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Psychological constructs related to health outcomes and well-being, such as metacognitive beliefs, have been linked to executive functions in general, and cognitive flexibility more specifically. However, such effects have previously only been discussed on a theoretical level and behavioral flexibility has most often been measured through self-report, only approximating information processing capacities. Objectively measured executive functions may be a more potent predictor of health outcomes. We set out to test whether cognitive flexibility capacity was associated with sick leave in a medium sized company. We included 111 subjects of widely different occupations and assessed their executive functions using Delis-Kaplan Executive Function System test battery (D-KEFS). To assess cognitive flexibility capacity, we included Design Fluency (DF) and Verbal Fluency (VF) and computed these into an index of cognitive flexibility (DFVF). Detailed information on sick leave for the last 5 years was gathered from the company. Our results showed that there was a significant negative correlation between DFVF and sick leave [rs(109) = -0.23, p = 0.015] in the full group as well as in the group that had at least 1 day of sick leave [rs(72) = -0.25, p = 0.03]. The results withstood adjustment for sex, age, occupation, and several core executive functions as well as autistic and ADHD-traits. The results remained for separate analyses using DF or VF. Our main findings were conceptually replicated in a group of bipolar disorder patients. This study shows that objectively measured capacity of cognitive flexibility is associated with key health outcomes such as sick leave. [ABSTRACT FROM AUTHOR]

Introduction: Psychiatric conditions in parents are associated not only with the same condition in offspring, but also with virtually all other psychiatric conditions. However, it remains unknown whether this intergenerational transmission of psychiatric conditions was attributable to broader psychopathology comorbidity or to specific conditions. Objectives: To estimate associations between general and specific factors of psychopathology in parents, and a wide range of register-based outcomes in their offspring. Methods: Based on Swedish national registers, we linked 2 947 703 individuals born in Sweden between 1970 and 2000 to their biological parents (1 705 780 pairs of parents) and followed them to December 31, 2013. First, we estimated one general and three unrelated (specific) psychopathology factors (capturing internalizing, externalizing, and psychotic problems, respectively, independently of general psychopathology) based on nine parental register-based psychiatric diagnoses and violent criminal court convictions. Second, we regressed each offspring outcome on the latent general and three specific factors simultaneously. Results: The general psychopathology factor in parents was significantly associated with all 31 offspring outcomes (mean Odds Ratio (OR) = 1.22; range: 1.08–1.40), which means that children whose parents scored one standard deviation above the mean on general psychopathology had, on average, a 23% higher probability of all outcomes. The specific psychotic factor in parents was primarily associated with psychotic-like outcomes (mean OR = 1.17; range: 1.05–1.25), and the specific internalizing factor in parents was primarily associated with offspring internalizing (mean OR = 1.11; range: 1.11–1.13) and neurodevelopmental outcomes (mean OR = 1.07; range: 1.02–1.10). The specific externalizing factor in parents was associated with externalizing (mean OR = 1.27; range: 1.21–1.32) and internalizing outcomes (mean OR = 1.10; range: 1.01–1.13). Conclusions: The intergenerational transmission of psychiatric conditions across different types of spectra appeared largely attributable to a parental general factor of psychopathology, whereas specific factors were primarily responsible for within-spectrum associations between parents and their offspring. Service providers (e.g., child psychologists, psychiatrists, teachers, and social workers) might benefit from taking the total number of parental mental health problems into account, regardless of type, when forecasting child mental health and social functions. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Introduction: Children with parents with psychiatric diagnoses have an increased probability for not only the same condition as their parent, but also for other conditions and behavioral and psychosocial problems. Whereas many studies have focused on parental severe mental illness due to their significant impairment, less attention has been paid to more common disorders despite their higher prevalence. In addition, because most past research only included one exposure or one outcome at a time, it remains difficult to examine and compare broad patterns of intergenerational transmission. Objectives: To examine associations between six parental psychiatric diagnoses in parents, and a broad range of psychiatric diagnoses, psychotropic medications, criminality, suicide, violent victimization, accidents, and school and labor performance in their offspring. Methods: Based on Swedish national registers, we linked all individuals born in Sweden between 1970 and 2000 to their biological parents (N = 3 286 293). We used a matched cohort design, analyzed with stratified Cox regression and conditional logistic regressions to examine associations between six psychiatric diagnoses in the parents, and 32 outcomes in their offspring. All exposed and unexposed children were followed from their date of birth to the date of emigration from Sweden, the death, or 31 December 2013 when the offspring were 14-44 years old. Results: In terms of absolute risk, most children who had parents with psychiatric diagnoses were not diagnosed in specialist care themselves, as the proportion of having any of the 16 types of psychiatric conditions ranged from 22.17% (exposed to parental depression) to 25.05% (exposed to parental drug-related disorders) at the end of follow-up. Nevertheless, in terms of relative risk, all six parental psychiatric diagnoses increased the probability of all 32 outcomes in their offspring, with the Hazard Ratio ranging from 1.04 to 8.91 for time-to-event outcomes, and the Odds Ratio ranging from 1.29 to 3.36 for binary outcomes. Some specificities were observed for parental psychotic and substance misuse diagnoses, which strongly predicted offspring psychotic-like and externalizing-related outcomes, respectively. Conclusions: The intergenerational transmission of parental psychiatric conditions appeared largely transdiagnostic, even for non-psychiatric outcomes in offspring. Given the broad spectrum of associations with the outcomes, service providers (e.g., psychiatrists, teachers, and social workers) should consider clients' broader psychiatric family history when predicting prognosis and planning interventions/treatment. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Objective: To investigate external factors that trigger manic and hypomanic relapses and how this is associated with personality and clinical outcome measured as number of affective episodes over a 7‐year period. Method: This is a prospective cohort study of 204 meticulously characterized Swedish bipolar disorder patients. Personality was evaluated at baseline using the Swedish universities Scales of Personality in 170 patients, and 90 patients were followed up after approximately 7 years in order to evaluate clinical outcomes. Results: We found that 44% of the patients reported trigger factors, including sleep disturbance, work‐ or family‐related issues, medication, and illicit drug use. There were no significant differences in any of the personality traits when comparing the 74 patients that reported triggers with the 90 patients that did not. At 7‐year follow‐up, there was no difference between the groups in number of affective episodes (depressive, hypomanic, manic, or mixed), involuntary commitments, suicide attempts, or self‐harm incidents since baseline. Conclusions: Around 40% of the patients reported external triggers for manic and hypomanic episodes. However, this was neither associated with personality traits nor number of affective episodes at 7‐year follow‐up. [ABSTRACT FROM AUTHOR]

Objective: Electroconvulsive therapy (ECT) is used in patients with severe forms of bipolar depression. ECT is effective but not all patients respond. The aim of this study was to determine prognostic factors for response to ECT in patients hospitalized for bipolar depression. Methods: Data were obtained from several national Swedish registers. All patients with bipolar depression treated with ECT in any hospital in Sweden between 2011 and 2016 for whom information about ECT response was available were included (n = 1251). Response was defined as a score on the Clinical Global Impression – Improvement scale of one or two. Univariate and multivariate logistic regression were conducted to investigate associations between socio‐demographic and clinical factors and response. Results: Response was achieved in 80.2% patients. Older age was associated with higher response rate to ECT. Patients with comorbid obsessive‐compulsive disorder or personality disorder, and patients previously treated with lamotrigine had lower response rate. Conclusion: Electroconvulsive therapy for bipolar depression was associated with very high response rates. The strongest prognostic factors were higher age, absence of comorbid obsessive‐compulsive disorder or personality disorder, and less prior pharmacologic treatment. [ABSTRACT FROM AUTHOR]

Objective: Bipolar 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. Method: A prospective cohort study using clinical data from the Swedish National Quality Register for Bipolar Affective Disorder (BipoläR). 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. Results: Of 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. Conclusions: Risk factors for suicide in bipolar disorder include factors associated with suicide in general, but also diagnosis‐specific factors. [ABSTRACT FROM AUTHOR]

Objective: Frontal cortical abnormalities and executive function impairment co‐occur in bipolar disorder. Recent studies have shown that bipolar subtypes differ in the degree of structural and functional impairments. The relationships between cognitive performance and cortical integrity have not been clarified and might differ across patients with bipolar disorder type I, II, and healthy subjects. Method: Using a vertex‐wise whole‐brain analysis, we investigated how cortical integrity, as measured by cortical thickness, correlates with executive performance in patients with bipolar disorder type I, II, and controls (N = 160). Results: We found focal associations between executive function and cortical thickness in the medial prefrontal cortex in bipolar II patients and controls, but not in bipolar I disorder. In bipolar II patients, we observed additional correlations in lateral prefrontal and occipital regions. Conclusions: Our findings suggest that bipolar disorder patients show altered structure–function relationships, and importantly that those relationships may differ between bipolar subtypes. The findings are line with studies suggesting subtype‐specific neurobiological and cognitive profiles. This study contributes to a better understanding of brain structure–function relationships in bipolar disorder and gives important insights into the neuropathophysiology of diagnostic subtypes. [ABSTRACT FROM AUTHOR]

Objective Our aim was to investigate the prevalence and magnitude of weight gain in-patients with bipolar disorder when treated with a second-generation antipsychotic as an add-on treatment to a mood stabilizer in routine clinical practice. Methods Data were derived from the quality register for bipolar disorder in Sweden (BipoläR). Patients with bipolar disorder who started add-on treatment with a SGA ( n = 575) were compared at next yearly follow-up with age and sex matched patients who were only treated with a mood stabilizer ( n = 566). The primary outcome measure was change in body weight and body mass index ( BMI). We also assessed the prevalence of clinically significant weight gain defined as ≥7% gain in body weight. Results The group that received add-on treatment with antipsychotics neither gained more weight nor were at higher risk for a clinically significant weight gain than the reference group. Instead, factors associated with clinically significant weight gain were female sex, young age, low-baseline BMI, and occurrence of manic/hypomanic episodes. Conclusion We found no evidence of an overall increased risk of weight gain for patients with bipolar disorder after receiving add-on SGA to a mood stabilizer in a routine clinical setting. [ABSTRACT FROM AUTHOR]

BackgroundAdvanced paternal age at childbirth is associated with psychiatric disorders in offspring, including schizophrenia, bipolar disorder and autism. However, few studies have investigated paternal age's relationship with eating disorders in offspring. In a large, population-based cohort, we examined the association between paternal age and offspring eating disorders, and whether that association remains after adjustment for potential confounders (e.g. parental education level) that may be related to late/early selection into fatherhood and to eating disorder incidence.MethodData for 2 276 809 individuals born in Sweden 1979–2001 were extracted from Swedish population and healthcare registers. The authors used Cox proportional hazards models to examine the effect of paternal age on the first incidence of healthcare-recorded anorexia nervosa (AN) and all eating disorders (AED) occurring 1987–2009. Models were adjusted for sex, birth order, maternal age at childbirth, and maternal and paternal covariates including country of birth, highest education level, and lifetime psychiatric and criminal history.ResultsEven after adjustment for covariates including maternal age, advanced paternal age was associated with increased risk, and younger paternal age with decreased risk, of AN and AED. For example, the fully adjusted hazard ratio for the 45+ years (v. the 25–29 years) paternal age category was 1.32 [95% confidence interval (CI) 1.14–1.53] for AN and 1.26 (95% CI 1.13–1.40) for AED.ConclusionsIn this large, population-based cohort, paternal age at childbirth was positively associated with eating disorders in offspring, even after adjustment for potential confounders. Future research should further explore potential explanations for the association, including de novo mutations in the paternal germline. [ABSTRACT FROM AUTHOR]

BackgroundThe concept of cognitive reserve (CR) hypothesizes that intellectually stimulating activities provide resilience against brain pathology/disease. Whereas brain abnormalities and cognitive impairment are frequently reported in bipolar disorder (BD), it is unknown whether the impact of brain alterations can be lessened by higher CR in BD.MethodWe tested if higher CR would reduce the influence of total volumes of deep white matter hypointensities (WMH), ventricular cerebrospinal fluid (CSF), and prefrontal cortex on memory, executive, and attention/speed functions in patients with BD (n = 75). Linear regression models with interaction terms for CR and brain volumes were applied to directly test if CR reduces the influence of brain pathology on cognitive domains.ResultsCR reduced the influence of total volumes of deep WMH (β = −0.38, Q = 0.003) and ventricular CSF (β = −41, Q = 006) on executive functions.ConclusionsThe interactions between CR and total volumes of deep WMH/ventricular CSF appear to account for executive functioning in BD. The results suggest that the concept of CR is applicable in BD. Higher reserve capacity in BD alters the relationship between brain pathology and clinical presentation. [ABSTRACT FROM PUBLISHER]

Background Darier disease is an autosomal dominant skin disorder caused by mutations in the ATP2A2 gene. Anecdotal reports suggest a relationship between Darier disease and intellectual disabilities, but these reports are based on small clinical samples and limited by absence of control populations. Objectives To examine the risk of intellectual disability and subclinical impairments in cognitive ability in Darier disease. Methods We conducted a matched cohort study based on Swedish Population-, Patient- and Conscript Registers. The risk of being diagnosed with intellectual disability was estimated in 770 individuals with Darier disease, compared with matched comparison individuals without Darier disease. Associations were examined with risk ratios from conditional logistic regressions. In addition, we analysed test-based cognitive ability data (i.e. IQ data) from the Swedish conscript examination, for a subset of patients without diagnosed intellectual disability. Results Individuals with Darier disease had a sixfold increased risk of being diagnosed with intellectual disability (risk ratio 6·2, 95% confidence interval 3·1-12·4). For conscripted individuals with Darier disease but no diagnosed intellectual disability, mean cognitive ability scores were about half a standard deviation lower than for comparison subjects. Conclusions Darier disease is associated with intellectual disability and subclinical impairments in cognitive ability. The Darier-causing mutations merit further attention in molecular genetic research on intellectual disability and cognitive ability. [ABSTRACT FROM AUTHOR]

Objective To investigate whether persons with bipolar disorder and their siblings have leadership traits and are overrepresented in executive professions. Method A nested case-control study based on longitudinal Swedish total population registries. Data from officer suitability interviews ( n = 1 126 519), and information on occupations were collected. Bipolar patients ( n = 68 915) and their healthy siblings were compared with controls. Results Bipolar patients without comorbidity ( pure; n = 22 980) were overrepresented in both the highest and lowest strata of officer suitability; their healthy siblings in the highest strata only. Patients with pure bipolar disorder were underrepresented in executive professions, whereas their siblings were overrepresented in these professions (particularly political professions). Patients with general bipolar disorder (including those with comorbidities) and their healthy siblings were overrepresented only in the lowest strata of officer suitability ratings. General bipolar patients were underrepresented in executive professions, whereas their siblings had similar rates of executive professions as controls. Adjusting results for IQ slightly attenuated point estimates, but resulted in pure bipolar patients and their siblings no longer being significantly overrepresented in superior strata of officer suitability, and siblings no longer being overrepresented in executive professions. Conclusion Results support that traits associated with bipolar disorder are linked to superior leadership qualities. [ABSTRACT FROM AUTHOR]

Bipolar disorder and schizophrenia are two often severe disorders with high heritabilities. Recent studies have demonstrated a large overlap of genetic risk loci between these disorders but diagnostic and molecular distinctions still remain. Here, we perform a combined genome-wide association study (GWAS) of 19 779 bipolar disorder (BP) and schizophrenia (SCZ) cases versus 19 423 controls, in addition to a direct comparison GWAS of 7129 SCZ cases versus 9252 BP cases. In our case-control analysis, we identify five previously identified regions reaching genome-wide significance (CACNA1C, IFI44L, MHC, TRANK1 and MAD1L1) and a novel locus near PIK3C2A. We create a polygenic risk score that is significantly different between BP and SCZ and show a significant correlation between a BP polygenic risk score and the clinical dimension of mania in SCZ patients. Our results indicate that first, combining diseases with similar genetic risk profiles improves power to detect shared risk loci and second, that future direct comparisons of BP and SCZ are likely to identify loci with significant differential effects. Identifying these loci should aid in the fundamental understanding of how these diseases differ biologically. These findings also indicate that combining clinical symptom dimensions and polygenic signatures could provide additional information that may someday be used clinically. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BD) is a polygenic disorder that shares substantial genetic risk factors with major depressive disorder (MDD). Genetic analyses have reported numerous BD susceptibility genes, while some variants, such as single-nucleotide polymorphisms (SNPs) in CACNA1C have been successfully replicated, many others have not and subsequently their effects on the intermediate phenotypes cannot be verified. Here, we studied the MDD-related gene CREB1 in a set of independent BD sample groups of European ancestry (a total of 64 888 subjects) and identified multiple SNPs significantly associated with BD (the most significant being SNP rs6785[A], P=6.32 × 10−5, odds ratio (OR)=1.090). Risk SNPs were then subjected to further analyses in healthy Europeans for intermediate phenotypes of BD, including hippocampal volume, hippocampal function and cognitive performance. Our results showed that the risk SNPs were significantly associated with hippocampal volume and hippocampal function, with the risk alleles showing a decreased hippocampal volume and diminished activation of the left hippocampus, adding further evidence for their involvement in BD susceptibility. We also found the risk SNPs were strongly associated with CREB1 expression in lymphoblastoid cells (P<0.005) and the prefrontal cortex (P<1.0 × 10−6). Remarkably, population genetic analysis indicated that CREB1 displayed striking differences in allele frequencies between continental populations, and the risk alleles were completely absent in East Asian populations. We demonstrated that the regional prevalence of the CREB1 risk alleles in Europeans is likely caused by genetic hitchhiking due to natural selection acting on a nearby gene. Our results suggest that differential population histories due to natural selection on regional populations may lead to genetic heterogeneity of susceptibility to complex diseases, such as BD, and explain inconsistencies in detecting the genetic markers of these diseases among different ethnic populations. [ABSTRACT FROM AUTHOR]

The kynurenine pathway metabolite kynurenic acid (KYNA), modulating glutamatergic and cholinergic neurotransmission, is increased in cerebrospinal fluid (CSF) of patients with schizophrenia or bipolar disorder type 1 with psychotic features. KYNA production is critically dependent on kynurenine 3-monooxygenase (KMO). KMO mRNA levels and activity in prefrontal cortex (PFC) are reduced in schizophrenia. We hypothesized that KMO expression in PFC would be reduced in bipolar disorder with psychotic features and that a functional genetic variant of KMO would associate with this disease, CSF KYNA level and KMO expression. KMO mRNA levels were reduced in PFC of bipolar disorder patients with lifetime psychotic features (P=0.005, n=19) or schizophrenia (P=0.02, n=36) compared with nonpsychotic patients and controls. KMO genetic association to psychotic features in bipolar disorder type 1 was studied in 493 patients and 1044 controls from Sweden. The KMO Arg452 allele was associated with psychotic features during manic episodes (P=0.003). KMO Arg452 was studied for association to CSF KYNA levels in an independent sample of 55 Swedish patients, and to KMO expression in 717 lymphoblastoid cell lines and 138 hippocampal biopsies. KMO Arg452 associated with increased levels of CSF KYNA (P=0.03) and reduced lymphoblastoid and hippocampal KMO expression (P0.05). Thus, findings from five independent cohorts suggest that genetic variation in KMO influences the risk for psychotic features in mania of bipolar disorder patients. This provides a possible mechanism for the previous findings of elevated CSF KYNA levels in those bipolar patients with lifetime psychotic features and positive association between KYNA levels and number of manic episodes. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to investigate outcomes of child psychiatric outpatient treatment as usual and to identify outcome predictors, with special regard to attention-deficit/hyperactivity disorder ( ADHD), mood disorder, obsessive-compulsive disorder and conduct disorder. Method Routinely collected data from 12 613 outpatients between July 2006 and January 2010 in Stockholm, Sweden were analysed. The outcome measure was change in Children's Global Assessment Scale ( CGAS) ratings between first visit and case closure (∆ CGAS). Results CGAS improved during the course of treatment across all diagnostic groups, ranging from a mean change of 4 (mental retardation) to 16 (suicide attempts). ∆ CGAS was two times higher in the mood disorder group compared with the ADHD group. In the mood disorder group, several psychotherapies were associated with better outcome but not medication. In the ADHD group, psychotherapeutic interventions were also associated with better outcome, but those who received treatment with central stimulants received less non-medical interventions. Conclusion Whereas the functional impairment and the level of improvement in mood disorder corresponded to previous efficacy studies, the ADHD patients were more impaired and improved less after treatment. This should prompt a critical discussion as to whether ADHD patients receive the best available treatment in CAMHS in Stockholm and elsewhere. [ABSTRACT FROM AUTHOR]

Sellgren C, Landén M, Lichtenstein P, Hultman CM, Långström N. Validity of bipolar disorder hospital discharge diagnoses: file review and multiple register linkage in Sweden. Objective: Hospital discharge registers (HDRs) are frequently used in epidemiological research. However, the validity of several important psychiatric diagnostic entities, including bipolar disorder, remains uncertain. Hence, we aimed to develop an optimal algorithm for register-based identification of DSM-IV-TR bipolar disorder. Method: We identified potential cases in the Swedish national HDR using two separate discharge diagnoses of bipolar disorder according to ICD versions 8-10 during January 1, 1973 to December 31, 2004. In a randomly selected subsample of 135 cases from the county of Sörmland, two senior psychiatrists reassessed the diagnostic status based on patients' medical records. We scrutinized false-positive cases and modified the initial algorithm to improve positive predictive value while minimizing false negatives. Finally, we externally validated resulting caseness algorithms by linking HDR diagnostic data with best-estimate clinical diagnoses from the National Quality Assurance Register for Bipolar Disorder (BipoläR), dispensed lithium prescriptions from the National Prescribed Drug Register, and the ICD-10 diagnoses from the National Outpatient Register respectively. Results: The algorithm with two discharge diagnoses of bipolar disorder yielded a positive predictive value of 0.81. Modification by excluding individuals diagnosed with ICD-8 296.20 (manic-depressive psychosis, depressed type), and/or ICD-9 296.B (unipolar affective psychosis, melancholic form), gave a positive positive predictive value of 0.92. The modified algorithm also had statistically superior external validity compared with the original algorithm. Conclusion: Our findings suggest that DSM-IV-TR bipolar disorder caseness based on two inpatient episodes with a bipolar disorder diagnosis is sufficiently sensitive and specific to be used in further epidemiological study of bipolar disorder. [ABSTRACT FROM AUTHOR]

Ekman CJ, Lind J, Rydén E, Ingvar M, Landén M. Manic episodes are associated with grey matter volume reduction - a voxel-based morphometry brain analysis. To investigate whether the lifetime number of affective episodes or illness duration is associated with changes in local grey matter volume, in patients with bipolar I disorder without comorbid conditions. Magnetic resonance imaging scans of 55 patients with bipolar I disorder were analysed using VBM. Smaller grey matter volume in the inferior frontal gyri of the dorsolateral prefrontal cortices (DLPFC) correlated significantly to the lifetime number of manic episodes. No association between local grey matter volume and the lifetime number of depression episodes or illness duration was found. We found strong evidence for a linear correlation between a decrease in DLPFC volume and the lifetime number of manic episodes in patients with bipolar I disorder. Interestingly, DLPFC is known to be important for executive functions and the findings in this study might hence be linked to the executive cognitive deficits associated with bipolar disorder. [ABSTRACT FROM AUTHOR]

BACKGROUND: Anxiety and depression are more prevalent in women with polycystic ovary syndrome (PCOS) than in those without this disorder. Possible confounding effects of overweight and obesity are suggested. The aim was to compare symptoms of anxiety and depression in women with PCOS and controls matched for age, body weight and body mass index (BMI). [ABSTRACT FROM PUBLISHER]

Objective: The occurrence of comorbid attention-deficit hyperactivity disorder (ADHD) might have an impact of the course of the bipolar disorder. Method: Patients with bipolar disorder ( n = 159) underwent a comprehensive evaluation with respect to affective symptoms. Independent psychiatrists assessed childhood and current ADHD, and an interview with a parent was undertaken. Results: The prevalence of adult ADHD was 16%. An additional 12% met the criteria for childhood ADHD without meeting criteria for adult ADHD. Both these groups had significantly earlier onset of their first affective episode, more frequent affective episodes (except manic episodes), and more interpersonal violence than the bipolar patients without a history of ADHD. Conclusion: The fact that bipolar patients with a history of childhood ADHD have a different clinical outcome than the pure bipolar group, regardless of whether the ADHD symptoms remained in adulthood or not, suggests that it represent a distinct early-onset phenotype of bipolar disorder. [ABSTRACT FROM AUTHOR]

BACKGROUND: Testosterone has been attributed importance for various aspects of behaviour. The aim of our study was to investigate the potential influence of 2 functional polymorphisms in the amino terminal of the androgen receptor on personality traits in men. METHODS: We assessed and genotyped 141 men born in 1944 recruited from the general population. We used 2 different instruments: the Karolinska Scales of Personality and the Temperament and Character Inventory. For replication, we similarly assessed 63 men recruited from a forensic psychiatry study group. RESULTS: In the population-recruited sample, the lengths of the androgen receptor repeats were associated with neuroticism, extraversion and self-transcendence. The association with extraversion was replicated in the independent sample. LIMITATIONS: Our 2 samples differed in size; sample 1 was of moderate size and sample 2 was small. In addition, the homogeneity of sample 1 probably enhanced our ability to detect significant associations between genotype and phenotype. CONCLUSION: Our results suggest that the repeat polymorphisms in the androgen receptor gene may influence personality traits in men. [ABSTRACT FROM AUTHOR]

Serum levels of relaxin in 25 women with premenstrual dysphoria and 25 age-matched controls were determined at three time points during the menstrual cycle. At the same time, levels of estradiol, progesterone, 17-β-OH-progesterone, free testosterone, total testosterone, sex hormone binding hormone, androstenedione, dehydroepiandrosterone sulphate, and 3-α-androstanediol glucuronide were determined. Detectable levels of relaxin were found in all women in both the follicular and luteal phase as well as around ovulation, the inter-individual variations being larger than intra-individual differences. The levels of relaxin were not influenced by the fluctuation of the other reproductive hormones. A significant difference between the two groups of women was observed, subjects with premenstrual dysphoria displaying reduced levels of relaxin ( p < 0.05) compared to controls. Also, when analysed with respect to a variable number of tandem repeats polymorphism (CT repeats followed by GT repeats) in the promotor region of the relaxin H2 gene, women with premenstrual dysphoria ( n = 29) were found to display significantly longer GT repeats than controls ( n = 35). [ABSTRACT FROM AUTHOR]

The associations were examined in women between personality traits and steroid hormones, particularly androgens, as well as polymorphisms in genes regulating androgen concentration and effects. Women, all 42 years of age and premenopausal (n = 270), were recruited randomly. Conventional 'masculine' and 'feminine' personality traits were examined by questionnaire and set in relation to psychosocial and socioeconomic conditions, behavior in childhood, hormones, risk factors for disease, and polymorphisms in microsatellites in the CYP aromatase and the androgen receptor gene. The proportions of personality traits considered as being dominated by 'masculinity' (M) or 'femininity' (F) were 44.9%, respectively 15.0%, the rest consisting of a combination of M and F (33.2%) or 'undifferentiated' (6.9%). M characteristics were positively associated with education, sporting, self-confidence, and good adaptation to work situation. M scores correlated with reports of 'tomboyism' as girls. There was essentially no difference in hormones or disease risk factors between M and F women. The number of (CAG) repeats in the microsatellite of the transactivating domain of the androgen receptor was 19 (2.3; M and SD). M characteristics were more pronounced in the presence of longer repeat stretches (n > 20). No associations were found with F scores. There were no significant associations to the number of tetranucleotide repeats (TTTA) in the fourth introne of the aromatase gene. It was concluded that a majority of women showed M type of personality traits, associated with normal hormones, somatic health, and a long microsatellite in the transactivating domain of the AR gene. [ABSTRACT FROM AUTHOR]

The associations were examined in women between personality traits and steroid hormones, particularly androgens, as well as polymorphisms in genes regulating androgen concentration and effects.Women, all 42 years of age and premenopausal (n= 270), were recruited randomly. Conventional "masculine" and "feminine" personality traits were examined by questionnaire and set in relation to psychosocial and socioeconomic conditions, behavior in childhood, hormones, risk factors for disease, and polymorphisms in microsatellites in the CYP aromatase and the androgen receptor gene. The proportions of personality traits considered as being dominated by "masculinity" (M) or "femininity" (F) were 44.9%, respectively 15.0%, the rest consisting of a combination ofMand F (33.2%) or "undifferentiated" (6.9%).Mcharacteristics were positively associated with education, sporting, self-confidence, and good adaptation to work situation. M scores correlated with reports of "tomboyism" as girls. There was essentially no difference in hormones or disease risk factors between M and F women. The number of (CAG) repeats in the microsatellite of the transactivating domain of the androgen receptor was 19 (2.3; M and SD). M characteristics were more pronounced in the presence of longer repeat stretches (n > 20). No associations were found with F scores. There were no significant associations to the number of tetranucleotide repeats (TTTA) in the fourth introne of the aromatase gene. It was concluded that a majority of women showedMtype of personality traits, associated with normal hormones, somatic health, and a long microsatellite in the transactivating domain of the AR gene. [ABSTRACT FROM AUTHOR]

Estrogens are known to play a key role in the regulation of various aspects of behavior. In order to study the potential contribution of genetic variation in the estrogen receptor (ER) alpha to specific personality traits, we investigated a repeat polymorphism in the ER alpha gene in 172 42-year-old women who had been assessed using the Karolinska Scales of Personality (KSP). Based on the hypothesis that there is a relationship between the length of a repeat polymorphism and gene function, the alleles were divided into two groups: short and long. In order to elucidate the possible influence of the ER alpha gene on the different aspects of personality measured by means of the KSP, the possible association between this gene and four different factors ('neuroticism', 'psychoticism', 'non-conformity', and 'extraversion') was analysed. 'Neuroticism', 'psychoticism', and 'non-conformity' all appeared to be associated with the ER alpha gene. After correction for multiple comparisons by means of permutation analysis, the associations with the factor 'non-conformity'— including the subscales 'indirect aggression' and 'irritability'—and the factor 'psychoticism'—including the subscale 'suspicion'—remained significant. The results suggest that the studied dinucleotide repeat polymorphism of the ER alpha gene may contribute to specific components of personality. [ABSTRACT FROM AUTHOR]

A general inventory of the views on sex reassignment and attitudes toward transsexuals in Sweden was attempted. Whether the view on these matters differ between people embracing biological theories in explanation of transsexualism and those embracing psychological theories was tested. Third, whether men and the older age groups hold a different view on transsexualism than women and younger age groups was investigated. For these purposes, in October-December 1998, a questionnaire was mailed to a randomly selected national sample of 992 Swedish residents; 668 persons returned the questionnaire, giving a 67% response rate. Results showed that a majority supports the possibility for transsexuals to undergo sex reassignment; however, 63% thought that the individual should bear the expenses for it. In addition, a majority supported transsexuals' right to get married in their new sex and their right to work with children. Transsexuals' right to adopt and raise children was supported by 43%, whereas 41% were opposed. Results indicated that those who believed that transsexualism is caused by biological factors had a less restrictive view on transsexualism than people who held a psychological view. Men and the older age group were found to hold a more restrictive view on these issues than women and the younger age group. Future studies should address these questions to elucidate differences between cultures and the process of change in attitudes over time. [ABSTRACT FROM AUTHOR]

Background and Objectives: Apolipoprotein E (apoE) has been implicated in regenerative processes in the brain after trauma, as well as in the pathogenesis of Alzheimer's disease. Inheritance of a specific apo epsilon allele (apo epsilon 4) determines in part the risk and the mean age at onset of Alzheimer's disease. ApoE has been found to bind isoform specifically to beta-amyloid protein, the major component of senile plaques, and to the microtubule associated protein tau, which forms paired helical filaments and neurofibrillary tangles. The aim was to further examine the relation between apo epsilon alleles, especially apo epsilon 4, and the development of neuropathological changes associated with Alzheimer's disease.Methods: Brains of patients with Alzheimer's disease (n = 44) and vascular dementia (n = 11) and of age matched controls (n = 29) were studied. Senile plaques and neurofibrillary tangles in the hippocampus and frontal cortex were quantified.Results: No correlation was found between the number of apo epsilon 4 alleles and the number of senile plaques and neurofibrillary tangles in the hippocampus or the frontal cortex of patients with Alzheimer's disease, or vascular dementia, or control groups. No significant differences in duration or severity of dementia were found between patients with or. without the apo epsilon 4 allele. No increased frequency of apo epsilon 4 was found in vascular dementia. CONCLUSION AND COMMENT: Although the apo epsilon genotype clearly affects whether Alzheimer's disease will develop or not, the present study suggests that it has no influence on pathology or clinical intellectual status, once the dementia has manifested itself. No increased apo epsilon 4 allele frequency was found in neuropathologically diagnosed patients with vascular dementia in whom concomitant Alzheimer's disease can be excluded. [ABSTRACT FROM AUTHOR]

A girl with high functioning autism who developed transsexualism is described. The literature to date has, to the authors' knowledge, not documented any similar case. The diagnosis of a coexisting psychiatric disorder in transsexualism has implications for the evaluation, prognosis, and appropriate management of the patient. The question of a possible relationship between autism and transsexualism and whether there is a predisposition to gender dysphoria in autism, is discussed. [ABSTRACT FROM AUTHOR]

A correction to the article "Allelic Differences Between Europeans and Chinese for CREB1 SNPs and Their Implications in Gene Expression Regulation, Hippocampal Structure and Function, and Bipolar Disorder susceptibility," published in April 9, 2013 issues of the journal is presented.