Gil Zalsman

Suicide prevention strategies revisited: 10-year systematic review.

BACKGROUND Many countries are developing suicide prevention strategies for which up-to-date, high-quality evidence is required. We present updated evidence for the effectiveness of suicide prevention interventions since 2005. METHODS We searched PubMed and the Cochrane Library using multiple terms related to suicide prevention for studies published between Jan 1, 2005, and Dec 31, 2014. We assessed seven interventions: public and physician education, media strategies, screening, restricting access to suicide means, treatments, and internet or hotline support. Data were extracted on primary outcomes of interest, namely suicidal behaviour (suicide, attempt, or ideation), and intermediate or secondary outcomes (treatment-seeking, identification of at-risk individuals, antidepressant prescription or use rates, or referrals). 18 suicide prevention experts from 13 European countries reviewed all articles and rated the strength of evidence using the Oxford criteria. Because the heterogeneity of populations and methodology did not permit formal meta-analysis, we present a narrative analysis. FINDINGS We identified 1797 studies, including 23 systematic reviews, 12 meta-analyses, 40 randomised controlled trials (RCTs), 67 cohort trials, and 22 ecological or population-based investigations. Evidence for restricting access to lethal means in prevention of suicide has strengthened since 2005, especially with regard to control of analgesics (overall decrease of 43% since 2005) and hot-spots for suicide by jumping (reduction of 86% since 2005, 79% to 91%). School-based awareness programmes have been shown to reduce suicide attempts (odds ratio [OR] 0·45, 95% CI 0·24-0·85; p=0·014) and suicidal ideation (0·5, 0·27-0·92; p=0·025). The anti-suicidal effects of clozapine and lithium have been substantiated, but might be less specific than previously thought. Effective pharmacological and psychological treatments of depression are important in prevention. Insufficient evidence exists to assess the possible benefits for suicide prevention of screening in primary care, in general public education and media guidelines. Other approaches that need further investigation include gatekeeper training, education of physicians, and internet and helpline support. The paucity of RCTs is a major limitation in the evaluation of preventive interventions. INTERPRETATION In the quest for effective suicide prevention initiatives, no single strategy clearly stands above the others. Combinations of evidence-based strategies at the individual level and the population level should be assessed with robust research designs. FUNDING The Expert Platform on Mental Health, Focus on Depression, and the European College of Neuropsychopharmacology.

Human 5-HT1A receptor C(−1019)G polymorphism and psychopathology

Dysfunction of the serotonin (5-HT1A) receptor (5-HTR1A) has been implicated in mood disorders, anxiety disorders, psychosis and the action of antidepressants. A common C(-1018)G [C(-1019)G] functional polymorphism in the promoter region of the human 5-HT1A receptor gene has been reported, which may be useful in identifying psychopathology associated with altered function of the human 5-HT1A receptor. We studied the relationship of this polymorphism to psychopathology and 5-HT1A binding in prefrontal cortex. The 5-HT1A receptor genotype for the C(-1019)G polymorphism was typed in 696 unrelated psychiatric subjects, 107 unrelated healthy volunteers, and in post-mortem brain samples from 241 cases. 5-HT1A receptor binding was assayed in post-mortem prefrontal cortex using [3H]8-OH-DPAT, and specific binding determined by 1 microM 5-HT. An association of genotype distribution and allele frequency of the 5-HTR1A C(-1019)G locus was observed in schizophrenia (chi2=9.51, d.f.=2, p=0.009; chi2=9.52, d.f.=1, p=0.002; Armitages trend test: chi2=9.07, d.f.=1, p=0.003), in substance use disorder (chi2=8.41, d.f.=2, p=0.015; chi2=8.35, d.f.=1, p=0.004; Armitages trend test: chi2=6.27, d.f.=1, p=0.0012), and in panic attack (chi2=6.31, d.f.=2, p=0.043; chi2=6.14, d.f.=1, p=0.013; Armitages trend test: chi2=6.27, d.f.=1, p=0.012). An association of the 5-HTR1A C(-1019)G locus with schizophrenia, substance use disorder, and panic attack was suggested by our results. In post-mortem brain samples, 5-HT1A receptor binding in prefrontal cortex and suicide were not associated with genotype. The relationship does not appear to be explained by binding differences, although we cannot rule out altered receptor affinity and transduction.

Association of serotonin 5-HT2A receptor binding and the T102C polymorphism in depressed and healthy Caucasian subjects.

Serotonin 5-HT2A receptor (5-HT2A) binding is reported to be altered in individuals with suicidal behavior, mood disorders, and aggressive–impulsive traits. Genetic association with major depression, suicidal behavior, and aggressive–impulsive traits has not been established. This study examines the possible association of the 5-HT2A gene C102T polymorphism with the receptor binding kinetics, and clinical overt phenotypes. The study population included 63 healthy volunteers and 152 subjects with mood disorders, 56 of whom had a history of suicide attempts. All were Caucasian. Platelet 5-HT2A binding kinetics (Bmax and KD) were assayed and adjusted for seasonal variation. All subjects were genotyped for the T102C polymorphism. Clinical phenotype was determined by structured clinical interview. The TT genotype was associated with higher Bmax in all subjects (F=3.53, df=2,211; p=0.03), controlling for diagnosis. Bonferroni-adjusted post hoc testing showed higher binding in the TT compared with TC genotype in the control group (F=7.56, df=2,60, p=0.001), but not in the mood-disordered subjects. No difference was found in genotype and allele distribution between the mood-disordered subjects, with and without suicide attempt history, and controls. Bmax was not related to a diagnosis of mood disorders. The TT genotype appears associated with higher platelet 5-HT2A Bmax in the healthy population, but this genotypic effect appears absent in mood disorders and unrelated to psychopathology.

Alcohol and adolescent suicide.

Adolescent suicide is a major public health problem. In this review, the authors discuss different aspects of the relation between alcohol abuse and suicidal behavior in adolescents, including epidemiology, role of family history, comorbidity, gender differences, neurobiology, treatment, and prevention. In the general population, about 2,000 adolescents in the United States die by suicide each year. Suicide continually ranks as the second or third leading cause of death of persons between the ages of 15 and 34 years old. The suicide rate in young people has more than doubled during the period from 1956 to 1993. This increasing suicide rate has been blamed on the increase of adolescent alcohol abuse. Availability of alcohol and guns at home may contribute to suicide risk in adolescents. Comorbid psychopathology, which is common among adolescent alcohol abusers, substantially increases risk for suicide completions and attempts. Depressed adolescents may use alcohol to self-medicate depressive symptoms. Alcohol abuse and suicidal behavior in adolescents and in adults has been found to have biochemical, genetic, and psychological correlates. Ideally, treatment of adolescents who receive a diagnosis of an alcohol use disorder and co-occurring suicidality should follow an integrated protocol that addresses both conditions. Future studies of psychological and neurobiological mechanisms of suicidality in adolescents with alcohol and/or substance abuse are merited.

Effectiveness, safety, and tolerability of risperidone in adolescents with schizophrenia: an open-label study.

Data on risperidones efficacy and tolerability in adolescents with schizophrenia are scarce. We found only one prospective, open-label study in this population. The aim of this open-label, prospective study was to estimate the effectiveness, safety, and tolerability of risperidone treatment in adolescents with first-episode schizophrenia. Subjects were adolescent inpatients diagnosed with Diagnostic and Statistical Manual of Mental Disorders (fourth edition) first-episode schizophrenia by the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present Episode version. Most of the patients (10/11) were drug naïve. Improvement was assessed during the first 6 weeks of treatment using the Positive and Negative Syndrome Scale (PANSS), the Brief Psychiatric Rating Scale (BPRS), and the Clinical Global Impression (CGI) scale. Side effects were monitored using the Abnormal Involuntary Movement Scale, the Simpson-Angus Scale, the Barnes Akathisia Rating Scale, and the Udvalg for Kliniske Undersogelser Side Effect Rating Scale. Eleven adolescents between 15.5 and 20 years of age (mean = 17.27, SD = 1.27 years) were included in this study. Risperidone in an average dose of 3.14 mg/day (SD = 1.60 mg/day) produced a significant improvement on the total PANSS score (28%, p < 0.01), BPRS score (30.11%, p < 0.01), and CGI-Severity score (31.36%, p < 0.01). Risperidone was ineffective in the treatment of negative signs as assessed by the PANSS. The major side effects were extrapyramidal side effects, somnolence, depression, and weight gain. In conclusion risperidone appears to be a safe, acceptably tolerated, and effective antipsychotic medication for the treatment of adolescent-onset schizophrenia.

Depression and suicidal behavior in adolescent inpatients with obsessive compulsive disorder

BACKGROUND To investigate the prevalence and correlations of suicidal behavior in obsessive compulsive disorder (OCD) among adolescent psychiatric inpatients. METHODS A total of 348 adolescents, representing consecutive admissions to an adolescent inpatient unit, were assessed. Of these, 40 patients had OCD, 118 had schizophrenia, 59 had an affective disorder, 81 had a conduct disorder and 50 had an eating disorder. In addition, 87 normal community controls were assessed. All subjects were assessed for suicidal behavior by the Childhood Suicide Potential Scale (CSPS), for depression by the Beck Depression Inventory, for impulsiveness by the Impulse Control Scale, for anxiety by the State-Trait Anxiety Scale and for aggression by the Yudowsky Overt Aggression Scale. RESULTS All the psychiatrically ill subjects, including those with OCD, had high levels of depression, anxiety and impulsiveness, which were far higher than those of the controls. The rate of attempted suicide was, however, much lower in the OCD subjects. In addition, there was a significant inverse correlation between suicidal behavior levels on the CSPS and depression in the OCD subjects, while all other subjects showed the expected significant positive correlation between level of suicidal behavior and depression. LIMITATIONS This study looked at a referred population and generalization to outpatient and community samples cannot be made. Distinguishing between the primary and the comorbid diagnosis is difficult and some findings are based on small sample size and therefore may be vulnerable to type I error. CONCLUSIONS Although suicidal ideation and depressive symptoms are common in OCD adolescent inpatients, they seem to be protected against suicide attempts. The inverse relationship between suicidal behavior and depression may mean that suicidal behavior is, in some ways, qualitatively different from that seen in other psychiatrically ill adolescents.

Depression, suicidal behavior and insight in adolescents with schizophrenia

ObjectivesTo investigate the interrelationships between depressive symptoms of adolescent schizophrenia, post-psychotic depression (PPD), negative signs, suicidal behavior and insights into the disease.MethodsThree groups of 16 adolescent inpatients were assessed with regard to: Schizophrenia alone, schizophrenia with PPD and major depressive disorder (MDD). The following measures were used: DSM IV diagnostic criteria, the Calgary Depression Scale for Schizophrenia (CDSS), the PANSS (Positive and Negative Signs of Schizophrenia Scale), (BDI) Beck Depression Inventory, (CCL) Cognitive Check List, (HS) Hopelessness Scale, (SRS) Suicide Risk Scale, (CSPS) Child Suicide Potential Scale and the (SAUMD) Scale to Assess Unawareness of Mental Disorder.ResultsCompared with MDD adolescents, PPD adolescents showed few somatic and behavioral symptoms of depression but had equally severe cognitive and affective depressive symptomatology. Suicide risk scores and actual suicidal behavior was prominent in PPD adolescents. A positive and significant correlation was found between PPD symptoms, suicide risk and awareness of disease (insight). Negative symptoms of schizophrenia could be distinguished from PPD symptoms and there was a negative correlation between blunted affect and PPD scores.ConclusionsPPD can be diagnosed in adolescent schizophrenia. The symptom pattern is different from MDD, therefore, there may be cause to modify DSM IV provisional criteria for this condition. Adolescents with schizophrenia who have insight into their illness are at higher risk for suicidal behavior and the development of PPD.

DRD4 exon III polymorphism and response to risperidone in Israeli adolescents with schizophrenia: a pilot pharmacogenetic study.

This study examined the possible association between the polymorphism in the dopamine receptor DRD4 gene and response to risperidone among 24 Israeli Jewish adolescent inpatients with first-episode schizophrenia. Response was categorically determined by a change of >40% on the Brief Psychiatric Rating Scale (BPRS). No significant association was found between the DRD4 genotype and clinical response, although carriers of <7 repeat alleles demonstrated higher response rate (10/20 vs. 0/4, P=0.11). Studies in larger groups of adolescent schizophrenia patients are warranted to clarify the possible association between DRD4 exon III repeat alleles and the response to risperidone.

Relationship of MAO-A promoter (u-VNTR) and COMT (V158M) gene polymorphisms to CSF monoamine metabolites levels in a psychiatric sample of caucasians: A preliminary report.

Monoamine oxidase A gene promoter (MAOA‐uVNTR) and catechol‐O‐methyltransferase V158M (COMT‐V158M) gene functional polymorphisms are reported to be associated with impulsive‐aggression, but a biological intermediate effect remains to be determined. This study assessed the association of these polymorphisms with cerebrospinal fluid (CSF) monoamine metabolites as endophenotypes. Ninety‐eight Caucasian psychiatric subjects were assessed for Axis I and II diagnosis. Subjects were genotyped for the functional polymorphisms, MAOA‐uVNTR and COMT‐V158M. CSF was obtained by lumbar puncture. Relationships of the two polymorphism to monoamine metabolites: HVA, 5‐HIAA, and MHPG were examined. The higher‐expressing MAOA‐uVNTR genotype was associated with higher CSF‐HVA levels in males only (n = 46) (195.80 pmol/ml, SD = 61.64 vs. 161.13, SD = 50.23, respectively; P = 0.042). No association was found with diagnosis. COMT‐V158M had no association with CSF monoamine metabolites. The association of MAOA‐uVNTR with dopaminergic activity in males is a preliminary finding that needs to be replicated in a larger sample of Caucasian males and relationships sought with clinical phenotypes. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148‐7299:1/suppmat/index.html.

Suicidal behavior and self-disclosure in adolescent psychiatric inpatients.

The inability to communicate feelings and thoughts to people close to oneself may be an important risk factor for suicidal behavior. This inability has been operationalized in the concept of self-disclosure. The purpose of this article was to evaluate the correlation of self-disclosure with suicidal behavior in adolescents. Eighty consecutive admissions to an adolescent psychiatric inpatient unit were evaluated. Thirty-four were suicide attempters, 18 were suicidal ideators, and 18 were nonsuicidal. Assessment measures included the Child Suicide Potential Scale, the Suicide Intent Scale, the Suicide Ideation Scale, and the Self-Disclosure Scale. The results show that low self-disclosure levels are associated with suicidal thinking, suicide attempts, and suicidal attitudes. Thus, low self-disclosure may well be a risk factor worthy of further evaluation in the attempt to understand adolescent suicidal behavior.