How Impulsivity is Associated with Adolescent Depression: The Role of Substance Use, Gender and Social Support.

Background: Some risk/protective factors of adolescent depression have been proposed but have not been comprehensively studied. Recent advances in neuroimaging techniques have provided greater insight into the underlying neuropsychiatric mechanisms of depression-related factors such as impulsivity, substance use, gender difference and social support. However, how these factors are interconnected and how they affect depression in the real world is poorly understood. This study aimed to explore the relationships between adolescent depression with trait impulsivity, substance use and gender. We also tested the hypothesis that social support may play a buffering role in preventing depression. By expanding the diathesis-stress model. Methods: The adolescents enrolled in this study were grade 1 senior high school students from northern Taiwan (N = 5879), and they were assessed for depression, trait impulsivity, and tobacco/alcohol use. Hierarchical multiple linear regression was performed to control possible confounders, including other depression-related diathesis and sociodemographic variables. Gender differences were also analyzed by separately examining variables significantly associated with depression. Results: A higher level of depression was associated with female gender, trait impulsivity, low self-esteem, negative attitude towards the future, tobacco use, alcohol use, family discord and difficulty in basic family needs. Good parental health, living with their biological family and social support were protective factors. Trait impulsivity was significantly associated with depression after controlling for the confounding factors. Gender-specific analysis showed that trait impulsivity and tobacco use had a significant synergistic interaction on female depression. Social support from parents/peers was significantly associated with depression, but social support from other family members/teachers was not. Conclusion: The current study advances the understanding of adolescent depression and highlights that trait impulsivity, addictive substance use, social support and their interaction may play an influential role in the emergence of adolescent depression. Gender-specific research and treatment approach are also crucial, and more investigations are necessary.

Psychometric properties of the Chinese Mandarin version of the Borderline Symptom List, short form (BSL-23) in suicidal adolescents.

BACKGROUND: The short form of the Borderline Symptom List (BSL-23) is a self-rated instrument developed from the initial 95-item German version of the Borderline Symptom List (BSL-95). It is widely used among Chinese adults, but its applicability, factor structure and validity remain uncertain in adolescents. This study aimed to evaluate the psychometric properties of the Chinese Mandarin version of the BSL-23 in a sample of suicidal adolescents. METHODS: The Chinese Mandarin BSL-23 was given to 279 outpatient adolescents with self-injurious thoughts or behaviors. The factor structure, reliability, convergent validity, criterion-related validity and cut-off value were investigated. RESULTS: The Chinese Mandarin version of the BSL-23 demonstrated a one-factor structure and replicated the original version. The scale had high reliability and good test-retest stability. The Chinese Mandarin BSL-23 was correlated with depression, hopelessness, impulsivity, emotional dysregulation, self-esteem, loneliness, childhood trauma and parental bonding patterns evaluated with a variety of scales. The measure showed good criterion-related validity and predictive accuracy (AUC = 0.87) for self-injurious and suicidal adolescents with borderline personality disorder (BPD) at a cut-off point of 60/61 (mean score 2.60/2.65), with a sensitivity of 0.76 and specificity of 0.83. CONCLUSIONS: The Chinese Mandarin version of the BSL-23 is a reliable and valid self-reported instrument to assess BPD symptomatology among suicidal adolescents.

Predictors of repeated adolescent self-harm: The display of multiple variables and mediators in a 2-year study.

BACKGROUND: Data on self-harm (SH) repetition in non-Western adolescents are limited; this study is to survey the predictors. METHODS: A total of 5879 adolescents (mean age 16.02 years) in Northern Taiwan were recruited. The participants filled in online questionnaires about their sociodemographic data, suicidality, depressive symptoms, self-esteem, social support, family discord, impulsivity, and alcohol and tobacco use at baseline (T1) and at the 1 year follow-up (T2). We used logistic regression analysis to examine the predictors of SH continuation. Generalized structural equation modeling (GSEM) was then estimated to analyze the treatable variables for both years and to investigate their relationships and mediating effects. RESULTS: A total of 125 students were identified as being in the SH continuation group; while 470 students were identified as being in the SH stop group. The SH continuation rate was 21%; no significant gender difference was found. Logistic regression analysis showed that the predictors of SH continuation were low school ranking, poor quality of listening from relatives, use of the cutting method for SH, and a suicide plan in the past year at T1, and more depressed mood, use of the cutting method for SH, more suicide ideation and plans at T2. Similar predictors were found by GSEM; self-esteem at T1 and depressed mood at T2 were found to be mediators in the pathways. CONCLUSION: The continuation rate of SH was similar to that reported in Western countries. These predictors should be included in the treatment plan to prevent SH continuation.

Prevalence and psychosocial risk factors associated with current cigarette smoking and hazardous alcohol drinking among adolescents in Taiwan.

BACKGROUND: Cigarette smoking and alcohol drinking are the most common types of substance use and misuse (SUM) among adolescents. This study aimed to estimate the prevalence and psychosocial factors associated with current cigarette smoking and hazardous alcohol drinking among adolescents in Taiwan. METHODS: Data were collected via self-administered questionnaires on computers from students at 14 senior high schools in Taipei, Taiwan. Hierarchical multiple regression strategies were used to determine the risk factors for SUM. RESULTS: A total of 5879 participants were recruited, the majority of whom were female (56.7%). The prevalence rates of current smoking and hazardous alcohol drinking were 3.84% and 7.38%, respectively. Risk factors associated with current smoking were similar to those for hazardous alcohol drinking, including male gender, low school ranking, and depression. In addition, current smoking was associated with increasing age, hazardous alcohol drinking, and fewer parents with whom they can talk, whereas hazardous alcohol drinking was associated with current smoking, not living with both biological parents, and more peers with whom they can talk. CONCLUSION: The potential coexistence of adolescent SUM and common psychosocial correlates demands an integrated approach. Health professionals should provide corresponding intervention programs and coordinate with parents and teachers to develop an anti-SUM environment, especially for males and high-risk schools. Preventive psychiatric services as an integral part of anti-SUM strategies for adolescents targeting to depression may be useful in reducing the risk.

Correlation of impulsivity with self-harm and suicidal attempt: a community study of adolescents in Taiwan.

OBJECTIVES: The aim of this study was to investigate differences and similarities in risk factors for deliberate self-harm (DSH) and suicidal attempt (SA), and the role of impulsivity among a group of community adolescents. SETTING: This is a cross-sectional study conducted at high schools in Northern Taiwan. DATA AND PARTICIPANTS: We recruited grade 1 students from 14 high schools. A total of 5879 participants (mean age 16.02 years, female adolescents: 57.7%) completed the online assessment. OUTCOME MEASURES: Participants completed online questionnaires about sociodemographic data, suicidality, history of DSH and SA, depressed mood, self-esteem, social support, family discord, impulsivity (Barratt Impulsiveness Scale Version 11 (BIS-11)) and the use of alcohol, tobacco and illicit drugs. A subsample was interviewed about lifetime SA, and the results were compared with those from the online questionnaires. RESULTS: In our sample, 25% of the students had lifetime DSH and 3.5% had lifetime SA. Two hundred and seventy-two students received face-to-face interviews. The concordance between the online questionnaires and interviews in terms of ascertaining cases of SA was moderate (concordance rate 82.76%; kappa value 0.59). Similar risk factors for DSH/SA among the whole sample included female gender, lower academic performance, depression, substance use (tobacco and alcohol) and low self-esteem. The BIS-11 score was correlated with DSH. Factor 3 score of the BIS-11 (novelty seeking) was correlated with DSH in both boys and girls, whereas factor 2 score (lack of self-control) was correlated with SA in boys. Social support was a protective factor against SA among the female adolescents. Gender modulated the association of impulsivity and DSH/SA. Associations between impulsivity and DSH and SA were particularly strong among boys. CONCLUSIONS: Risk factors for DSH and SA were similar, but not identical. Early identification of those at risk and appropriate interventions may be helpful.

Relationship Between Predictors of Incident Deliberate Self-Harm and Suicide Attempts Among Adolescents.

PURPOSE: Data on the incidence of deliberate self-harm (DSH) and suicide attempts (SAs) are lacking in non-Western adolescents, and no studies have investigated differences in incident DSH and SA worldwide. This study aimed to investigate the incidence rates and relationships between predictors in DSH and SA. METHODS: The Taiwanese Adolescent Self-Harm Project was a longitudinal study of DSH among adolescents. We recruited 5,879 students from 14 senior high schools in northern Taiwan. Online questionnaires on sociodemographic data, suicidality, depressive symptoms, self-esteem, social support, family discord, impulsivity, and alcohol and tobacco use were assessed at baseline (T1) and at 1 year of follow-up (T2). Logistic regression analyses were performed to evaluate the predictors of incident DSH and SA. RESULTS: The mean age was 16.02 years, and 56.73% of the cohort was female. At T1, the lifetime prevalence rates of DSH and SA were 25.04% and 3.50%, respectively. At T2, 4,331 (73.67%) students had completed follow-up assessments. The 1-year incidence rates of DSH and SA were 4.04% and 1.53%, respectively. The predictors of incident DSH included perceived family discord and more depressive symptoms at T1. The predictors of incident SA were lifetime suicide ideation, more depressive symptoms, and tobacco use at T1. CONCLUSIONS: The incidence rates of DSH and SA were similar to those reported in Western countries. The predictors of incident DSH and SA were similar but not identical. Our results highlight the risk factors which should be considered in terms of early identification and intervention among adolescents to prevent suicidality.

Self-harm and its association with internet addiction and internet exposure to suicidal thought in adolescents.

BACKGROUND/PURPOSE: Self-harm (SH) is a risk factor for suicide. We aimed to determine whether internet addiction and internet exposure to confided suicidal ideation are associated with SH in adolescents. METHODS: This study was a cross-sectional survey of students who self-completed a series of online questionnaires including a sociodemographic information questionnaire, questionnaire for suicidality and SH, Chen Internet Addiction Scale (CIAS), Patient Health Questionnaire (PHQ-9), multi-dimensional support scale (MDSS), Rosenberg self-esteem scale (RSES), Alcohol Use Disorder Identification Test-Consumption (AUDIT-C), and questionnaire for substance abuse. RESULTS: A total of 2479 students completed the questionnaires (response rate = 62.1%). They had a mean age of 15.44 years (range 14-19 years; standard deviation 0.61), and were mostly female (n = 1494; 60.3%). The prevalence of SH within the previous year was 10.1% (n = 250). Among the participants, 17.1% had internet addiction (n = 425) and 3.3% had been exposed to suicidal content on the internet (n = 82). In the hierarchical logistic regression analysis, internet addiction and internet exposure to suicidal thoughts were both significantly related to an increased risk of SH, after controlling for gender, family factors, exposure to suicidal thoughts in the real life, depression, alcohol/tobacco use, concurrent suicidality, and perceived social support. However, the association between internet addiction and SH weakened after adjusting for the level of self-esteem, while internet exposure to suicidal thoughts remained significantly related to an increased risk of SH (odds ratio = 1.96; 95% confidence interval: 1.06-3.64). CONCLUSION: Online experiences are associated with SH in adolescents. Preventive strategies may include education to increase social awareness, to identify the youths most at risk, and to provide prompt help.

Treatment effects of combining social skill training and parent training in Taiwanese children with attention deficit hyperactivity disorder.

BACKGROUND/PURPOSE: Children with attention-deficit/hyperactivity disorder (ADHD) often have problems in social interactions. We investigated the social and behavioral effects of providing both social skill training and parent training to school-aged children with ADHD in Taiwan. METHODS: Seven consecutive 8-week behavioral-based social skill training (SST) group sessions were held for 48 children with ADHD; parallel 8-week parent group sessions were provided simultaneously. Fifty-five children with ADHD were recruited as a control group. All children took medication as prescribed by their doctors. The effects were assessed using the teacher and parent version of the Chinese version of Swanson, Nolan, and Pelham, version IV scale (SNAP-IV), the Chinese version of the Child Behavior Check List (CBCL-C), child and teacher version of the modified Social Skill Rating System (SSRS-C and SSRS-T), at baseline, post-treatment, and 4 months from baseline. The doses of methylphenidate and drug compliance were controlled during the analysis. RESULTS: The mixed-effects model demonstrated the main effect of group sessions on the Oppositional subscale of SNAP-P, the Anxious/Depressed subscale of CBCL-C, the Self Control subscale of SSRS-C, and the Active Participation subscale of SSRS-T, all in favor of the experimental group. However, the improvement on the Oppositional subscale of SNAP-P and the Self Control subscale of SSRS-C were noted only between baseline and post-treatment period and were not sustained at the end of the follow-up period. CONCLUSION: Our study demonstrated that children with ADHD could benefit from this low intensity psychosocial program, although some improvements were not maintained at follow-up assessment.

Patient health questionnaire for school-based depression screening among Chinese adolescents.

OBJECTIVE: The aim of this study was to determine the reliability and validity of a Chinese version of the Patient Health Questionnaire-9 item (PHQ-9) and its 2 subscales (1 item and 2 items) for the screening of major depressive disorder (MDD) among adolescents in Taiwan. METHODS: A total of 2257 adolescents were recruited from high schools in Taipei. The participants completed assessments including demographic information, the Chinese version of the PHQ-9, and the Rosenberg Self-Esteem Scale, and data on the number of physical illnesses and mental health service utilizations were recorded. Among them, 430 were retested using the PHQ-9 within 2 weeks. Child psychiatrists interviewed a subsample of the adolescents (n = 165) using the Kiddie-Schedule for Affective Disorder and Schizophrenia Epidemiological Version as the criterion standard. RESULTS: The PHQ-9 had good internal consistency (α = 0.84) and acceptable test-retest reliability (0.80). The participants with higher PHQ-9 scores were more likely to have MDD. Principal component factor analysis of the PHQ-9 yielded a 1-factor structure, which accounted for 45.3% of the variance. A PHQ-9 score ≥15 had a sensitivity of 0.72 and a specificity of 0.95 for recognizing MDD. The area under the receiver operating characteristic curve was 0.90. The screening accuracy of the 2 subscales was also satisfactory, with a Patient Health Questionnaire-2 item cutoff of ≥3 being 94.4% sensitive and 82.5% specific and a Patient Health Questionnaire-1 item cutoff of ≥2 being 61.1% sensitive and 87.7% specific. CONCLUSIONS: The PHQ-9 and its 2 subscales appear to be reliable and valid for detecting MDD among ethnic Chinese adolescents in Taiwan.

Effects of various drug therapies on Kleine-Levin syndrome: a case report.

Kleine-Levin syndrome (KLS) is a rare sleep disorder, predominantly affecting adolescent males, which presents as recurrent episodes of hypersomnia, behavioral and cognitive disturbances, hyperphagia and sometimes hypersexuality (Lisk, "Kleine-Levin syndrome." Pract Neurol 2009;9:42-45). Modafinil has been reported to show an effect in shortening the duration of symptomatic periods, but does not affect the recurrence rate (Huang et al., "Kleine-Levin syndrome: current status." Med Clin N Am 2010;94:557-562). However, no single drug therapy has been consistently successful, despite various psychotropic agents, including lithium, anticonvulsants and antidepressants, having been systematically tried (Arnulf et al., "Kleine-Levin syndrome: a systematic study of 108 patients." Ann Neurol 2008;63:482-492). This study reports a male adolescent with KLS who received several courses of drug therapy, providing a chance to compare differential drug effects over time.

Naturalistic exploration of the effect of osmotic release oral system-methylphenidate on remission rate and functional improvement in Taiwanese children with attention-deficit-hyperactivity disorder.

AIM: To determine the differences in the remission rate, recovery rate, functional improvement, and treatment adherence related to treatment with short-acting immediate-release methylphenidate (IR-MPH) and long-acting osmotic-release oral system-methylphenidate (OROS-MPH) in a naturalistic setting among Taiwanese children with attention-deficit-hyperactivity disorder (ADHD). METHODS: A total of 757 children with ADHD, aged 6-18 years, was evaluated using the following in order determine functional improvement and treatment adherence: the Chinese version of the Swanson, Nolan, and Pelham, version IV scale (SNAP-IV-C), Clinical Global Impression-ADHD-Severity (CGI-S) to measure remission and recovery rates, the Chinese version of the Social Adjustment Inventory for Children and Adolescents (CSAICA), and caregiver's satisfaction rate, treatment adherence, and frequency of adverse effects. RESULTS: According to the SNAP-IV-C scores, the remission rate was 30.72%, and the recovery rate was 16.38%. Compared to short-acting IR-MPH, OROS-MPH was associated with greater functional improvement and treatment adherence among children with ADHD. CONCLUSION: OROS-MPH treatment at the adequate dosage can achieve higher remission and recovery rates, produce greater functional improvement, and result in better treatment adherence than IR-MPH treatment.

Suppression of inflammatory mediators by cruciferous vegetable-derived indole-3-carbinol and phenylethyl isothiocyanate in lipopolysaccharide-activated macrophages.

This study was aimed to examine the effects of indole-3-carbinol (I3C) and beta-phenylethyl isothiocyanate (PEITC), bioactive components present in cruciferous vegetable, on the production of inflammatory mediators, including nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10), in lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophages. Possible mechanisms of the NO-inhibitory effects were also explored. The results indicated that I3C and PEITC inhibited NO production, and this suppression was associated with decreased production of TNF-alpha and IL-10 by activated macrophages. In addition, I3C suppressed NO production even after the inducible nitric oxide synthase (iNOS) protein had been produced, but such an inhibitory effect was not observed in cells treated with PEITC. Furthermore, both compounds reduced the NO contents generated from an NO donor in a cell-free condition, suggesting that the increased NO clearance may have contributed to the NO-inhibitory effects. In summary, both I3C and PEITC possessed antiinflammatory effects by inhibiting the productions of NO, TNF-alpha, and IL-10, although the NO-inhibitory effects may have involved in different mechanisms.

Combination treatment with luteolin and quercetin enhances antiproliferative effects in nicotine-treated MDA-MB-231 cells by down-regulating nicotinic acetylcholine receptors.

Large-scale epidemiological cohort studies performed in the United States indicate that breast cancer risk is associated with active and passive smoking. As of yet, however, there is no direct evidence of antitumor effects by agents that block the effect of tobacco compound nicotine (Nic) on relevant nicotinic receptors (nAChR) involved in breast tumorigenesis. In the present study, the expression profiles of different nAChR subunits in the human breast cancer cell line (MDA-MB-231) were characterized by RT-PCR. Nic (>0.1 microM, 6 h) significantly increased alpha9-nAChR mRNA and protein expression levels in human breast cancer cells (MDA-MB-231 cells). On the other hand, combined treatment with luteolin (Lut, 0.5 microM) and quercetin (Que, 0.5 microM) profoundly decreased MDA-MB-231 proliferation by down-regulating alpha9-nAChR expression. MDA-MB-231 cells were cultured in soft agar to evaluate anchorage-independent colony formation; combined treatment of Lut+Que inhibited Nic-induced MDA-MB-231 colony formation. Interestingly, the number of colonies formed was profoundly reduced in alpha9-nAChR knockdown (Si alpha9) cells in the combined (Lut+Que)-treated group as compared to the relevant control groups. Such results show that Lut- or Que-induced antitransforming activities were not limited to specific inhibition of the alpha9-nAChR receptor. Both alpha5- and alpha9-nAChR appear to be important molecular targets for Lut- and Que-induced antitumor effects in human breast cancer cells.

Metformin for metabolic dysregulation in schizophrenic patients treated with olanzapine.

The second generation antipsychotic drugs, such as risperidone, olanzapine, and quetiapine, are effective in treating patients with schizophrenia and have been considered as the first line therapy. Recently, increasing attention has been drawn to the potential diabetogenic effect of these novel antipsychotics. The goal of this study was to evaluate the effect of metformin treatment on the olanzapine-induced metabolic disturbance in schizophrenic patients. Twenty-four schizophrenic subjects who had received olanzapine treatment at least 3 months were assigned to the therapy with metformin 1500 mg/day for 8 weeks. The metabolic parameters were quantitatively assessed at baseline, weeks 2, 4, and 8 by using the intravenous glucose tolerance test. After an 8-week treatment with metformin, the body weight, fasting levels of glucose, triglyceride, and insulin, insulin secretion, and insulin resistance significantly decreased. Half of study subjects with metabolic syndrome obtained improvement after the metformin trial. Subjects' psychopathological condition remained unchanged during the study period. The olanzapine-induced metabolic disturbance could be reversed after 8-week metformin treatment. Based on the results of this study, we hypothesize that metformin could modulate the effect of olanzapine-induced metabolic disturbance.

The early effect of olanzapine and risperidone on insulin secretion in atypical-naïve schizophrenic patients.

Recently, increasing attention has been drawn to the potential diabetogenic effect of atypical antipsychotics. The goal of this prospective study is to evaluate the early effect of olanzapine and risperidone treatment on pancreatic beta-cell function in atypical-naive schizophrenic patients. Twenty-six subjects were assigned randomly to therapy with olanzapine or risperidone for 14 days. The metabolic parameters were quantitatively assessed by using the intravenous glucose tolerance test. The levels of fasting glucose, fasting insulin, lipid profiles, and leptin were also assessed. There were no significant within-group changes in weight or body mass index for both groups after 2 weeks of treatment. The levels of fasting glucose, fasting insulin, cholesterol, or leptin did not change in both groups. The triglyceride level significantly increased in olanzapine group. Glucose disappearance rate and insulin sensitivity did not change in both groups. Insulin secretion significantly decreased in olanzapine group. After 2 weeks of olanzapine treatment, schizophrenic patients decreased insulin secretory response to a hyperglycemic challenge. The results of this study support the hypothesis that olanzapine might directly impair pancreatic beta-cell function.

Dose-dependent alternations in the pharmacokinetics of olanzapine during coadministration of fluvoxamine in patients with schizophrenia.

Olanzapine, an atypical antipsychotic agent, is a substrate of the cytochrome P4501A2 (CYP1A2) enzyme. Administration of a potent CYP1A2 inhibitor (eg, fluvoxamine) may alter the pharmacokinetics of olanzapine. This study investigated the pharmacokinetic interactions between olanzapine and fluvoxamine in patients with schizophrenia. Ten male smokers were administrated a single dose of olanzapine 10 mg at baseline, followed by 2 weeks of fluvoxamine 50 mg/day and another 2 weeks of fluvoxamine 100 mg/day. Olanzapine 10 mg was given at day 10 during each fluvoxamine treatment. After pretreatment with fluvoxamine, the area under the curve, maximal plasma concentration, and half-time of olanzapine were significantly increased by 30% to 55%, 12% to 64%, and 25% to 32%, respectively. Volume of distribution and apparent clearance were significantly reduced by 4% to 26% and 26% t O 38%, respectively, after administration of fluvoxamine. Increases in area under the plasma concentration-time curve from time 0 to infinity appear to be dose dependent. Presumably, altered olanzapine pharmacokinetics are attributed to the inhibition of CYP1A2. Patients treated with the combination of olanzapine and fluvoxamine should be monitored carefully.