| 1. |
- Arathimos, R, et al.
(författare)
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Latent subtypes of manic and/or irritable episode symptoms in two population-based cohorts
- 2022
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Ingår i: The British journal of psychiatry : the journal of mental science. - : Royal College of Psychiatrists. - 1472-1465. ; 221:6, s. 722-731
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Tidskriftsartikel (refereegranskat)abstract
- Mood disorders are characterised by pronounced symptom heterogeneity, which presents a substantial challenge both to clinical practice and research. Identification of subgroups of individuals with homogeneous symptom profiles that cut across current diagnostic categories could provide insights in to the transdiagnostic relevance of individual symptoms, which current categorical diagnostic systems cannot impart.AimsTo identify groups of people with homogeneous clinical characteristics, using symptoms of manic and/or irritable mood, and explore differences between groups in diagnoses, functional outcomes and genetic liability.MethodWe used latent class analysis on eight binary self-reported symptoms of manic and irritable mood in the UK Biobank and PROTECT studies, to investigate how individuals formed latent subgroups. We tested associations between the latent classes and diagnoses of psychiatric disorders, sociodemographic characteristics and polygenic risk scores.ResultsFive latent classes were derived in UK Biobank (N = 42 183) and were replicated in the independent PROTECT cohort (N = 4445), including ‘minimally affected’, ‘inactive restless’, active restless’, ‘focused creative’ and ‘extensively affected’ individuals. These classes differed in disorder risk, polygenic risk score and functional outcomes. One class that experienced disruptive episodes of mostly irritable mood largely comprised cases of depression/anxiety, and a class of individuals with increased confidence/creativity reported comparatively lower disruptiveness and functional impairment.ConclusionsFindings suggest that data-driven investigations of psychopathological symptoms that include sub-diagnostic threshold conditions can complement research of clinical diagnoses. Improved classification systems of psychopathology could investigate a weighted approach to symptoms, toward a more dimensional classification of mood disorders.
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| 2. |
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| 3. |
- Asherson, PJ, et al.
(författare)
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Randomised controlled trial of the short-term effects of osmotic-release oral system methylphenidate on symptoms and behavioural outcomes in young male prisoners with attention deficit hyperactivity disorder: CIAO-II study
- 2023
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Ingår i: The British journal of psychiatry : the journal of mental science. - : Royal College of Psychiatrists. - 1472-1465. ; 222:1, s. 7-17
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Tidskriftsartikel (refereegranskat)abstract
- Research has shown that 20–30% of prisoners meet the diagnostic criteria for attention-deficit hyperactivity disorder (ADHD). Methylphenidate reduces ADHD symptoms, but effects in prisoners are uncertain because of comorbid mental health and substance use disorders.AimsTo estimate the efficacy of an osmotic-release oral system methylphenidate (OROS-methylphenidate) in reducing ADHD symptoms in young adult prisoners with ADHD.MethodWe conducted an 8-week parallel-arm, double-blind, randomised placebo-controlled trial of OROS-methylphenidate versus placebo in male prisoners (aged 16–25 years) meeting the DSM-5 criteria for ADHD. Primary outcome was ADHD symptoms at 8 weeks, using the investigator-rated Connors Adult ADHD Rating Scale (CAARS-O). Thirteen secondary outcomes were measured, including emotional dysregulation, mind wandering, violent attitudes, mental health symptoms, and prison officer and educational staff ratings of behaviour and aggression.ResultsIn the OROS-methylphenidate arm, mean CAARS-O score at 8 weeks was estimated to be reduced by 0.57 points relative to the placebo arm (95% CI −2.41 to 3.56), and non-significant. The responder rate, defined as a 20% reduction in CAARS-O score, was 48.3% for the OROS-methylphenidate arm and 47.9% for the placebo arm. No statistically significant trial arm differences were detected for any of the secondary outcomes. Mean final titrated dose was 53.8 mg in the OROS-methylphenidate arm.ConclusionsADHD symptoms did not respond to OROS-methylphenidate in young adult prisoners. The findings do not support routine treatment with OROS-methylphenidate in this population. Further research is needed to evaluate effects of higher average dosing and adherence to treatment, multi-modal treatments and preventative interventions in the community.
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| 5. |
- Baumeister, S, et al.
(författare)
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Processing of social and monetary rewards in autism spectrum disorders
- 2023
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Ingår i: The British journal of psychiatry : the journal of mental science. - : Royal College of Psychiatrists. - 1472-1465. ; 222:3, s. 100-111
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Tidskriftsartikel (refereegranskat)abstract
- Reward processing has been proposed to underpin the atypical social feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social reward processing in ASD.AimsUtilising a large sample, we aimed to assess reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD.MethodFunctional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6–30.6 years of age) and 181 typically developing participants (7.6–30.8 years of age).ResultsAcross social and monetary reward anticipation, whole-brain analyses showed hypoactivation of the right ventral striatum in participants with ASD compared with typically developing participants. Further, region of interest analysis across both reward types yielded ASD-related hypoactivation in both the left and right ventral striatum. Across delivery of social and monetary reward, hyperactivation of the ventral striatum in individuals with ASD did not survive correction for multiple comparisons. Dimensional analyses of autism and attention-deficit hyperactivity disorder (ADHD) scores were not significant. In categorical analyses, post hoc comparisons showed that ASD effects were most pronounced in participants with ASD without co-occurring ADHD.ConclusionsOur results do not support current theories linking atypical social interaction in ASD to specific alterations in social reward processing. Instead, they point towards a generalised hypoactivity of ventral striatum in ASD during anticipation of both social and monetary rewards. We suggest this indicates attenuated reward seeking in ASD independent of social content and that elevated ADHD symptoms may attenuate altered reward seeking in ASD.
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| 6. |
- Bjorkenstam, E, et al.
(författare)
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Mental disorders, suicide attempt and suicide: differences in the association in refugees compared with Swedish-born individuals
- 2020
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Ingår i: The British journal of psychiatry : the journal of mental science. - : Royal College of Psychiatrists. - 1472-1465. ; 217:6, s. 679-685
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Tidskriftsartikel (refereegranskat)abstract
- Mental disorders are associated with an elevated risk for suicide attempt and suicide. Whether the strength of the associations also holds for refugees is unclear.AimsTo examine the relationship between specific mental disorders and suicide attempt and suicide in refugees and Swedish-born individuals.MethodThis longitudinal cohort study included 5 083 447 individuals aged 16–64 years, residing in Sweden in 2004, where 196 757 were refugees. Mental disorders were defined as having a diagnosis in psychiatric care during 2000–2004. Estimates of risk of suicide attempt and suicide were calculated as hazard ratios with 95% confidence intervals. Adjustments were made for important confounding factors, including history of attempt. The reference group comprised Swedish-born individuals without mental disorders.ResultsRates for suicide attempt in individuals with a mental disorder were lower in refugees compared with Swedish-born individuals (480 v. 850 per 100 000 person-years, respectively). This pattern was true for most specific disorders: compared with the reference group, among refugees, multivariable-adjusted hazard ratios for suicide attempt ranged from 3.0 (anxiety) to 7.4 (substance misuse), and among Swedish-born individuals, from 4.9 (stress-related disorder) to 9.3 (substance misuse). For schizophrenia, bipolar disorder and personality disorder, estimates for suicide attempt were comparable between refugees and Swedish-born individuals. Similar patterns were seen for suicide.ConclusionsFor most mental disorders, refugees were less likely to be admitted to hospital for suicide attempt or die by suicide compared with Swedish-born individuals. Further research on risk and protective factors for suicide attempt and suicide among refugees with mental disorders is warranted.Declaration of interestNone.
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| 7. |
- Brannigan, R, et al.
(författare)
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The role of prenatal stress as a pathway to personality disorder: longitudinal birth cohort study
- 2020
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Ingår i: The British journal of psychiatry : the journal of mental science. - : Royal College of Psychiatrists. - 1472-1465. ; 216:2, s. 85-89
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Tidskriftsartikel (refereegranskat)abstract
- Many studies have reported associations between prenatal stress and the development of psychotic, anxiety and depressive disorders; however, to date no studies have investigated potential associations with personality disorders.AimsThis study investigated potential associations between exposure to prenatal stress and personality disorder in offspring.MethodIn a subsample (N = 3626) of a large Finnish birth cohort, we used logistic regression models to examine associations between self-reported maternal stress during pregnancy, collected monthly during antenatal clinic appointments, and personality disorder in offspring. Familial and outcome information were obtained by linking data from the Finnish Hospital Discharge Register and the Finnish Population Register.ResultsCompared with those unexposed, children exposed to any maternal stress during gestation had three times the odds of developing a personality disorder (odds ratio 2.76, 95% CI 1.59–4.80, P = 0.000). Those exposed to moderate stress had three times the odds (odds ratio 3.13, 95% CI 1.42–6.88, P = 0.005) and those exposed to severe stress had seven times the odds (odds ratio 7.06, 95% CI 2.10–23.81, P = 0.002) of developing a personality disorder. These associations remained after adjusting for parental psychiatric history, comorbid psychiatric diagnoses, prenatal smoking and antenatal depression.*ConclusionsExposure to stress during gestation increases the odds of personality disorder in offspring, independent of other psychiatric disorders. These results suggest the assessment of maternal stress and well-being during pregnancy may be useful in identifying those at greatest risk of developing personality disorder, and highlight the importance of prenatal care for good maternal mental health during pregnancy.
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| 9. |
- Cearns, M., et al.
(författare)
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Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach
- 2022
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Ingår i: British Journal of Psychiatry. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 220:4, s. 219-228
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Tidskriftsartikel (refereegranskat)abstract
- Background Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment. Aims To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder. Method This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi(+)Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework. Results The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data. Conclusions Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
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