A comparison of patient ratings and staff ratings of disability using the World Health Organisation Disability Assessment Schedule in individuals with psychotic spectrum disorders who are forensic psychiatric inpatients.

BACKGROUND: Psychosocial rehabilitation in forensic psychiatric services requires sound measurement of patient and staff perceptions of psychosocial function. The recommended World Health Organisation Disability Assessment Schedule 2.0 (WHODAS), designed for this, has not been examined with offender patients. AIMS: To examine patient and staff WHODAS ratings of secure hospital inpatients with psychosis, any differences between them and explore associations with other clinical factors. METHODS: Seventy-three patients self-rated on the WHODAS after 3 months as inpatients. An occupational therapist interviewed the patient's primary nurse and care team at about the same time (staff ratings). Scores were calculated according to the WHODAS manual. WHODAS scores and interview-rated symptom severity, cognitive measures, daily antipsychotic dose and duration of care were compared. RESULTS: Patient ratings indicated less disability than staff ratings for total score and for the domains of understanding and communicating, getting along and life activities. Self-care and participation ratings were similar. Patients were more likely to rate themselves as disabled in getting around (mobility). Only one-fifth of patient- and staff- ratings (16, 22%) were similar, while for nearly a third of the patients (23, 32%) self-ratings were higher than staff ratings. More severe positive symptoms were associated with higher self-rated WHODAS disability after accounting for treatment duration, negative symptoms, cognitive score and antipsychotic dose. No variable accounted for the staff/patient differences in ratings. CONCLUSION: Our mean WHODAS score findings echoed those in other patient samples-of patient underestimation of disability, linked to severity of symptoms. In this study using the WHODAS for the first time in a forensic mental health secure inpatient service, however, we found that, by comparing individuals, half of the patients reported equivalent or greater disability than did staff. Future research should focus on elucidating from patients what contributes to their self-ratings. Understanding their thought processes in rating may enhance rehabilitation planning.

Relationships and gender differences within and between assessments used in Swedish home rehabilitation - a cross-sectional study.

BACKGROUND: Home rehabilitation programmes are increasingly implemented in many countries to promote independent living. Home rehabilitation should include a comprehensive assessment of functioning, but the scientific knowledge about the assessment instruments used in this context is limited. The aim of this study was to explore relationships between standardised tests and a self-reported questionnaire used in a home rehabilitation programme. We specifically studied whether there were gender differences within and between assessments. METHOD: De-identified data from 302 community-dwelling citizens that participated in a municipal home rehabilitation project in Sweden was analysed. A Mann Whitney test and an independent t-test were used to analyse differences within the following assessment instruments: the Sunnaas Activity of Daily Living Index, the General Motor Function assessment scale and the European Quality of Life Five Dimension Five Level Scale. Spearman's bivariate correlation test was used to analyse relationships between the instruments, and a Fischer's Z test was performed to compare the strengths of the correlation coefficients. RESULT: Gender differences were found both within and between the assessment instruments. Women were more independent in instrumental activities of daily living than men. The ability to reach down and touch one's toes while performing personal activities of daily living was stronger for men. There was a difference between men's self-reported performance of usual activities that included instrumental activities of daily living and the standardised assessment in performing instrumental activities of daily living. The result also showed an overall difference between the self-reported assessment and the standardised test of motor function for the total group. CONCLUSION: The results indicate that a comprehensive assessment with the combination of standardised tests, questionnaires and patient-specific instruments should be considered in a home rehabilitation context in order to capture different dimensions of functioning. Assessment instruments that facilitate a person-centred home rehabilitation supporting personally meaningful activities for both men and women should be applied in daily practice. Further research about gender-biased instruments is needed to facilitate agreement on which specific instruments to use at both individual and organisation levels to promote gender-neutral practice.

Factors associated to functioning and health in relation to home rehabilitation in Sweden: a non-randomized pre-post intervention study.

BACKGROUND: Home rehabilitation is a growing rehabilitation service in many countries, but scientific knowledge of its components and outcomes is still limited. The aim of this study was to investigate; 1) which changes in functioning and self-rated health could be identified in relation to a home rehabilitation program in a population of community-dwelling citizens, and 2) how socio-demographic factors, health conditions and home rehabilitation interventions were associated to change in functioning and self-rated health after the home rehabilitation program. METHOD: The sample consisted of participants in a municipal home rehabilitation project in Sweden and consisted of 165 community-dwelling citizens. General Linear Models (ANOVA repeated measures) was used for identifying changes in rehabilitation outcomes. Logistic regressions analysis was used to investigate associations between rehabilitation outcomes and potential factors associated to outcome. RESULT: Overall improvements in functioning and self-rated health were found after the home rehabilitation program. Higher frequencies of training sessions with occupational therapists, length of home rehabilitation, and orthopaedic conditions of upper extremities and spine as the main health condition, were associated with rehabilitation outcomes. CONCLUSION: The result indicates that the duration of home rehabilitation interventions and intensity of occupational therapy, as well as the main medical condition may have an impact on the outcomes of home rehabilitation and needs to be considered when planning such programs. However, more research is needed to guide practice and policymaking.

Variations among Viruses in Influent Water and Effluent Water at a Wastewater Plant over One Year as Assessed by Quantitative PCR and Metagenomics.

Influent wastewater and effluent wastewater at the Rya treatment plant in Gothenburg, Sweden, were continuously monitored for enteric viruses by quantitative PCR (qPCR) during 1 year. Viruses in effluent wastewater were also identified by next-generation sequencing (NGS) in samples collected during spring, early summer, and winter. Samples of incoming wastewater were collected every second week. Seasonal variations in viral concentrations in incoming wastewater were found for noroviruses GII, sapovirus, rotavirus, parechovirus, and astrovirus. Norovirus GI and GIV and Aichi virus were present in various amounts during most weeks throughout the year, while hepatitis A virus, enterovirus, and adenovirus were identified less frequently. Fluctuations in viral concentrations in incoming wastewater were related to the number of diagnosed patients. The viruses were also detected in treated wastewater, however, with a 3- to 6-log10 reduction in concentration. Seven different hepatitis E virus (HEV) strains were identified in the effluents. Five of these strains belonged to genotype 3 and have been isolated in Sweden from swine, wild boars, and humans and in drinking water. The other two strains were divergent and had not been identified previously. They were similar to strains infecting rats and humans. Surveillance of enteric viruses in wastewater is a tool for early detection and follow-up of gastroenteritis outbreaks in society and for the identification of new viruses that can cause infection in humans.IMPORTANCE Both influent wastewater and treated wastewater at a wastewater treatment plant (WWTP) contain a high variety of human viral pathogens with seasonal variability when followed for 1 year. The peak of the amount of 11 different viruses in the inlet wastewater preceded the peak of the number of diagnosed patients by 2 to 4 weeks. The treatment of wastewater reduced viral concentrations by 3 to 6 log10 Despite the treatment of wastewater, up to 5 log10 virus particles per liter were released from into the surrounding river. Hepatitis E virus (HEV) strains previously identified in drinking water and two new strains, similar to those infecting rats and humans, were identified in the treated wastewater released from the WWTP.

Psychotically driven aggression is associated with greater mentalizing challenges in psychotic spectrum disorders.

BACKGROUND: Some aggressive acts committed by individuals with psychotic spectrum disorders (PSD) are understandable in the context of interpersonal conflict or goal attainment, yet others are unpredictable, arising from delusions or hallucinations (psychotically driven aggressive acts, PDA). It is unknown if there are underlying differences in cognitive or perceptive social cognition in relation to aggression motivation in PSD. METHOD: We compared differences in social cognition performance between 49 individuals with PSD who had committed PDA with those exhibiting other types of aggression (n = 31) (non-PDA) and to community controls (n = 81) on the Swedish version of Double Movie for the Assessment of Social Cognition - Multiple Choice (DMASC-MC). Participants with PSD had more than 3 months of clinical stability and substance use abstention and stable antipsychotic medication doses. General intellectual ability was assessed with the information and matrix reasoning subtests of the Wechsler Intelligence Scales. RESULTS: The PSD group with a history of PDA exhibited lower total and perceptive social cognition scores on the DMASC-MC than the non-PDA group and controls. In addition, they also showed lower cognitive scores compared to typical controls. Lower total scores were associated with lower scores on Wechsler intelligence subtests information and matrix reasoning. Taking this into account, the PDA group still had lower social cognition scores. There were no associations of antipsychotic medication dosages, positive or negative symptoms with social cognition scores. Higher antipsychotic dosage at the time of DMASC-MC testing and social cognition scores predicted a past history of PDA. CONCLUSIONS: We conclude that impaired social cognition, particularly perceptive social cognition, is associated with PDA in individuals with PSD.

Electroconvulsive therapy suppresses the neurotoxic branch of the kynurenine pathway in treatment-resistant depressed patients.

BACKGROUND: Neuroinflammation is increasingly recognized as contributing to the pathogenesis of depression. Key inflammatory markers as well as kynurenic acid (KYNA) and quinolinic acid (QUIN), both tryptophan metabolites, have been associated with depressive symptoms and suicidality. The aim of the present study is to investigate the peripheral concentration of cytokines and tryptophan and kynurenine metabolites in patients with unipolar treatment-resistant depression before and after electroconvulsive therapy (ECT), the most effective treatment for depression. METHODS: Cytokines in plasma from patients with major depressive disorder (MDD; n = 19) and healthy volunteers (n = 14) were analyzed with electrochemiluminescence detection. Tryptophan and kynurenine metabolites were detected with high-performance liquid chromatography (HPLC) and LC/MS. KYNA was analyzed in a second healthy control cohort (n = 22). RESULTS: Patients with MDD had increased plasma levels of interleukin (IL)-6 compared to healthy volunteers (P < 0.05). We also found an altered kynurenine metabolism in these patients displayed by decreased plasma levels of KYNA (P < 0.0001) as well as a significantly increased QUIN/KYNA ratio (P < 0.001). Plasma levels of tryptophan, kynurenine, and QUIN did not differ between patients and controls. Treatment with ECT was associated with a significant decrease in the plasma levels of tryptophan (P < 0.05), kynurenine (P < 0.01), and QUIN (P < 0.001), whereas plasma levels of KYNA did not change. The QUIN/KYNA ratio was found to significantly decrease in ECT-treated patients (P < 0.05). There was a significant inverse correlation between symptom severity and kynurenine levels at baseline (r = -0.67, P = 0.002). CONCLUSIONS: This study confirms an imbalanced kynurenine pathway in MDD supporting the hypothesis of a netstimulation of N-methyl-D-aspartic acid (NMDA) receptors in the disorder. Treatment with ECT profoundly decreased QUIN, an NMDA-receptor agonist previously suggested to be implicated in the pathogenesis of depression, an effect that might have bearing for the good clinical outcome of ECT.

Prevalence of shoulder pain in Swedish flatwater kayakers and its relation to range of motion and scapula stability of the shoulder joint.

Few studies have investigated the incidence of injuries in kayakers. The aim was to study the prevalence of shoulder pain in competitive flatwater kayakers and to evaluate any differences in range of motion or scapula stability of the shoulder joint among kayakers with or without the history of shoulder pain. Thirty-one kayakers were participated in the study, and a questionnaire including background data was used. Shoulder range of motion was measured with a goniometer, and the participants were observed for scapula dyskinesis in flexion and abduction. Of the participating kayakers, 54.8% (n = 17) had experienced shoulder pain. Kayakers who had experienced shoulder pain showed a significantly lower degree of internal rotational range of motion versus kayakers with no reported shoulder pain, with a mean degree of internal rotation in the right shoulder 49.3 vs. 60.0 (P = 0.017) and the left shoulder 51.9 vs. 66.0 (P = 0.000). Kayakers who had experienced shoulder pain were also observed with a scapular dyskinesis (n = 15 of 17 kayakers) to a significantly higher degree (P = 0.001) than kayakers with no reported shoulder pain. Findings suggest that screening for scapular dyskinesis and testing for rotational range of motion in the shoulder joint is essential in order to treat and maybe prevent shoulder pain in kayakers.

Increased cerebrospinal fluid interleukin-8 in bipolar disorder patients associated with lithium and antipsychotic treatment.

Inflammation has been linked to the pathophysiology of bipolar disorder based on studies of inflammation markers, such as cytokine concentrations, in plasma and serum samples from cases and controls. However, peripheral measurements of cytokines do not readily translate to immunological activity in the brain. The aim of the present study was to study brain immune and inflammatory activity. To this end, we analyzed cytokines in cerebrospinal fluid from 121 euthymic bipolar disorder patients and 71 age and sex matched control subjects. Concentrations of 11 different cytokines were determined using immunoassays. Cerebrospinal fluid IL-8 concentrations were significantly higher in patients as compared to controls. The other cytokines measured were only detectable in part of the sample. IL-8 concentrations were positively associated to lithium- and antipsychotic treatment. The findings might reflect immune aberrations in bipolar disorder, or be due to the effects of medication.

Decreased cerebrospinal fluid secretogranin II concentrations in severe forms of bipolar disorder.

BACKGROUND: Bipolar disorder is a common psychiatric mood disorder that is defined by recurrent episodes of abnormally elevated mood and depression. Progressive structural brain changes in individuals with bipolar disorder have been suggested to be associated with defects in the secretion of neurotrophic factors. We sought to assess how the regulated secretory pathway in the brain is affected in patients with bipolar disorder by measuring chromogranin B and secretogranin II, which are 2 cerebrospinal fluid (CSF) biological markers for this process. METHODS: We measured the concentrations of chromogranin B (peptide 439-451) and secretogranin II (peptide 154-165) in the CSF of patients with well-defined bipolar disorder and healthy controls. The lifetime severity of bipolar disorder was rated using the Clinical Global Impression (CGI) scale. RESULTS: We included 126 patients with bipolar disorder and 71 healthy controls in our analysis. Concentrations of secretogranin II were significantly lower in patients with bipolar disorder type I than in healthy controls. The reduction was most pronounced in patients with high CGI scores (i.e., severe disease). LIMITATIONS: The cross-sectional design of the current study limits the ability to pinpoint the causalities behind the observed associations. CONCLUSION: This study shows that the CSF marker secretogranin II has the potential to act as a biological marker for severe forms of bipolar disorder. Our findings indicate that patients with bipolar disorder possess defects in the regulatory secretory pathway, which may be of relevance to the progressive structural brain changes seen in those with severe forms of the disease.

Neurocognitive function in bipolar disorder: a comparison between bipolar I and II disorder and matched controls.

BACKGROUND: Cognitive deficits have been documented in patients with bipolar disorder. Further, it has been suggested that the degree and type of cognitive impairment differ between bipolar I and bipolar II disorder, but data is conflicting and remains inconclusive. This study aimed to clarify the suggested differences in cognitive impairment between patients with bipolar I and II disorder in a relatively large, clinically stable sample while controlling for potential confounders. METHODS: 67 patients with bipolar I disorder, 43 with bipolar II disorder, and 86 randomly selected population-based healthy controls were compared. A number of neuropsychological tests were administered, assessing verbal and visual memory and executive functions. Patients were in a stable phase during testing. RESULTS: Patients with bipolar type I and type II were cognitively impaired compared to healthy controls, but there were no statistically significant differences between the two subtypes. The strongest predictor of cognitive impairment within the patient group was current antipsychotic treatment. CONCLUSIONS: The present study suggests that the type and degree of cognitive dysfunction is similar in bipolar I and II patients. Notably, treatment with antipsychotics - but not a history of psychosis - was associated with more severe cognitive impairment. Given that patients with bipolar I disorder are more likely to be on antipsychotic drugs, this might explain why some previous studies have found that patients with type I bipolar disorder are more cognitively impaired than those with type II.

Cognition, prior aggression, and psychopathic traits in relation to impaired multimodal emotion recognition in psychotic spectrum disorders.

Background: Psychopathic traits have been associated with impaired emotion recognition in criminal, clinical and community samples. A recent study however, suggested that cognitive impairment reduced the relationship between psychopathy and emotion recognition. We therefore investigated if reasoning ability and psychomotor speed were impacting emotion recognition in individuals with psychotic spectrum disorders (PSD) with and without a history of aggression, as well as in healthy individuals, more than self-rated psychopathy ratings on the Triarchic Psychopathy Measure (TriPM). Methods: Eighty individuals with PSD (schizophrenia, schizoaffective disorder, delusional disorder, other psychoses, psychotic bipolar disorder) and documented history of aggression (PSD+Agg) were compared with 54 individuals with PSD without prior aggression (PSD-Agg) and with 86 healthy individuals on the Emotion Recognition Assessment in Multiple Modalities (ERAM test). Individuals were psychiatrically stable and in remission from possible substance use disorders. Scaled scores on matrix reasoning, averages of dominant hand psychomotor speed and self-rated TriPM scores were obtained. Results: Associations existed between low reasoning ability, low psychomotor speed, patient status and prior aggression with total accuracy on the ERAM test. PSD groups performed worse than the healthy group. Whole group correlations between total and subscale scores of TriPM to ERAM were found, but no associations with TriPM scores within each group or in general linear models when accounting for reasoning ability, psychomotor speed, understanding of emotion words and prior aggression. Conclusion: Self-rated psychopathy was not independently linked to emotion recognition in PSD groups when considering prior aggression, patient status, reasoning ability, psychomotor speed and emotion word understanding.

Measures against COVID-19 affected the spread of human enteric viruses in a Swedish community, as found when monitoring wastewater.

The quantification of viral genomes in wastewater reflects the prevalence of viral infections within the community. Knowledge of how the spread of common enteric viruses in the community was affected by the Swedish COVID-19 interventions is limited. To investigate this, the weekly wastewater samples collected for monitoring SARS-CoV-2 throughout the COVID-19 pandemic at the Rya sewage treatment plant in Gothenburg were also analyzed for adenovirus, norovirus GII, astrovirus, and rotavirus. The amount of each viral genome was quantified by real-time-qPCR and compared with the quantity of these viral genomes in wastewater from 2017. The results showed that the winter seasonality of norovirus GII and rotavirus in wastewater observed in 2017 was interrupted shortly after the introduction of the COVID-19 interventions, and they remained at low level throughout the pandemic. The circulation pattern of astrovirus and adenovirus was less affected. When the COVID-19 restrictions were lifted in 2022, a dramatic increase was observed in the amount of norovirus GII, rotavirus, and adenovirus genomes in wastewater. The changes in abundance and seasonality of some viruses identified through wastewater monitoring were consistent with changes in the number of patients diagnosed with these viruses. These findings suggest that moderate intervention to prevent COVID-19 significantly reduced the spread of some enteric viruses in the community. The results show that wastewater monitoring is a valuable tool for detecting the spread and outbreaks of viral infections that may cause gastroenteritis also when people do not seek medical help, such as during the COVID-19 pandemic.

The amount of SARS-CoV-2 RNA in wastewater relates to the development of the pandemic and its burden on the health system.

Virus surveillance in wastewater can be a useful indicator of the development of the COVID-19 pandemic in communities. However, knowledge about how the amount of SARS-CoV-2 RNA in wastewater relates to different data on the burden on the health system is still limited. Herein, we monitored the amount of SARS-CoV-2 RNA and the spectrum of virus variants in weekly pooled wastewater samples for two years from mid-February 2020 and compared them with several clinical data. The two-year monitoring showed the weekly changes in the amount of viral RNA in wastewater preceded the hospital care needs for COVID-19 and the number of acute calls on adult acute respiratory distress by 1-2 weeks during the first three waves of COVID-19. Our study demonstrates that virus surveillance in wastewater can predict the development of a pandemic and its burden on the health system, regardless of society's test capacity and possibility of tracking infected cases.

Valuable aspects of home rehabilitation in Sweden: Experiences from older adults.

BACKGROUND AND AIM: Home rehabilitation is an increasing service in many countries due to the aging population. The body of knowledge in home rehabilitation is growing but results are inconsistent, and there is still lack of knowledge from user perspectives to guide practice and home rehabilitation programs. The purpose of this study was to explore valuable aspects of home rehabilitation experienced by older adults. METHODS: Fourteen older persons (nine older adults and five next of kins) were interviewed about their experiences of receiving rehabilitation in their homes. Nine de-identified interviews were analyzed as secondary data and with qualitative content analysis. RESULTS: A familiar home environment, inclusive collaboration, and the mastering of everyday life were aspects of value for older adults in home rehabilitation. Creating a tailor-made rehabilitation together with competent staff, building trust, and providing a sense of security in their homes were also considered valuable. CONCLUSION: When using the home as an arena for rehabilitation and collaboration, interventions can be planned based on the older adult's unique conditions and the knowledge and skills of the multidisciplinary team, including the older adult and their next of kin. A valuable home rehabilitation can then be achieved that creates motivation, which in the long term probably also generates desired effects for the older adult. More research is needed on older adult's experiences of content in home rehabilitation programs so that practice develops in accordance with citizens' needs, individual resources, and relationships.

Surveillance of wastewater revealed peaks of SARS-CoV-2 preceding those of hospitalized patients with COVID-19.

SARS-CoV-2 was discovered among humans in Wuhan, China in late 2019, and then spread rapidly, causing a global pandemic. The virus was found to be transmitted mainly by respiratory droplets from infected persons or by direct contact. It was also shown to be excreted in feces, why we investigated whether the virus could be detected in wastewater and if so, to which extent its levels reflects its spread in society. Samples of wastewater from the city of Gothenburg, and surrounding municipalities in Sweden were collected daily from mid-February until June 2020 at the Rya wastewater treatment plant. Flow proportional samples of wastewater were collected to ensure that comparable amounts were obtained for analysis. Daily samples were pooled into weekly samples. Virus was concentrated on a filter and analyzed by RT-qPCR. The amount of SARS-CoV-2 varied with peaks approximately every four week, preceding variations in number of newly hospitalized patients by 19-21 days. At that time virus testing for COVID-19 was limited to patients with severe symptoms. Local differences in viral spread was shown by analyzing weekly composite samples of wastewater from five sampling sites for four weeks. The highest amount of virus was found from the central, eastern, and northern parts of the city. SARS-CoV-2 was also found in the treated effluent wastewater from the WWTP discharged into the recipient, the Göta River, although with a reduction of 4-log10. The viral peaks with regular temporal intervals indicated that SARS-CoV-2 may have a cluster spread, probably reflecting that the majority of infected persons only spread the disease during a few days. Our results are important for both the planning of hospital care and to rapidly identify and intervene against local spread of the virus.

Impaired facial emotion perception of briefly presented double masked stimuli in violent offenders with schizophrenia spectrum disorders.

Social interactions require decoding of subtle rapidly changing emotional cues in others to facilitate socially appropriate behaviour. It is possible that impairments in the ability to detect and decode these signals may increase the risk for aggression. Therefore, we examined violent offenders with schizophrenia spectrum disorders (SSD) and compared these with healthy controls on a computerized paradigm of briefly presented double masked faces exhibiting 7 basic emotions. Our hypotheses were that impaired semantic understanding of emotion words and low cognitive ability would yield lowest emotion recognition. SSD exhibited lower accuracy of emotion perception than controls (46.1% compared with 64.5%, p = 0.026), even when considering the unbiased hit rate (22.4% compared with 43%, Z = 2.62, p < 0.01). Raw data showed uncommon but significant misclassifications of fear as sad, disgust as sad, sad as happy and angry as surprise. Once guessing and presentation frequencies were considered, only overall accuracy differed between SSD and healthy controls. There were significant correlations between cognitive ability, antipsychotic dose, speed and emotion accuracy in the SSD group. In conclusion, that there were no specific emotion biases in the SSD group compared to healthy controls, but particular individuals may have greater impairments in facial emotion perception, being influenced by intellectual ability, psychomotor speed and medication dosages, rather than specifically emotion word understanding. This implies that both state and trait factors influence emotion perception in the aggressive SSD group and may reveal one source of potential misunderstanding of social situations which may lead to boundary violations and aggression.

Synthesis and Pharmacological Characterization of 2-(2,6-Dichlorophenyl)-1-((1S,3R)-5-(3-hydroxy-3-methylbutyl)-3-(hydroxymethyl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)ethan-1-one (LY3154207), a Potent, Subtype Selective, and Orally Available Positive Allosteric Modulator of the Human Dopamine D1 Receptor.

Clinical development of catechol-based orthosteric agonists of the dopamine D1 receptor has thus far been unsuccessful due to multiple challenges. To address these issues, we identified LY3154207 (3) as a novel, potent, and subtype selective human D1 positive allosteric modulator (PAM) with minimal allosteric agonist activity. Conformational studies showed LY3154207 adopts an unusual boat conformation, and a binding pose with the human D1 receptor was proposed based on this observation. In contrast to orthosteric agonists, LY3154207 showed a distinct pharmacological profile without a bell-shaped dose-response relationship or tachyphylaxis in preclinical models. Identification of a crystalline form of free LY3154207 from the discovery lots was not successful. Instead, a novel cocrystal form with superior solubility was discovered and determined to be suitable for development. This cocrystal form was advanced to clinical development as a potential first-in-class D1 PAM and is now in phase 2 studies for Lewy body dementia.

Women with polycystic ovary syndrome are often depressed or anxious--a case control study.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common hyperandrogenic endocrine disorder affecting women of fertile age. The aim of this study was to survey whether the rate of clinical psychiatric disorders in PCOS differs from the normal population. METHOD: Women with PCOS (n=49) meeting the Rotterdam criteria for PCOS, and 49 age-matched controls identified from the population registry, were recruited. Trained clinicians used the MINI International Neuropsychiatric Interview to establish lifetime occurrence of Axis I DSM diagnoses. Serum-testosterone and sex hormone binding globulin were analyzed. RESULTS: Women with PCOS had higher lifetime incidence of depressive episodes, social phobia, and eating disorders than controls. Suicide attempts were seven times more common in the PCOS group than in the controls. Current as well as lifetime use of antidepressants and anxiolytic drugs were more common in the PCOS group. CONCLUSIONS: Previous studies have found that PCOS is associated with decreased quality of life and self-rated mental symptoms. This study demonstrates that PCOS is also linked to psychiatric syndromes as verified by structured clinical assessments. The clinical implication of this study is that clinicians treating women with PCOS should be aware that these women are a high risk group for common affective and anxiety disorders as well as suicide attempts.

Egg yolk carotenoids in relation to habitat and reproductive investment in the great tit Parus major.

Maternal allocation of antioxidants to egg yolk has been shown to affect early embryonic development and nestling survival. In environments with high levels of anthropogenic pollution, antioxidants (such as carotenoids) are important to protect the body from elevated oxidative stress. Thus, female allocation of antioxidants to yolk may be traded off against self-maintenance. Here we investigate maternal reproductive investment with respect to yolk carotenoid content and composition in relation to subsequent female condition and carotenoid status in urban and rural great tits Parus major. We found no differences between the urban and rural populations in total yolk carotenoids, egg mass, clutch size, hatching success, or female carotenoid status. Interestingly, however, rural eggs contained more zeaxanthin, a more potent antioxidant than lutein, which suggests that rural embryos have better antioxidant protection than urban embryos. Whether rural females actively transfer more zeaxanthin to the yolk or whether it passively reflects differences in dietary access or uptake needs to be further investigated. This highlights the importance of carotenoid identity and composition in future studies of carotenoid physiology, ecology, and signaling.

A History of Psychosis in Bipolar Disorder is Associated With Gray Matter Volume Reduction.

Psychotic symptoms are prevalent in schizophrenia, bipolar disorder, and other psychiatric and neurological disorders, yet the neurobiological underpinnings of psychosis remain obscure. In the last decade, a large number of magnetic resonance imaging studies have shown differences in local gray matter volume between patients with different psychiatric syndromes and healthy controls. Few studies have focused on the symptoms, which these syndromes are constituted of. Here, we test the association between psychosis and gray matter volume by using a sample of 167 subjects with bipolar disorder, with and without a history of psychosis, and 102 healthy controls. Magnetic resonance images were analyzed on group level using a voxel-wise mass univariate analysis (Voxel-Based Morphometry). We found that patients with a history of psychosis had smaller gray matter volume in left fusiform gyrus, the right rostral dorsolateral prefrontal cortex, and the left inferior frontal gyrus compared with patients without psychosis and with healthy controls. There was no volume difference in these areas between the no-psychosis group and healthy controls. These areas have previously been structurally and functionally coupled to delusions and hallucinations. Our finding adds further evidence to the probability of these regions as key areas in the development of psychotic symptoms.