Suicide Attempts After a Diagnosis of Polycystic Ovary Syndrome : A Cohort Study.

BACKGROUND: Limited evidence exists about suicide risk in persons with polycystic ovary syndrome (PCOS). OBJECTIVE: To assess suicide risk in persons with PCOS, accounting for psychiatric comorbid conditions and age group. DESIGN: Cohort study. SETTING: Data from the Taiwanese nationwide database from 1997 to 2012. PATIENTS: A cohort of 18 960 patients diagnosed with PCOS, each matched with control participants in a 1:10 ratio on the basis of age, psychiatric comorbid conditions, urbanization level, and income. Suicide attempts were evaluated using Cox regression models. MEASUREMENTS: Suicide risk with hazard ratios (HRs). RESULTS: Participants with PCOS had a notable 8.47-fold increase in risk for suicide attempt compared with the control group (HR, 8.47 [95% CI, 7.54 to 9.51]), after adjustment for demographic characteristics, psychiatric comorbid conditions, Charlson Comorbidity Index scores, and frequency of all-cause clinical visits. The elevated risk was evident across the adolescent (HR, 5.38 [CI, 3.93 to 7.37]), young adult (<40 years; HR, 9.15 [CI, 8.03 to 10.42]), and older adult (HR, 3.75 [CI, 2.23 to 6.28]) groups. Sensitivity analyses involving the exclusion of data from the first year or the first 3 years of observation yielded consistent results. LIMITATION: Potential underestimation of PCOS and mental disorder prevalence due to use of administrative claims data; lack of clinical data, such as body mass index and depressive symptoms; and no assessment of a confounding effect of valproic acid exposure. CONCLUSION: This study underscores the heightened risk for suicide attempt that persons with PCOS face, even after adjustment for demographics, psychiatric comorbid conditions, physical conditions, and all-cause clinical visits. This suggests the importance of routine monitoring of mental health and suicide risk in persons diagnosed with PCOS. PRIMARY FUNDING SOURCE: Taipei Veterans General Hospital, Yen Tjing Ling Medical Foundation, and Ministry of Science and Technology of Taiwan.

Hellebrigenin induces oral cancer cell apoptosis by modulating MAPK signalling and XIAP expression.

Oral squamous cell carcinoma (OSCC), which accounts for 90% of all oral cancers, has become a public health crisis worldwide. despite advances in therapeutic interventions, the prognosis remains poor for advanced-stage OSCC. In this study, we investigate the anticancer activity and the mode of action of hellebrigenin in human OSCC. The findings demonstrated that hellebrigenin exerted cytotoxic effects in OSCC cells through cell cycle arrest at the G2/M phase and downregulation of cell cycle-related proteins (cyclins A2, B1 and D3, Cdc2, CDK4 and CDK6). Moreover, hellebrigenin caused activation of PARP and caspase 3, 8 and 9, followed by downregulation of antiapoptotic proteins (Bcl-2 and Bcl-xL) and upregulation of pro-apoptotic proteins (Bax and Bak). The hellebrigenin treatment also increased Fas, DR5, DcR2 and DcR3 expressions in oral cancer cells, indicating the compound causes oral cancer cell apoptosis through both intrinsic and extrinsic pathways. Regarding upstream signalling, hellebrigenin was found to reduce the phosphorylation of ERK, p38, and JNK, indicating that hellebrigenin triggers caspase-mediated apoptosis by downregulating MAPK signalling pathway. Finally, the human apoptosis array findings revealed that hellebrigenin specifically suppressed the expression of XIAP to execute its pro-apoptotic activities. Taken together, the study suggests that hellebrigenin can act as a potent anticancer compound in human OSCC.

CLPs-miR-103a-2-5p inhibits proliferation and promotes cell apoptosis in AML cells by targeting LILRB3 and Nrf2/HO-1 axis, regulating CD8 + T cell response.

BACKGROUND: LILRB3, a member of the leukocyte immunoglobulin-like receptor B (LILRB) family, has immunosuppressive functions and directly regulates cancer development, which indicates that LILRB3 is an attractive target for cancer diagnosis and therapy. Novel therapeutic treatments for acute myeloid leukemia (AML) are urgent and important, and RNA therapeutics including microRNAs (miRNAs) could be an effective option. Here, we investigate the role of dysregulated miRNA targeting LILRB3 in the AML microenvironment. METHODS: Potential miRNAs binding to the 3'-untranslated region (3'-UTR) of the LILRB3 mRNA were predicted by bioinformatics websites. Then, we screened miRNAs targeting LILRB3 by quantitative real-time PCR, and the dual luciferase reporter assay. The expression of LILRB3 and microRNA (miR)-103a-2-5p in AML were determined and then their interactions were also analyzed. In vitro, the effects of miR-103a-2-5p were determined by CCK8, colony formation assay, and transwell assay, while cell apoptosis and cell cycle were analyzed by flow cytometry. Cationic liposomes (CLPs) were used for the delivery of miR-103a-2-5p in the AML mouse model, which was to validate the potential roles of miR-103a-2-5p in vivo. RESULTS: LILRB3 was upregulated in AML cells while miR-103a-2-5p was dramatically downregulated. Thus, a negative correlation was found between them. MiR-103a-2-5p directly targeted LILRB3 in AML cells. Overexpressed miR-103a-2-5p significantly suppressed the mRNA and protein levels of LILRB3, thereby inhibiting AML cell growth and reducing CD8 + T cell apoptosis. In addition, overexpressed miR-103a-2-5p reduced both the relative expression of Nrf2/HO-1 pathway-related proteins and the ratio of GSH/ROS, leading to the excessive intracellular ROS that may promote AML cell apoptosis. In the mouse model, the delivery of miR-103a-2-5p through CLPs could inhibit tumor growth. CONCLUSIONS: MiR-103a-2-5p serves as a tumor suppressor that could inhibit AML cell proliferation and promote their apoptosis by downregulating LILRB3 expression, suppressing the Nrf2/HO-1 axis, and reducing the ratio of GSH/ROS. Besides, our findings indicate that miR-103a-2-5p may enhance the CD8 + T cell response by inhibiting LILRB3 expression. Therefore, the delivery of miR-103a-2-5p through CLPs could be useful for the treatment of AML.

Biomimetic Asymmetric Reduction Based on the Regenerable Coenzyme NAD(P)H Models.

ConspectusIn nature, the coenzyme NAD(P)H is utilized for the transfer of hydrogen and electrons in biocatalytic reduction, which involves the process of recycling, coenzyme usage, and reduction. Inspired by the biological system, a series of nonregenerable achiral and chiral NAD(P)H models were synthesized and employed. However, this approach faced intractable limitations, such as the need for an equivalent amount of mimics, accompanied by the production of byproducts, which resulted in poor atom economy and difficult separation of products. Therefore, the development of new and efficient methodologies for synthesis, regeneration, and application of the NAD(P)H models in organic synthesis is greatly desired.To tackle these challenges, the regenerable achiral and chiral coenzyme NAD(P)H models were designed and synthesized based on the principles of biocatalytic reduction and applied them in biomimetic asymmetric reduction (BMAR) reactions. This Account summarizes our endeavors in rational design, synthesis, regeneration, and application of the NAD(P)H models. First, we will introduce the design and synthesis of regenerable and achiral coenzyme NAD(P)H models (dihydrophenanthridine and dihydropyrroloquinoxaline), which were successfully applied to BMAR of imines and heteroaromatics using homogeneous ruthenium complex as a regeneration catalyst, chiral phosphoric acid as a transfer catalyst, and hydrogen as the terminal reductant. Regenerable and achiral NAD(P)H models require the addition of chiral catalysts or chiral ligands for stereoselective control during the BMAR process. However, the screening of the chiral transfer catalysts is tedious. Narrow substrate scope further limited their application in organic synthesis. Therefore, we designed and synthesized regenerable and chiral NAD(P)H models (CYNAM and FENAM) with planar chirality, which were successfully applied in asymmetric reduction of imines and heteroaromatics using commercially available achiral Brønsted acids, Lewis acids, or organocatalysts as transfer catalysts and a homogeneous ruthenium complex as a regeneration catalyst. Notably, the original factor of enantioselective control is from the chiral NAD(P)H models. In addition, this strategy could also realize the asymmetric reduction of a myriad of electron-deficient tetrasubstituted alkenes, which are challenging substrates in transition metal catalyzed asymmetric hydrogenation. This methodology provides an efficient strategy for the synthesis of chiral building blocks and bioactive molecules. Finally, the detailed mechanism of BMAR, based on the regenerable NAD(P)H models, was elaborated through a combination of experiments and density functional theory calculations. In summary, we believe that the results presented in this Account hold significant implications beyond our work and have the potential for further applications in the field of biomimetic asymmetric catalysis and synthetic methodology.

Computational simulation of multi-wavelength light-field thermometry based on a chromatic meta-lens.

This Letter proposes a light-field meta-lens multi-wavelength thermometry (MMT) system that is capable of modulating a full-spectrum incident radiation into four separate wavelength beams. The chromatic meta-lens is designed using finite-difference time-domain (FDTD) software to function as a filter, ensuring its ability to separate four wavelengths. The chromatic meta-lens is positioned on the back focus plane of the main lens to replace the microlens used in traditional light-field systems and simplify the overall system. After detecting the acquired wavelengths and intensities of the image on photodiodes, a raw multispectral image can be decoupled and processed using the Chameleon swarm algorithm (CSA). Four full-spectrum incident radiations corresponding to four temperature characteristic curves are detected. The high accuracy of the reverse temperature calculation enables the measurement of surface high-temperature distribution with precision.

Risk of traumatic brain injury among patients with ADHD and their unaffected siblings.

BACKGROUND: As the relationship between attention deficit hyperactivity disorder (ADHD) and traumatic brain injury (TBI) is gaining increasing attention, the TBI risk in patients with ADHD, unaffected siblings of ADHD probands, and non-ADHD controls remains unclear. METHODS: Overall, 18,645 patients with ADHD, 18,880 unaffected siblings of ADHD probands, and 188,800 age-/sex-matched controls were followed up from enrollment to the end of 2011. The cases of TBI and TBI requiring hospitalization were identified during follow-up. RESULTS: Patients with ADHD (hazard ratio [HR]: 1.57) and unaffected siblings (HR: 1.20) had an increased risk of any TBI compared with non-ADHD controls. Surprisingly, the likelihood of developing TBI requiring hospitalization during follow-up was higher in the unaffected siblings group (HR: 1.21) than in the control group, whereas it was lower in the ADHD probands group (HR: 0.86). CONCLUSIONS: Patients with ADHD and unaffected siblings of ADHD probands were more likely to develop any TBI during follow-up than controls. Unaffected siblings of patients with ADHD exhibited the highest risk of subsequent TBI requiring hospitalization compared with patients with ADHD and healthy controls. Therefore, TBI risk in patients with ADHD and their unaffected siblings would require further investigation. IMPACT: ADHD diagnosis and ADHD trait are associated with risk of traumatic brain injury (TBI). Both patients with ADHD and their unaffected siblings were more likely to develop TBI during the follow-up compared with the control group. TBI requiring hospitalization occurred more in the sibling group than in the proband group. TBI risk should be closely monitored among unaffected siblings of patients with ADHD.

Iridium-Catalyzed Asymmetric Hydrogenation of Heteroaromatics with Multiple N Atoms via Substrate Activation: An Entry to 4,5,6,7-Tetrahydropyrazolo[1,5-a]pyrimidine-3-carbonitrile Core of a Potent BTK Inhibitor.

The chiral 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine is the key core skeleton of potent Bruton's tyrosine kinase (BTK) inhibitor Zanubrutinib, and the catalyst-controlled asymmetric hydrogenation of planar multinuclear pyrimidine heteroarenes with multiple N atoms could provide an efficient route toward its synthesis. Owing to the strong aromaticity and poisoning effect toward chiral transition metal catalyst, asymmetric hydrogenation of pyrazolo[1,5-a]pyrimidines with multiple nitrogen atoms is still a challenge for synthesizing the chiral 4,5,6,7-tetrahydropyrazolo[1,5-a]-pyrimidine. Herein, an efficient iridium-catalyzed asymmetric hydrogenation of pyrazolo[1,5-a]pyrimidines has been developed using substrate activation strategy, with up to 99% ee. The decagram scale synthesis further demonstrated the potential and promise of this procedure in the synthesis of Zanubrutinib. In addition, a mechanistic study indicated that the hydrogenation starts with 1,2-hydrogenation.

Artificial Intelligence in Meta-optics.

Recent years have witnessed promising artificial intelligence (AI) applications in many disciplines, including optics, engineering, medicine, economics, and education. In particular, the synergy of AI and meta-optics has greatly benefited both fields. Meta-optics are advanced flat optics with novel functions and light-manipulation abilities. The optical properties can be engineered with a unique design to meet various optical demands. This review offers comprehensive coverage of meta-optics and artificial intelligence in synergy. After providing an overview of AI and meta-optics, we categorize and discuss the recent developments integrated by these two topics, namely AI for meta-optics and meta-optics for AI. The former describes how to apply AI to the research of meta-optics for design, simulation, optical information analysis, and application. The latter reports the development of the optical Al system and computation via meta-optics. This review will also provide an in-depth discussion of the challenges of this interdisciplinary field and indicate future directions. We expect that this review will inspire researchers in these fields and benefit the next generation of intelligent optical device design.

A cross-sectional study of SARS-CoV-2 antibodies among healthcare workers in a tertiary care hospital in Taiwan: implications for protection against the Omicron variants.

BACKGROUND: Taiwan, deeply impacted by the 2003 SARS outbreak, promptly implemented rigorous infection control and prevention (ICP) measures in January 2020 to combat the global COVID-19 pandemic. This cross-sectional serologic study was conducted among healthcare workers (HCWs) in a tertiary care hospital in Taiwan from August 1, 2022, to February 28, 2023. The study aimed to assess HCWs' antibody responses to COVID-19 vaccination against Omicron subvariants BA.1, BA.4, and BA.5, considering variations in prior infection. Additionally, it evaluated the effectiveness of ICP and vaccination policies within the hospital setting in Taiwan. METHODS: A cross-sectional serology study was conducted in Taiwan to investigate the seroprevalence rates of Omicron subvariants BA.1, BA.4, and BA.5 among HCWs. A total of 777 HCWs participated in this study. A structured questionnaire was collected to obtain the epidemiological characteristics and risk factors for potential exposure. Enzyme-linked immunosorbent assay was used to detect antibody responses. Serum samples were selected for protection against Omicron subvariants BA.1, BA.4, and BA.5 by using a pseudotyped-based neutralization assay. RESULTS: More than 99% of the participants had received SARS-CoV-2 vaccination. Overall, 57.7% had been infected with SARS-CoV-2, with some being asymptomatic. The SARS-CoV-2 Anti-Spike S1 protein IgG (Anti-S) distribution was 40,000 AU/mL for 20.2% (157/777) of participants, with a mean ± standard deviation of 23,442 ± 22,086. The decay curve for Anti-S was less than 20,000 AU/ml after 120 days. The probability curve of 50% neutralization showed an Anti-S of 55,000 AU/ml. The optimum Anti-S was 41,328 AU/mL (equal to 5,869 WHO's standard BAU/mL), with 86.1% sensitivity and 63.5% specificity. CONCLUSIONS: In this significant study, 20.2% of HCWs achieved seroprotection against Omicron subvariants BA.1, BA.4, and BA.5. Their immunity against Omicron subvariants was further reinforced through recommended vaccinations and the development of natural immunity from SARS-CoV-2 exposure, collectively enhancing their protection against Omicron.

Risk of autoimmune diseases after post-traumatic stress disorder: a nationwide cohort study.

This longitudinal study aimed to investigate the risk of subsequent autoimmune disease in patients with post-traumatic stress disorder (PTSD) in Asian population. Between 2002 and 2009, we enrolled 5273 patients with PTSD and 1:4 matched controls from the National Health Insurance Database of Taiwan, and followed up the patients until December 31, 2011, or death. The investigated autoimmune diseases included thyroiditis, lupus, rheumatic arthritis, inflammatory bowel disease, Sjogren's syndrome, dermatomyositis, and polymyositis. The Cox regression model was used to estimate the risk of developing autoimmune diseases, with adjustment for demographics and psychiatric and medical comorbidities. Furthermore, we examined the psychiatric clinics utility of patients with PTSD indicating the severity of PTSD in association with autoimmune diseases. After adjusting for confounders, patients with PTSD had a 2.26-fold higher risk of developing any autoimmune diseases (reported as hazard ratios with 95% confidence intervals: 1.82-2.80) than the controls. For specific autoimmune diseases, patients with PTSD had a 2.70-fold higher risk (1.98-3.68) of thyroiditis, a 2.95-fold higher risk (1.20-7.30) of lupus, and a 6.32-fold higher risk (3.44-11.60) of Sjogren's syndrome. Moreover, the PTSD severity was associated with the risk of autoimmune diseases in a dose-dependent manner. The patient with the highest psychiatric clinics utility was associated with an 8.23-fold higher risk (6.21-10.90) of any autoimmune diseases than the controls. Patients with PTSD had an increased risk of autoimmune diseases, and such risk was associated with the severity of PTSD in a dose-dependent manner. However, the present study did not provide a direct effect between PTSD and autoimmune diseases, but rather an association. Further studies are warranted to examine the underlying pathophysiological mechanisms.

Exposure to psychotropic drugs and breast cancer risk in patients with bipolar disorder and major depressive disorder: a nested case-control study.

Breast cancer is one of the most prevalent and serious types of cancer globally. Previous literature has shown that women with mental illness may have an increased risk of breast cancer, however whether this risk is associated with the use of psychotropic drugs has yet to be elucidated. This study aimed to assess such risk among women with major depressive disorder (MDD) and bipolar disorder (BD). A nested case-control study design was used with data obtained from the Taiwan National Health Insurance Research Database. Logistic regression analysis with adjustments for demographic characteristics, medical and mental comorbidities, and all-cause clinical visits was performed to estimate the risk of breast cancer according to the cumulative defined daily dose (cDDD) of psychotropic drugs. The study included 1564 women with MDD or BD who had breast cancer, and 15,540 women with MDD or BD who did not have breast cancer. After adjusting for important confounders, the long-term use of valproic acid (odds ratio, 95% confidence interval: 0.58, 0.39-0.56, cDDD ≥ 365), citalopram (0.58, 0.37-0.91, cDDD 180-365), and sertraline (0.77, 0.61-0.91, cDDD ≥ 365) was associated with a lower risk of breast cancer compared to a cDDD < 30. The short-term use of fluvoxamine (0.82, 0.69-0.96, cDDD 30-180), olanzapine (0.54, 0.33-0.89, cDDD 30-179), risperidone (0.7, 0.51-0.98, cDDD 30-179), and chlorpromazine (0.48, 0.25-0.90, cDDD 30-179) was associated with a lower risk of breast cancer. We found no evidence of an increased risk of breast cancer in patients with MDD or BD receiving psychotropic drugs.

Proinflammatory cytokine levels, cognitive function, and suicidal symptoms of adolescents and young adults with major depressive disorder.

Whether proinflammatory cytokine dysregulation and cognitive dysfunction are associated with suicidal symptoms in adolescents and young adults with major depressive disorder (MDD) remains uncertain. We assessed the cognitive function and proinflammatory cytokine levels of 43 and 51 patients aged 15-29 years with MDD and severe and mild suicidal symptoms, respectively, as well as those of 85 age- and sex-matched healthy controls. Specifically, we measured serum levels of C-reactive protein, tumor necrosis factor-α (TNF-α), interleukin-2, and interleukin-6 and assessed cognitive function by using working memory and go/no-go tasks. The severity of the patients' suicidal symptoms was based on Item 10 of the Montgomery-Åsberg Depression Rating Scale; scores of ≤ 2 and ≥ 4 indicated mild and severe symptoms, respectively. The patients with MDD and severe suicidal symptoms had higher levels of C-reactive protein (p = .019) and TNF-α (p = .002) than did the patients with mild symptoms or the healthy controls. The number of errors committed on the go/no-go by patients with MDD and severe suicidal symptoms (p = .001) was significantly higher than those by patients with MDD and mild symptoms or by controls. After adjusting for nonsuicidal depressive symptoms, we observed suicidal symptoms to be positively associated with TNF-α levels (p = .050) and errors on the go/no-go task (p = .021). Compared with mild suicidal symptoms, severe symptoms are associated with greater serum levels of proinflammatory cytokines and inferior cognitive function in adolescents and young adults with MDD.

Hepatocyte mitochondrial DNA mediates macrophage immune response in liver injury induced by trichloroethylene.

We have previously shown that excessive activation of macrophage proinflammatory activity plays a key role in TCE-induced immune liver injury, but the mechanism of polarization is unclear. Recent studies have shown that TLR9 activation plays an important regulatory role in macrophage polarization. In the present study, we demonstrated that elevated levels of oxidative stress in hepatocytes mediate the release of mtDNA into the bloodstream, leading to the activation of TLR9 in macrophages to regulate macrophage polarization. In vivo experiments revealed that pretreatment with SS-31, a mitochondria-targeting antioxidant peptide, reduced the level of oxidative stress in hepatocytes, leading to a decrease in mtDNA release. Importantly, SS-31 pretreatment inhibited TLR9 activation in macrophages, suggesting that hepatocyte mtDNA may activate TLR9 in macrophages. Further studies revealed that pharmacological inhibition of TLR9 by ODN2088 partially blocked macrophage activation, suggesting that the level of macrophage activation is dependent on TLR9 activation. In vitro experiments involving the extraction of mtDNA from TCE-sensitized mice treated with RAW264.7 cells further confirmed that hepatocyte mtDNA can activate TLR9 in mouse peritoneal macrophages, leading to macrophage polarization. In summary, our study comprehensively confirmed that TLR9 activation in macrophages is dependent on mtDNA released by elevated levels of oxidative stress in hepatocytes and that TLR9 activation in macrophages plays a key role in regulating macrophage polarization. These findings reveal the mechanism of macrophage activation in TCE-induced immune liver injury and provide new perspectives and therapeutic targets for the treatment of OMDT-induced immune liver injury.

Elevated risk of sexually transmitted infections among adolescents and young adults with borderline personality disorder: a retrospective longitudinal nationwide population-based study.

In this study, we examined the risk of sexually transmitted infections (STIs) among adolescents and young adults (AYAs) with borderline personality disorder (BPD). A total of 4649 AYAs with BPD and 46,490 age-, sex-, and socioeconomic-matched controls without BPD were enrolled from the National Health Insurance Research Database of Taiwan from 2001 to 2009 and were followed up until the end of 2011. Participants who contracted any STI during the follow-up period were identified. Cox regression analysis was conducted to examine the risk of contracting any STI among both patients and controls. A total of 4649 AYAs with BPD and 46,490 age-, sex-, and socioeconomic-matched controls without BPD were enrolled from the National Health Insurance Research Database of Taiwan from 2001 to 2009 and were followed up until the end of 2011. Participants who contracted any STI (ICD-9-CM code 042, 091-097, 087.11, 078.8, 078.88, 131, and 054.1) during the follow-up period were identified. Cox regression and sub-analyses stratified by sex, age, psychiatric comorbidity subgroups, and psychotropic medication usage were conducted to assess STI risk. AYAs with BPD were at a higher risk of contracting any STI (hazard ratio [HR] = 50.79, 95% confidence interval [CI] = 33.45-77.11) in comparison with controls, including HIV, syphilis, genital warts, gonorrhea, chlamydia, trichomoniasis, and genital herpes. The association of BPD with an increased risk of any STI was prevalent in both sexes, adolescents, and young adult patients. BPD with or without psychiatric comorbid subgroup were all associated with an elevated risk of contracting any STI relative to the control group. AYAs with BPD are highly susceptible to contracting STIs. Future studies should examine the role of the core symptoms of BPD, sexual orientation, risky sex behaviors, depressive and anxiety symptoms, and substance use before sex in the risk of STIs among AYAs with BPD.

Appetite hormone dysregulation and executive dysfunction among adolescents with bipolar disorder and disruptive mood dysregulation disorder.

Appetite hormone dysregulation may play a role in the pathomechanisms of bipolar disorder and chronic irritability. However, its association with executive dysfunction in adolescents with bipolar disorder and those with disruptive mood dysregulation disorder (DMDD) remains unclear. We included 20 adolescents with bipolar disorder, 20 adolescents with DMDD, and 47 healthy controls. Fasting serum levels of appetite hormones, including leptin, ghrelin, insulin, and adiponectin were examined. All participants completed the Wisconsin Card Sorting Test. Generalized linear models with adjustments for age, sex, body mass index, and clinical symptoms revealed that patients with DMDD had elevated fasting log-transformed insulin levels (p = .023) compared to the control group. Adolescents with DMDD performed worse in terms of the number of tries required to complete tasks associated with the first category (p = .035), and adolescents with bipolar disorder performed worse in terms of the number of categories completed (p = .035). A positive correlation was observed between log-transformed insulin levels and the number of tries required for the first category (ß = 1.847, p = .032). Adolescents with DMDD, but not those with bipolar disorder, were more likely to exhibit appetite hormone dysregulation compared to healthy controls. Increased insulin levels were also related to executive dysfunction in these patients. Prospective studies should elucidate the temporal association between appetite hormone dysregulation, executive dysfunction, and emotional dysregulation.

Longitudinal study on all-cause and suicide mortality among individuals with attention deficit hyperactivity disorder.

BACKGROUND: Previous research has linked attention deficit hyperactivity disorder (ADHD) with an increased risk of all-cause mortality, primarily owing to unnatural causes such as accidents and suicides. This increase may be attributable to the co-occurrence of major psychiatric disorders, including schizophrenia (SCZ), bipolar disorder (BD), major depressive disorder (MDD), autism spectrum disorder (ASD), anxiety disorders, substance use disorders (SUDs), and personality disorders (PDs). This study examined the all-cause and specific-cause mortality rates in individuals with ADHD and the influence of psychiatric comorbidities. METHODS: Between 2003 and 2017, 1.17 million individuals were enrolled in the study, of which 233,886 received a diagnosis of ADHD from the Taiwan's National Health Insurance Research Database. A 1:4 sex- and birth year-matched control group without ADHD was also included. Hazard ratios (HRs) for mortality rates were estimated between groups after adjusting for demographic data. RESULTS: During the follow-up period, 781 individuals with ADHD died. The HR for all-cause mortality was 1.45 (95% confidence interval [CI]: 1.30-1.61), largely owing to unnatural causes, particularly suicide. Suicide rates were particularly high in individuals with ADHD and psychiatric comorbidities: the HRs for suicide were 47.06 in ADHD with SUDs (95% CI: 6.12-361.99), 32.02 in ADHD with SCZ (7.99-128.29), 23.60 in ADHD with PDs (7.27-76.66), 10.11 in ADHD with anxiety disorders (5.74-17.82), 9.30 in ADHD with BD (4.48-19.33), 8.36 in ADHD with MDD (5.66-12.35), and 6.42 in ADHD with ASD (1.83-22.53) relative to ADHD only. DISCUSSION: ADHD was associated with increased mortality rates, primarily owing to suicide. The presence of major psychiatric comorbidities was associated with a further increase in suicide mortality risk.

Sexually transmitted infection and teenage pregnancy in adolescents having parents with schizophrenia: a retrospective cohort study of 64,350 participants.

BACKGROUND: The risks of sexually transmitted infections (STIs) and teenage pregnancy in the offspring of parents with schizophrenia remain unknown. METHODS: From the Taiwan National Health Insurance Research Database, 5,850 individuals born between 1980 and 1999 having any parent with schizophrenia and 58,500 age-, sex-, income- and residence-matched controls without parents with severe mental disorders were enrolled in 1996 or on their birthdate and followed up to the end of 2011. Those who contracted any STI or became pregnant in adolescence during the follow-up period were identified. RESULTS: Cox regression analyses demonstrated that offspring of parents with schizophrenia (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 1.02-1.44), especially daughters (HR: 1.30, 95% CI: 1.06-1.58), were more likely to contract any STI later in life than the control comparisons. In addition, daughters of parents with schizophrenia had an elevated risk of being pregnant in their adolescence (HR: 1.47, 95% CI: 1.29-1.67) compared with those having no parents with severe mental disorders. DISCUSSION: The positive relationship between parental schizophrenia and offspring STIs and teenage pregnancy necessitates clinicians and public health officers to closely monitor the sexual health in the offspring of parents with schizophrenia so that optimal and prompt preventive measures can be taken in the at-risk group.

Parental mental disorders in patients with comorbid schizophrenia and obsessive-compulsive disorder: a nationwide family-link study.

Schizophrenia is highly comorbid with obsessive-compulsive disorder (OCD); both conditions share numerous pathophysiological etiologies. We, thus, examined the risk of mental disorders in the parents of probands with schizophrenia, OCD, or both conditions. Between 2001 and 2011, we enrolled a nationwide cohort of 69,813 patients with schizophrenia, OCD, or both. The control cohort included 698,130 individuals matched for demographics. Poisson regression models were employed to examine the risk of six mental disorders in their parents, including schizophrenia, bipolar disorder, depressive disorder, OCD, alcohol use disorder, and substance use disorder. We stratified patients into schizophrenia-only, OCD-only, and dual-diagnosis groups, and the dual-diagnosis group was further divided into schizophrenia-first, OCD-first, and simultaneously diagnosed groups. Compared with controls, the schizophrenia, OCD, and dual-diagnosis groups had higher risks for the six mental disorders in their parents (range of odds ratio [OR] 1.50-7.83). The sub-analysis of the dual-diagnosis group showed that the schizophrenia-first, OCD-first, and simultaneously diagnosed groups had higher odds for schizophrenia, bipolar disorder, depressive disorder, and OCD (range of OR 1.64-6.45) in their parents than the control group; the simultaneously diagnosed and OCD-first diagnosed groups had a higher odds of parental substance use disorder, while the schizophrenia-first diagnosed group had a higher odds of parental alcohol use disorder. The interrelationship between OCD and schizophrenia is linked to bipolar disorder, depressive disorder, alcohol use disorder, and substance use disorder. The results have implications for mental health policy and future research.

Diagnostic conversion to bipolar disorder among adolescents and young adults with major depressive disorder: a nationwide longitudinal study.

Although several studies have examined a diagnostic conversion from major depressive disorder (MDD) to bipolar disorder (BD), only a few studies specifically focused on adolescents and young adults who are at the peak ages of BD onset. Data from participants (N = 130,793) aged 10-29 years who were diagnosed with MDD were extracted from the Taiwan National Health Insurance Research Database. We applied demographic analyses, survival analysis, Aalen Johansen curves, and Cox regression, investigating the diagnostic conversion rate and factors that were most or less predictive of conversion. Among the adolescents and young adults with MDD, the number of participant conversion subsample is 14,187 and the conversion rate was 13.80% (95% confidence interval: 13.54-14.06%) during the 11-year follow-up. The conversion rate was highest in the first year (4.50%; 4.39-4.61%) and decreased over time. The significant predictors were younger age of diagnosis with MDD (p < 0.001), moderate and high antidepressant resistance (p < 0.001), obesity (p < 0.001), psychiatric comorbidities (attention-deficit/hyperactivity disorder, substance use disorder, and cluster B and C personality disorder, all p < 0.001), a family history of mental disorders (schizophrenia and mood disorders, all p < 0.05), lower monthly income (p < 0.001), and more mental health visits to the clinic each year (p < 0.001). A composite of demographic characteristics, antidepressant resistance, physical and psychiatric comorbidities, and family history significantly predicted diagnostic conversion from MDD to BD (area under the curve = 0.795, p < 0.001). Compared to adult population, the adolescents and young adults had different factors that were most or less predictive of conversion, which warrants further investigation.

Risk of major mental disorders in the offspring of parents with migraine.

BACKGROUND: Migraine has been associated with mental disorders, however whether parental migraine is associated with an increased risk of major mental disorders (MMDs) in offspring has not been investigated. We aimed to examine the risk of the development of MMDs in the offspring of parents with migraine compared with those of parents without migraine. METHODS: This study used data derived from the Taiwan National Health Insurance Research Database. Offspring of parents with migraine and a control group consisting of offspring of parents without migraine matched for demographic and parental mental disorders were included. Cox regression was used to estimate the risk of MMDs, including schizophrenia, depressive disorder, bipolar disorder, autistic spectrum disorder (ASD), and attention deficit/hyperactivity disorder (ADHD). Sub-analyses stratified by the fathers and mothers were further performed to separately clarify the risks of MMDs among the offspring. RESULTS: We included 22,747 offspring of parents with migraine and 227,470 offspring of parents without migraine as the controls. Parental migraine was significantly associated with an increased risk of ADHD (reported as hazard ratios with 95% confidence intervals: 1.37, 1.25-1.50), bipolar disorder (1.35, 1.06-1.71), and depressive disorder (1.33, 1.21-1.47) compared to the offspring of parents without migraine. Importantly, sub-analyses showed that only maternal migraine was significantly associated with these risks. CONCLUSIONS: Due to the heavy burden of MMDs, healthcare workers should be aware of the risk of MMDs in the offspring of parents with migraine, particular in mothers.