Intergenerational Transmission of Psychiatric Conditions and Psychiatric, Behavioral, and Psychosocial Outcomes in Offspring.

Importance: Psychiatric conditions in parents are associated with many psychiatric and nonpsychiatric outcomes in offspring. However, it remains unknown whether this intergenerational transmission is attributable to broader psychopathology comorbidity or to specific conditions. Objective: To estimate associations between general and specific psychopathology factors in parents and a wide range of register-based outcomes in their offspring. Design, Setting, and Participants: This Swedish national register-based cohort study included 2 947 703 individuals born between 1970 and 2000 and followed up with participants through December 31, 2013. Statistical analysis was performed from October 2022 to October 2023. Exposures: Hierarchical factor model consisting of 1 general and 3 specific psychopathology factors fit to 9 parental psychiatric diagnoses and violent criminal court convictions. Main Outcomes and Measures: A total of 31 outcomes were measured in offspring and sorted into 6 broad clusters: psychotic-like outcomes, neurodevelopmental outcomes, internalizing outcomes, externalizing outcomes, behavior and accidents, and psychosocial outcomes. Results: Of 2 947 703 individuals, 1 518 252 (51.5%) were male, and the mean (SD) age at the end of follow-up was 28.7 (8.9) years. The general psychopathology factor in parents was significantly associated with all 31 offspring outcomes (range: odds ratio [OR] for accidents, 1.08 [95% CI, 1.07-1.08] to OR for social welfare recipiency, 1.40 [95% CI, 1.39-1.40]), which means that children whose parents scored 1 SD above the mean on the general psychopathology factor had an 8% to 40% higher odds of different studied outcomes. The specific psychotic factor in parents was primarily associated with all 5 psychotic-like outcomes (range: OR for prescription of antiepileptics, 1.05 [95% CI, 1.04-1.06] to OR for schizophrenia, 1.25 [95% CI, 1.23-1.28]) and the specific internalizing factor in parents was primarily associated with all 6 internalizing outcomes (range: OR for prescription of anxiolytics, 1.10 [95% CI, 1.09-1.10] to OR for depression, 1.13 [95% CI, 1.12-1.13]) and all 6 neurodevelopmental outcomes (range: OR for intellectual disability, 1.02 [95% CI, 1.01-1.03] to OR for autism spectrum disorder, 1.10 [95% CI, 1.09-1.11]) in offspring. The specific externalizing factor in parents was associated with all 6 externalizing outcomes (range: OR for violent crimes, 1.21 [95% CI, 1.19-1.23] to OR for oppositional defiant disorder, 1.32 [95% CI, 1.32-1.33]) and all 6 internalizing outcomes (range: OR for obsessive-compulsive disorder, 1.01 [95% CI, 1.00-1.02] to OR for posttraumatic stress disorder, 1.13 [95% CI, 1.12-1.13]) in offspring. Conclusions and Relevance: This cohort study of the Swedish population suggests that the intergenerational transmission of psychiatric conditions across different types of spectra may largely be attributable to a parental general psychopathology factor, whereas specific factors appeared to be primarily responsible for within-spectrum associations between parents and their offspring. Professionals who work with children (eg, child psychologists, psychiatrists, teachers, and social workers) might benefit from taking the total number of parental psychiatric conditions into account, regardless of type, when forecasting child mental health and social functions.

Patient educational level and management of bipolar disorder.

BACKGROUND: Socioeconomic factors can affect healthcare management. AIMS: The aim was to investigate if patient educational attainment is associated with management of bipolar disorder. METHOD: We included patients with bipolar disorder type 1 (n = 4289), type 2 (n = 4020) and not otherwise specified (n = 1756), from the Swedish National Quality Register for Bipolar Disorder (BipoläR). The association between patients' educational level and pharmacological and psychological interventions was analysed by binary logistic regression. We calculated odds ratios after adjusting for demographic and clinical variables. RESULTS: Higher education was associated with increased likelihood of receiving psychotherapy (adjusted odds ratio 1.34, 95% CI 91.22-1.46) and psychoeducation (adjusted odds ratio 1.18, 95% CI 1.07-1.46), but with lower likelihood of receiving first-generation antipsychotics (adjusted odds ratio 0.76, 95% CI 0.62-0.94) and tricyclic antidepressants (adjusted odds ratio 0.76, 95% CI 0.59-0.97). Higher education was also associated with lower risk for compulsory in-patient care (adjusted odds ratio 0.79, 95% CI 0.67-0.93). CONCLUSIONS: Pharmacological and psychological treatment of bipolar disorder differ depending on patients' educational attainment. The reasons for these disparities remain to be explained.

Prospective cohort study of early biosignatures of response to lithium in bipolar-I-disorders: overview of the H2020-funded R-LiNK initiative.

BACKGROUND: Lithium is recommended as a first line treatment for bipolar disorders. However, only 30% of patients show an optimal outcome and variability in lithium response and tolerability is poorly understood. It remains difficult for clinicians to reliably predict which patients will benefit without recourse to a lengthy treatment trial. Greater precision in the early identification of individuals who are likely to respond to lithium is a significant unmet clinical need. STRUCTURE: The H2020-funded Response to Lithium Network (R-LiNK; http://www.r-link.eu.com/ ) will undertake a prospective cohort study of over 300 individuals with bipolar-I-disorder who have agreed to commence a trial of lithium treatment following a recommendation by their treating clinician. The study aims to examine the early prediction of lithium response, non-response and tolerability by combining systematic clinical syndrome subtyping with examination of multi-modal biomarkers (or biosignatures), including omics, neuroimaging, and actigraphy, etc. Individuals will be followed up for 24 months and an independent panel will assess and classify each participants' response to lithium according to predefined criteria that consider evidence of relapse, recurrence, remission, changes in illness activity or treatment failure (e.g. stopping lithium; new prescriptions of other mood stabilizers) and exposure to lithium. Novel elements of this study include the recruitment of a large, multinational, clinically representative sample specifically for the purpose of studying candidate biomarkers and biosignatures; the application of lithium-7 magnetic resonance imaging to explore the distribution of lithium in the brain; development of a digital phenotype (using actigraphy and ecological momentary assessment) to monitor daily variability in symptoms; and economic modelling of the cost-effectiveness of introducing biomarker tests for the customisation of lithium treatment into clinical practice. Also, study participants with sub-optimal medication adherence will be offered brief interventions (which can be delivered via a clinician or smartphone app) to enhance treatment engagement and to minimize confounding of lithium non-response with non-adherence. CONCLUSIONS: The paper outlines the rationale, design and methodology of the first study being undertaken by the newly established R-LiNK collaboration and describes how the project may help to refine the clinical response phenotype and could translate into the personalization of lithium treatment.

Lithium-Associated Hypercalcemia: Pathophysiology, Prevalence, Management.

BACKGROUND: Lithium-associated hypercalcemia (LAH) is an ill-defined endocrinopathy. The aim of the present study was to determine the prevalence of hypercalcemia in a cohort of bipolar patients (BP) with and without concomitant lithium treatment and to study surgical outcomes for lithium-associated hyperparathyroidism. METHODS: Retrospective data, including laboratory results, surgical outcomes and medications, were collected from 313 BP treated with lithium from two psychiatric outpatient units in central Sweden. In addition, data were collected from 148 BP without lithium and a randomly selected control population of 102 individuals. Logistic regression was used to compare odds of hypercalcemia in these respective populations. RESULTS: The prevalence of lithium-associated hypercalcemia was 26%. Mild hypercalcemia was detected in 87 out of 563 study participants. The odds of hypercalcemia were significantly higher in BP with lithium treatment compared with BP unexposed to lithium (adjusted OR 13.45; 95% CI 3.09, 58.55; p = 0.001). No significant difference was detected between BP without lithium and control population (adjusted OR 2.40; 95% CI 0.38, 15.41; p = 0.355). Seven BP with lithium underwent surgery where an average of two parathyroid glands was removed. Parathyroid hyperplasia was present in four patients (57%) at the initial operation. One patient had persistent disease after the initial operation, and six patients had recurrent disease at follow-up time which was on average 10 years. CONCLUSION: The high prevalence of LAH justifies the regular monitoring of calcium homeostasis, particularly in high-risk groups. If surgery is necessary, bilateral neck exploration should be considered in patients on chronic lithium treatment. Prospective studies are needed.

Dietary intake, resting energy expenditure, and eating behavior in women with and without polycystic ovary syndrome.

BACKGROUND: Data on dietary intake, meal patterns, and eating attitudes from women with polycystic ovary syndrome (PCOS) is limited despite the fact that PCOS is associated with obesity. We aimed to test the hypothesis that women with PCOS display altered dietary intakes and eating behaviors compared to controls. METHODS: Women with PCOS (n = 72) as defined according to the modified Rotterdam criteria were compared with healthy controls (n = 30). Anthropometry included measurement of waist circumference and determination of the resting metabolic rate via indirect calorimetry. All women completed questionnaires regarding eating behavior; Three-Factor Eating Questionnaire (TFEQ-R21) and eating attitudes; Eating Attitudes Test (EAT). Group comparisons were done by Mann-Whitney U test and logistic regression analysis was used for adjustments of age and BMI in a non-parametric way. RESULTS: BMI was higher in women with PCOS compared to controls. Resting metabolic rate did not differ between women with women with and without PCOS after adjustment for age and BMI [1411 ± 229 kcal/day versus 1325 ± 193 kcal per day (P = 0.07)], whereas the respiratory exchange ratio was higher in women with PCOS than in controls [0.83 ± 0.07 versus 0.78 ± 0.08 (P = 0.02 after adjustments for age and BMI)]. Energy percent (E%) carbohydrates was higher in women with PCOS compared to controls (P = 0.017), but E% alcohol was lower (P = 0.036) after adjustment for age and BMI. The average total EAT scores and EAT dieting subscale scores were higher in women with PCOS compared with controls (P = 0.001 and P = 0.024, respectively) after adjustment for age and BMI. No difference was found for previous or current symptoms of bulimia nervosa. CONCLUSIONS: Independent of BMI and age, the resting metabolic rate did not differ between women with and without PCOS indicating that women with PCOS should have equal abilities in terms of energy metabolism to lose weight as women without PCOS. Women with PCOS showed greater concerns about their weight and dieting, and this indicates that anxiety about weight is one of the psychological symptoms of PCOS.

The societal cost of bipolar disorder in Sweden.

PURPOSE: There is a lack of comprehensive cost-of-illness studies in bipolar disorder, in particular studies based on patient-level data. The purpose of this study was to estimate the societal cost of bipolar disorder and to relate costs to disease severity, depressive episodes, hospitalisation and patient functioning. METHODS: Retrospective resource use data in inpatient and outpatient care during 2006-2008, as well as ICD-10 diagnoses and Global Assessment of Functioning (GAF) scores, were obtained from the Northern Stockholm psychiatric clinic with a catchment area including 47% of the adult inhabitants in Stockholm. This dataset was combined with national register data on prescription pharmaceuticals and sick leave to estimate the societal cost of bipolar disorder. The study was conducted from a societal perspective, with indirect costs valued according to the human capital method. RESULTS: The average annual cost per patient was 28,011 in 2008 (n = 1,846). Indirect costs due to sick leave and early retirement represented 75%, inpatient costs 13%, outpatient costs 8%, pharmaceuticals 2% and community care another 2% of the total cost. Total costs were considerably higher during mood episodes (six times higher than in remission), for hospitalised patients (55,500 vs. 22,200) and for patients with low GAF scores. CONCLUSIONS: The high cost of bipolar disorder is driven primarily by indirect costs. Costs were strongly associated with mood episodes, hospitalisations and low GAF scores. This suggests that treatment that reduces the risk for relapses and hospitalizations and improve functioning may decrease both the societal cost of bipolar disorder and patient suffering.

The societal cost of schizophrenia in Sweden.

BACKGROUND: Schizophrenia is a disabling psychiatric disorder that has severe consequences for patients and their families. Moreover, the expensive treatment of schizophrenia imposes a burden on health care providers and the wider society. Existing cost estimates for Sweden, however, are based on relatively small patient populations and need to be confirmed in a large register-based study. AIMS OF THE STUDY: To investigate the health care resource utilization and cost-of-illness in patients with schizophrenia in Sweden and to relate the costs to hospitalizations and global assessment of functioning (GAF). METHODS: Hospital-based registry data were combined with national registry data from a large patient population to get reliable estimates of the costs of schizophrenia in Sweden. Schizophrenia was defined by ICD-10 codes F20; F21; F23.1,2,8,9; F25.1,8,9. Registry data on socio-demographics and disease-related healthcare resource use in outpatient and inpatient care were obtained from Northern Stockholm Psychiatry. Data on pharmaceuticals were obtained from the National Board of Health and Welfare, and data on sick leave and early retirement were obtained from the Swedish Social Insurance Agency. Costs for community mental health care were not available at the individual level, but were estimated based on previous studies and aggregate cost data from Stockholm. Resource use data from the registries were combined with unit costs from publicly available sources. The study was conducted from a societal perspective, with indirect costs valued according to the human capital method. RESULTS: The average annual psychiatric cost per patient with schizophrenia in 2008 was EUR 42700 (95% CI: EUR 41500-44000), based on a sample of 2161 patients. To this should be added costs for community mental health care of EUR 12400 per patient, giving a total cost of EUR 55100 per patient. The two largest cost items in the total costs were indirect costs due to lost productivity (60%) and community mental health care (22% of the total cost). Patients who were hospitalized in 2008 had greater psychiatric costs than those who were not, EUR 71700 vs. EUR 37700 (p<0.0001). Psychiatric costs were significantly and negatively correlated with GAF (p<0.001). DISCUSSION: The major strengths of the study are the relatively large sample, and the linkage of patient-level clinical data on inpatient and outpatient care with national registry data on prescription pharmaceuticals, and days on social insurance. A limitation was that costs for informal care and primary care were not included in the data, but previous studies suggest that these costs items are small compared to other costs for schizophrenia. IMPLICATIONS FOR HEALTH POLICIES AND FUTURE RESEARCH: Costs were strongly related to hospitalization and GAF, suggesting that attempts to improve global functioning and avoid hospitalizations by means of effective treatment and rehabilitation might not only decrease suffering for patients and relatives, but also reduce the societal cost of schizophrenia. A detailed knowledge of the societal costs can also be helpful in evaluating the cost-effectiveness of new treatment strategies to improve the care for patients with schizophrenia.

A comparison of seminar and computer based training on the accuracy and reliability of raters using the Children's Global Assessment Scale (CGAS).

The aim of this study was to compare two methods to conduct CGAS rater training. A total of 648 raters were randomized to training (CD or seminar), and rated five cases before and 12 months after training. The ICC at baseline/end of study was 0.71/0.78 (seminar), 0.76/0.78 (CD), and 0.67/0.79 (comparison). There were no differences in training effect in terms of agreement with expert ratings, which speaks in favor of using the less resource-demanding CD. However, the effect was modest in both groups, and untrained comparison group improved of the same order of magnitude, which proposes more extensive training.

Sexuality and psychological wellbeing in women with polycystic ovary syndrome compared with healthy controls.

OBJECTIVES: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting women of fertile age. The aim was to study whether PCOS has an effect on sexual functioning. STUDY DESIGN: Women meeting the Rotterdam criteria for PCOS (n=49), and 49 age-matched controls identified from the population registry, were recruited. Sexual functioning was assessed by means of (i) an in-person, structured interview covering various aspects of sexuality, and (ii) the nine-item McCoy questionnaire of female sexual satisfaction. Participants also completed the Psychological General Well-Being Index. RESULTS: Almost half the women with PCOS reported that the disorder had a great impact on their sex life. Despite having the same number of partners and about the same frequency of sexual intercourse, women with PCOS were generally less satisfied with their sex lives compared to the population-based controls. Within the group of women with PCOS, high body mass index had only a minor effect on sexual functioning, while the total serum level of testosterone correlated positively to sexual satisfaction. PCOS women scored numerically lower than controls on the McCoy total score, but this difference was not statistically significant. CONCLUSION: Women with PCOS reported decreased satisfaction with their sex life. Sexual function should be taken into account in treatment trials of PCOS, which traditionally target only symptoms related to insulin resistance, overweight, and hirsutism.

Children's Global Assessment Scale (CGAS) in a naturalistic clinical setting: Inter-rater reliability and comparison with expert ratings.

The Children's Global Assessment Scale (CGAS) is a tool to assess the overall level of functioning of children in Child and Adolescent Mental Health Services (CAMHS). Even though the use of this rating scale requires trained raters, it is commonly deployed without prior training in clinical settings. The aim of this study was to investigate the reliability and the agreement of CGAS ratings with an expert rating, in a clinical setting with untrained raters. Five experienced clinicians rated five vignettes to provide expert ratings. These vignettes were then rated by 703 health-care professionals representing 33 Swedish CAMHS. The health-care professionals rated the vignettes significantly higher (showing better global functioning) than the expert ratings. There was a wide range between the minimum and maximum ratings. The intraclass correlation coefficient was 0.73, which indicates moderate inter-rater reliability. Neither clinical experience nor earlier experience of using CGAS influenced the agreement with the expert ratings. The inter-rater reliability is moderate when CGAS is used in a clinical setting with untrained raters. Further, the untrained raters differed substantially from the experts. This stresses the importance of proper training in conjunction with the introduction of new rating scales.

The lean woman.

OBJECTIVE: In the current obesity epidemic, the ability to remain lean is beginning to be uncommon. Therefore, it was considered of interest to characterize such subjects. RESEARCH METHODS AND PROCEDURES: From a population of premenopausal women (n = 270), all 40 years of age, those with a similar body mass index (BMI) as women at the age of 21 years, born the same year (BMI = 21.1 kg/m(2)) were selected among nonsmokers and compared with the remaining nonsmoking women. RESULTS: Lean women showed, as expected, low waist-to-hip circumference ratio and abdominal sagittal diameter as well as absence of other disease risk factors. Compared with the remaining women, 17 beta-estradiol was high and androgens were low, whereas insulin-like growth factor I and thyroid hormones showed no differences. Dihydroepiandrosterone sulfate was lower, whereas cortisol, measured in saliva repeatedly over a day, and adrenocorticotropin hormone were not different. Results from questionnaires indicated higher education and socioeconomic status, frequent sports activities, and better psychosocial adaptation and psychological health. A tetranucleotide repeat polymorphism in the fourth [corrected] intron of the aromatase P450 gene was longer among the lean (187 base pairs) than the rest of the women. Women with opposite phylogenetic characteristic have a short microsatellite (168 base pairs) in this gene locus. DISCUSSION: Lean, nonsmoking women enjoy an excellent health in not only anthropometric and metabolic factors, but also in neuroendocrine, endocrine, and psychological variables. The endocrine measurements suggest a well-functioning aromatase, which in turn might have a genetic background, contributing to health. The aromatase gene might be important for regulation of body fat mass.