Study protocol for a randomized controlled trial with rituximab for psychotic disorder in adults (RCT-Rits).

BACKGROUND: The role of inflammation in the aetiology of schizophrenia has gained wide attention and research on the association shows an exponential growth in the last 15 years. Autoimmune diseases and severe infections are risk factors for the later development of schizophrenia, elevated inflammatory markers in childhood or adolescence are associated with a greater risk of schizophrenia in adulthood, individuals with schizophrenia have increased levels of pro-inflammatory cytokines compared to healthy controls, and autoimmune diseases are overrepresented in schizophrenia. However, treatments with anti-inflammatory agents are so far of doubtful clinical relevance. The primary objective of this study is to test whether the monoclonal antibody rituximab, directed against the B-cell antigen CD20 ameliorates psychotic symptoms in adults with schizophrenia or schizoaffective disorder and to examine potential mechanisms. A secondary objective is to examine characteristics of inflammation-associated psychosis and to identify pre-treatment biochemical characteristics of rituximab responders. A third objective is to interview a subset of patients and informants on their experiences of the trial to obtain insights that rating scales may not capture. METHODS: A proof-of-concept study employing a randomised, parallel-group, double-blind, placebo-controlled design testing the effect of B-cell depletion in patients with psychosis. 120 participants with a diagnosis of schizophrenia spectrum disorders (SSD) (ICD-10 codes F20, F25) will receive either one intravenous infusion of rituximab (1000 mg) or saline. Psychiatric measures and blood samples will be collected at baseline, week 12, and week 24 post-infusion. Brief assessments will also be made in weeks 2 and 7. Neuroimaging and lumbar puncture, both optional, will be performed at baseline and endpoints. Approximately 40 of the patients and their informants will be interviewed for qualitative analyses on the perceived changes in well-being and emotional qualities, in addition to their views on the research. DISCUSSION: This is the first RCT investigating add-on treatment with rituximab in unselected SSD patients. If the treatment is helpful, it may transform the treatment of patients with psychotic disorders. It may also heighten the awareness of immune-psychiatric disorders and reduce stigma. TRIAL REGISTRATION: NCT05622201, EudraCT-nr 2022-000220-37 version 2.1. registered 14th of October 2022.

Alterations in inflammasome-related immunometabolites in individuals with severe psychiatric disorders.

INTRODUCTION: Psychiatric disorders are common and significantly impact the quality of life. Inflammatory processes are proposed to contribute to the emergence of psychiatric disorders. In addition to inflammation, disturbances in metabolic pathways have been observed in individuals with different psychiatric disorders. A suggested key player in the interaction between inflammation and metabolism is the Nod-like receptor 3 (NLRP3) inflammasome, and NLRP3 is known to react to a number of specific metabolites. However, little is known about the interplay between these immunometabolites and the NLRP3 inflammasome in mental health disorders. AIM: To assess the interplay between immunometabolites and inflammasome function in a transdiagnostic cohort of individuals with severe mental disorders. METHODS: Mass spectrometry-based analysis of selected immunometabolites, previously known to affect inflammasome function, were performed in plasma from low-functioning individuals with severe mental disorders (n = 39) and sex and aged-matched healthy controls (n = 39) using a transdiagnostic approach. Mann Whitney U test was used to test differences in immunometabolites between psychiatric patients and controls. To assess the relationship between inflammasome parameters, disease severity, and the immunometabolites, Spearman's rank-order correlation test was used. Conditional logistic regression was used to control for potential confounding variables. Principal component analysis was performed to explore immunometabolic patterns. RESULTS: Among the selected immunometabolites (n = 9), serine, glutamine, and lactic acid were significantly higher in the patient group compared to the controls. After adjusting for confounders, the differences remained significant for all three immunometabolites. No significant correlations were found between immunometabolites and disease severity. CONCLUSION: Previous research on metabolic changes in mental disorders has not been conclusive. This study shows that severely ill patients have common metabolic perturbations. The changes in serine, glutamine, and lactic acid could constitute a direct contribution to the low-grade inflammation observed in severe psychiatric disorders.

Rituximab as an adjunctive treatment for schizophrenia spectrum disorder or obsessive-compulsive disorder: Two open-label pilot studies on treatment-resistant patients.

In this explorative study, we investigated if an adjunctive treatment with one single dose of the monoclonal antibody rituximab would improve symptoms and function in treatment-resistant patients with schizophrenia spectrum disorder (SSD, n = 9) or obsessive-compulsive disorder (OCD, n = 10), based on the inflammatory hypothesis for mental disorders. Patients were followed for one year. Disability was measured with the Personal and Social Performance score (PSP). At baseline, the mean PANSS score in the SSD group was 99 ± 32 and the mean Y-BOCS score in the OCD group was 27.5 ± 7. Mean PSP scores were 32 ± 10.2 and 42.5 ± 9.9 in the SSD and OCD groups, respectively. Seven had Paediatric Acute-Onset Neuropsychiatric Syndrome (PANS) in retrospect, and 3 SSD patients had schizo-obsessive subtype. 4/8 SSD patients showed a ≥40% reduction in PANSS at endpoint I week 20, however, 7/9 were similarly improved already at week 12. Among the OCD patients, 2/10 showed a ≥35% reduction in Y-BOCS at week 20. Disability was significantly improved only in the SSD group. The percentual decrease of PANSS scores in SSD patients was associated with the increase in immunoglobulin levels week 20 (n = 8: IgG r = 0.85, p = .007; IgA r = 0.79, p = .019; IgM r = 0.73, p = .038). Rituximab was generally well tolerated in these patients. Self-rated improvements since baseline were reported for psychic (p = .021), neurological (p = .059), and autonomic (p < .001) side effects (UKU-SERS-Pat side-effect scale). Anxiety was commonly reported by OCD patients, while an initial increase in psychotic symptoms was seen in a few SSD patients. An RCT is underway to evaluate rituximab in SSD.

Apathy as a Predictor for Conversion From Mild Cognitive Impairment to Dementia: A Systematic Review and Meta-Analysis of Longitudinal Studies.

BACKGROUND: Apathy is one of the most prevalent neurobehavioral manifestations in mild cognitive impairment (MCI) and is included among the behavioral and psychological symptoms of dementia (BPSD). Studies suggest that the presence of apathy could be associated with increased dementia risk. The role of apathy in conversion from MCI to dementia, and whether apathy could be a relevant predictor for dementia progression, are still matters of investigation. AIM: To study the relationship between apathy and progression to dementia in individuals with MCI. METHODS: A systematic literature search in Medline, Embase, Cochrane Library, Epistemonikos, PsychINFO, and CINAHL was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search included longitudinal studies reporting on the association between apathy and dementia. RESULTS: The main outcome was pooled unadjusted hazard ratios (HR) of apathy in dementia conversion and included 11 studies with 9504 individuals. There was a significant association between apathy and dementia conversion, HR = 1.54; 95% CI, 1.29, 1.84. Subgroup analysis showed a significant association between apathy and progression to AD. CONCLUSION: Apathy was associated with an increased risk of conversion to AD and all-cause dementia in patients with MCI. The role of apathy as a marker for incident dementia needs to be investigated in large, high-quality studies.

The impact of schizotypy on quality of life among adults with autism spectrum disorder.

BACKGROUND: Autism spectrum disorder (ASD) and schizotypal personality disorder can be difficult to distinguish. Deficits in social relationships and social interaction, present in both conditions, are known to impair quality of life. The aim of the present study was to investigate if schizotypal symptoms affect quality of life among adults diagnosed with autism spectrum disorder and to study the association between schizotypy and autistic traits among them. METHODS: Participants diagnosed with autism spectrum disorder (n = 110) completed questionnaires exploring schizotypy (Schizotypal Personality Questionnaire - Brief Revised (SPQ-BR)), autistic traits (The Ritvo Autism, Asperger Diagnostic Scale-Revised Screen 14 items), anxiety and depression (The Hospital Anxiety and Depression scale) and quality of life (Brunnsviken Brief Quality of Life Scale and the European quality of life index version 5D). RESULTS: Schizotypy was found to be associated with anxiety, depressive and autistic symptoms, and poor quality of life. Although schizotypy was a predictor for impaired quality of life, this relationship was mediated by symptoms of anxiety and depression, plausibly inherent to autism. Autistic traits were positively associated with all higher order constructs of the SPQ-BR, i.e. positive and negative schizotypy, disorganization and social anxiety, as well as with poor quality of life. CONCLUSIONS: There is considerable overlap between schizotypy and autism that needs to be considered in research. Prominent schizotypal traits in people with ASD may constitute an endophenotype coinciding with a particularly poor quality of life. TRIAL REGISTRATION: ClinicalTrials.gov identifier:  NCT03570372 : Internet-based Treatment for Adults with Autism Spectrum Disorder (MILAS).

Potential Transdiagnostic Lipid Mediators of Inflammatory Activity in Individuals With Serious Mental Illness.

Mental disorders are heterogeneous and psychiatric comorbidities are common. Previous studies have suggested a link between inflammation and mental disorders. This link can manifest as increased levels of proinflammatory mediators in circulation and as signs of neuroinflammation. Furthermore, there is strong evidence that individuals suffering from psychiatric disorders have increased risk of developing metabolic comorbidities. Our group has previously shown that, in a cohort of low-functioning individuals with serious mental disorders, there is increased expression of genes associated with the NLRP3 inflammasome, a known sensor of metabolic perturbations, as well as increased levels of IL-1-family cytokines. In the current study, we set out to explore the interplay between disease-specific changes in lipid metabolism and known markers of inflammation. To this end, we performed mass spectrometry-based lipidomic analysis of plasma samples from low-functioning individuals with serious mental disorders (n = 39) and matched healthy controls (n = 39). By identifying non-spurious immune-lipid associations, we derived a partial correlation network of inflammatory markers and molecular lipids. We identified levels of lipids as being altered between individuals with serious mental disorders and controls, showing associations between lipids and inflammatory mediators, e.g., osteopontin and IL-1 receptor antagonist. These results indicate that, in low-functioning individuals with serious mental disorders, changes in specific lipids associate with immune mediators that are known to affect neuroinflammatory diseases.

Joint Hypermobility in Paediatric Acute-Onset Neuropsychiatric Syndrome-A Preliminary Case-Control Study.

Background: Individuals with generalised joint hypermobility (GJH, present in 10-20% of the general population) are at increased risk of being diagnosed with a range of psychiatric and rheumatological conditions. It is unknown whether Paediatric acute-onset neuropsychiatric syndrome (PANS), characterised by childhood onset obsessive-compulsive disorder or restricted eating and typically associated with several comorbid neuropsychiatric symptoms, is associated with GJH. It is also unknown whether extensive psychiatric comorbidity is associated with GJH. Method: This is a case-control study including 105 participants. We compared three groups: Individuals with PANS, individuals with other mental disorders and healthy controls. Joint mobility was assessed with the Beighton scoring system, psychiatric comorbidity with the M.I.N.I. or MINI-KID interview and symptoms of PANS with the PsychoNeuroInflammatory related Signs and Symptoms Inventory (PNISSI). Results: Hypermobility was similar across groups, and high rates of psychiatric comorbidity was not associated with higher Beighton scores. Conclusion: Although GJH is associated with several psychiatric conditions, such as ADHD and anxiety, this does not seem to be the case for PANS according to this preliminary study.

The Association between Carotid Intima-Media Thickness and Cognitive Impairment: A Systematic Review and Meta-Analysis.

BACKGROUND: Emerging evidence suggests that cognitive impairment (CI) and different etiologies of dementia, including Alzheimer's disease (AD), are associated with vascular risk factors and atherosclerosis. In clinical practice, carotid intima-media thickness (CIMT) measured by ultrasonography may be a marker of atherosclerosis. Many studies report increased CIMT in patients with dementia and CI although a firm association has not yet been established. AIM: This systematic review and meta-analysis were conducted to study the relationship between CIMT, dementia, and CI. METHODS: The literature search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and included the following databases: Medline, Embase, Cochrane Library, and Epistemonikos. The search spanned from 2000 to 2020 and was limited to English and Scandinavian languages. RESULTS: The main analysis of CIMT in subjects with CI compared to subjects with no cognitive impairment (NCI) included 12 studies; 1,089 subjects with CI and 5,223 with NCI. There was no significant difference in CIMT between the CI and NCI groups. However, subgroup analyses revealed significantly higher CIMT in the mild cognitive impairment (MCI) and dementia groups than the NCI group. In addition, patients with dementia had increased CIMT compared to patients with MCI, and patients with AD demonstrated higher CIMT than those with vascular cognitive impairment (VCI). CONCLUSION: CIMT may be higher in subjects with CI than in cognitively healthy subjects although no significant difference was observed in our main analysis. CIMT was higher in the dementia group than the MCI group and in the AD group compared to the VCI group.

Association between adult attention-deficit hyperactivity disorder and generalised joint hypermobility: A cross-sectional case control comparison.

Growing evidence suggests an unexpected association between generalised joint hypermobility (GJH) and several psychiatric conditions, and a shared pathophysiology has been proposed. No previous studies on adult attention-deficit/hyperactivity disorder (ADHD) are available. This study aimed to evaluate the association between adult ADHD and GJH. A total of 431 adults with ADHD and 417 non-ADHD controls were included in this cross-sectional comparative study. GJH was assessed by physical examination following the Beighton scoring system (BSS). Furthermore, musculoskeletal symptoms and skin abnormalities were queried to create a proxy for symptomatic GJH (e.g., Hypermobility spectrum disorders and Ehlers-Danlos syndrome) to differentiate this from non-specified GJH defined by BSS only. Logistic regression examined the influence of ADHD and candidate covariates (age, sex, ethnicity) on GJH and symptomatic GJH, respectively. ADHD was significantly associated with GJH, as defined by the BSS, with adjusted odds ratios of 4.7 (95% confidence interval [CI] 3.0-7.2, p < .005). Likewise, ADHD was significantly associated with symptomatic GJH, as defined by the BSS and additional symptoms, with adjusted odds ratios of 6.9 (CI 95% 4.1-11.9, p < .005). Our results suggest that GJH may represent a marker for an underlying systemic disorder involving both connective tissue and the central nervous system. GJH with additional musculoskeletal symptoms and/or skin abnormalities has a considerable stronger link to adult ADHD than non-specified GJH has, and may need awareness in ADHD management. Future studies should investigate the mechanisms behind this association and how comorbid GJH affects ADHD outcome.

The Relationship Between Generalised Joint Hypermobility and Autism Spectrum Disorder in Adults: A Large, Cross-Sectional, Case Control Comparison.

Autism spectrum disorder (ASD) and generalised joint hypermobility (GJH) share a number of clinical manifestations including proprioceptive impairment, motor difficulties, sensory hypersensitivity, and autonomic dysfunction. Clinical observations suggest that GJH is overrepresented in ASD. However, there are currently few systematic studies available. Knowledge about comorbidities may unfold common aetiopathological pathways underlying the association and improve the clinical management. The aim of this large, cross-sectional comparative study is to evaluate the relationship between ASD and GJH in adults. Data on joint hypermobility, symptoms associated with both hypermobility spectrum disorders (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS), lifetime psychiatric diagnoses, psychiatric rating scales for ASD and attention deficit hyperactivity disorder (ADHD), and socio-demographics was collected for 199 individuals with ASD and 419 non-ASD community controls. Logistic regression models adjusting for covariates (age, sex, ethnicity) revealed a significant relationship between ASD and GJH and between ASD and symptomatic GJH, with adjusted odds ratios of 3.1 (95% CI: 1.9, 5.2; p < 0.001) and 4.9 (95% CI: 2.6, 9.0; p < 0.001), respectively. However, the high prevalence of comorbid ADHD in the study sample reduces the generalizability of the results among individuals with ASD without comorbid ADHD. Possibly, an additional ADHD phenotype is the primary driver of the association between ASD and GJH. Furthermore, GJH with additional self-reported symptoms, suggestive of HSD/hEDS, showed a stronger association with ASD than did non-specified GJH, indicating that symptomatic GJH plays a greater role in the relationship than non-specified GJH does. Therefore, the current study underscores the need of careful sample subclassifications. ASD with GJH may represent a novel subgroup of ASD in terms of aetiopathology and clinical presentation. Future research should elucidate the aetiological factors behind the association between ASD and GJH and evaluate how the comorbidity of GJH affects ASD outcomes.

Self-rated joint hypermobility: the five-part questionnaire evaluated in a Swedish non-clinical adult population.

BACKGROUND: The conventional way to identify generalised joint hypermobility is by a physical examination according to the Beighton Score. However, a physical examination is time-consuming in clinical practise and may be unfeasible in population-based studies. The self-assessment five-part questionnaire on hypermobility (5PQ) offers a more practicable way to identify GJH. The aim of this study was to test validity and reliability of the five-part questionnaire on hypermobility (5PQ) translated into Swedish on a non-clinical adult population. METHODS: A structured procedure was used for the translation of the 5PQ into Swedish. The Beighton Score was used as reference standard for generalised joint hypermobility. Test-retest reliability was tested in a separate group who filled in the questionnaire twice with a ten-week interval. Participants consisted of a convenience sample recruited in Stockholm, Sweden (2017). RESULTS: A total of 328 participants were included in the study, 297 participants in the validity group and 31 participants in the reliability group. When evaluated against a present Beighton Score with an age-dependent cut-off, the Swedish 5PQ attained a sensitivity of 91%, a specificity of 75% and an area under the curve of 0.87. The Swedish 5PQ showed substantial to almost perfect test-retest reliability. CONCLUSIONS: The Swedish 5PQ is a valid and reliable instrument to screen for or to identify generalised joint hypermobility.

Generalised joint hypermobility and neurodevelopmental traits in a non-clinical adult population.

BACKGROUND: Generalised joint hypermobility (GJH) is reportedly overrepresented among clinical cases of attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and developmental coordination disorder (DCD). It is unknown if these associations are dimensional and, therefore, also relevant among non-clinical populations. AIMS: To investigate if GJH correlates with sub-syndromal neurodevelopmental symptoms in a normal population. METHOD: Hakim-Grahame's 5-part questionnaire (5PQ) on GJH, neuropsychiatric screening scales measuring ADHD and ASD traits, and a DCD-related question concerning clumsiness were distributed to a non-clinical, adult, Swedish population (n=1039). RESULTS: In total, 887 individuals met our entry criteria. We found no associations between GJH and sub-syndromal symptoms of ADHD, ASD or DCD. CONCLUSIONS: Although GJH is overrepresented in clinical cases with neurodevelopmental disorders, such an association seems absent in a normal population. Thus, if GJH serves as a biomarker cutting across diagnostic boundaries, this association is presumably limited to clinical populations. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

Brainstem Auditory Evoked Potentials for diagnosing Autism Spectrum Disorder, ADHD and Schizophrenia Spectrum Disorders in adults. A blinded study.

The aim of the present study was to examine the clinical utility of complex auditory brainstem response (c-ABR) and investigate if c-ABR is helpful in the diagnostic procedure. Thirty-one adult psychiatric patients, thoroughly diagnosed with autism spectrum disorder (ASD) (n=16), ADHD (n=8), or schizophrenia spectrum disorder (SSD) (n=7) and 15 healthy controls (HC), were blindly assessed with SensoDetect BERA. This c-ABR correctly identified psychiatric diagnoses in 4 patients (13%) and provided partially correct diagnoses in 11 more patients. Of the 15 HC, 6 were misclassified as psychiatric patients. The Cohen´s kappa coefficient (κ) was substantial for HC (κ=0.67), fair for SSD (κ=0.37), slight for ADHD (κ=0.09) and without agreement in ASD (κ=-0.03). In conclusion, we found the c-ABR method unhelpful and unreliable as a tool in clinical diagnostics.

Orgasm, Serotonin Reuptake Inhibition, and Plasma Oxytocin in Obsessive-Compulsive Disorder. Gleaning From a Distant Randomized Clinical Trial.

INTRODUCTION: Serotonin reuptake inhibitors (SRIs) are widely used for the treatment of psychiatric disorders, including obsessive-compulsive disorder (OCD). SRIs commonly cause delayed orgasm, the mechanism of which is poorly understood. Oxytocin is involved in sexual function and is interconnected with serotonin within the brain. SRIs are reported to affect the oxytocin system, but possible relations between SRI-induced changes of sexual function and oxytocin are unexplored in humans. In a randomized, double-blinded, placebo-controlled trial of OCD, the anti-obsessive efficacy and adverse events of SRIs and oxytocin measurements were studied. AIMS: To identify possible correlates between oxytocin levels and sexual function; find out whether sexual side effects correlate with levels of oxytocin and/or paroxetine and clomipramine; and test whether changes in sexual functioning are related to an anti-obsessive response. METHODS: Reported sexual function and oxytocin plasma levels at rest were studied in 31 adults (15 men and 16 women) with OCD who participated in a randomized, double-blinded trial comparing the SRIs clomipramine and paroxetine with placebo. Sexual adverse effects were quantified by a clinician-administered semistructured interview. Anti-obsessive response was based on the Yale-Brown Obsessive-Compulsive Scale. MAIN OUTCOME MEASURES: Ratings on the Sexual Symptom Checklist, plasma oxytocin, serum paroxetine and clomipramine levels, and Yale-Brown Obsessive-Compulsive Scale scores. RESULTS: Baseline oxytocin levels were positively correlated with baseline OCD severity, but not with sexual functioning. Impaired orgasm at week 6 was reported by 73% of SRI-treated and 20% of placebo-treated patients (P = .03). Impaired orgasm was related to higher oxytocin levels after 4 weeks of SRI treatment (P < .01) but not to SRI concentrations. In men, an association between impaired orgasm and anti-obsessive treatment response was found (P = .028). CONCLUSION: This pilot study suggests that some collateral effects of SRIs, particularly delayed orgasm, might be influenced by changes within the oxytocinergic system and are related to anti-obsessive mechanisms. Early-onset delayed orgasm in SRI-treated patients could serve as a predictor for OCD treatment response.

Internet-Based Cognitive Behavioral Therapy for Residual Symptoms in Bipolar Disorder Type II: A Single-Subject Design Pilot Study.

BACKGROUND: Bipolar disorder is a chronic condition with recurring episodes that often lead to suffering, decreased functioning, and sick leave. Pharmacotherapy in the form of mood stabilizers is widely available, but does not eliminate the risk of a new depressive or (hypo)manic episode. One way to reduce the risk of future episodes is to combine pharmacological treatment with individual or group psychological interventions. However, access to such interventions is often limited due to a shortage of trained therapists. In unipolar depression there is now robust evidence of the effectiveness of Internet-based psychological interventions, usually comprising psychoeducation and cognitive behavioral therapy (CBT). Internet-based interventions for persons suffering from bipolar disorder could increase access to psychological treatment. OBJECTIVE: The aim of this study was to investigate the feasibility of an Internet-based intervention, as well as its effect on residual depressive symptoms in persons diagnosed with bipolar disorder type II (BP-II). The most important outcomes were depressive symptoms, treatment adherence, and whether the patient perceived the intervention as helpful. METHODS: A total of 7 patients diagnosed with bipolar disorder type II at a Swedish psychiatric outpatient clinic were offered the opportunity to participate. Of the 7 patients, 3 (43%) dropped out before treatment began, and 4 (57%) were treated by means of an online, Internet-based intervention based on CBT (iCBT). The intervention was primarily aimed at psychoeducation, treatment of residual depressive symptoms, emotion regulation, and improved sleep. All patients had ongoing pharmacological treatment at recruitment and established contact with a psychiatrist. The duration of BP-II among the treated patients was between 6 and 31 years. A single-subject design was used and the results of the 4 participating patients were presented individually. RESULTS: Initiating treatment was perceived as too demanding under current life circumstances for 3 patients who consequently dropped out during baseline assessment. Self-ratings using the Montgomery-Åsberg Depression Rating Scale-Self-rated (MADRS-S) showed symptom reduction in 3 (75%) of the 4 treated cases during iCBT. In the evaluation of the treatment, 2 patients reported that they perceived that the treatment had reduced symptoms a little, 1 that it had reduced symptoms very much, and 1 not at all. Treatment adherence (ie, module completion) was fairly high in 3 cases. In general, the modules were perceived as fairly helpful or very helpful by the patients. In one case, there was a reliable change-according to the Reliable Change Index-in self-rated symptoms of depression and perseverative thinking. CONCLUSIONS: The treatment seemed to have acceptable feasibility. The iCBT intervention could be an effective way to treat residual symptoms in some patients with bipolar disorder type II. This should be investigated in a larger study. TRIAL REGISTRATION: ClinicalTrials.gov NCT01742351; https://clinicaltrials.gov/ct2/show/NCT01742351 (Archived by WebCite at http://www.webcitation.org/6XnVpv4C3).

The prevalence of lithium-associated hyperparathyroidism in a large Swedish population attending psychiatric outpatient units.

OBJECTIVE: This retrospective study determined the prevalence of lithium-associated hyperparathyroidism (LHPT) in 2 geographically defined, equivalent populations in Sweden, with no other selection bias. METHODS: The medical journals of all patients receiving lithium treatment were examined specifically regarding their biochemistry: calcium, parathyroid hormone (PTH), creatinine, and vitamin D. The condition LHPT was defined biochemically. All patient data were noted, and the prevalence of the condition could thereby be calculated. RESULTS: A total of 423 patients were included (251 women and 172 men; 3:2), treated over a mean of 13.5 years (range, 1-46 years), aged 19 to 92. 77 patients (18%) were identified with LHTP whose median serum calcium was 2.55 mmol/L and PTH was 99 ng/L. A further 21% showed tendencies toward hypercalcemia. Forty-three percent had vitamin D insufficiency. Five patients (approximately 1%) had undergone parathyroidectomy. CONCLUSION: The prevalence of LHPT is high and often goes undetected. Vitamin D insufficiency is common as is polypharmacy. Surgery, for unclear reasons, has not been performed extensively, possibly because of limited knowledge of the underlying pathophysiology or surgery's significance. We present standard recommendations on patient management and suggest continual, specific follow-up including the monitoring of calcium, PTH, and vitamin D at least annually. Surgery should be considered with intention to improve psychiatric well-being and provide multiorgan protection.

Autism spectrum disorder and low vitamin D at birth: a sibling control study.

BACKGROUND: Insufficient vitamin D activity has attracted increasing interest as a possible underlying risk factor in disorders of the central nervous system, including autism. METHODS: In this study, 25-hydroxyvitamin D (25(OH)D) was analysed in 58 Sweden-born sibling pairs, in which one child had autism spectrum disorder (ASD) and the other did not. The study group consisted of two representative samples; 47 Gothenburg sibling pairs with mixed ethnicities and 11 Stockholm sibling pairs with Somali background. 25(OH)D levels were analysed in the stored dried blood spots taken in the neonatal period for metabolic screening. RESULTS: The collapsed group of children with ASD had significantly lower vitamin D levels (M = 24.0 nM, SD = 19.6) as compared with their siblings (M = 31.9 nM, SD = 27.7), according to a paired samples t-test (P = 0.013). The difference was - most likely - not only accounted for by a difference in season of birth between ASD and non-ASD siblings since the mean 25(OH)D levels differed with similar effect size between the sibling pairs born during winter and summer, respectively. All children with African/Middle East background, both the children with ASD and their non-ASD siblings, had vitamin D deficiency. CONCLUSIONS: The findings suggest that low prenatal vitamin D may act as a risk factor for ASD, however, there is a need for replication with larger samples. Future research should study whether or not adequate supplementation of vitamin D to pregnant women might lower the risk for ASD in the offspring.