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.

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.

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.

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).

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.

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.

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.

The Brief Obsessive-Compulsive Scale (BOCS): a self-report scale for OCD and obsessive-compulsive related disorders.

BACKGROUND: The Brief Obsessive Compulsive Scale (BOCS), derived from the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the children's version (CY-BOCS), is a short self-report tool used to aid in the assessment of obsessive-compulsive symptoms and diagnosis of obsessive-compulsive disorder (OCD). It is widely used throughout child, adolescent and adult psychiatry settings in Sweden but has not been validated up to date. AIM: The aim of the current study was to examine the psychometric properties of the BOCS amongst a psychiatric outpatient population. METHOD: The BOCS consists of a 15-item Symptom Checklist including three items (hoarding, dysmorphophobia and self-harm) related to the DSM-5 category "Obsessive-compulsive related disorders", accompanied by a single six-item Severity Scale for obsessions and compulsions combined. It encompasses the revisions made in the Y-BOCS-II severity scale by including obsessive-compulsive free intervals, extent of avoidance and excluding the resistance item. 402 adult psychiatric outpatients with OCD, attention-deficit/hyperactivity disorder, autism spectrum disorder and other psychiatric disorders completed the BOCS. RESULTS: Principal component factor analysis produced five subscales titled "Symmetry", "Forbidden thoughts", "Contamination", "Magical thoughts" and "Dysmorphic thoughts". The OCD group scored higher than the other diagnostic groups in all subscales (P < 0.001). Sensitivities, specificities and internal consistency for both the Symptom Checklist and the Severity Scale emerged high (Symptom Checklist: sensitivity = 85%, specificities = 62-70% Cronbach's α = 0.81; Severity Scale: sensitivity = 72%, specificities = 75-84%, Cronbach's α = 0.94). CONCLUSIONS: The BOCS has the ability to discriminate OCD from other non-OCD related psychiatric disorders. The current study provides strong support for the utility of the BOCS in the assessment of obsessive-compulsive symptoms in clinical psychiatry.

[Diagnosis and therapy are still challenging, despite the rapid growth of knowledge]. / Diagnostik och terapi utmanar än, trots snabb tillväxt av kunskap.

Psychiatric diagnoses are not reflections of the aetiology of the disorder, but rather lists of symptoms with considerable overlaps, which hamper research and may cause confusion. The diagnoses of autism spectrum disorder, attention deficit hyperactivity disorder and tic disorder are often comorbid along with a number of other symptomatic syndromes. Individual immune responsivity is possibly involved in pathophysiological mechanisms. Multiple environmental factors may contribute to the clinical phenotypes. Recent research supports to some extent the involvement of dietary and nutritional factors in ADHD. In spite of impressive progress in the molecular biological understanding of the pathophysiology of these disorders, treatment options are still limited and more research is warranted.

Childhood clumsiness and peer victimization: a case-control study of psychiatric patients.

BACKGROUND: Poor motor and social skills as well as peer victimization are commonly reported in both ADHD and autism spectrum disorder. Positive relationships between poor motor and poor social skills, and between poor social skills and peer victimization, are well documented, but the relationship between poor motor skills and peer victimization has not been studied in psychiatric populations. METHOD: 277 patients (133 males, 144 females), mean age 31 years, investigated for ADHD or autism spectrum disorder in adulthood and with normal intelligence, were interviewed about childhood peer victimization and examined for gross motor skills. The parents completed a comprehensive questionnaire on childhood problems, the Five to Fifteen. The Five to Fifteen is a validated questionnaire with 181 statements that covers various symptoms in childhood across eight different domains, one of them targeting motor skills. Regression models were used to evaluate the relationship between motor skills and the risk and duration of peer victimization, adjusted for sex and diagnosis. RESULTS: Victims were described as more clumsy in childhood than their non-victimized counterparts. A significant independent association was found between reportedly poor childhood gross motor skills and peer victimization (adjusted odds ratio: 2.97 [95% confidence interval: 1.46-6.07], n = 235, p = 0.003). In adulthood, the victimized group performed worse on vertical jumps, a gross motor task, and were lonelier. Other factors that were expected to be associated with peer victimization were not found in this highly selected group. CONCLUSION: Poor gross motor skills constitute a strong and independent risk factor for peer victimization in childhood, regardless of sex, childhood psychiatric care and diagnosis.

Plasma oxytocin changes and anti-obsessive response during serotonin reuptake inhibitor treatment: a placebo controlled study.

BACKGROUND: The drug treatments of choice for obsessive-compulsive disorder (OCD) are serotonin reuptake inhibitors (SRIs). However, a correlation between the neuropeptide oxytocin in cerebrospinal fluid and the severity of OCD has previously been shown, and oxytocin and serotonin are interconnected within the brain. Few studies have investigated whether SRIs have any effect on oxytocin; thus, our aim was to explore the possibility that oxytocinergic mechanisms contribute to the anti-obsessive effect of SRIs. METHOD: In a randomized, double-blind trial, comparing SRIs (clomipramine and paroxetine) with placebo in 36 adults with OCD (characterized for subtypes), plasma oxytocin was measured with radioimmunoassay after plasma extraction, at baseline, after 1 week, and after 4 weeks of treatment, and related to baseline severity and clinical response after 12 weeks, as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). RESULTS: Baseline oxytocin levels correlated positively with baseline Y-BOCS ratings, but only among the future SRI responders. Patients with early onset of OCD had higher baseline oxytocin. During treatment, plasma oxytocin did not differ between SRI and placebo treatment. In SRI responders, plasma oxytocin first decreased and then increased; in non-responders (to SRI as well as to placebo), the reverse was the case. After 4 weeks, treatment responders had attained higher oxytocin levels compared to non-responders. The intra-individual range (i.e., the variability) of plasma oxytocin between measurements was the measure that best differentiated responders from non-responders. This range was higher in responders than non-responders, and lower in patients with autistic traits. CONCLUSIONS: SRIs have highly variable effects on plasma oxytocin between individuals. The associations between baseline oxytocin and OCD severity and between oxytocin changes and treatment response support the notions that oxytocin is involved in OCD pathophysiology, and that the anti-obsessive effects of SRIs are partly exerted through oxytocinergic mechanisms.

Poor motor skills: a risk marker for bully victimization.

Children who are clumsy are often bullied. Nevertheless, motor skills have been overlooked in research on bullying victimization. A total of 2,730 Swedish adults (83% females) responded to retrospective questions on bullying, their talents in physical education (i.e., coordination and balls skills) and school academics. Poor talents were used as indicators of poor gross motor skills and poor academic skills. A subset of participants also provided information on educational level in adulthood, childhood obesity, belonging to an ethic minority in school and socioeconomic status relative to schoolmates. A total of 29.4% of adults reported being bullied in school, and 18.4% reported having below average gross motor skills. Of those with below average motor skills, 48.6% were bullied in school. Below average motor skills in childhood were associated with an increased risk (OR 3.01 [95% CI: 1.97-4.60]) of being bullied, even after adjusting for the influence of lower socioeconomic status, poor academic performance, being overweight, and being a bully. Higher odds for bully victimization were also associated with lower socioeconomic status (OR 2.29 [95% CI: 1.45-3.63]), being overweight (OR 1.71 [95% CI: 1.18-2.47]) and being a bully (OR 2.18 [95% CI: 1.53-3.11]). The findings indicate that poor gross motor skills constitute a robust risk-marker for vulnerability for bully victimization.

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.

The extreme male brain revisited: gender coherence in adults with autism spectrum disorder.

BACKGROUND: The 'extreme male brain' theory suggests that autism spectrum disorder (ASD) is an extreme variant of male intelligence. However, somewhat paradoxically, many individuals with ASD display androgynous physical features regardless of gender. AIMS: To assess physical measures, supposedly related to androgen influence, in adults with and without ASD. METHOD: Serum hormone levels, anthropometry, the ratio of 2nd to 4th digit length (2D:4D) and psychiatric symptomatology were measured in 50 adults with high-functioning ASD and age- and gender-matched neurotypical controls. Photographs of face and body, as well as voice recordings, were obtained and assessed with respect to gender coherence, blindly and independently, by eight assessors. RESULTS: Women with ASD had higher total and bioactive testosterone levels, less feminine facial features and a larger head circumference than female controls. Men in the ASD group were assessed as having less masculine body characteristics and voice quality, and displayed higher (i.e. less masculine) 2D:4D ratios, but similar testosterone levels to controls. Androgynous facial features correlated strongly and positively with autistic traits measured with the Autism-Spectrum Quotient in the total sample. In males and females with ASD dehydroepiandrosterone sulfate did not decrease with age, in contrast to the control group. CONCLUSIONS: Women with ASD had elevated testosterone levels and several masculinised characteristics compared with controls, whereas men with ASD displayed several feminised characteristics. Our findings suggest that ASD, rather than being characterised by masculinisation in both genders, may constitute a gender defiant disorder.

Poor performance in physical education - a risk factor for bully victimization. A case-control study.

AIM: Poor social skills are a risk factor for becoming bullied, which could explain why this frequently occurs to children with autism spectrum disorders (ASD) and attention-deficit hyperactivity disorder (ADHD). Poor social skills tend to coexist with clumsiness. According to a pilot study, poor performance in physical education (PE) was correlated with bully victimization. METHODS: Sixty-nine healthy university students reported performance in PE and bully victimization in childhood. In addition, the participants responded to questionnaires for ADHD and ASDs to assess personality traits related to increased risk for bully victimization. RESULTS: Below average performance in PE was a risk factor of being bullied in school with an odds ratio of 3.6 [95% confidence interval: 1.23-10.5; p = 0.017]. Strong correlations between poor performance in PE and long duration of victimization (p = 0.007) and poor performance in PE and high frequency of victimization (p = 0.008) were found. Autistic traits were related to performance below average in PE. CONCLUSION: Poor motor skills are a strong risk factor for becoming bullied. Prevention programmes that identify, protect and empower the clumsy children could be an important step to avoid bullying of the most vulnerable children.

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.

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.