| 31. |
- Engberg, Hedvig, et al.
(author)
-
Congenital adrenal hyperplasia and risk for psychiatric disorders in girls and women born between 1915 and 2010: A total population study.
- 2015
-
In: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 60, s. 195-205
-
Journal article (peer-reviewed)abstract
- Congenital adrenal hyperplasia (CAH) is a chronic condition and individuals are exposed to elevated androgen levels in utero as a result of the endogenous cortisol deficiency. Prenatal androgen exposure has been suggested to influence mental health, but population based studies on psychiatric morbidity among girls and women with CAH are lacking. Therefore, we performed a cohort study based on Swedish nationwide registers linked with the national CAH register. Girls and women with CAH due to 21-hydroxylase deficiency (n=335) born between January 1915 and January 2010 were compared with aged-matched female (n=33500) and male controls (n=33500). Analyses were stratified by phenotype [salt wasting (SW), simple virilizing (SV), and non-classical type (NC)] and by CYP21A2 genotype subgroups (null, I2splice, I172N, and P30L). Results are presented as estimated risks (OR, 95%CI) of psychiatric disorders among girls and women with CAH compared with age-matched controls. Any psychiatric diagnoses were more common in CAH females compared with female and male population controls [1.9 (1.4-2.5), and 2.2 (1.7-2.9)]. In particular, the risk of alcohol misuse was increased compared with female and male population controls [2.8 (1.7-4.7) and 2.1 (1.2-3.5)], and appeared most common among the girls and women with the most severe null genotype [6.7 (2.6-17.8)]. The risk of stress and adjustment disorders was doubled compared with female population controls [2.1 (1.3-3.6)]. Girls and women with CAH have an increased risk of psychiatric disorders in general and substance use disorders in particular compared with unexposed females, with the highest risk among those with the most severe genotype. Prenatal androgen exposure and deficient endogenous cortisol and/or adrenaline production may provide explanations for these findings, but other factors related to CAH cannot be excluded.
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| 32. |
- Genovese, G., et al.
(author)
-
Increased burden of ultra-rare protein-altering variants among 4,877 individuals with schizophrenia
- 2016
-
In: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1097-6256 .- 1546-1726. ; 19:11, s. 1433-1441
-
Journal article (peer-reviewed)abstract
- By analyzing the exomes of 12,332 unrelated Swedish individuals, including 4,877 individuals affected with schizophrenia, in ways informed by exome sequences from 45,376 other individuals, we identified 244,246 coding-sequence and splice-site ultra-rare variants (URVs) that were unique to individual Swedes. We found that gene-disruptive and putatively protein-damaging URVs (but not synonymous URVs) were more abundant among individuals with schizophrenia than among controls (P = 1.3 x 10(-10)). This elevation of protein-compromising URVs was several times larger than an analogously elevated rate for de novo mutations, suggesting that most rare-variant effects on schizophrenia risk are inherited. Among individuals with schizophrenia, the elevated frequency of protein-compromising URVs was concentrated in brain-expressed genes, particularly in neuronally expressed genes; most of this elevation arose from large sets of genes whose RNAs have been found to interact with synaptically localized proteins. Our results suggest that synaptic dysfunction may mediate a large fraction of strong, individually rare genetic influences on schizophrenia risk.
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| 33. |
- Goes, Fernando S, et al.
(author)
-
Exome Sequencing of Familial Bipolar Disorder.
- 2016
-
In: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 73:6, s. 590-7
-
Journal article (peer-reviewed)abstract
- Complex disorders, such as bipolar disorder (BD), likely result from the influence of both common and rare susceptibility alleles. While common variation has been widely studied, rare variant discovery has only recently become feasible with next-generation sequencing.
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| 34. |
- Gotby, A. O., et al.
(author)
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Congenital Adrenal Hyperplasia, Polycystic Ovary Syndrome and criminal behavior: A Swedish population based study
- 2015
-
In: Psychiatry Research. - : Elsevier BV. - 0165-1781 .- 1872-7123. ; 229:3, s. 953-959
-
Journal article (peer-reviewed)abstract
- Both prenatal and circulating testosterone and other androgens have been suggested to influence the individual's propensity to commit crime, but empirical evidence is limited and inconsistent. Congenital Adrenal Hyperplasia (CAH) and Polycystic Ovary Syndrome (PCOS) are both hyperandrogenic conditions but with an important difference; whereas subjects with CAH are exposed to high concentrations of androgens in utero, women with PCOS are subjected to high androgens in adulthood. Comparing these groups can therefore yield important insights of androgenic effects on behavior. In the current study, information on medical diagnoses and convicted crimes were gathered from Swedish population-based registers. The associations between diagnoses of CAH or PCOS and any crime, violent crime or sex crime were estimated with conditional logistic regression. Results showed that CAH in women and men did not predict criminality, whereas an increased risk for any crime and violent crime was found in PCOS women. Our findings indicate that female hyperandrogenism in adulthood, but not prenatal hyperandrogenism, is associated with risk for criminal behavior. Further research into hyperandrogenic conditions holds opportunities to deepen our understanding of the etiology of crime and psychopathology. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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| 35. |
- Hansson, Caroline, 1981, et al.
(author)
-
Risk factors for suicide in bipolar disorder: a cohort study of 12 850 patients
- 2018
-
In: Acta Psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 138:5, s. 456-463
-
Journal article (peer-reviewed)abstract
- ObjectiveMethodBipolar disorder carries a high risk of suicide. Identification of risk factors is important. The aim of this study was to study risk factors for suicide in a large cohort of men and women with bipolar disorder. A prospective cohort study using clinical data from the Swedish National Quality Register for Bipolar Affective Disorder (BipolaR). The outcome variable was suicide captured in the Cause of Death Register between 2004 and 2014. Hazard ratios (HR) were calculated using Cox proportional hazards models. ResultsConclusionsOf 12 850 persons (4844 men and 8006 women) with bipolar disorder, 90 (55 men and 35 women) died by suicide during the follow-up period (between 1 and 10 years). Male sex (HR 2.56), living alone (HR 2.45), previous suicide attempts (HR 4.10), comorbid psychiatric disorder (HR 2.64), recent affective episodes (HR 2.39), criminal conviction (HR 4.43), psychiatric inpatient care (HR 2.79), and involuntary commitment (HR 3.50) were significant risk factors for suicide. Several of the statistically significant risk factors for suicide in bipolar disorder differed between men and women. Risk factors for suicide in bipolar disorder include factors associated with suicide in general, but also diagnosis-specific factors.
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| 36. |
- Hibar, D. P., et al.
(author)
-
Cortical abnormalities in bipolar disorder: An MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group
- 2018
-
In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23:4, s. 932-942
-
Journal article (peer-reviewed)abstract
- Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d='0.293; P=1.71 × 10 '21), left fusiform gyrus (d='0.288; P=8.25 × 10 '21) and left rostral middle frontal cortex (d='0.276; P=2.99 × 10 '19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD. © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
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| 37. |
- Hibar, D. P., et al.
(author)
-
Subcortical volumetric abnormalities in bipolar disorder
- 2016
-
In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 21:12, s. 1710-1716
-
Journal article (peer-reviewed)abstract
- Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=-0.232; P=3.50 × 10 -7) and thalamus (d=-0.148; P=4.27 × 10 -3) and enlarged lateral ventricles (d=-0.260; P=3.93 × 10 -5) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons. © 2016 Macmillan Publishers Limited, part of Springer Nature.
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| 38. |
- Hollis, Chris, et al.
(author)
-
Methylphenidate and the risk of psychosis in adolescents and young adults : a population-based cohort study
- 2019
-
In: Lancet psychiatry. - : Elsevier. - 2215-0374 .- 2215-0366. ; 6:8, s. 651-658
-
Journal article (peer-reviewed)abstract
- Background: There is a clinical concern that prescribing methylphenidate, the most common pharmacological treatment for attention-deficit hyperactivity disorder (ADHD), might increase the risk of psychotic events, particularly in young people with a history of psychosis. We aimed to determine whether the risk of psychotic events increases immediately after initiation of methylphenidate treatment or, in the longer term, 1 year after treatment initiation in adolescents and young adults with and without a previously diagnosed psychotic disorder.Methods: In this cohort study, we used population-based observational data from the Swedish Prescribed Drug Register, the National Patient Register, and the Total Population Register, three population-based registers containing data on all individuals in Sweden, to attain data on sex, birth, death, migration, medication use, and psychotic events for all eligible participants. We screened individuals on these registers to identify those receiving methylphenidate treatment, and who were aged 12-30 years at the start of treatment, for their inclusion in the study. We used a within-individual design to compare the incidence of psychotic events in these individuals during the 12-week periods immediately before and after methylphenidate initiation. Longer term risk was assessed by comparing the incidence of psychotic events 12 weeks before methylphenidate initiation and during a 12-week period one calendar year before the initiation of methylphenidate with the incidence of these events during the 12-week period one calendar year after methylphenidate initiation. We estimated the incidence rate ratios (IRR) and 95% CIs of psychotic events after the initation of methylphenidate treatment, relative to the events before treatment, which were defined as any hospital visit (inpatient admission or outpatient attendance, based on data from the National Patient Register) because of psychosis, using the International Classification of Diseases version 10 definition. Analyses were stratified by whether the individual had a history of psychosis.Findings: We searched the Swedish Prescribed Drug Register to find eligible individuals who had received methylphenidate between Jan 1, 2007 and June 30, 2012. 61 814 individuals were screened, of whom 23 898 (38.7%) individuals were assessed and 37 916 (61.3%) were excluded from the study because they were outside of the age criteria at the start of treatment, they had immigrated, emigrated, or died during the study period, or because they were administered other ADHD medications. The median age at methylphenidate initiation was 17 years, and a history of psychosis was reported in 479 (2.0%) participants. The IRR of psychotic events in the 12-week period after initiation of methylphenidate treatment relative to that in the 12-week period before treatment start was 1.04 (95% CI 0.80-1.34) in adolescents and young adults without a history of psychosis and 0.95 (0.69-1.30) among those with a history of psychosis.Interpretation: Contrary to clinical concerns, we found no evidence that initiation of methylphenidate treatment increases the risk of psychotic events in adolescents and young adults, including in those individuals with a history of psychosis. Our study should reassure clinicians considering initiating methylphenidate treatment for ADHD in adolescents and young adults, and it challenges the widely held view in clinical practice that methylphenidate should be avoided, or its use restricted, in individuals with a history of psychosis.
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| 39. |
- Holm, Jonas, et al.
(author)
-
Improvement of cycloid psychosis following electroconvulsive therapy
- 2017
-
In: Nordic Journal of Psychiatry. - : TAYLOR & FRANCIS LTD. - 0803-9488 .- 1502-4725. ; 71:6, s. 405-410
-
Journal article (peer-reviewed)abstract
- Background: The treatment of choice for cycloid psychosis has traditionally been electroconvulsive therapy (ECT), but there is a lack of studies on its effectiveness.Aims: The primary aim of this register study was to determine the rates of remission and response after ECT for cycloid psychosis. The secondary aim was to examine possible predictors of outcome.Methods: Data were obtained from the National Quality Register for ECT in Sweden. The study population was patients (n=42) who received ECT for acute polymorphic psychotic disorder without symptoms of schizophrenia or for cycloid psychosis between 2011-2015 in 13 hospitals. Remission and response rates were calculated using Clinical Global Impression-Severity (CGI-S) and -Improvement scores, respectively. Variables with possible predictive value were tested using Chi-square and Fisher's exact test.Results: The response rate was 90.5%. The remission rate was 45.2%. Of 42 patients, 40 improved their CGI-S score after ECT (p<0.001). The mean number of ECT treatments was 2.5 for non-responders and 7.0 for responders (p=0.010). The mean number of ECT treatments did not differ significantly between remitters and non-remitters (7.2 vs 6.1, p=0.31). None of the other investigated potential predictors was statistically significantly associated with outcome.Conclusions: ECT is an effective treatment for cycloid psychosis. Future studies need to compare the outcome of ECT to that of other treatment strategies. Clinical implications: The high response rate with ECT indicates that cycloid psychosis is a clinically useful diagnosis.
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| 40. |
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