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1.
  • Humble, Mats B., 1952-, et al. (author)
  • Plasma oxytocin changes and anti-obsessive response during serotonin reuptake inhibitor treatment : a placebo controlled study
  • 2013
  • In: BMC Psychiatry. - 1471-244X. ; 13, s. 344-
  • Journal article (peer-reviewed)abstract
    • 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.
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  • Meehan, Adrian D., 1973-, et al. (author)
  • The prevalence of lithium-associated hyperparathyroidism in a large Swedish population attending psychiatric outpatient units
  • 2015
  • In: Journal of Clinical Psychopharmacology. - 0271-0749 .- 1533-712X. ; 35:3, s. 279-285
  • Journal article (peer-reviewed)abstract
    • 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.
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  • Bejerot, Susanne, 1955-, et al. (author)
  • Childhood clumsiness and peer victimization : a case-control study of psychiatric patients
  • 2013
  • In: BMC Psychiatry. - London, United Kingdom : BioMed Central. - 1471-244X. ; 13
  • Journal article (peer-reviewed)abstract
    • 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.
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  • Bejerot, Susanne, 1955-, et al. (author)
  • Diagnostik och terapi utmanar än, trots snabb tillväxt av kunskap [Diagnosis and therapy are still challenging, despite the rapid growth of knowledge]
  • 2014
  • In: Läkartidningen. - Stockholm, Sweden : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; 111:39, s. 1638-1641
  • Research review (peer-reviewed)abstract
    • 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.
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  • Bejerot, Susanne, 1955-, et al. (author)
  • Joint Hypermobility in Paediatric Acute-Onset Neuropsychiatric Syndrome : A Preliminary Case-Control Study
  • 2021
  • In: Frontiers in Psychiatry. - : Frontiers Media S.A.. - 1664-0640. ; 12
  • Journal article (peer-reviewed)abstract
    • 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.
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  • Bejerot, Susanne, 1955-, et al. (author)
  • Low prevalence of smoking among patients with obsessive-compulsive disorder
  • 1999
  • In: Comprehensive Psychiatry. - Philadelphia, USA : Saunders Elsevier. - 0010-440X .- 1532-8384. ; 40:4, s. 268-272
  • Journal article (peer-reviewed)abstract
    • Tobacco smoking is common among psychiatric patients, especially among those with schizophrenia, where the prevalence is extremely high, 74% to 88%, compared with 45% to 70% in patients with other psychiatric diagnoses. Patients with anxiety disorders are less well investigated in this respect, particularly obsessive-compulsive disorder (OCD) patients. Eighty-three psychiatric outpatients with OCD and 110 members of the Swedish OCD Association responded to questions concerning their smoking habits. Among OCD patients, 14% were current smokers (compared with 25% in the general population of Sweden), 72% had never smoked, and 11 previous smokers had stopped, mostly without any difficulties. Since a decreased smoking rate among OCD subjects was confirmed, the smoking prevalences in schizophrenia and OCD, respectively, seem to represent either end of a continuum, and OCD may also differ significantly from other anxiety disorders in this respect. Possible implications of this finding for the purported frontal lobe dysregulation in OCD are discussed.
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  • Bejerot, Susanne, 1955-, et al. (author)
  • Poor performance in physical education - a risk factor for bully victimization A case-control study
  • 2011
  • In: Acta Paediatrica. - Malden, USA : Wiley. - 0803-5253 .- 1651-2227. ; 100:3, s. 413-419
  • Journal article (peer-reviewed)abstract
    • 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.
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  • Bejerot, Susanne, 1955-, et al. (author)
  • Rituximab as an adjunctive treatment for schizophrenia spectrum disorder or obsessive-compulsive disorder : Two open-label pilot studies on treatment-resistant patients
  • 2023
  • In: Journal of Psychiatric Research. - : Elsevier. - 0022-3956 .- 1879-1379. ; 158, s. 319-329
  • Journal article (peer-reviewed)abstract
    • 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.
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  • Bejerot, Susanne, 1955-, et al. (author)
  • Study protocol for a randomized controlled trial with rituximab for psychotic disorder in adults (RCT-Rits)
  • 2023
  • In: BMC Psychiatry. - : BioMed Central (BMC). - 1471-244X. ; 23:1
  • Journal article (peer-reviewed)abstract
    • 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.
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  • Bejerot, Susanne, 1955-, et al. (author)
  • The Brief Obsessive-Compulsive Scale (BOCS) : a self-report scale for OCD and obsessive-compulsive related disorders
  • 2014
  • In: Nordic Journal of Psychiatry. - : Informa Healthcare. - 0803-9488 .- 1502-4725. ; 68:8, s. 549-559
  • Journal article (peer-reviewed)abstract
    • 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 alpha = 0.81; Severity Scale: sensitivity = 72%, specificities = 75-84%, Cronbach's alpha = 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.
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  • Bejerot, Susanne, 1955-, et al. (author)
  • The extreme male brain revisited: gender coherence in adults with autism spectrum disorder
  • 2012
  • In: British Journal of Psychiatry. - London, United Kingdom : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 201:2, s. 116-123
  • Journal article (peer-reviewed)abstract
    • 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.
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  • Fernell, Elisabeth, 1948, et al. (author)
  • Autism spectrum disorder and low vitamin D at birth : a sibling control study
  • 2015
  • In: Molecular Autism. - : Springer Science and Business Media LLC. - 2040-2392. ; 6
  • Journal article (peer-reviewed)abstract
    • 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.
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  • Fresnais, David, et al. (author)
  • Apathy as a Predictor for Conversion From Mild Cognitive Impairment to Dementia : A Systematic Review and Meta-Analysis of Longitudinal Studies
  • 2023
  • In: Journal of Geriatric Psychiatry and Neurology. - : Sage Publications. - 0891-9887 .- 1552-5708. ; 36:1, s. 3-17
  • Research review (peer-reviewed)abstract
    • 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.
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  • Fresnais, David, et al. (author)
  • The Association between Carotid Intima-Media Thickness and Cognitive Impairment : A Systematic Review and Meta-Analysis
  • 2021
  • In: Dementia and Geriatric Cognitive Disorders. - : S. Karger. - 1420-8008 .- 1421-9824. ; 50:4, s. 305-317
  • Research review (peer-reviewed)abstract
    • 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.
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  • Glans, Martin, 1985-, et al. (author)
  • Association between adult adhd and generalised joint hypermobility, with and without systemic manifestations : A case-control study
  • 2021
  • In: European psychiatry. - : Cambridge University Press. - 0924-9338 .- 1778-3585. ; 64:Suppl. 1, s. S89-S89
  • Journal article (other academic/artistic)abstract
    • Introduction: There is growing evidence that generalised joint hypermobility (GJH) is associated with several psychiatric conditions. There are no previous studies on adult ADHD.Objectives: To evaluate, in a large Swedish sample, if generalised joint hypermobility and adult ADHD are associated.Methods: 431 adults with ADHD and 417 controls were included. GJH was assessed by the Beighton Score, a physical examination, and the 5PQ, a self-report screening tool. Exploratively, reported musculoskeletal symptoms and abnormal skin manifestations suggestive of symptomatic GJH (e.g. Ehlers-Danlos syndrome), were assessed to differentiate this group from the general GJH group. Logistic regressions determined the influence of an ADHD diagnosis and known covariates (age, sex and ethnicity) on GJH and symptomatic GJH respectively.Results: ADHD was associated to GJH, as defined by the Beighton Score and the 5PQ, with adjusted odds ratios of 4.65 (CI 95% 3.01-7.18, p<.005) and 1.86 (CI 95% 1.39-2.48, p<.005), respectively. Likewise, ADHD and symptomatic GJH were associated withadjusted odds ratios of 6.94 (CI 95% 4.05-11.89, p<.005) and 2.66 (CI 95% 1.94-3.66, p<.005).Conclusions: GJH and adult ADHD are associated conditions. Symptomatic GJH, defined as additional symptoms of pain and/or skin manifestations, has a considerably stronger link to adult ADHD than unspecific GJH has. GJH may represent a marker of an underlying systemic disorder with physical manifestations in connective tissue as well as behavioural manifestations including hyperactivity, impulsiveness and inattentiveness. Future studies should investigate if this represents a novel subtype of ADHD and if symptomatic GJH affects the ADHD management.
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  • Glans, Martin, 1985-, et al. (author)
  • Association between adult attention-deficit hyperactivity disorder and generalised joint hypermobility : A cross-sectional case control comparison
  • 2021
  • In: Journal of Psychiatric Research. - : Elsevier. - 0022-3956 .- 1879-1379. ; 143, s. 334-340
  • Journal article (peer-reviewed)abstract
    • 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.
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  • Glans, Martin, 1985-, et al. (author)
  • Generalised joint hypermobility and neurodevelopmental traits in a non-clinical adult population
  • 2017
  • In: BJPsych Open. - : Royal College of Psychiatrists. - 2056-4724. ; 3:5, s. 236-242
  • Journal article (peer-reviewed)abstract
    • 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.
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  • Glans, Martin, 1985-, et al. (author)
  • Self-rated joint hypermobility : the five-part questionnaire evaluated in a Swedish non-clinical adult population
  • 2020
  • In: BMC Musculoskeletal Disorders. - : BioMed Central. - 1471-2474. ; 21:1
  • Journal article (peer-reviewed)abstract
    • 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.
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  • Glans, M., et al. (author)
  • Symptomatic generalised joint hypermobility and autism spectrum disorder are associated in adults
  • 2022
  • In: European psychiatry. - : Cambridge University Press. - 0924-9338 .- 1778-3585. ; 65:Suppl. 1, s. S452-S452
  • Journal article (other academic/artistic)abstract
    • Introduction: Intriguingly, autism spectrum disorders (ASD) and symptomatic generalised joint hypermobility (S-GJH) (e.g. hypermobility spectrum disorders and Ehlers Danlos Syndrome) share several clinical manifestations including motor difficulties, sensory hypersensitivity and autonomic dysfunction. Moreover, many syndromic forms of ASD manifest a hypermobile phenotype. Despite the increased interest in the area, few systematic studies are available.Objectives: This large cross-sectional comparative study aimed to examine the association between S-GJH and ASD in adults.Methods: We assessed GJH by physical examination using the Beighton Scoring System (BSS) and collected data on musculoskeletal symptoms and skin abnormalities amongst 156 adult patients with ASD and 413 adult community controls. A proxy for S-GJH was created by combining a positive BSS with at least one additional musculoskeletal symptom or skin abnormality.Results: The prevalence of S-GJH was significantly higher amongst patients with ASD than amongst controls (16.7% vs 4.8%, p< .001). A logistic regression model, adjusting for candidate covariates of GJH (age, sex, race), revealed a significant influence of ASD on S-GJH with adjusted odds ratio of 5.4 (95% CI 2.8-10.5, p< .001).Conclusions: ASD and S-GJH are associated in adults. If recognised, musculoskeletal complications related to S-GJH can be relieved by physiotherapy. Clinicians should be familiar with that symptoms frequently occurring in GJH such as pain, fatigue and orthostatic intolerance may mimic or aggravate psychiatric symptoms (e.g. depression, anxiety). Knowledge about comorbidities may provide clues to underlying aethiopathological factors. Future research to clarify the mechanisms behind this association and to evaluate how comorbid S-GJH affects ASD outcome is warranted.
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30.
  • Glans, Martin, 1985-, et al. (author)
  • The Relationship Between Generalised Joint Hypermobility and Autism Spectrum Disorder in Adults : A Large, Cross-Sectional, Case Control Comparison
  • 2022
  • In: Frontiers in Psychiatry. - : Frontiers Media S.A.. - 1664-0640. ; 12
  • Journal article (peer-reviewed)abstract
    • 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.
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31.
  • Holländare, Fredrik, 1972-, et al. (author)
  • Internet-Based Cognitive Behavioral Therapy for Residual Symptoms in Bipolar Disorder Type II : A Single-Subject Design Pilot Study
  • 2015
  • In: JMIR Research Protocols. - : JMIR publications. - 1929-0748. ; 4:2
  • Journal article (peer-reviewed)abstract
    • 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-sberg 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.
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32.
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33.
  • Humble, Mats B., 1952-, et al. (author)
  • Low serum levels of 25-hydroxyvitamin D (25-OHD) among psychiatric out-patients in Sweden : Relations with season, age, ethnic origin and psychiatric diagnosis
  • 2010
  • In: Journal of Steroid Biochemistry and Molecular Biology. - Oxford, United Kingdom : Elsevier BV. - 0960-0760 .- 1879-1220. ; 121:1-2, s. 467-470
  • Journal article (peer-reviewed)abstract
    • In a chart review at a psychiatric out-patient department, latitude 59.3 degrees N, a sample of patients with tests of serum 25-hydroxy-vitamin D (25-OHD) and plasma intact parathyroid hormone (iPTH) was collected, together with demographic data and psychiatric diagnoses. During 19 months, 117 patients were included. Their median 25-0HD was 45 nmol/l; considerably lower than published reports on Swedish healthy populations. Only 14.5% had recommended levels (over 75). In 56.4%, 25-OHD was under 50 nmol/l, which is related to several unfavourable health outcomes. Seasonal variation of 25-OHD was blunted. Patients with ADHD had unexpectedly low iPTH levels. Middle East, South-East Asian or African ethnic origin, being a young male and having a diagnosis of autism spectrum disorder or schizophrenia predicted low 25-OHD levels. Hence, the diagnoses that have been hypothetically linked to developmental (prenatal) vitamin D deficiency, schizophrenia and autism, had the lowest 25-OHD levels in this adult sample, supporting the notion that vitamin D deficiency may not only be a predisposing developmental factor but also relate to the adult patients' psychiatric state. This is further supported by the considerable psychiatric improvement that coincided with vitamin D treatment in some of the patients whose deficiency was treated.
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34.
  • Humble, Mats B., 1952- (author)
  • Obsessive-compulsive disorder, serotonin and oxytocin : treatment response and side effects
  • 2016
  • Doctoral thesis (other academic/artistic)abstract
    • Obsessive-compulsive disorder (OCD), with a prevalence of 1-2 %, frequently leads a chronic course. Persons with OCD are often reluctant to seek help and, if they do, their OCD is often missed. This is unfortunate, since active treatment may substantially improve social function and quality of life. Serotonin reuptake inhibitors (SRIs) have welldocumented efficacy in OCD, but delayed response may be problematic. Methods to predict response have been lacking. Because SRIs are effective, pathophysiological research on OCD has focussed on serotonin. However, no clear aberrations of serotonin have been found, thus other mechanisms ought to be involved.Our aims were to facilitate clinical detection and assessment of OCD, to search for biochemical correlates of response and side-effects in SRI treatment of OCD and to identify any possible involvement of oxytocin in the pathophysiology of OCD.In study I, we tested in 402 psychiatric out-patients the psychometric properties of a concise rating scale, “Brief Obsessive Compulsive Scale” (BOCS). BOCS was shown to be easy to use and have excellent discriminant validity in relation to other common psychiatric diagnoses.Studies II-V were based on 36 OCD patients from a randomised controlled trial of paroxetine, clomipramine or placebo. In study II, contrary to expectation, we found that the change (decrease) of serotonin in whole blood was most pronounced in non-responders to SRI. This is likely to reflect inflammatory influence on platelet turnover rather than serotonergic processes within the central nervous system.In studies IV-V, we found relations between changes of oxytocin in plasma and the anti-obsessive response, and between oxytocin and the SRI related delay of orgasm, respectively. In both cases, the relation to central oxytocinergic mechanisms is unclear. In males, delayed orgasm predicted anti-obsessive response.
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35.
  • Humble, Mats B., 1952-, et al. (author)
  • Orgasm, Serotonin Reuptake Inhibition, and Plasma Oxytocin in Obsessive-Compulsive Disorder. Gleaning From a Distant Randomized Clinical Trial
  • 2016
  • In: Sexual Medicine. - Oxford, United Kingdom : Elsevier. - 2050-1161. ; 4:3, s. e145-e155
  • Journal article (peer-reviewed)abstract
    • 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.
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36.
  • Humble, Mats B., 1952-, et al. (author)
  • Paroxetine concentrations in obsessive-compulsive disorder : Support for a therapeutic interval
  • 2017
  • In: European psychiatry. - : Elsevier. - 0924-9338 .- 1778-3585. ; 41:Suppl., s. S322-S322
  • Journal article (other academic/artistic)abstract
    • Introduction: Previous studies of concentrations of serotonin reuptake inhibitors (SRIs) versus therapeutic efficacy have yielded inconsistent results. Even if the relationships between the individual's serotonergic system and the clinical symptoms of obsessive-compulsive disorder (OCD) are poorly understood, the SRIs are consistently effective in OCD. However, studies on SRI concentrations in OCD treatment are rare.Objectives/aims: To identify possible links between paroxetine concentrations and anti-obsessive response.Methods: In a randomised, double-blind trial, comparing clomipramine, paroxetine and placebo in OCD treatment, serum paroxetine levels were measured after 1 week and after 4 weeks of treatment in 18 patients. Anti-obsessive response was assessed with Yale-Brown obsessive compulsive scale (Y-BOCS) and patients’ global evaluation (PGE), after 12 weeks of treatment.Results: Serum paroxetine concentrations after 4 weeks suggested a therapeutic interval between 50 and 240 nmol/L (13–63 ng/mL). The mean Y-BOCS decrease was 54% inside versus 7% outside this interval (t = 3.96; P = 0.0011).Conclusions: Paroxetine levels seemingly predicted clinical outcome. Studies with a greater number of patients are necessary in order to confirm this finding and to discern whether it is useful in clinical practice.
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37.
  • Humble, Mats B., 1952-, et al. (author)
  • Rituximab for treatment-resistant schizophrenia and/or obsessive-compulsive disorder (OCD) : functional connectivity and cytokines associated with symptomatic improvements
  • 2023
  • In: European psychiatry. - : Cambridge University Press. - 0924-9338 .- 1778-3585. ; 66:Suppl. 1, s. S629-S629
  • Journal article (other academic/artistic)abstract
    • Introduction: Immunological mechanisms may contribute to the causation of mental illness. Autoimmunity is most convincingly shown for anti-NMDA-R encephalitis and Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS); disorders that overlap clinically with schizophrenia and OCD. Altered inflammatory cytokine production, glial activation and auto-antibodies have also been associated with schizophrenia and OCD. In these disorders, however, the treatment results with anti-inflammatory or immunomodulating drugs have hitherto been limited and inconsistent. Yet other targets within the immune system may still be effective and new options are warranted for treatment-resistant patients. Rituximab targets B-lymphocytes and is often used in autoimmune disorders such as rheumatoid arthritis, multiple sclerosis and anti-NMDA-R encephalitis.Objectives: We aimed to investigate whether rituximab is clinically effective, safe and tolerable as add-on therapy in markedly ill, treatment-resistant adult psychiatric patients with schizophrenia or OCD. We also wanted to identify putative mediating mechanisms in treatment responders, such as cytokine changes and functional connectivity (FC).Methods: In an open pilot study, adults (18-39 years) with treatment-resistant schizophrenia and/or OCD were included. They received an intravenous infusion of rituximab 1000 mg, once at baseline, in addition to their regular psychiatric medication and were followed for 1 year. The main outcome measures were the Positive and Negative Syndrome Scale (PANSS) or Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the Clinical Global Impression-Improvement scale (CGI-I) and the Personal and Social Performance scale (PSP). Treatment response was defined as ≥ 40 % decrease in PANSS or ≥ 35 % decrease in Y-BOCS, and much improved according to CGI-I. Resting-state fMRI was applied at baseline and after 5 months. Plasma cytokines were measured at 0, 3 and 5 months. Cognitive tests and the recently developed PsychoNeuroinflammatory Related Signs and Symptoms Inventory (PNISSI) were used to identify and measure symptoms related to neuro-inflammation and cognitive function.Results: Nineteen patients were treated with rituximab. 3-5 months after treatment, 6/9 patients with schizophrenia and 1/10 with OCD responded. One schizophrenia patient continues with rituximab every 6 months and has reportedly done well for almost 3 years. No severe side effects were reported apart from recurrent abdominal pain in a schizophrenia patient and one case of post-COVID-19 syndrome. Significant changes of FC were detected in responders only and correlated with PSP changes.Conclusions: Aberrant B-cell activities may contribute to treatment-resistant schizophrenia and be amenable to treatment with rituximab. However, the results of this pilot study need confirmation in placebo-controlled trials.
  •  
38.
  • Humble, Mats, 1952-, et al. (author)
  • Reactivity of serotonin in whole blood : relationship with drug response in obsessive-compulsive disorder
  • 2001
  • In: Biological Psychiatry. - New York, USA : Elsevier. - 0006-3223 .- 1873-2402. ; 49:4, s. 360-368
  • Journal article (peer-reviewed)abstract
    • Background: Obsessive-compulsive disorder responds almost only to potent serotonin reuptake inhibitors. Previous studies have suggested a relation between serotonergic function and clinical outcome in serotonin reuptake inhibitor treatment of obsessive-compulsive disorder.Methods: In a randomized, double-blind trial, comparing clomipramine, paroxetine, and a placebo in obsessive-compulsive disorder, serotonin levels in whole blood (WB-5-HT) were measured at baseline, after 1 week, and after 4 weeks of treatment and related to clinical outcome in 36 patients.Results: In patients treated with serotonin reuptake inhibitors there was a pronounced decrease of WB-5-HT, variable after 1 week and uniformly maximal after 4 weeks. The decrease of WB-5-HT after 1 week of serotonin reuptake inhibitor treatment correlated negatively with clinical outcome after 12 weeks (r = -.61, p =.0006); hence, patients with slower WB-5-HT reactivity eventually responded better to treatment. Baseline WB-5-HT, but not WB-5-HT reactivity, was related to season. Depression, autistic traits, and previous serotonin reuptake inhibitor treatment predicted nonresponse.Conclusions: A fast decrease of WB-5-HT was associated with poor clinical outcome. This may be related to faster serotonin efflux from platelets, which has previously been linked to autism. Further studies are necessary to identify the underlying mechanism and discern whether serotonin reuptake inhibitor-induced WB-5-HT decrease is clinically useful.
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39.
  • Hylén, Ulrika, 1977-, et al. (author)
  • Alterations in inflammasome-related immunometabolites in individuals with severe psychiatric disorders
  • 2023
  • In: BMC Psychiatry. - : BioMed Central (BMC). - 1471-244X. ; 23:1
  • Journal article (peer-reviewed)abstract
    • 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.
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40.
  •  
41.
  • Hylén, Ulrika, 1977-, et al. (author)
  • Increased inflammasome activity in markedly ill psychiatric patients : An explorative study
  • 2020
  • In: Journal of Neuroimmunology. - : Elsevier. - 0165-5728 .- 1872-8421. ; 339
  • Journal article (peer-reviewed)abstract
    • The aim of this study was to investigate inflammatory perturbations in 40 patients with severe and complex psychiatric disorders by studying the activity of the NLRP3 inflammasome, with a trans-diagnostic approach. Gene expression of CASP1, NLRP3, PYCARD, IL1B, IL1RN, TNF showed a significant increase in the patient group compared to a matched control group. Plasma levels of IL1Ra, IL-18, TNF, IL-6 and CRP were increased in the patient group. Within the patient group, increased gene expression of inflammatory markers correlated with increased disease severity. The findings support the inflammation hypothesis for markedly ill psychiatric patients across diagnostic groups.
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42.
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43.
  • Hylén, Ulrika, 1977-, et al. (author)
  • Potential Transdiagnostic Lipid Mediators of Inflammatory Activity in Individuals With Serious Mental Illness
  • 2021
  • In: Frontiers in Psychiatry. - : Frontiers Media S.A.. - 1664-0640. ; 12
  • Journal article (peer-reviewed)abstract
    • 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.
  •  
44.
  • Klang, Albin, et al. (author)
  • The impact of schizotypy on quality of life among adults with autism spectrum disorder
  • 2022
  • In: BMC Psychiatry. - : BioMed Central. - 1471-244X. ; 22:1
  • Journal article (peer-reviewed)abstract
    • 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).
  •  
45.
  • Manouilenko, Irina, et al. (author)
  • Brainstem Auditory Evoked Potentials for diagnosing Autism Spectrum Disorder, ADHD and Schizophrenia Spectrum Disorders in adults : A blinded study
  • 2017
  • In: Psychiatry Research. - Clare, Ireland : Elsevier. - 0165-1781 .- 1872-7123. ; 257, s. 21-26
  • Journal article (peer-reviewed)abstract
    • 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.
  •  
46.
  • Manouilenko, Irina, et al. (author)
  • Minor physical anomalies in adults with autism spectrum disorder and healthy controls
  • 2014
  • In: Autism Research and Treatment. - New York, USA : Hindawi Publishing Corporation. - 2090-1925 .- 2090-1933.
  • Journal article (peer-reviewed)abstract
    • Minor Physical Anomalies (MPAs) are subtle abnormalities of the head, face, and limbs, without significant cosmetic or functional impact to the individual. They are assumed to represent external markers of developmental deviations during foetal life. MPAs have been suggested to indicate severity in mental illness and constitute external markers for atypical brain development. Higher frequencies of MPAs can be found in children with autism. The aims of the present study were to examine the prevalence and patterns of MPAs in adults with autism spectrum disorder (ASD) and to investigate whether MPAs are associated with symptom severity and overall functioning. Fifty adults with ASD and intelligence within the normal range and 53 healthy controls were examined with the Waldrop scale, an instrument for assessing MPAs. Face and feet were photographed enabling blinded assessment. Significant differences between the ASD and the control group were found on the MPA total scores, and also in the craniofacial region scores. Moreover, the shape of the ears was associated with autistic traits, in the ASD group. High MPA total scores were associated with poorer functioning. The findings suggest a link between MPAs, autistic traits, and level of functioning. Assessment of MPAs may assist in the diagnostic procedure of psychiatric disorders.
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