. Symptoms appeared to be a manifestation of neurosarcoidosis. Diagnostic assessment: The differential diagnosis of psychosis is broad and should include pertinent auto-immune disorders, paraneoplastic, oncologic, metabolic, and neurodegenerative disorders. Basic systemic screening should include blood and urinary tests, a chest X-ray, brain CT scan and ECG. If neurosarcoidosis is suspected, an MRI of the brain with contrast and lumbar puncture are most appropriate. Multidisciplinary collaboration is essential to arrive at a correct diagnosis and effective management of the patient. Discussion: Despite the large number of sarcoidosis and psychosis studies, the etiology and pathogenesis of both illnesses remain incompletely understood. A common inflammatory etiopathological pathway has been postulated. Conclusions: Clinicians should consider organic causes when confronted with a middle-aged patient experiencing a first psychotic episode with an atypical onset, catatonic features, or dysfunction in orientation and/or memory, a complete lack of a positive familial psychiatric history and/or an atypical response to (psycho)pharmacological treatment.

Attitudes of patients with schizophrenia spectrum or bipolar disorders towards medication self-management during hospitalisation.

BACKGROUND: Medication self-management (MSM) is defined as a person's ability to cope with medication treatment for a chronic condition, along with the associated physical and psychosocial effects that the medication causes in their daily lives. For many patients, it is important to be able to self-manage their medication successfully, as they will often be expected to do after discharge. AIM: The aim of this study was to describe the willingness and attitudes of patients with schizophrenia spectrum or bipolar disorders regarding MSM during hospital admission. A secondary aim was to identify various factors associated with patient willingness to participate in MSM and to describe their assumptions concerning needs and necessary conditions, as well as their attitudes towards their medication. METHODS: A multicentre, quantitative cross-sectional observational design was used to study the willingness and attitudes of psychiatric patients regarding MSM during hospitalisation. The study adhered to guidelines for Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). RESULTS: In this study, 84 patients, of which 43 were patients with schizophrenia spectrum disorders and 41 were patients with bipolar disorders, participated. A majority of the patients (81%) were willing to participate in MSM during their hospitalisation. Analysis revealed patients are more willing to MSM if they are younger (r = -.417, p < .001) and a decreasing number of medicines (r = -.373, p = .003). Patients' willingness was positively associated with the extent of support by significant others during and after hospitalisation (Pearson's r = .298, p = .011). Patients were convinced that they would take their medication more correctly if MSM were to be allowed during hospitalisation (65%). CONCLUSION: Most of the patients were willing to self-manage their medication during hospitalisation, however, under specific conditions such as being motivated to take their medication correctly and to understand the benefits of their medication. RELEVANCE TO CLINICAL PRACTICE: From a policy point of view, our study provided useful insights into how patients look at MSM to enable the development of future strategies. Since patients are willing to self-manage their medication during hospitalisation, this may facilitate its implementation. PATIENT CONTRIBUTION: Patients were recruited for this study. Participation was voluntary, and signed informed consent was obtained from all participants prior to the questionnaire.

An exploration of suicidal ideation and attempts, and care use and unmet need among suicide-ideators in a Belgian population study.

BACKGROUND: Suicidal ideation, or thinking about death and suicide, is common across all layers of society. The aim of this paper is to add to the understanding of suicidal ideation in the general population, as well as help-seeking behaviors and perceived unmet mental health needs among those who report suicidal thoughts. METHODS: The research is part of a representative population-based survey study of mental wellbeing in Antwerp (Flanders, Belgium) carried out in 2021. A total of 1202 participants between 15 and 80 years old answered the Ask Suicide-Screening Questions (ASQ), and an additional question about suicide plans. Participation was by invitation only and possible online or via a postal paper questionnaire. Univariate and multivariate logistic regression analyses were used to explore the association between both current suicidal ideation and self-reported lifetime suicide attempt with the sociodemographic factors age, gender, educational level, origin and financial distress. Moreover, formal care use for mental health was examined among those experiencing suicidal ideation, and logistic regression analyses were used to assess associated sociodemographic factors. Finally, perceived unmet mental health needs were assessed among suicide ideators. RESULTS: The point-prevalence of suicidal ideation was 8.6% and was higher among younger age groups and individuals reporting financial distress. The lifetime-prevalence of suicide attempts is 6.5% and was higher in younger people and individuals with a primary educational level and with financial distress. About half (45.6%) of those with suicidal ideation consulted a professional for mental health problems in the past twelve months. Men and those with a primary educational level were less likely to seek help. Half of suicide ideators without care use perceived some need for mental health care, and a third of suicide ideators who used care perceived the obtained help as insufficient, resulting in a population prevalence of 3.6% suicide ideators with a fully or partially perceived unmet need. CONCLUSIONS: The prevalence of suicide attempts, suicidal ideation and unmet needs among suicide-ideators is high in this Belgian sample. Mental health care need perception in suicide ideators needs further investigation.

TSPO PET brain inflammation imaging: A transdiagnostic systematic review and meta-analysis of 156 case-control studies.

INTRODUCTION: The 18-kDa translocator protein (TSPO) is increasingly recognized as a molecular target for PET imaging of inflammatory responses in various central nervous system (CNS) disorders. However, the reported sensitivity and specificity of TSPO PET to identify brain inflammatory processes appears to vary greatly across disorders, disease stages, and applied quantification methods. To advance TSPO PET as a potential biomarker to evaluate brain inflammation and anti-inflammatory therapies, a better understanding of its applicability across disorders is needed. We conducted a transdiagnostic systematic review and meta-analysis of all in vivo human TSPO PET imaging case-control studies in the CNS. Specifically, we investigated the direction, strength, and heterogeneity associated with the TSPO PET signal across disorders in pre-specified brain regions, and explored the demographic and methodological sources of heterogeneity. METHODS: We searched for English peer-reviewed articles that reported in vivo human case-control TSPO PET differences. We extracted the demographic details, TSPO PET outcomes, and technical variables of the PET procedure. A random-effects meta-analysis was applied to estimate case-control standardized mean differences (SMD) of the TSPO PET signal in the lobar/whole-brain cortical grey matter (cGM), thalamus, and cortico-limbic circuitry between different illness categories. Heterogeneity was evaluated with the I2 statistic and explored using subgroup and meta-regression analyses for radioligand generation, PET quantification method, age, sex, and publication year. Significance was set at the False Discovery Rate (FDR)-corrected P < 0.05. RESULTS: 156 individual case-control studies were included in the systematic review, incorporating data for 2381 healthy controls and 2626 patients. 139 studies documented meta-analysable data and were grouped into 11 illness categories. Across all the illness categories, we observed a significantly higher TSPO PET signal in cases compared to controls for the cGM (n = 121 studies, SMD = 0.358, PFDR < 0.001, I2 = 68%), with a significant difference between the illness categories (P = 0.004). cGM increases were only significant for Alzheimer's disease (SMD = 0.693, PFDR < 0.001, I2 = 64%) and other neurodegenerative disorders (SMD = 0.929, PFDR < 0.001, I2 = 73%). Cortico-limbic increases (n = 97 studies, SMD = 0.541, P < 0.001, I2 = 67%) were most prominent for Alzheimer's disease, mild cognitive impairment, other neurodegenerative disorders, mood disorders and multiple sclerosis. Thalamic involvement (n = 79 studies, SMD = 0.393, P < 0.001, I2 = 71%) was observed for Alzheimer's disease, other neurodegenerative disorders, multiple sclerosis, and chronic pain and functional disorders (all PFDR < 0.05). Main outcomes for systemic immunological disorders, viral infections, substance use disorders, schizophrenia and traumatic brain injury were not significant. We identified multiple sources of between-study variance to the TSPO PET signal including a strong transdiagnostic effect of the quantification method (explaining 25% of between-study variance; VT-based SMD = 0.000 versus reference tissue-based studies SMD = 0.630; F = 20.49, df = 1;103, P < 0.001), patient age (9% of variance), and radioligand generation (5% of variance). CONCLUSION: This study is the first overarching transdiagnostic meta-analysis of case-control TSPO PET findings in humans across several brain regions. We observed robust increases in the TSPO signal for specific types of disorders, which were widespread or focal depending on illness category. We also found a large and transdiagnostic horizontal (positive) shift of the effect estimates of reference tissue-based compared to VT-based studies. Our results can support future studies to optimize experimental design and power calculations, by taking into account the type of disorder, brain region-of-interest, radioligand, and quantification method.

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 attitude of healthcare providers towards medication self-management in hospitalized patients diagnosed with schizophrenia or bipolar disorders.

BACKGROUND: Medication self-management (MSM) is considered an important aspect of pharmacotherapy and plays an essential role in the treatment of various illnesses. To date, research into the willingness and attitude of psychiatric healthcare providers toward MSM in patients diagnosed with schizophrenia or bipolar disorders during hospitalization is lacking. AIM: The aim of this study was to identify healthcare providers' willingness to MSM and assess their attitude, conditions, benefits, and ability toward it during hospitalization. METHODS: A multicenter, quantitative cross-sectional observational design was used to study psychiatric healthcare providers' attitude to MSM during hospitalization in patients diagnosed with schizophrenia or bipolar disorders. RESULTS: In this study, 173 healthcare providers, of which 147 were nurses and 26 psychiatrists, participated. During hospitalization, 86% of the healthcare providers were willing to MSM. Regularly evaluating patients' ability regarding MSM during hospitalization was seen as an important condition (94%). Psychiatrists were significantly less convinced that MSM during hospitalization has a positive impact on adherence when compared to nurses (respectively 54% vs. 77%, p = .009). DISCUSSION: Most healthcare providers indicated that they were willing to MSM in patients diagnosed with schizophrenia or bipolar disorders during hospitalization under specific conditions.

Contributions of age and clinical depression to metacognitive performance.

One aspect of metacognition is the ability to judge the accuracy of our own performance, even in the absence of external feedback, which is often measured using confidence ratings. Past research suggests that confidence is lower in Major Depressive Disorder (MDD). Less is known about the ability of MDD patients to discriminate correct from incorrect performance (metacognitive efficiency). The metacognitive performance of aged MDD patients (62-89y) was compared to an age-matched control group. A younger control group (21-28y) was included to also explore the relationshipbetweenageandmetacognitive performance. We found no difference in confidence bias nor metacognitive efficiency between MDD patients and age-matched controls.We found age-related differences in metacognition:normal aging was associated with higher confidencebut lower metacognitive efficiency. The overconfidence was specifically driven by overconfidence in incorrect trials. Our results point to the importance ofage while investigating the relation between MDD and metacognitive performance.

Medication Self-Management in Hospitalised Patients with Schizophrenia or Bipolar Disorder: The Perceptions of Patients and Healthcare Providers.

AIM(S): The aim of the study was to explore perspectives of hospitalised patients with schizophrenia or a bipolar disorder and their healthcare providers on medication self-management. METHODS: In a qualitative descriptive design, semi-structured interviews were used. Forty-nine interviews were completed (nurses n = 18; psychiatrists n = 3; hospital pharmacists n = 2; patients n = 26). Data analysis was iterative using an inductive and thematic approach. RESULTS: From the thematic analysis of the interviews, three main themes emerged: monitoring and shared decision-making, relationship based on trust, and patient satisfaction and rehabilitation; as well as three sub-themes: available tools, patient readiness, and safety. Regular monitoring and follow-ups were considered conditions for medication self-management. All stakeholders considered that the patient, the nursing staff, and the psychiatrist should all be involved in the process of medication self-management. All healthcare providers emphasized the importance of regular re-evaluations of the patient and were worried about medication errors and misuse. Most patients considered medication self-management during hospitalisation to increase their confidence, self-reliance, and satisfaction. Many participants thought it would make a positive contribution to the recovery process. DISCUSSION: All stakeholders were positive towards medication self-management under specific conditions. According to the participants, medication self-management offered many benefits, including the implementation of more structure for the patient, an ameliorated preparatory phase towards discharge, and an actual improvement of future adherence. All participants considered medication self-management to contribute to more profound medication knowledge and an overall improvement of their health literacy. Implications and future perspectives: These findings will be used to develop a medication self-management tool in hospitalised patients with schizophrenia or bipolar disorders.

Association between serum lithium level and incidence of COVID-19 infection.

An antiviral effect of lithium has been proposed, but never investigated for coronavirus disease 2019 (COVID-19). Using electronic health records of 26 554 patients with documented serum lithium levels during the pandemic, we show that the 6-month COVID-19 infection incidence was lower among matched patients with 'therapeutic' (0.50-1.00) versus 'subtherapeutic' (0.05-0.50) lithium levels (hazard ratio (HR) = 0.82, 95% CI 0.69-0.97, P = 0.017) and among patients with 'therapeutic' lithium levels versus matched patients using valproate (HR = 0.79, 95% CI 0.67-0.92, P = 0.0023). Lower rates of infection were observed for both new COVID-19 diagnoses and positive polymerase chain reaction tests, regardless of underlying psychiatric diagnosis and vaccination status.

Resting-state fMRI in depressive and (hypo)manic mood states in bipolar disorders: A systematic review.

OBJECTIVE: Abnormalities in spontaneous brain activity, measured with resting-state functional magnetic resonance imaging (rs-fMRI), may be key biomarkers for bipolar disorders. This systematic review compares rs-fMRI findings in people experiencing a bipolar depressive or (hypo)manic episode to bipolar euthymia and/or healthy participants. METHODS: Medline, Web of Science and Embase were searched up until April 2021. Studies without control group, or including minors, neurological co-morbidities or mixed episodes, were excluded. Qualitative synthesis was used to report results and risk of bias was assessed using the National Heart, Lung and Blood Institute tool for case-control studies. RESULTS: Seventy-one studies were included (3167 bipolar depressed/706 (hypo)manic). In bipolar depression, studies demonstrated default-mode (DMN) and frontoparietal network (FPN) dysfunction, altered baseline activity in the precuneus, insula, striatum, cingulate, frontal and temporal cortex, and disturbed regional homogeneity in parietal, temporal and pericentral areas. Functional connectivity was altered in thalamocortical circuits and between the cingulate cortex and precuneus. In (hypo)mania, studies reported altered functional connectivity in the amygdala, frontal and cingulate cortex. Finally, rs-fMRI disturbances in the insula and putamen correlate with depressive symptoms, cerebellar resting-state alterations could evolve with disease progression and altered amygdala connectivity might mediate lithium effects. CONCLUSIONS: Our results suggest DMN and FPN dysfunction in bipolar depression, whereas local rs-fMRI alterations might differentiate mood states. Future studies should consider controlling rs-fMRI findings for potential clinical confounding factors such as medication. Considerable heterogeneity of methodology between studies limits conclusions. Standardised clinical reporting and consistent analysis approaches would increase coherence in this promising field.

The polysemous concepts of psychomotricity and catatonia: A European multi-consensus perspective.

Current classification systems use the terms "catatonia" and "psychomotor phenomena" as mere a-theoretical descriptors, forgetting about their theoretical embedment. This was the source of misunderstandings among clinicians and researchers of the European collaboration on movement and sensorimotor/psychomotor functioning in schizophrenia and other psychoses or ECSP. Here, we review the different perspectives, their historical roots and highlight discrepancies. In 1844, Wilhelm Griesinger coined the term "psychic-motor" to name the physiological process accounting for volition. While deriving from this idea, the term "psychomotor" actually refers to systems that receive miscellaneous intrapsychic inputs, convert them into coherent behavioral outputs send to the motor systems. More recently, the sensorimotor approach has drawn on neuroscience to redefine the motor signs and symptoms observed in psychoses. In 1874, Karl Kahlbaum conceived catatonia as a brain disease emphasizing its somatic - particularly motor - features. In conceptualizing dementia praecox Emil Kraepelin rephrased catatonic phenomena in purely mental terms, putting aside motor signs which could not be explained in this way. Conversely, the Wernicke-Kleist-Leonhard school pursued Kahlbaum's neuropsychiatric approach and described many new psychomotor signs, e.g. parakinesias, Gegenhalten. They distinguished 8 psychomotor phenotypes of which only 7 are catatonias. These barely overlap with consensus classifications, raising the risk of misunderstanding. Although coming from different traditions, the authors agreed that their differences could be a source of mutual enrichment, but that an important effort of conceptual clarification remained to be made. This narrative review is a first step in this direction.

The Role of Kynurenines in Cognitive Dysfunction in Bipolar Disorder.

INTRODUCTION: Chronic low-grade inflammation is suggested to play a pathophysiological role in bipolar disorder (BD) and its related cognitive dysfunctions. Although kynurenine (KYN) pathway metabolites are key inflammatory mediators, studies investigating the association between KYN metabolism and cognition in BD are scarce. We aimed to explore the relationship between KYN metabolism and cognitive functioning across different mood states in BD. METHODS: Sixty-seven patients with BD (35 depressed and 32 [hypo] manic) and 29 healthy controls were included. Cognitive functioning was assessed at 3 time intervals (baseline, 4, and 8 months) assessing processing speed, sustained attention, verbal memory, working memory, and response inhibition. Plasma samples for quantification of 3-hydroxykynurenine, quinolinic acid, and kynurenic acid (KYNA) were concurrently provided. Linear mixed models were used for statistical analysis. RESULTS: The manic group showed deficits in all assessed cognitive domains with the exception of verbal memory at all test moments. The bipolar depression group showed deficits in the processing speed at all test moments. Throughout the whole follow-up period, KYNA was significantly lower in both patient groups than in controls. Only in the bipolar depression group, low KYNA was associated with worse global cognitive functioning (B = 0.114, p = 0.02) and slower processing speed in particular (B = 0.139, p = 0.03). CONCLUSION: Only in the bipolar depression group, lower KYNA was associated with worse cognitive functioning. Future large-scale longitudinal studies are warranted to confirm the role of KYN metabolites in cognitive impairment in patients with BD and the possible therapeutic implications of this relationship.

The Biology of BDSM: A Systematic Review.

INTRODUCTION: 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. In recent years, attention has shifted from the idea of BDSM as a pathological and tabooed niche practice towards viewing BDSM as a healthy form of intimacy. AIM: This systematic review brings together all existing literature on the biology of BDSM and places it in a broader biological context. METHODS: A systematic search was conducted on PubMed, Web of Science and PsycARTICLES, of which 10 articles are included and discussed in this systematic review. RESULTS: There is evidence for cortisol changes in submissives as a result of a BDSM interaction, suggesting involvement of the physiological stress system. Endocannabinoid changes implicate the pleasure and reward system. In dominants, this biologically measured pleasure seemed to be dependent on power play rather than pain play. Testosterone and oxytocin are also implicated in BDSM, though their role is less evident. Research into brain region activity patterns related to BDSM interest suggests a role for the parietal operculum and ventral striatum in the context of the pleasure and reward system, the primary and secondary somatosensory cortex in the context of pain perception, empathy-related circuits such as the anterior insula, anterior midcingulate cortex and sensorimotor cortex and the left frontal cortex in the context of social and sexual interactions. Pain thresholds are shown to be higher in submissive individuals and a BDSM interaction may cause pain thresholds to rise in submissives as well. CONCLUSION: BDSM interactions are complex and influenced by several psychological, social and biological processes. Though research is limited, there is emerging evidence for an interaction between several biological systems involved in these types of interests and activities. This means there is an important role for future research to replicate and supplement current results. Wuyts E, Morrens M. The Biology of BDSM: A Systematic Review. J Sex Med 2022;19:144-157.

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.

Akathisia after chronic usage of synthetic cathinones: A case study.

Introduction: Synthetic cathinones are a heterogenous group of new psychoactive substances (NPS) with a surging prevalence of use. They are sold under the name of "Bath Salts," "Legal Highs" or "Research Chemical." It is a heterogeneous group of substances that have a varying binding selectivity and affinity. Due to limited availability of NPS screening tests, inadequate legislation, the exponential increases in availability of new NPS and the comorbid use of other illicit substances, scientific research remains scarce. As a result, insight in their mental and psychomotor effects is limited. Case description: We present a case of a 21-year-old woman with daily usage of synthetic cathinones, more specifically α-Pyrrolidinopentiophenone (α-PVP-better known as "Flakka"), α-Pyrrolidinohexiophenone (α-PHP) and alpha-Pyrrolidinoisohexaphenone (α-PHiP). Besides a severe paranoid psychotic state of mind, characterized by persecutory and somatic delusions, there was also a very pronounced psychomotor restlessness during the whole period of hospitalization which was diagnosed as akathisia. She reported that she was unable to sit during meals, had difficulty standing still and felt a constant urge to pay attention to the restlessness. The patient did not take any antipsychotic medication at admission. Results: The patient was treated in accordance with the current guidelines concerning akathisia with a combination of Quetiapine 200 mg, Propranolol 80 mg, Diazepam 10 mg, Biperiden 4 mg, and Mirtazapine 15 mg without any sufficient alleviation of complaints. Before the start of the treatment, Barnes Akathisia Rating Scale (BARS) score was 11 out of 14 which evolved toward a score of 7 over the course of the 40 day hospitalization, implying persisting severe akathisia which only improved modestly. Conclusion: The current case suggests that besides cocaine, amphetamines and methamphetamines, synthetic cathinones can also increase the risk for development of extrapyramidal symptoms such as akathisia. Especially a-PVP-analogs as used by the current patient and Pyrovalerone-analogs such as Methylenedioxypyrovalerone (MDPV) are very powerful dopamine reuptake-inhibitors which might lead to strong locomotor activation. Up to this day it remains very difficult to establish a guideline concerning the treatment of intoxication with synthetic cathinones or dependence thereof.

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.