Early identification of bipolar disorder among young adults - a 22-year community birth cohort.

OBJECTIVE: We set forth to build a prediction model of individuals who would develop bipolar disorder (BD) using machine learning techniques in a large birth cohort. METHODS: A total of 3748 subjects were studied at birth, 11, 15, 18, and 22 years of age in a community birth cohort. We used the elastic net algorithm with 10-fold cross-validation to predict which individuals would develop BD at endpoint (22 years) at each follow-up visit before diagnosis (from birth up to 18 years). Afterward, we used the best model to calculate the subgroups of subjects at higher and lower risk of developing BD and analyzed the clinical differences among them. RESULTS: A total of 107 (2.8%) individuals within the cohort presented with BD type I, 26 (0.6%) with BD type II, and 87 (2.3%) with BD not otherwise specified. Frequency of female individuals was 58.82% (n = 150) in the BD sample and 53.02% (n = 1868) among the unaffected population. The model with variables assessed at the 18-year follow-up visit achieved the best performance: AUC 0.82 (CI 0.75-0.88), balanced accuracy 0.75, sensitivity 0.72, and specificity 0.77. The most important variables to detect BD at the 18-year follow-up visit were suicide risk, generalized anxiety disorder, parental physical abuse, and financial problems. Additionally, the high-risk subgroup of BD showed a high frequency of drug use and depressive symptoms. CONCLUSIONS: We developed a risk calculator for BD incorporating both demographic and clinical variables from a 22-year birth cohort. Our findings support previous studies in high-risk samples showing the significance of suicide risk and generalized anxiety disorder prior to the onset of BD, and highlight the role of social factors and adverse life events.

Lifetime prevalence of psychiatric comorbidities in patients with bipolar disorder: A systematic review and meta-analysis.

BACKGROUND: Bipolar disorder (BD) is a severe psychiatric disease and part of its burden is related to the high rates of lifetime psychiatric comorbidity (PC), with diagnostic, therapeutic, and prognostic implications. METHODS: Registered in PROSPERO (CRD42021282356). Meta-analyses were performed, searching for relevant papers published from 1993 to 2022 in Medline/PubMed (including E-Pub Ahead of Print), Embase, Cochrane Library (Central), PsycINFO, Scopus, Web of Science and via hand-searching, without language restrictions. 12.698 studies were initially identified, 114 of which were ultimately chosen based on the eligibility criteria. We performed two meta-analyses (prevalence and risk ratio) of mental health conditions among subjects with BD and then conducted a comprehensive examination of moderator effects using multivariable meta-regression models for moderators identified as significant in the univariable analysis. FINDINGS: Overall PC prevalence of at least one disorder was 38.91 % (95 % CI 35.24-42.70) and the most frequent disorders were: anxiety (40.4 % [34.97-46.06]), SUD (30.7 % [23.73-38.73]), ADHD (18.6 % [10.66-30.33]) and Disruptive, impulse-control and conduct disorder (15 % [6.21-31.84). The moderators with higher association with individual prevalences were UN's Human Development Index (HDI), female gender, age, suicide attempt, and age at onset (AAO). INTERPRETATION: It becomes evident that the prevalence of PC among individuals with BD is notably high, surpassing rates observed in the general population. This heightened prevalence persists despite significant heterogeneity across studies. Consequently, it is imperative to redirect clinical focus towards comprehensive mental health assessments, emphasizing personalized and routine screening. Additionally, there is a pressing need for the enhancement of public policies to create a supportive environment for individuals with BD, ensuring better therapeutic conditions and sustained assistance. By addressing these aspects, we can collectively strive towards fostering improved mental health outcomes for individuals with BD.

Analytical reliability of four oral fluid point-of-collection testing devices for drug detection in drivers.

BACKGROUND: Point-of-collection testing (POCT) devices for psychoactive substance detection through oral fluid samples are used in several countries for traffic enforcement. However, the reported reliability of such devices is quite heterogeneous among studies, and evaluating and comparing their analytical performance is of paramount importance to guide enforcement policies. AIM: To evaluate the analytical reliability of four POCT devices for the detection of cocaine and cannabinoids using oral fluid samples of Brazilian drivers. METHOD: A total of 168 drivers were recruited during standard roadblockfI procedures in Southern Brazil. Subjects were screened using one of the following POCT devices: the DDS2™, the DOA MultiScreen™, the Dräger Drug Test 5000™ and the Multi-Drug Multi-Line Twist Screen Device™ (MDML). Results of the screening tests were compared with chromatographic analyses in order to obtain the reliability parameters. RESULTS: The prevalence of confirmed positive samples for cocaine and cannabinoids were 9 % and 4.4 %, respectively. For cocaine, three POCT devices (MDML™, Dräger DrugTest 5000™, DOA MultiScreen™) showed good reliability, greater than 80 % of performance measures, using guidelines for research on drugged driving published by Walsh et al. (cutoff 10ng/mL). However, for cannabinoids, the devices had low reliability-only Dräger DrugTest 5000™ had good performance using cut-offs proposed by Walsh et al. (cutoff 2ng/mL). CONCLUSION: We observed a high prevalence of drivers testing positive for cocaine and cannabinoids. Most devices achieved good reliability performance for cocaine detection using cutoffs proposed by Walsh et al. or using the device's own cutoff. Instead, the reliability for cannabinoid detection obtained the desired parameters in just one device using cut-offs proposed by Walsh et al. and its own cutoff. Difficulties in detecting cannabinoids at the roadside should be better evaluated before the implementation of such tests.

Bone homeostasis in growth hormone receptor-null mice is restored by IGF-I but independent of Stat5.

Growth hormone (GH) regulates both bone growth and remodeling, but it is unclear whether these actions are mediated directly by the GH receptor (GHR) and/or IGF-I signaling. The actions of GH are transduced by the Jak/Stat signaling pathway via Stat5, which is thought to regulate IGF-I expression. To determine the respective roles of GHR and IGF-I in bone growth and remodeling, we examined bones of wild-type, GHR knockout (GHR(-/-)), Stat5ab(-/-), and GHR(-/-) mice treated with IGF-I. Reduced bone growth in GHR(-/-) mice, due to a premature reduction in chondrocyte proliferation and cortical bone growth, was detected after 2 weeks of age. Additionally, although trabecular bone volume was unchanged, bone turnover was significantly reduced in GHR(-/-) mice, indicating GH involvement in the high bone-turnover level during growth. IGF-I treatment almost completely rescued all effects of the GHR(-/-) on both bone growth and remodeling, supporting a direct effect of IGF-I on both osteoblasts and chondrocytes. Whereas bone length was reduced in Stat5ab(-/-) mice, there was no reduction in trabecular bone remodeling or growth-plate width as observed in GHR(-/-) mice, indicating that the effects of GH in bone may not involve Stat5 activation.

Evidence for a visceral smooth muscle abnormality in Okamoto spontaneous hypertension.

1. In order to discover whether the changes in reactivity are related to the primary cause of hypertension in spontaneously hypertensive rats (SHR) or are just an adaptation induced by the high arterial blood pressure we tested the contractile response of a visceral smooth muscle from such rats. 2. Longitudinal strips of the fundus from 20 week old male and female SHR and Wistar normotensive (NW) rats were used. Dose-response curves to Ba2+ in SHR strips were displaced to the right as compared to NW rats. Maximal responses were identical. Male SHR fundus strips contracted much more with Sr2+ (SHR: 42+/-3% of maximum response to Ba2+, n=10; NW: 19+/-4%, n=10, P less than 0.01) than NW strips. There was no difference in the response to both BaCl2 and SrCl2 between female SHR and NW fundus strips, and MnCl2 and LaCl3 were relaxant in all cases. 3. Dose-response curves to Ca2+ of depolarized SHR and NW fundus strips were obtained and the effect of diazoxide on Ca2+ contractions was observed. The contractile action of Ca2+ in depolarized preparations was enhanced in both male and female SHR strips. The effect of diazoxide was more marked in SHR strips than in NW fundus strips. 4. SHR fundus smooth muscle shows the same modification of reactivity to Ba2+, Sr2+, Ca2+ and diazoxide that was previously described in arterial smooth muscle. This indicates that the cellular modification responsible for the increase of vascular tonus in SHR is not an adaptive reaction to high blood pressure. The differences between female SHR and male SHR responses are not unexpected, considering the natural evolution of hypertension in Okamoto rats which is milder in the female.