BTRX-246040 Acts Through the Ventrolateral Periaqueductal Gray to Exert Antidepressant-Relevant Actions in Mice.

BACKGROUND: BTRX-246040, a nociceptin/orphanin FQ peptide receptor antagonist, is being developed for the treatment of depressive patients. However, the underlying mechanism of this potential antidepressant is still largely unclear. Here, we studied the antidepressant-related actions of BTRX-246040 in the ventrolateral periaqueductal gray (vlPAG). METHODS: The tail suspension test, forced swim test, female urine sniffing test, sucrose preference test, and learned helplessness (LH) combined with pharmacological approaches were employed to examine the antidepressant-like effects and drug effects on LH-induced depressive-like behavior in C57BL/6J mice. Electrophysiological recordings in vlPAG neurons were used to study synaptic activity. RESULTS: Intraperitoneal administration of BTRX-246040 produced antidepressant-like behavioral effects in a dose-dependent manner. Systemic BTRX-246040 (10 mg/kg) resulted in an increased frequency and amplitude of miniature excitatory postsynaptic currents (EPSCs) in the vlPAG. Moreover, slice perfusion of BTRX-246040 directly elevated the frequency and amplitude of miniature EPSCs and enhanced the evoked EPSCs in the vlPAG, which were blocked by pretreatment with the nociceptin/orphanin FQ peptide receptor agonist Ro 64-6198. In addition, intra-vlPAG application of BTRX-246040 produced antidepressant-like behavioral effects in a dose-dependent manner. Moreover, intra-vlPAG pretreatment with 6-cyano-7-nitroquinoxaline-2,3-dione reversed both systemic and local BTRX-246040-mediated antidepressant-like behavioral effects. Furthermore, both systemic and local BTRX-246040 decreased the LH phenotype and reduced LH-induced depressive-like behavior. CONCLUSIONS: The results suggested that BTRX-246040 may act through the vlPAG to exert antidepressant-relevant actions. The present study provides new insight into a vlPAG-dependent mechanism underlying the antidepressant-like actions of BTRX-246040.

Interactive association of maternal education and peer relationship with oppositional defiant disorder: an observational study.

BACKGROUND: The objectives of this research were to gain insights on the interactive effects, by measuring familial and peer-related risk factors in youths with oppositional defiant disorder (ODD). METHODS: Participants were college students recruited nationwide, with age between 18 and 25. Through the consensus of expert meetings, a set of questionnaires were used to evaluate the familial status, participant's peer group conditions, high-risk environment of illicit substance use, and oppositional symptoms. The logistic regression was performed to see the independent and interactive risk factors for ODD. RESULTS: A total of 981 subjects were enrolled. Six variables significantly associated with ODD at the multivariate logistic regression, including male, night division, poor academic performance, high risk environment, peer with illicit substance use and high maternal education level. High maternal education exerted independent protective effect on the development of ODD (adjusted odds ratio, aOR = 0.65, 95% CI = 0.44-0.99). Peer with illicit substance use was more likely to associate with ODD in the low maternal education group. The 2-way interactive effect of maternal education and peer with substance use on the development of ODD was OR = 4.96 (2.96, 8.31). CONCLUSION: The present study highlights the influence of maternal education level to ODD and its interaction with peer of illicit substance use. Our findings imply that the familial attachment and peer interaction are essential stages for the development of human behavior. TRIAL REGISTRATION: The research protocol was reviewed and approved by the ethical review committee of National Taiwan University Hospital (number 201505057RINC ) and registered at clinical trial systems at National Taiwan University. In addition, subjects' information was anonymous and de-identified prior to any analysis.

Risk of suicide within 1 year of cancer diagnosis.

The association of the risk of suicide with cancer at different time points after a new cancer diagnosis is unclear. This study explored the suicide hazard at different time points after a first cancer diagnosis during the 1-year period before suicide. This case-crossover study included 2,907 suicide cases from 2002 to 2012 in Taiwan and compared the odds of suicide risk at different time points during one year after any cancer diagnosis with self-matched periods. The 13th month preceding the suicide date was used as the control period, and the hazard period was the duration from the 1st to 12th month in the conditional logistic regression for case-crossover comparisons. Among major groups of cancers, group of lip, oral cavity and pharynx cancers tended to have higher risk of suicide than other groups of cancers. The first month of cancer diagnosis was associated with the highest risk of suicide compared with the 13th month before suicide. The odds ratio (OR) of suicide were significantly in the first six months after cancer diagnosis but declined afterwards. For example, the adjusted OR was 3.47 [95% confidence interval (CI) = 2.60-4.62] in the first month and 1.53 (95% CI = 1.11-2.12) in the sixth month following cancer diagnosis. These findings provide clinicians with a vital reference period during which sufficient support and necessary referral to mental health support should be provided to reduce the risk of suicide among patients with newly diagnosed cancer morbidity.

Variant GADL1 and response to lithium therapy in bipolar I disorder.

BACKGROUND: Lithium has been a first-line choice for maintenance treatment of bipolar disorders to prevent relapse of mania and depression, but many patients do not have a response to lithium treatment. METHODS: We selected subgroups from a sample of 1761 patients of Han Chinese descent with bipolar I disorder who were recruited by the Taiwan Bipolar Consortium. We assessed their response to lithium treatment using the Alda scale and performed a genomewide association study on samples from one subgroup of 294 patients with bipolar I disorder who were receiving lithium treatment. We then tested the single-nucleotide polymorphisms (SNPs) that showed the strongest association with a response to lithium for association in a replication sample of 100 patients and tested them further in a follow-up sample of 24 patients. We sequenced the exons, exon-intron boundaries, and part of the promoter of the gene encoding glutamate decarboxylase-like protein 1 (GADL1) in 94 patients who had a response to lithium and in 94 patients who did not have a response in the genomewide association sample. RESULTS: Two SNPs in high linkage disequilibrium, rs17026688 and rs17026651, that are located in the introns of GADL1 showed the strongest associations in the genomewide association study (P=5.50×10(-37) and P=2.52×10(-37), respectively) and in the replication sample of 100 patients (P=9.19×10(-15) for each SNP). These two SNPs had a sensitivity of 93% for predicting a response to lithium and differentiated between patients with a good response and those with a poor response in the follow-up cohort. Resequencing of GADL1 revealed a novel variant, IVS8+48delG, which lies in intron 8 of the gene, is in complete linkage disequilibrium with rs17026688 and is predicted to affect splicing. CONCLUSIONS: Genetic variations in GADL1 are associated with the response to lithium maintenance treatment for bipolar I disorder in patients of Han Chinese descent. (Funded by Academia Sinica and others.).

Association Study of Gene Polymorphisms in GABA, Serotonin, Dopamine, and Alcohol Metabolism Pathways with Alcohol Dependence in Taiwanese Han Men.

BACKGROUND: The roles of GABA, serotonin, dopamine, and alcohol metabolism pathways in alcohol dependence (AD) are evident from animal models and human studies. Aims of this study were to investigate associations between genes in the 4 pathways and AD. METHODS: Male subjects from 2 independent samples of Taiwanese Han descent, a family sample of 179 trios and a case-control sample of 262 AD cases and 273 normal controls, were included in this study. The Schedules for Clinical Assessment in Neuropsychiatry was used for phenotype assessment of AD. We genotyped 282 single nucleotide polymorphisms (SNPs) located in 61 candidate genes involving alcohol metabolism, serotonin, and GABA systems among the family sample and replicated the top hits in the case-control sample. RESULTS: Fifteen SNPs located in 10 genes showed signals of associations (FBAT test p < 0.05) with AD in the family sample. Three SNPs, rs1229984 in ADH1B, rs671 in ALDH2, and rs2000292 in HTR1B, were significantly replicated in the case-control sample (p = 5.87 × 10(-14) , 5.12 × 10(-14) , and 0.0051, respectively). In the combined meta-analysis, these 3 SNPs and 1 additional SNP, rs698 in ADH1C, showed significant association after correcting for multiple comparisons, and rs1229984 and rs671 showed the strongest association (p < 10(-16) ). Logistic regression conditioning on rs1229984 and rs671 in the case-control sample showed that rs2000292 in HTR1B remained nominally significant. CONCLUSIONS: Genes in alcohol metabolism pathway, especially ADH1B and ALDH2, conferred the major genetic risk for AD in Taiwanese Han population. Some genes in GABA and serotonin pathways showed nominal association with AD.

Changing trends in the prevalence of common mental disorders in Taiwan: a 20-year repeated cross-sectional survey.

BACKGROUND: Macrosocial changes might affect mental health. We investigated whether the prevalence of common mental disorders (CMDs) changed over a 20-year period of industrialisation in Taiwan. METHODS: We used the 12-item Chinese Health Questionnaire to assess mental status of Taiwanese adults in 1990, 1995, 2000, 2005, and 2010. Respondents with scores of 3 or higher were classified as having probable CMDs. We assessed trends of probable CMDs with the Cochran-Armitage test and their risk factors (sex, age, marital status, educational level, employment status, and physical health) with multivariable logistic regression. The trends were compared with national rates of unemployment, divorce, and suicide. FINDINGS: Of 10,548 respondents, 9079 (86·1%) completed questionnaires. The prevalence of probable CMDs doubled from 11·5% in 1990 to 23·8% in 2010 (time trend p<0·001). Increases paralleled rises in national rates of unemployment, divorce, and suicide at all five timepoints. Significant risk factors for probable CMDs were female sex (adjusted odds ratio 1·6, 95% CI 1·4-1·8), 6 or fewer years of education (1·3, 1·1-1·5), unemployment (1·4, 1·1-1·7), and poor physical health that limited daily activities (6·5, 5·4-8·0). When we controlled for these factors in multivariable models, the time trends remained significant (p<0·0001). INTERPRETATION: National rates of unemployment, divorce, and suicide increased in parallel with prevalence of probable CMDs in Taiwan. Therefore, clinical and social preventive measures both seem important during times of change to the economy and labour market. FUNDING: Taiwan National Science Council.

Blue light at night produces stress-evoked heightened aggression by enhancing brain-derived neurotrophic factor in the basolateral amygdala.

Light is an underappreciated mood manipulator. People are often exposed to electronic equipment, which results in nocturnal blue light exposure in modern society. Light pollution drastically shortens the night phase of the circadian rhythm. Preclinical and clinical studies have reported that nocturnal light exposure can influence mood, such as depressive-like phenotypes. However, the effects of blue light at night (BLAN) on other moods and how it alters mood remain unclear. Here, we explored the impact of BLAN on stress-provoked aggression in male Sprague‒Dawley rats, focusing on its influence on basolateral amygdala (BLA) activity. Resident-intruder tests, extracellular electrophysiological recordings, and enzyme-linked immunosorbent assays were performed. The results indicated that BLAN produces stress-induced heightened aggressive and anxiety-like phenotypes. Moreover, BLAN not only potentiates long-term potentiation and long-term depression in the BLA but also results in stress-induced elevation of brain-derived neurotrophic factor (BDNF), mature BDNF, and phosphorylation of tyrosine receptor kinase B expression in the BLA. Intra-BLA microinfusion of BDNF RNAi, BDNF neutralizing antibody, K252a, and rapamycin blocked stress-induced heightened aggressive behavior in BLAN rats. In addition, intra-BLA application of BDNF and 7,8-DHF caused stress-induced heightened aggressive behavior in naïve rats. Collectively, these results suggest that BLAN results in stress-evoked heightened aggressive phenotypes, which may work by enhancing BLA BDNF signaling and synaptic plasticity. This study reveals that nocturnal blue light exposure may have an impact on stress-provoked aggression. Moreover, this study provides novel insights into the BLA BDNF-dependent mechanism underlying the impact of the BLAN on mood.

Lights at night mediate depression-like behavioral and molecular phenotypes in a glucocorticoid-dependent manner in male rats.

Nocturnal light pollution, an underappreciated mood manipulator, disturbs the circadian rhythms of individuals in modern society. Preclinical and clinical studies have suggested that exposure to lights at night (LANs) results in depression-like phenotypes. However, the mechanism underlying the action of LANs remains unclear. Therefore, this study explored the potential influence of LANs on depression-related brain regions by testing brain-derived neurotrophic factor (BDNF), synaptic transmission, and plasticity in male Sprague-Dawley rats. Depression-related behavioral tests, enzyme-linked immunosorbent assays, and intracellular and extracellular electrophysiological recordings were performed. Resultantly, rats exposed to either white or blue LAN for 5 or 21 days exhibited depression-like behaviors. Both white and blue LANs reduced BDNF expression in the medial prefrontal cortex (mPFC) and ventrolateral periaqueductal gray (vlPAG). Moreover, both lights at night (LANs) elevated the plasma corticosterone levels. Pharmacologically, the activation of glucocorticoid receptors mimics the LAN-mediated effects on depression-like behaviors and reduces BDNF levels, whereas the inhibition of glucocorticoid receptors blocks LAN-mediated behavioral and molecular actions. Electrophysiologically, both LANs attenuated the stimulation-response curve, increased the paired-pulse ratio, and decreased the frequency and amplitude of miniature excitatory postsynaptic currents in the vlPAG. In the mPFC, LANs attenuate long-term potentiation and long-term depression. Collectively, these results suggested that white and blue LANs disturbed BDNF expression, synaptic transmission, and plasticity in the vlPAG and mPFC in a glucocorticoid-dependent manner. The results of the present study provide a theoretical basis for understanding the effects of nocturnal light exposure on depression-like phenotypes.

Metabolic syndrome and the risk of suicide: a community-based integrated screening samples cohort study.

OBJECTIVE: Metabolic syndrome (MetS) is reportedly associated with mental disorders that are known to increase the risk of suicide. However, it is not known whether this association is independent of other risk indicators of suicide. This study therefore investigated whether metabolic abnormalities increase the risk of suicide during a 10-year follow-up period. METHODS: This prospective study enrolled participants from a community-based integrated screening samples cohort in Taiwan. Of the 76,297 people recruited for this study, 12,094 had MetS at baseline. The independent variables were MetS and its components such as high blood pressure and high blood lipid levels. The outcome was death from suicide (n = 146). RESULTS: MetS was associated with an increased risk of suicide risk by 16% per MetS component (95% confidence interval [CI] = 1%-33%), adjusting for demographics, life-style factors, and clinical correlates. Of the five MetS components, elevated blood pressure was independently associated with suicide-related mortality (adjusted hazard ratio [aHR] = 1.49, 95% CI = 1.03-2.15). CONCLUSIONS: This analysis of community-based longitudinal data showed that MetS and its components, particularly elevated blood pressure, correlated positively with suicide risk after controlling other factors. Therefore, public mental health interventions targeting suicide reduction may need to specifically focus on individuals with hypertension and other components of the MetS.

Incidence of first onset alcohol use disorder: a 16-year follow-up in the Taiwanese aborigines.

PURPOSE: To investigate the incidence and cumulative risk of first onset alcohol use disorder (AUD) in a 16-year follow-up among Taiwanese aboriginal populations. METHODS: Participants included in this study were cohort subjects free from any AUD at phase 1 survey (n = 428 for DSM-3-R and 451 for DSM-4) of the Taiwan aboriginal study project conducted in 1986-1988. They were reassessed approximately 16 years later, with a response rate of 98.8 %. A Chinese version of the WHO schedules for clinical assessment in neuropsychiatry was employed to assess the lifetime drinking history and AUD. RESULTS: Age-standardized annual incidence rates of AUD in all groups were 2.26 and 1.75 % according to DSM-3-R and DSM-4, respectively. The overall incidence rates of AUD were comparable to most of other studies in Caucasian populations, but the sex ratios of women to men were higher in this study (1:2-3) than in the latter (1:6). The incidence of AUD was higher with DSM-3-R than with DSM-4 criteria in this study, attributable to the exclusion of physical/psychological harm in DSM-4 alcohol abuse. The cumulative risks of DSM-4 AUD in this study were very high, being 72.2 ± 19.8 for men and 48.7 ± 8.2 for women up to the age of 65 years. CONCLUSIONS: High incidence rates and cumulative risks of AUD in Taiwanese aborigines demand effective prevention strategy.

(2R,6R)-hydroxynorketamine targeting the basolateral amygdala regulates fear memory.

(2R,6R)-Hydroxynorketamine (HNK), a ketamine metabolite, has been proposed as an ideal next-generation antidepressant due to its rapid-acting and long-lasting antidepression-relevant actions. Interestingly, recent studies have shown that (2R,6R)-HNK may have diverse impacts on memory formation. However, its effect on fear memory extinction is still unknown. In the present study, we assessed the effects of (2R,6R)-HNK on synaptic transmission and plasticity in the basolateral amygdala (BLA) and explored its actions on auditory fear memory extinction. Adult male C57BL/6J mice were used in this study. The extracellular electrophysiological recording was conducted to assay synaptic transmission and plasticity. The auditory fear conditioning paradigm was performed to test fear extinction. The results showed that (2R,6R)-HNK at 30 mg/kg increased the number of c-fos-positive cells in the BLA. Moreover, (2R,6R)-HNK enhanced the induction and maintenance of long-term potentiation (LTP) in the BLA in a dose-dependent manner (at 1, 10, and 30 mg/kg). In addition, (2R,6R)-HNK at 30 mg/kg and directly slice perfusion of (2R,6R)-HNK enhanced BLA synaptic transmission. Furthermore, intra-BLA application and systemic administration of (2R,6R)-HNK reduced the retrieval of recent fear memory and decreased the retrieval of remote fear memory. Both local and systemic (2R,6R)-HNK also inhibited the spontaneous recovery of remote fear memory. Taken together, these results indicated that (2R,6R)-HNK could regulate BLA synaptic transmission and plasticity and act through the BLA to modulate fear memory. The results revealed that (2R,6R)-HNK may be a potential drug to treat posttraumatic stress disorder (PTSD) patients.

Subclinical alterations of resting state functional brain network for adjunctive bright light therapy in nonseasonal major depressive disorder: A double blind randomized controlled trial.

Introduction: The treatment effect of bright light therapy (BLT) on major depressive disorder (MDD) has been proven, but the underlying mechanism remains unclear. Neuroimaging biomarkers regarding disease alterations in MDD and treatment response are rarely focused on BLT. This study aimed to identify the modulatory mechanism of BLT in MDD using resting-state functional magnetic resonance imaging (rfMRI). Materials and methods: This double-blind, randomized controlled clinical trial included a dim red light (dRL) control group and a BLT experimental group. All participants received light therapy for 30 min every morning for 4 weeks. The assessment of the Hamilton Depression Rating Scale-24 (HAMD-24) and brain MRI exam were performed at the baseline and the 4-week endpoint. The four networks in interest, including the default mode network (DMN), frontoparietal network (FPN), salience network (SN), and sensorimotor network (SMN), were analyzed. Between-group differences of the change in these four networks were evaluated. Results: There were 22 and 21 participants in the BLT and dRL groups, respectively. Age, sex, years of education, baseline severity, and improvement in depressive symptoms were not significantly different between the two groups. The baseline rfMRI data did not show any significant functional connectivity differences within the DMN, FPN, SN, and SMN between the two groups. Compared with the dRL group, the BTL group showed significantly increased functional connectivity after treatment within the DMN, FPN, SN, and SMN. Graph analysis of the BLT group demonstrated an enhancement of betweenness centrality and global efficiency. Conclusion: BLT can enhance intra-network functional connectivity in the DMN, FPN, SN, and SMN for MDD patients. Furthermore, BLT improves the information processing of the whole brain. Clinical trial registration: The ClinicalTrials.gov identifier was NCT03941301.

Taiwan Expert Consensus Recommendations for Switching to Aripiprazole Long-Acting Once-Monthly in Patients with Schizophrenia.

In the last decade, long-acting injectable antipsychotics has been widely used in schizophrenia. Aripiprazole long-acting once-monthly (AOM) is the only long-acting dopamine partial agonist antipsychotic approved for schizophrenia; however, a literature search revealed no guidance on safely switching from oral and long-acting injectable antipsychotics to AOM. This study aimed to develop recommendations of AOM use based on existing data and expert consensus. A committee of 30 experts in psychopharmacology from major hospitals across Taiwan was invited. A modified Delphi method was conducted, consisting of two rounds of questionnaires, literature review, three rounds of face-to-face discussion meeting, and two rounds of anonymous voting. The consensus recommendations were developed based on existing data, clinical experiences, and consensus opinions, with 80% agreement among panel members required for final adoption. The panel developed nine consensus statements of switching to AOM for both acute and stable schizophrenia patients receiving oral or long-acting injectable atypical antipsychotics. Recommendations regarding dose adjustment of oral medication and pregnancy/breastfeeding were also included. The nine consensus recommendations provide a guidance on safely switching to AOM. Substantial gaps in knowledge, and more research is necessary.

Screening illicit substance use in college students: The Chinese version of the Drug Abuse Screening Test.

BACKGROUND: This study investigated the applicability of the Chinese versions of Drug Abuse Screening Test (DAST) to detect illicit substance use in college students. METHODS: The data arising from a campus prevention program, Screening for Illicit Substance Use in College (SISUC), were utilized to explore the psychometrics of 26 items (DAST-26) and 10 items (DAST-10) versions of DAST in college students (CS group). A group of youth with illicit substance use were enrolled as the Illicit Substance Use group (IS group). A set of self-report questionnaires, including the Chinese version of DAST, were administered. RESULTS: A total of 1214 participants were recruited as the CS group and 208 as the IS group. The Cronbach's alpha of DAST-26 was 0.74 in CS and 0.90 in IS; while 0.59 in CS and 0.78 in IS for the DAST-10. At a cut-off of 4 for DAST-26, the sensitivity was 87 % and specificity 97 %. As to DAST-10, a cut-off of 2 produced the sensitivity of 86 % and specificity of 96 %. The area under the curve was 0.943 for DAST-26 and 0.940 for DAST-10. The confirmatory factor analyses found a single-factor solution for the DAST-26 and DAST-10. CONCLUSIONS: With comparison to the DAST-26, the shorter version, DAST-10, may offer promise for detecting illicit substance use in college students.

Immunophenotypes associated with bipolar disorder and lithium treatment.

Immune dysfunction is implicated in the etiology of bipolar disorder. The single-nucleotide polymorphism rs17026688 in the gene encoding glutamate decarboxylase-like protein 1 (GADL1) has been found to be associated with lithium response in Han Chinese patients with bipolar I disorder (BDI). However, whether patients with GADL1 polymorphisms have different immunophenotypes is unknown. To address this issue, differences in the immune profiles based on analysis of peripheral blood mononuclear cells (PBMCs) were compared among BDI patients and healthy controls who lack or carry the T allele of rs17026688. BDI patients had significantly higher percentages of total T cells, CD4+ T cells, activated B cells, and monocytes than healthy controls, suggesting that immunologic imbalance might be involved in BDI development or progression. Treatment of BDI patients-derived PBMCs with lithium in vitro increased the percentage of CD14+ monocytes and dendritic cells, suggesting that lithium plays an immunomodulatory role in CD14+ monocytes and dendritic cells. Among BDI patients, non-T carriers had a significantly higher percentage of CD11b+/CD33lo/HLA-DR- myeloid-derived suppressor cells than T carriers. Moreover, only T carriers exhibited differential sensitivity to lithium therapeutic use with respect to the percentage of myeloid cells. These findings suggest that rs17026688 polymorphisms in GADL1 are associated with immune dysfunction in BDI patients.

Lithium and GADL1 regulate glycogen synthase kinase-3 activity to modulate KCTD12 expression.

Potassium channel tetramerization domain containing 12 (KCTD12), the auxiliary GABAB receptor subunit, is identified as a susceptibility gene for bipolar I (BPI) disorder in the Han Chinese population. Moreover, the single-nucleotide polymorphism (SNP) rs17026688 in glutamate decarboxylase-like protein 1 (GADL1) is shown to be associated with lithium response in Han Chinese BPI patients. In this study, we demonstrated for the first time the relationship among lithium, GADL1, and KCTD12. In circulating CD11b+ macrophage cells, BPI patients showed a significantly higher percentage of KCTD12 expression than healthy controls. Among BPI patients, carriers of the 'T' allele (i.e., CT or TT) at site rs17026688 were found to secrete lower amounts of GADL1 but higher amounts of GABA b receptor 2 (GABBR2) in the plasma. In human SH-SY5Y neuroblastoma cells, lithium treatment increased the percentage of KCTD12 expression. Through inhibition of glycogen synthase kinase-3 (GSK-3), lithium induced cyclic AMP-response element binding protein (CREB)-mediated KCTD12 promoter activation. On the other hand, GADL1 overexpression enhanced GSK-3 activation and inhibited KCTD12 expression. We found that lithium induced, whereas GADL1 inhibited, KCTD12 expression. These findings suggested that KCTD12 may be an important gene with respect to neuron excitability and lithium response in BPI patients. Therefore, targeting GSK-3 activity and/or KCTD12 expression may constitute a possible therapeutic strategy for treating patients with BPI disorder.

Comorbid diseases as risk factors for incident posttraumatic stress disorder (PTSD) in a large community cohort (KCIS no.PSY4).

Nature disasters and terrorist attacks have occurred globally in recent years. Posttraumatic stress disorder (PTSD) has gained increasing attention, but its incidence and comorbidities in the general population are different from those inside the disaster areas. The present study estimated incident PTSD and comorbid diseases for over a decade in a cohort from a community-based integrated screening program. Factors associated with the incidence of PTSD were analyzed using Cox regression models. PTSD incidence was estimated as 81 per 105 person-years. Incidence was higher in females than in males and one-year increments in age lowered the risk for PTSD by 3%. Adjusting for other factors, cardiovascular heart disease (adjusted hazard ratio (aHR) = 1.45, 95% confidence interval (CI): 1.03-2.04), bipolar disorder (aHR = 1.86, 95% CI: 1.07-3.24) and major depressive disorder (aHR = 7.03, 95% CI: 5.02-9.85) all significantly increased 45%, 86% and 603%, respectively, the risk of developing PTSD. The low rate of people with incident PTSD receiving treatment in this community health screening population implies there is room for improvement in terms of early detection and intervention. Clinical preventive efforts may be made for patients seeking general medical help, especially those with cardiovascular disorders or mood disorders.

GADL1 variant and medication adherence in predicting response to lithium maintenance treatment in bipolar I disorder.

BACKGROUND: Genetic variants and medication adherence have been identified to be the main factors contributing to lithium treatment response in bipolar disorders. AIMS: To simultaneously examine effects of variant glutamate decarboxylase-like protein 1 (GADL1) and medication adherence on response to lithium maintenance treatment in Han Chinese patients with bipolar I (BPI) disorder. METHOD: Frequencies of manic and depressive episodes between carriers and non-carriers of the effective GADL1 rs17026688 T allele during the cumulative periods of off-lithium, poor adherence to lithium treatment and good adherence to lithium treatment were compared in Han Chinese patients with BPI disorder (n=215). RESULTS: GADL1 rs17026688 T carriers had significantly lower frequencies of recurrent affective episodes than non-T carriers during the cumulative period of good adherence, but not during those of poor adherence. CONCLUSIONS: GADL1 rs17026688 and medication adherence jointly predict response to lithium maintenance treatment in Han Chinese BPI patients. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.