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Background and ObjectivesMild cognitive impairment (MCI) is an at-risk state for dementia; however, not all individuals with MCI transition to dementia, and some revert to normal cognition (NC). Here, we investigate whether mild behavioral impairment (MBI), the late-life onset of persistent neuropsychiatric symptoms (NPS), improves the prognostic specificity of MCI.MethodsParticipants with MCI from the National Alzheimer's Coordinating Center Uniform Data Set were included. NPS were operationalized with the Neuropsychiatric Inventory Questionnaire to identify participants without NPS and those with MBI (persistent, late-onset NPS). Individuals with late-onset NPS not meeting the MBI persistence criterion (NPS_NOT_MBI) were retained for secondary analyses. Progression to dementia, stable MCI, and reversion to NC after 3 years of follow-up were defined per National Institute on Aging–Alzheimer’s Association and Petersen criteria.ResultsThe primary sample consisted of 739 participants (NPS− n = 409 and MBI+ n = 330; 75.16 ± 8.6 years old, 40.5% female). After 3 years, 238 participants (33.6%) progressed to dementia, and 90 (12.2%) reverted to NC. Compared to participants without NPS, participants with MBI were significantly more likely to progress to dementia (adjusted odds ratio [AOR] 2.13, 95% CI 1.52–2.99), with an annual progression rate of 14.7% (vs 8.3% for participants with MCI without NPS). Compared to participants without NPS, participants with MBI were less likely to revert to NC (AOR 0.48, 95% CI 0.28–0.83, 2.5% vs 5.3% annual reversion rate). The NPS_NOT_MBI group (n = 331, 76.5 ± 8.6 years old, 45.9% female) were more likely to progress to dementia (AOR 2.18, 95% CI 1.56–3.03, 14.3% annual progression rate) but not less likely to revert to NC than those without NPS. Accordingly, both NPS_NOT_MBI and MBI+ participants had lower Mini-Mental State Examination scores than NPS− participants after 3 years.DiscussionLate-onset NPS improve the specificity of MCI as an at-risk state for progression to dementia. However, only persistent late-onset NPS are associated with a lower likelihood of reversion to NC, with transient NPS (i.e., NPS_NOT_MBI) not differing from the NPS− group. Clinical prognostication can be improved by incorporating late-onset NPS, especially those that persist (i.e., MBI), into risk assessments. Clinical trials may benefit from enrichment with these higher-risk participants with MCI.

Background: Mild behavioral impairment (MBI) and subjective cognitive decline (SCD) are dementia risk states, and potentially represent neurobehavioral and neurocognitive manifestations, respectively, of early stage neurodegeneration. Both MBI and SCD predict incident cognitive decline and dementia, are associated with known dementia biomarkers, and are both represented in the NIA-AA research framework for AD in Stage 2 (preclinical disease). Objective: To assess the associations of MBI and SCD, alone and in combination, with incident cognitive and functional decline in a population of older adults. We tested the hypothesis that MBI and SCD confer additive risk for decline. Methods: Cognitively normal participants were followed up annually at Alzheimer’s Disease Centers. Logistic regression assessed the relationship between baseline classification (MBI-SCD-, MBI-SCD+, MBI+SCD-, or MBI+SCD+) and 3-year outcome. Results: Of 2,769 participants (mean age=76), 1,536 were MBI-SCD-, 254 MBI-SCD+, 743 MBI+SCD-, and 236 MBI+SCD+. At 3 years, 349 (12.6%) declined to CDR >0, including 23.1% of the MBI+group, 23.5% of the SCD+group, and 30.9% of the intersection group of both MBI+and SCD+participants. Compared to SCD-MBI-, we observed an ordinal progression in risk (ORs [95% CI]): 3.61 [2.42–5.38] for MBI-SCD+ (16.5% progression), 4.76 [3.57–6.34] for MBI+SCD- (20.7%), and 8.15 [5.71–11.64] for MBI+SCD+(30.9%). Conclusion: MBI and SCD together were associated with the greatest risk of decline. These complementary dementia risk syndromes can be used as simple and scalable methods to identify high-risk patients for workup or for clinical trial enrichment.

Objectives Major Depressive Disorder (MDD) is associated with glutamatergic alterations, including the N-methyl-D-aspartate receptor (NMDA-R). The NMDA-R plays an important role in synaptic plasticity, and individuals with MDD have been shown to have impairments in repetitive Transcranial Magnetic Stimulation (rTMS) motor plasticity. Here, we test whether D-cycloserine, a NMDA-R partial agonist, can rescue TMS motor plasticity in MDD. Methods We conducted randomized double-blind placebo-controlled crossover studies in healthy (n = 12) and MDD (n = 12) participants. We stimulated motor cortex using TMS intermittent theta burst stimulation (iTBS) with placebo or D-cycloserine (100 mg). Motor evoked potentials (MEPs) were sampled before and after iTBS. Stimulus response curves (SRC) were characterized at baseline, +90 minutes, and the following day. Results Acute iTBS MEP facilitation is reduced in MDD and is not rescued by D-cycloserine. After iTBS, SRCs shift to indicate sustained decrease in excitability in healthy participants, yet increased in excitability in MDD participants. D-cycloserine normalized SRC changes from baseline to the following day in MDD participants. In both healthy and MDD participants, D-cycloserine stabilized changes in SRC. Conclusion MDD is associated with alterations in motor plasticity that are rescued and stabilized by NMDA-R agonism. Significance Agonism of NMDA receptors rescues iTBS motor plasticity in MDD.

Objectives This open-label pilot study explored the effects of a course of accelerated high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) on two neurocognitive domains (decision-making and impulse control) in patients with major depressive disorder (MDD). Methods Participants with MDD and a treatment resistant major depressive episode (n=24) underwent twice-daily HF-rTMS targeted at the left dorsolateral prefrontal cortex (lDLPFC) over two weeks. Psychopathology was assessed by clinician-administered and self-reported measures of depression and anxiety; decision-making was assessed by the Iowa Gambling Task, the Balloon Analog Risk Task and the Game of Dice Task; impulse control was assessed by the Stroop Color-Word Task, the Continuous Performance Task and the Stop-Signal Task. Results Depression and anxiety scores significantly improved from pre-post HF-rTMS treatment. However, none of the decision-making or impulse control variables of interest changed significantly from pre-post HF-rTMS. Moreover, there was no correlation between changes in psychopathological symptoms and in neurocognition. Limitations This is a moderately sized open label trial, and the confounds of ongoing psychotropics and illness chronicity can not be excluded in this treatment resistant sample. Conclusions There is dissociation between acute symptomatic benefit after a course of accelerated HF-rTMS applied to the lDLPFC in treatment resistant MDD and performance on tests of decision making and impulse control. Though rTMS appears cognitively safe, additional research is warranted to understand this potential dissociation and its putative clinical implications.

Theta burst stimulation (TBS) has been proposed as a novel treatment for major depression (MD). However, randomized and sham-controlled trials (RCTs) published to date have yielded heterogeneous clinical results and we have thus carried out the present systematic review and exploratory meta-analysis of RCTs to evaluate this issue. We searched the literature for RCTs on TBS for MD from January 2001 through September 2016 using MEDLINE, EMBASE, PsycINFO, and CENTRAL. We then performed a random-effects meta-analysis with the main outcome measures including pre-post score changes in the Hamilton Depression Rating Scale (HAM-D) as well as rates of response, remission and dropout. Data were obtained from 5 RCTs, totalling 221 subjects with MD. The pooled Hedges' g for pre-post change in HAM-D scores was 1.0 (p = 0.003), indicating a significant and large-sized difference in outcome favouring active TBS. Furthermore, active TBS was associated with significantly higher response rates when compared to sham TBS (35.6% vs. 17.5%, respectively; p = 0.005), although the groups did not differ in terms of rates of remission (18.6% vs. 10.7%, respectively; p = 0.1) and dropout (4.2% vs. 7.8%, respectively; p = 0.5). Finally, subgroup analyses indicated that bilateral TBS and unilateral intermittent TBS seem to be the most promising protocols. In conclusion, although TBS is a promising novel therapeutic intervention for MD, future studies should identify more clinically-relevant stimulation parameters as well as neurobiological predictors of treatment outcome, and include larger sample sizes, active comparators and longer follow-up periods.

Background Repetitive Transcranial Magnetic Stimulation (rTMS) is an efficacious treatment for major depressive disorder (MDD), however there is limited safety and efficacy data in the peripartum period. The purpose of this review is to systematically examine the safety, acceptability and effectiveness of rTMS administered during the peripartum period as an intervention for MDD. Methods We searched MEDLINE, EMBASE and PsychINFO from 2008 to January 2019 to identify peer reviewed publications evaluating rTMS during the peripartum period as an intervention for peripartum MDD. We systematically extracted reported adverse events, side effects, rates of discontinuation, as well as clinical response and remission. Results Data was synthesized from 1 randomized control trial, 3 uncontrolled trials, 3 case series and 5 case studies, representing a total of 87 patients. No serious adverse events were reported. Side effects occurred at rates comparable to those observed in the non-peripartum population, and obstetric and neonatal complications are infrequent and do not separate from sham-rTMS. Randomized controlled data suggests antidepressant efficacy with an effect size of 0.87. Uncontrolled studies report rates of clinical response between 41.4% and 71.4%, and rates of clinical remission between 20.7 and 30.0%. The treatment appears acceptable, with few patients opting to discontinue treatment. Limitations Due to the paucity of research in this population, majority of data comes from sources with inherently higher risk of bias. Conclusions: rTMS in the peripartum period appears to be efficacious, acceptable and well tolerated. Additional research is required, however rTMS's risk benefit profile may be attractive to women in the peripartum period.

Importance Major depressive episodes in bipolar disorder are common and debilitating. Repetitive transcranial magnetic stimulation is well established in the treatment of major depressive disorder, and the intermittent theta burst stimulation (iTBS) protocol is replacing conventional protocols because of noninferiority and reduced delivery time. However, iTBS has not been adequately studied in bipolar disorder and, therefore, its efficacy is uncertain. Objective To determine whether iTBS to the left dorsolateral prefrontal cortex (LDLPFC) is safe and efficacious in the treatment of acute bipolar depression. Design, Setting, and Participants This study was a double-blind, 4-week, randomized clinical trial of iTBS targeting the LDLPFC. Two Canadian academic centers recruited patients between 2016 and 2020. Adults with bipolar disorder type I or type II experiencing an acute major depressive episode were eligible if they had not benefited from a first-line treatment for acute bipolar depression recommended by the Canadian Network for Mood and Anxiety Treatments and were currently treated with a mood stabilizer, an atypical antipsychotic, or their combination. Seventy-one participants were assessed for eligibility, and 37 were randomized to daily sham iTBS or active iTBS using a random number sequence, stratified according to current pharmacotherapy. Data analysis was performed from April to September 2020. Interventions Four weeks of daily active iTBS (120% resting motor threshold) or sham iTBS to the LDLPFC. Nonresponders were eligible for 4 weeks of open-label iTBS. Main Outcomes and Measures The primary outcome was the change in score on the Montgomery-Asberg Depression Rating Scale from baseline to study end. Secondary outcomes included clinical response, remission, and treatment-emergent mania or hypomania. Results The trial was terminated for futility after 37 participants (23 women [62%]; mean [SD] age, 43.86 [13.87] years; age range, 20-68 years) were randomized, 19 to sham iTBS and 18 to active iTBS. There were no significant differences in Montgomery-Asberg Depression Rating Scale score changes (least squares mean difference between groups, −1.36 [95% CI, −8.92 to 6.19;P = .91] in favor of sham iTBS), and rates of clinical response were low in both the double-blind phase (3 of 19 participants [15.8%] in the sham iTBS group and 3 of 18 participants [16.7%] in the active iTBS group) and open-label phase (5 of 21 participants [23.8%]). One active iTBS participant had a treatment emergent hypomania, and a second episode occurred during open-label treatment. Conclusions and Relevance iTBS targeting the LDLPFC is not efficacious in the treatment of acute bipolar depression in patients receiving antimanic or mood stabilizing agents. Additional research is required to understand how transcranial magnetic stimulation treatment protocols differ in efficacy between unipolar and bipolar depression. Trial Registration ClinicalTrials.gov Identifier:NCT02749006

Background Decision-making and impulse control (both cognitive and motor) are complex interrelated processes which rely on a distributed neural network that includes multiple cortical and subcortical regions. Among them, the orbitofrontal cortex (OFC) seems to be particularly relevant as demonstrated by several neuropsychological and neuroimaging investigations. Methods In the present study we assessed whether transcranial direct current stimulation (tDCS) applied bilaterally over the OFC is able to modulate decision-making and cognitive impulse control. More specifically, 45 healthy subjects were randomized to receive a single 30-min session of active or sham anodal tDCS (1.5 mA) applied over either the left or the right OFC (coupled with contralateral cathodal tDCS). They were also assessed pre- and post-tDCS with a battery of computerized tasks. Results Our results show that participants who received active anodal tDCS (irrespective of laterality), vs. those who received sham tDCS, displayed more advantageous decision-making (i.e., increased Iowa Gambling Task “net scores” [ p = 0.04]), as well as improved cognitive impulse control (i.e., decreased “interference” in the Stroop Word-Colour Task [ p = 0.007]). However, we did not observe tDCS-related effects on mood (assessed by visual analogue scales), attentional levels (assessed by the Continuous Performance Task) or motor impulse control (assessed by the Stop-Signal Task). Conclusions Our study potentially serves as a key translational step towards the development of novel non-invasive neuromodulation-based therapeutic interventions directly targeting vulnerability factors for psychiatric conditions such as suicidal behaviour and addiction.

Background First episode mania (FEM) cohorts provide an opportunity to identify windows for intervention to potentially alter the course of bipolar disorder (BD). Despite several efforts to prospectively characterize first episode patients, follow-up of such cohorts has seldom exceeded 1 year. We present 4-year outcomes from the STOP-EM FEM cohort. Method Of 101 identified FEM patients, 81 had longitudinal follow-up. Clinical evaluations including substance misuse, sociodemographics and family history were characterized using semi-structured instruments. Clinical reassessments occurred every 6 months. Results Within one year, all patients had remitted and 95% recovered. Recurrence following remission occurred in 58% of patients by 1 year and 74% by 4 years (60% depressive, 28% manic and 12% hypomanic). Recurrence within one year was associated with a higher rate of recurrence thereafter. Older age was associated with a shorter time to remission. Substance misuse was associated with delayed recovery and earlier recurrence. Limitations This prospective multiwave longitudinal design employed may be limited by the assessment schedule and associated recall bias. The influences of attrition of this sample should be considered when attempting to generalize our findings. Conclusions Best practices in FEM result in remission and recovery. While recurrence is common, minimizing recurrence within the first year through risk factor modification may alter the course of the BD.

Background Prognostication is poor in repetitive transcranial magnetic stimulation (rTMS) treatment for major depressive disorder (MDD). Personality traits, particularly extraversion and neuroticism, have attracted increasing attention for both trait- and state-dependent characteristics in predicting response to pharmacotherapy, psychotherapy, and more recently to therapeutic neuromodulation for MDD. The advent of deep rTMS (DTMS) allows stimulation of deeper cortical regions, and we aimed to prospectively characterize personality dimensions and antidepressant response to DTMS in treatment-resistant MDD. Methods A convenience sample of 15 patients with treatment-resistant MDD received four weeks of daily sessions of DTMS (20 Hz, 3000 pulses/session) of the left dorsolateral prefrontal cortex (DLFPC). At baseline and at the conclusion of treatment, patients completed the Big Five Inventory, a five-factor assessment of major personality dimensions. Clinical response was measured using the 21-item Hamilton Depression Rating Scale. Results Four weeks of DTMS treatment were not associated with changes in personality measures. Clinical remission was associated with higher baseline levels of agreeableness (score ≥29:100% sensitive and 72.7% specific) and conscientiousness (score ≥30:75% sensitive and 81.8% specific). Levels of agreeableness and extraversion were linearly associated with antidepressant response. Neuroticism was not associated with the antidepressant effects of DTMS in this cohort. Conclusions Five-factor personality assessment may have prognostic value in DTMS for resistant MDD. Agreeableness, extraversion, and conscientiousness are associated with decreases in depressive symptoms during treatment with DTMS.

Gender differences in suicidal behaviour entail a challenging paradox: more women attempt suicide than men, while more men commit suicide than women. The majority of suicide victims have a history of major depressive disorder (MDD), though only a small minority of those suffering from MDD will die by suicide. The present study aimed to explore the moderating role of gender in suicide completion, with particular focus on personality predispositions, Axis I and II psychopathology, while controlling for the effect of MDD. In the context of a case-control design, 201 suicide completers (160 men and 41 women) and 129 living controls (90 men and 39 women) with a history of MDD were recruited in Montreal, Canada. Participants were evaluated via the psychological autopsy method. Differences were found between men and women in the significant risk factors, suggesting that psychopathology and predispositions related to impulsivity-aggressivity and impulse-dyscontrol may have different relative contributions to suicide in depressed men and women.%%%%Les differences dans le comportement suicidaire entre les hommes et les femmes, un paradoxe: Plus de femmes que d'hommes font des tentatives de suicide bien que plus d'hommes que de femmes les reussissent. La majorite des vicitimes du suicide ont des antecedents de trouble de depression majeur (MDD), meme si seulement une faible minorite des personnes atteintes de MDD vont mettre fin a leurs jours. La presente etude entend relativiser l'importance du genre chez les personnes qui se sont suicidees en mettant l'accent plus particulierement sur les predispositions propres a chaque individu, la psychopathologie de l'axe I et II, en controlant les effets du MDD. Les cas presentes, 201 suicides (160 hommes et 41 femmes) et 129 tentatives de suicide (90 hommes et 39 femmes) ont ete recrutes a Montreal, Canada. Les participants ont ete evalues selon la methode de l'autopsie psychologique. En ce qui a trait aux facteurs de risque, des differences ont ete notees entre les hommes et les femmes, ce qui laisse entendre que la psychopathologie et les predispositions relatives a l'impulsivite-agressivite ainsi qu'au non-controle-impulsif peuvent avoir contribues differement au suicide chez les hommes et les femmes en depression.

The neurobiological underpinnings of bipolar I disorder are not yet understood. Previous structural neuroimaging studies of bipolar disorder have produced rather conflicting results. We hypothesise that clinical sub-phenotypes of bipolar I disorder defined by their psychotic symptoms, especially those with mood-incongruent psychotic features, may have more extensive structural brain abnormalities.We investigated structural brain alterations in patients with first-episode mania (n = 55) with mood-congruent (n = 16) and mood-incongruent (n = 32) psychotic features, as well as those without psychotic symptoms (n = 7), relative to healthy subjects (n = 56).Total intracranial volume was significantly reduced in patients with mood-incongruent psychosis compared to healthy subjects while cerebrospinal fluid (CSF) volume was significantly increased. Patients with mood-congruent psychosis showed significant reduction in total white matter volume and significant CSF volume increase. Patients with psychosis had significant volume reduction in anterior cingulate and medial prefrontal cortices. Relative to mood-congruent psychotic features, mood-incongruent psychotic features were associated with volume reduction in the left middle temporal gyrus, right inferior parietal gyrus, right fusiform gyrus, left middle orbitofrontal gyrus and cerebellum.While preliminary, our findings suggest that the presence and type of psychosis in first-episode mania may be phenotypic markers of underlying biological variants of bipolar disorder.

Cognitive dysfunction is a core feature of dementia and a prominent feature in psychiatric disease. As non-redundant regulators of intracellular cAMP gradients, phosphodiesterases (PDE) mediate fundamental aspects of brain function relevant to learning, memory, and higher cognitive functions. Phosphodiesterase-4B (PDE4B) is an important phosphodiesterase in the hippocampal formation, is a major Disrupted in Schizophrenia 1 (DISC1) binding partner and is itself a risk gene for psychiatric illness. To define the effects of specific inhibition of the PDE4B subtype, we generated mice with a catalytic domain mutant form of PDE4B (Y358C) that has decreased ability to hydrolyze cAMP. Structural modeling predictions of decreased function and impaired binding with DISC1 were confirmed in cell assays. Phenotypic characterization of the PDE4BY358C mice revealed facilitated phosphorylation of CREB, decreased binding to DISC1, and upregulation of DISC1 and β-Arrestin in hippocampus and amygdala. In behavioral assays, PDE4BY358C mice displayed decreased anxiety and increased exploration, as well as cognitive enhancement across several tests of learning and memory, consistent with synaptic changes including enhanced long-term potentiation and impaired depotentiation ex vivo. PDE4BY358C mice also demonstrated enhanced neurogenesis. Contextual fear memory, though intact at 24 h, was decreased at 7 days in PDE4BY358C mice, an effect replicated pharmacologically with a non-selective PDE4 inhibitor, implicating cAMP signaling by PDE4B in a very late phase of consolidation. No effect of the PDE4BY358C mutation was observed in the prepulse inhibition and forced swim tests. Our data establish specific inhibition of PDE4B as a promising therapeutic approach for disorders of cognition and anxiety, and a putative target for pathological fear memory.

Objective Idiopathic normal pressure hydrocephalus (iNPH) is considered sporadic, yet familial cases involving single pedigrees are being increasingly recognized. As current evidence does not extend beyond isolated pedigrees, we aimed to determine the putative heritability of iNPH by examining the prevalence of the iNPH triad among the family members of iNPH probands. Method We present a case–control family study of the iNPH symptom triad among the relatives of iNPH patients (n = 20) identified from a cohort of patients undergoing CSF diversion and matched comparison subjects (n = 21). A total of 291 first-degree relatives from 41 families were characterized using semi-structured family history interviews. Independent from the family study, we present a novel well-characterized familial case of iNPH. Results ≥ 2 insidious, progressive and idiopathic iNPH symptoms were identified among first degree relatives in 6 iNPH pedigrees (2 multiply affected) and 1 control pedigree, with an incidence of 7.1% among iNPH relatives and 0.7% among control relatives (OR = 11.53). Gait disturbance and memory impairment began at a younger age among the relatives of iNPH probands. Independent of our family study, we present a novel case report of a large iNPH pedigree with multiple affected relatives. Interpretation Our family study and novel familial case suggest familial aggregation of iNPH. A larger family study with full characterization of affected and unaffected relatives is warranted. Confirmation of heritability may allow identification of individuals at high-risk for iNPH, early intervention, and improved aetiological elucidation.

Objectives Bipolar I disorder (BD-I) is associated with gray matter volume (GMV) alterations in neural regions important for emotional regulation. Reductions found in patients with multiple episodes are not seen at illness onset, suggesting that changes occur with illness progression, although no prospective studies to date have examined this. In the present study, we assessed GMV at baseline and one year following a first manic episode, examining the impact of episode recurrence on the trajectory of change. Methods A total of 41 recently remitted first manic episode patients with BD-I and 25 healthy subjects (HS) underwent 3T magnetic resonance imaging at baseline and one year later. Using voxel-based morphometry, we compared GMV change between HS, patients who experienced a recurrence of a mood episode (BDrecurr), and patients in sustained remission (BDwell). Results The GMV change from baseline to one year did not differ significantly between HS and the full BD-I group or BDwell and HS. However, the BDrecurr group had greater GMV loss than HS in left frontal and bilateral temporal regions, and BDwell patients involving bilateral frontal, temporal and left parietal regions. Conclusions GMV change early in the course of BD-I is associated with clinical outcome, such that neuroprogression found in patients who experience a recurrence of a mood episode is not seen in those with sustained remission. These findings have important implications for the treatment of BD-I as they suggest that prevention of recurrence might minimize neuroprogression of the disease, possibly requiring a multipronged early intervention approach to achieve this goal.

To assess, in a sample of subjects with current major depressive disorder, whether high frequency repetitive transcranial magnetic stimulation (HF-rTMS) is able to influence affective "theory of mind" (ToM).We conducted a pilot naturalistic trial in which 14 subjects with MDD were treated with daily HF-rTMS over their left dorsolateral prefrontal cortex for 4 weeks. Objective depressive symptoms and affective ToM (as assessed, respectively, by the 21-item Hamilton Depression Rating Scale and the Reading the Mind in the Eyes Test [RMET]) were measured pre-post HF-rTMS treatment.Our findings indicated the absence of a significant main effect for pre-post RMET scores, yet a significant interaction between pre-post RMET performance and change in depressive symptoms. Therefore, depressed subjects in our sample exhibited ToM improvements in proportion to their antidepressant response.We have shown that HF-rTMS is able to influence ToM in subjects with MDD. We hypothesize that this effect could be associated, at least in part, with clinical improvement over time. However, further studies with larger samples and controlled designs are needed to better clarify our preliminary findings.

Objective: There is substantial evidence suggesting that suicide aggregates in families. However, the extent of overlap between the liability to suicide and psychiatric disorders, particularly major depressive disorder, remains an important issue. Similarly, factors that account for the familial transmission of suicidal behavior remain unclear. Thus, through direct and blind assessment of first-degree relatives, the authors conducted a family study of suicide by examining three proband groups: probands who committed suicide in the context of major depressive disorder, living depressed probands with no history of suicidal behavior, and psychiatrically normal community comparison probands. Method: Participants were 718 first-degree relatives from 120 families: 296 relatives of 51 depressed probands who committed suicide, 185 relatives of 34 nonsuicidal depressed probands, and 237 relatives of 35 community comparison subjects. Psychopathology, suicidal behavior, and behavioral measures were assessed via interviews. Results: The relatives of probands who committed suicide had higher levels of suicidal behavior (10.8%) than the relatives of nonsuicidal depressed probands (6.5%) and community comparison probands (3.4%). Testing cluster B traits as intermediate phenotypes of suicide showed that the relatives of depressed probands who committed suicide had elevated levels of cluster B traits; familial predisposition to suicide was associated with increased levels of cluster B traits; cluster B traits demonstrated familial aggregation and were associated with suicide attempts among relatives; and cluster B traits mediated, at least in part, the relationship between familial predisposition and suicide attempts among relatives. Analyses were repeated for severity of attempts, where cluster B traits also met criteria for endophenotypes of suicide. Conclusions: Familial transmission of suicide and major depression, while partially overlapping, are distinct. Cluster B traits and impulsive-aggressive behavior represent intermediate phenotypes of suicide.

OBJECTIVE: In the present paper we describe a case-control study on the utilization of health care services prior to suicide (across different time periods) among children and adolescents aged 11 to 18 years in the Province of Quebec, Canada and matched healthy controls. METHOD: Utilization of services (i.e., contact with general practitioners, mental health professionals, psychiatrists and/or youth protection groups) was examined at different time periods in 55 child and adolescent suicide victims and 54 matched community controls using proxy-based interviews and questionnaires. In addition, we examined the rates of detection of psychopathology by health care professionals, the use of psychotropic medications and the subjects' compliance with treatment. RESULTS: Although more than 90% of child and adolescent suicide completers in our sample suffered from mental disorders, a significant proportion of them were left without appropriate healthcare support (including psychiatric consultation) in the period preceding their suicide. Also, 20% of suicide completers and no control subject made prior suicide attempts. More specifically, over two-thirds of suicide completers had no treatment contact within the month prior to the completion, while only 12.7% (n=7) of them were in contact with psychiatric services during that same period. Moreover, 56.4% (n=31) of the suicide completers had not been diagnosed as having a mental disorder at the time of their death, and 54.5% of the subjects' that received treatment (12 out of 22) were considered poorly compliant or not compliant at all according to their medical/psychosocial records. Finally, we also found that females seemed to have more psychiatric and mental health service contacts in the past month, that subjects with depressive and anxious disorders received more psychiatric and general mental health services in the past year, and that past month hospitalization was more often associated with alcohol abuse and psychosis. LIMITATIONS: Relatively small sample size, and cross-sectional design. CONCLUSIONS: Our findings indicate the need for an overall increase in the rates of healthcare services delivered to young subjects at risk for suicide, as well as better training of health professionals in detecting and treating youth psychopathology. Language: en

Objective: To clarify whether certain Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), borderline personality disorder (BPD) symptoms are more prevalent among people who die by suicide, and thereby better predict suicide risk. Method: A psychological autopsy method with best informants was used to investigate DSM-IV BPD symptoms and suicide risk among people who died by suicide and met criteria for BPD ( n = 62), and BPD control subjects ( n = 35). Results: BPD symptoms in people who died by suicide were less likely to include affective instability and paranoid ideation–dissociative symptoms. The negative association between paranoid ideation–dissociative symptoms and suicide was independent of all other BPD symptoms, Cluster B comorbidity, and alcohol dependence. Conclusions: We found that discrete DSM-IV BPD symptoms differentiate people with BPD who die by suicide and those who do not. People with BPD who go on to die by suicide appear to constitute a specific subgroup of those who meet criteria for BPD, characterized by different general clinical presentation, but also by different characteristics within BPD.

Quality of life (QOL) in depression could be of great value as an outcome measure, especially in determining the effectiveness of treatment strategies. However, for this aim to be accomplished, it is important to clarify the relationship between QOL and a number of potentially mediating factors, such as sociodemographic and clinical variables. For this purpose, we assessed 140 depressed outpatients with the Mini International Neuropsychiatric Interview, the WHOQOL BREF, and the Beck Depression Inventory (BDI). After standard and stepwise multiple regression analyses, the following variables were found to be independent predictors of QOL: BDI score for the physical (adjusted R(2)=0.125) and psychological (adjusted R(2)=0.23) domains, and for the overall QOL estimate (adjusted R(2)=0.226); age, suicidality according to the MINI and BDI score for the social relations domain (adjusted R(2)=0.244); and ethnicity, psychiatric comorbidity, psychotic symptoms and BDI score for the environmental domain (adjusted R(2)=0.328). Limitations of the study include its cross-sectional design, relatively small sample size, and lack of objective measures of depressive symptomatology. Sociodemographic and clinical variables appear to explain less than 32.8% of the variance of QOL in subjects with depressive disorders. Clearly, further studies are needed to clarify which additional factors play a role in determining QOL in major depression.

Background Schizophrenia and schizoaffective disorder are diagnostic categories that are particularly at risk for suicide. A number of risk factors have been proposed to play a role in vulnerability to suicide, but it is unclear whether these are specific to certain diagnostic groups at risk for suicide or generalizable across disorders. It remains to be better understood what differentiates schizophrenic from non-schizophrenic suicides and whether or not these two groups share a common suicide liability. Methods Five hundred and twenty seven consecutive suicides, 43 of whom met criteria for schizophrenia and schizoaffective disorder, were investigated by means of proxy-based interviews using structured diagnostic instruments and personality trait assessments. Results Compared to other suicides, we found that schizophrenic and schizoaffective suicides presented comparably elevated levels of impulsive aggressive traits. They also had comparable levels of family history of suicidal behaviour among first degree relatives. Overall, schizophrenics and schizoaffective suicides met criteria for fewer psychiatric disorders, and were less likely to meet criteria for more than one disorder. Compared to suicides without schizophrenia or schizoaffective disorders, lower levels depressive disorders, of current and lifetime comorbid alcohol abuse, and personality disorders were found within those suicides who met criteria schizophrenia and schizoaffective disorders. Conclusions Elevated levels of impulsive–aggressive personality traits, considered as indicative of an elevated risk for suicide in other diagnostic categories, are also found among schizophrenic and schizoaffective suicide completers. Elevated levels of impulsive aggressive behaviours may serve as a common liability to suicide across major psychopathological categories, including schizophrenia and schizoaffective disorder.

Objectives The current study tested the diathesis-stress component of the hopelessness theory (HT) in a sample of youth using (1) a weakest link approach towards operationalizing cognitive vulnerability (e.g. a child's degree of vulnerability is determined by his/her most depressogenic inferential style; DIS) and (2) an idiographic approach towards operationalizing high stress (e.g. high stress is when a child is experiencing a level of stress that is higher than his/her own average level of stress). We also examined whether the association between within-subject fluctuations in hassles and depressive symptoms in cognitively vulnerable youth was moderated by absolute stress levels (the between-subject effect of stress). Design A multi-wave longitudinal design was used to examine whether the association between within-subject fluctuations in hassles and depressive symptoms was moderated by a depressogenic weakest link. Methods At Time 1, 140 children (between 6 and 14 years of age) of parents with a history of major depressive episodes completed measures assessing DISs and depressive symptoms. Every 6 weeks, for the subsequent year, children completed measures assessing depressive symptoms and hassles. Results The results of hierarchical linear modelling analyses indicated that a depressogenic weakest link was associated with greater elevations in depressive symptoms following elevations in hassles in girls but not in boys. Conclusions Results provide partial support for the applicability of the diathesis-stress component of the HT to youth. Integration of the current findings with those obtained in past research examining the diathesis-stress component of the hopelessness theory in youth suggests the utilization of an idiographic approach to examining vulnerability-stress theories may potentially lead to an increased understanding of gender differences in depression.

BACKGROUND: Borderline personality disorder is a major risk factor for suicidal behavior, yet prediction of suicide completion remains unclear. It has been proposed that impulsivity and aggression interact to increase suicide risk. Death by suicide in borderline personality disorder, then, may be the result of impulsivity, a core feature of the disorder, interacting with violent-aggressive tendencies. Using a case-control design, this study investigated clinical and behavioral risk factors for suicide completion in borderline personality disorder. METHOD: One hundred twenty subjects meeting DSM-IV criteria for borderline personality disorder, 50 controls and 70 who died by suicide between 2001 and 2005, were investigated by means of proxy-based interviews using structured diagnostic instruments and personality trait assessments. RESULTS: Borderline personality disorder suicides had fewer psychiatric hospitalizations and suicide attempts than borderline personality disorder controls. Borderline personality disorder suicides were also more likely to meet criteria for current and lifetime substance dependence disorders. They had higher levels of current and lifetime Axis I comorbidity, novelty seeking, impulsivity, hostility, and comorbid personality disorders, while exhibiting lower levels of harm avoidance. Most importantly, borderline personality disorder suicides were more likely to have cluster B comorbidity. Impulsivity and aggression interacted to predict suicide, though not after controlling for cluster B comorbidity. CONCLUSIONS: Borderline personality disorder individuals who die by suicide differ from those borderlines typically encountered in acute psychiatric settings. Our results suggest that the lethality of borderline personality disorder suicide attempts results from an interaction between impulsivity and the violent-aggressive features associated with cluster B comorbidity. Further, the anxious trait of harm avoidance appears to be protective against suicidal behavior resulting in death. Language: en

Impulsive-aggressive behaviors (IABs) are regarded as possible suicide intermediate phenotypes, mediating the relationship between genes and suicide outcome. In this study, we aimed to investigate the putative relationship between genetic variation at the 5-HT1B receptor gene, which in animal models is involved in impulse-aggression control, IABs, and suicide risk. We investigated the relationship of variation at five 5-HT1B loci and IAB measures in a sample of 696 subjects, including 338 individuals who died by suicide and 358 normal epidemiological controls. We found that variation at the 5-HT1B promoter A-161T locus had a significant effect on levels of IABs, as measured by the Buss-Durkee Hostility Inventory (BDHI). Suicides also differed from controls in distribution of variants at this locus. The A-161T locus, which seems to impact 5-HT1B transcription, could play a role in suicide predisposition by means of mediating impulsive-aggressive behaviors.

BackgroundNeurosurgery may involve significant blood loss and frequently requires allogeneic red blood cell (RBC) transfusion. Preoperative recombinant erythropoietin (EPO) may be used to improve erythroid status and recovery, and used either alone or in combination with preoperative autologous donation (PAD) it may reduce exposure to allogeneic RBC. We wished to study the use of EPO with and without PAD and the risk of RBC transfusion in neurosurgery.MethodsUsing a retrospective case-control design, 57 patients who received EPO preoperatively were matched 2:1 for age, sex, year of surgery, and International Classification of Diseases code most responsible for surgery (three were excluded because of stringent matching criteria, leaving 54 cases and 108 comparison subjects). Thirty-two cases participated in PAD. Medical and anesthetic records as well as laboratory investigations were reviewed and extracted.ResultsAllogeneic RBC exposure was identical for EPO cases and comparison subjects (18.5%). Concomitant PAD and EPO did not reduce allogeneic RBC exposure (21.9%), and resulted in a greater number of RBC units transfused. Last recorded hemoglobin levels suggested that autologous RBCs were not more liberally used. Patients who engaged in PAD and EPO suffered from iatrogenic anemia. A significant proportion (58.6%) of the autologous RBCs was ultimately not used and discarded.ConclusionFurther research is needed to determine the efficacy of EPO in neurological surgery. PAD does not appear to reduce the risk of allogeneic RBC transfusion, despite concomitant EPO. Indeed, PAD resulted in iatrogenic anemia and increased transfusion requirements. The cost-effectiveness of blood conservation efforts in neurosurgery deserves additional research.

Background: Major depressive disorder (MDD) is a significant cause of worldwide disability and treatment resistance is common. High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has emerged as a treatment for MDD, and while efficacious, the daily commitment for typical 4–6 weeks of treatment poses a significant challenge. We aimed to determine the effectiveness and acceptability of an accelerated rTMS protocol for MDD. Methods: In this naturalistic trial, 27 patients with moderate to severe chronic and treatment-resistant MDD were treated with twice-daily HF-rTMS (10 Hz) applied over the left dorsolateral prefrontal cortex for 2 consecutive weeks (60,000 pulses). The primary outcomes were rates of clinical remission and response (16-item Quick Inventory of Depressive Symptomatology post-treatment score r6, andZ50% reduction, respectively). Secondary outcomes were self-reported anxious symptoms, depressive symptoms and quality of life, and dropout rates as a proxy for acceptability. Results: Ten (37.0%) patients met criteria for clinical remission and 15 (55.6%) were classified as responders, with comparable outcomes for both moderate and severe MDD. Clinician-rated improvements in depressive symptoms were paralleled in self-reported depressive and anxious symptoms, as well as quality of life. No patient discontinued treatment. Limitations: This study is limited by short treatment duration that might be lengthened with corresponding improvements in effectiveness, limited duration of follow-up, small sample size, and an open-label design requiring randomized controlled replication. Conclusion: An accelerated protocol involving twice-daily sessions of HF-rTMS over the left DLPFC for 2 weeks was effective in treatment-resistant MDD, and had excellent acceptability. Additional research is required to optimize accelerated rTMS treatment protocols and determine efficacy using sham-controlled trials.

Somatic symptom disorders are common causes of disability and suffering, and can pose significant management challenges. Idiopathic burning mouth syndrome is a challenging somatic symptom disorder with relatively high prevalence, particularly among post-menopausal women. Here, we present the case of a woman with severe treatment refractory idiopathic burning mouth syndrome and comorbid major depressive disorder, who was successfully treated with bitemporal electroconvulsive therapy. This case highlights the potential effectiveness of electroconvulsive therapy in idiopathic burning mouth syndrome when other treatment options have been exhausted.

Several randomized, controlled trials have found high frequency repetitive transcranial magnetic stimulation (HF-rTMS) to be effective for treating major depressive disorder (MDD), but its antidepressant mechanisms have yet to be firmly understood. In this context, pre-treatment personality traits and subsequent changes in personality concomitant to treatment may be relevant for our understanding of these mechanisms. To investigate this issue we conducted a naturalistic trial in which 14 subjects with moderate to severe depression were treated with daily HF-rTMS over the left dorsolateral prefrontal cortex for 4 weeks. Objective depressive symptoms (as assessed by the HAM-D(21)) and the major personality dimensions of neuroticism and extraversion were measured pre-post HF-rTMS. Pre-rTMS levels of extraversion predicted subsequent decrease in depressive symptoms. Also, HF-rTMS treatment resulted in a decrease in neuroticism scores, and this relative decrease was associated with the relative decrease in depression. Our results suggest that HF-rTMS may positively affect the personality dimension of neuroticism. Also, pre-treatment levels of extraversion may predict the subsequent antidepressant response to HF-rTMS. However, further studies with larger samples and controlled designs are needed to better clarify these preliminary findings.

Background Suicide aggregates within families and the relatives of suicide completers are at an increased risk for suicide. Though neurocognitive changes are gaining increasing attention as part of the vulnerability for suicide, the literature on neurocognitive alterations among suicide relatives as possible endophenotypes of suicide is sparse. Method Normothymic first-degree relatives ( n =14) of suicide completers without personal histories of suicide attempts were compared to individuals without family histories of suicide ( n =14) matched for age-, sex- and education. Participants completed the Wisconsin card sorting test, a well validated test of cognitive control in a changing environment. Results First-degree relatives of suicide completers made significantly more perseverative errors and have a lower level of conceptual responses than comparison subjects. Conclusion Alterations found in first-degree relatives of suicide completers suggest a decreased responsiveness to changing, yet unambiguous, conditions. These neurocognitive impairments are similar to deficits observed among individuals engaging in suicide attempts. Neurocognitive impairments revealed by the Wisconsin card sorting test may represent a neurocognitive endophenotype of suicide.

Late-life suicide is an under-investigated public health problem. Among the putative vulnerabilities for this complex multifactorial behaviour are deficits in cognitive control, an ability to integrate and prioritize multiple cognitive processes in order to flexibly adapt behaviour and meet situational demands. We investigated cognitive control during rule learning in a complex and changing environment in older individuals with suicide attempts of varying lethality.Ninety-three participants over the age of 60 (30 healthy controls, 29 depressed never suicidal, 20 low-lethality suicide attempters, 14 high-lethality suicide attempters) underwent structured clinical and cognitive assessments. Participants then completed the Wisconsin Card Sorting Test (WCST), a well-studied task of cognitive control during rule learning.High-lethality attempters demonstrated a pattern of deficits involving poor conceptual reasoning, perseverative errors and total errors. Compared to low-lethality attempters and healthy controls, high-lethality attempters demonstrated poor conceptual reasoning, as well as increased rates of perseverative errors and total errors. Compared to non-suicidal depressed participants, high-lethality attempters also made more conceptual errors.High-lethality suicide attempts among older people are associated with impaired cognitive control during rule learning as detected by the WCST. Our data suggest that impairment in cognitive control during rule learning may represent a vulnerability distinct from the impulsive diathesis, typically manifesting in young, low-lethality attempters. This vulnerability may contribute to the high incidence of serious or, often, fatal suicidal acts in old age.

The first objective was to identify the provoking events of suicide in patients with schizophrenia or schizoid-type disorder, and to assess the humiliation component of these events. The second objective was to verify if quality of care during childhood is a vulnerability factor for suicide in patients with schizophrenia or schizoid-type psychosis. Thirty-three cases of suicide with a diagnosis of schizophrenia or schizoid-type psychosis were compared with 34 living patients with a similar diagnosis. The psychological autopsy method was used. The assessments were made with the Structured Clinical Interview for the Diagnostic and Statistical Manual for Axis I mental disorders, the Life Events and Difficulties Schedule, and the Child Experiences and Child Abuse Interview. The suicide group (SG) experienced more often a recent severe event, usually of a humiliation nature, than the control group (CG). It also experienced more severe events associated with aggressive behavior or with psychiatric impairment. Contrary to expectations, the CG had worse scores than the SG for quality of care during childhood. In conclusion, suicide in schizophrenia is related both to environmental stress and to psychiatric impairment.

Background: Suicidal behaviour aggregates in families, and the hypothalamic‐pituitary‐adrenal (HPA) axis and noradrenergic dysregulation may play a role in suicide risk. It is unclear whether stress dysregulation is a heritable trait of suicide or how it might increase risk. We investigated stress reactivity of the autonomic nervous system and the HPA axis in suicide predisposition and characterized the effect of this dysregulation on neuropsychologic function. Methods: In this family-based study of first-degree relatives (n = 14) of suicide completers and matched controls with no family or personal history of suicidal behaviour (n = 14), participants underwent the Trier Social Stress Test (TSST). We used salivary α-amylase and cortisol levels to characterize stress reactivity and diurnal variation. We administered a series of neuropsychologic and executive function tests before and after the TSST. Results: Despite normal diurnal variation, relatives of suicide completers exhibited blunted cortisol and α-amylase TSST reactivity. Although there were no baseline differences in conceptual reasoning, sustained attention or executive function, the relatives of suicide completers did not improve on measures of in hibition upon repeated testing after TSST. Secondary analyses suggested that these effects were related to suicide vulnerability independ ent of major depression. Limitations: The sample size was small, and the design prevents us from disentangling our findings from the possible traumatic consequences of losing a relative by suicide. Conclusions: Blunted stress response may be a trait of suicide risk, and impairment of stress-induced executive function may contribute to suicide vulnerability.

Background Suicidal behaviour aggregates in families and HPA-axis dysregulation may help explain part of this familial aggregation. Nevertheless, exogenous manipulation of the HPA-axis has yielded mixed results. Naturalistic and non-pharmacological inductions of the HPA-axis do not suggest hyper-responsiveness, yet suggest greater cognitive consequences of stress in individuals at risk for suicide. In this study, we aimed to characterize the relationship between plasma cortisol and an increased risk for suicide, as defined by family history. Method Patients (N = 148) with depressive disorders underwent psychopathological assessment, including structured investigation of past suicidal behaviour and underwent laboratory blood testing of cortisol. They also completed a family history interview investigating family psychopathology and suicidal behaviour, representing data on 848 first degree relatives. The relationship between plasma cortisol, past suicidal behaviour and suicidal behaviour among first degree relatives was examined. Results Lower levels of plasma cortisol were associated with a personal and family history of suicidal behaviour, as well as a family history of depression among first degree relatives. Multivariate analyses controlling for significant psychopathology replicated the association between lower levels of plasma cortisol, a family history of suicidal behaviour and personal history of suicide attempts, but not a family history of depression. Controlling for personal history of suicide attempts revealed an independent association between plasma cortisol and family history of suicidal behaviour, with an additional contribution by family history of depression in predicting the latter. Conclusions Lower plasma cortisol is associated with a family history of suicide among depressed outpatients, independent of psychopathology and previous suicide attempts.

BACKGROUND: There is considerable debate as to whether suicide is more likely to occur early in the course of major depressive disorder or by cumulative risk, with an increasing risk with each subsequent major depressive episode (MDE). By considering the number of MDEs among representative suicides, we aimed to further investigate the relationship between suicide outcome and the course of major depressive disorder. METHOD: A psychological autopsy method with best informants was used to investigate 154 consecutive suicides who died in the context of a DSM-IV MDE. Proxy-based interviews were conducted by using the Structured Clinical Interview for DSM-III-R; the Structured Clinical Interview for DSM-IV Axis II; and a series of behavioral and personality-trait assessments. Second, 143 living depressed outpatients of comparable age to the suicide group were assessed for their history of MDEs. The study was conducted between 2000 and 2005. RESULTS: The distribution of MDEs among depressed suicide completers was as follows: first MDE, 74.7%; second MDE, 18.8%; more than 2 MDEs, 6.5%. This distribution is compared to 32.9% of depressed living outpatients with a single MDE. Increased levels of hostility were associated with single MDE suicide completers. The anxious trait of harm avoidance increased among multiple MDE suicide completers. Alcohol abuse increased among first MDE suicide completers. CONCLUSIONS: Suicide in major depressive disorder is most likely to occur during the first MDE, and this appears to be related to increased levels of the impulsive-aggressive diathesis. Language: en

Objective The present study was designed to evaluate psychiatric risk factors for child and adolescent suicide, and to determine the association between impulsive-aggressive and other personality traits, and suicide completion in this population. Method Psychiatric diagnoses, impulsive-aggressive and other personality traits were assessed in 55 child and adolescent suicide victims and 55 community controls using semi-structured proxy-based interviews and questionnaires. Results The most significant psychiatric risk factors associated with child and adolescent suicide were depressive disorders (OR = 48.414, 95% CI 6.247–375.185), substance/alcohol abuse disorder (OR = 5.365, 95% CI 1.434–20.076), and disruptive disorders (OR = 13.643, 95% CI 2.292–23.16). Additionally, suicide victims showed higher scores on lifetime aggression/impulsivity, and harm avoidance. However, after logistic regression, the only independent significant predictors of suicide in this age group were the presence of depressive disorders (Adjusted OR (AOR) = 39.652, 95% CI 4.501–349.345), substance/alcohol abuse disorders (AOR = 7.325, 95% CI 1.127–47.62), and disruptive disorders (AOR = 6.464, 95% CI 1.422–29.38). Limitations Relatively small sample size, and cross-sectional design. Conclusions Our findings confirm the existence of a particular clinical profile of children and adolescents at high risk for suicide. Additionally, our results reinforce the need for improved understanding of the interrelationships between stressors, depression, substance/alcohol abuse disorders, disruptive disorders and personality traits/dimensions in youth suicidal behavior.

OBJECTIVE: It is unclear whether clinical and behavioral suicide risk factors, identified primarily among men, can be extended to women. We therefore explored sex differences in psychopathology and personality variants among suicide completers. METHOD: Using the psychological autopsy method, we compared personality variants and the prevalence of psychopathology as a function of sex among 351 consecutive suicides in a large, urban community. Psychiatric diagnoses were obtained using the Structured Clinical Interview for DSM-IV-TR Axis I Disorders and the Structured Clinical Interview for DSM-IV Axis II Personality Disorders, and measures of impulsive aggression, temperament, and character were administered. Subsequently, we carried out secondary analyses between male and female suicides matched 2:1 for age, current depression, and number of lifetime depressive episodes. The study was conducted from late 2000 to 2005. RESULTS: Females were less likely to meet criteria for current and lifetime alcohol abuse, but those who did were less likely than males to have concurrent depression. On average, females were less impulsive, yet similar proportions of males and females were highly impulsive and impulsivity was associated with alcohol abuse irrespective of gender. Females were more likely to meet criteria for lifetime anxiety disorders; these were associated with nonviolent suicide methods, irrespective of gender. CONCLUSIONS: Despite a lower prevalence among females, high levels of impulsivity and alcohol abuse appear to be valid risk factors for both sexes. Researchers should focus on females for the identification of other suicide mediators. Language: en

Research examining the diathesis-stress component of the hopelessness theory (HT) in youth has provided mixed support for the theory. One explanation for inconsistent findings is the failure to consider relationships among the three inferential styles posited to serve as vulnerability factors by the theory. The weakest link hypothesis posits that an individual is as vulnerable to depression as his/her most depressogenic inferential style (DIS) makes him/her. A second explanation is that researchers have operationalized "high stress" from a nomothetic, as opposed to an idiographic, perspective. The current study tested the diathesis-stress component of the HT in 230 third-grade and 152 seventh-grade schoolchildren using both a weakest link and an idiographic approach towards analysis. Children completed measures assessing depressive symptoms and DISs. Children subsequently completed measures assessing depressive symptoms and negative events once a week for 6 weeks. Hierarchical linear modeling and time-lagged analyses indicated that a depressogenic weakest link was associated with greater elevations in depressive symptoms following elevations in stress.

Background It is unclear whether certain DSM-IV depressive symptoms are more prevalent among individuals who die in the context of a major depressive episode and those who do not, whether this is associated with proximal or distal suicide risk, and whether depressive symptoms cluster to indicate suicide risk. Method A psychological autopsy method with best informants was used to investigate DSM-IV depressive symptoms among 156 suicides who died in the context of a major depressive episode and 81 major depressive controls. Results Suicides' depressive symptoms were more likely to include weight or appetite loss, insomnia, feelings of worthlessness or inappropriate guilt as well as recurrent thoughts of death or suicidal ideation. Fatigue and difficulties concentrating or indecisiveness were less prevalent among depressed suicides. These associations were independent of concomitant axis I and II psychopathology. The concomitant presence of (a) fatigue as well as impaired concentration or indecisiveness and (b) weight or appetite gain and hypersomnia was associated with decreased suicide risk. Inter-episode symptom concordance suggests that insomnia is an immediate indicator of suicide risk, while weight or appetite loss and feelings of worthlessness or guilt are not. Limitations This study employed proxy-based interviews. Conclusions We found that discrete DSM-IV depressive symptoms and clusters of depressive symptoms help differentiate depressed individuals who die by suicide and those who do not. Moreover, some DSM-IV depressive symptoms are associated with an immediate risk for suicide, while others may result from an etiology of depression common to suicide without directly increasing suicide risk.

BACKGROUND:From a retrospective study of youth centres (YCs) and coroner's files, we investigated youths' history of medical service utilization who died by suicide. This is the second of two papers on YCs population, the first paper having shown that the rate of psychopathology was higher in the YCs population compared to the general adolescent population.METHODS:From 1995 to 2000, 422 youths, aged 18 years and younger, died as a result of suicide in Quebec. More than one-third received services from YCs at some point. Using the provincial physician payment and hospitalization database, we examined physical and psychiatric service utilization according to time intervals, as well as hospitalization for psychiatric reasons in the individuals' lifetime and in the year preceding suicide. Suicides were matched to living YCs youths for age, sex, and geographic area. YCs controls were then subdivided into two groups based on file information pertaining to the presence or absence of suicidal behavior or ideation.RESULTS:Compared to living YCs youths, suicides had a higher rate of psychiatric service utilization in the week, month, 90 days, and year preceding suicide, as well as higher levels of lifetime hospitalization for psychiatric reasons than controls with or without a history of suicidal behavior or ideation. We found that 28.3% YCs suicides made use of psychiatric services in the year preceding suicide.CONCLUSION:The rate of psychiatric service utilization by YCs youth suicides is substantially inferior to the needs of this population. Our study underscores the need for appropriate recognition of psychiatric and suicidal problems among YCs population by social and psycho-educational professionals. At the same time, it highlights the issues of general practitioners' risk identification, psychiatric referral and treatment. Our findings suggest the need for improved organization and coordination of psychiatric services to ameliorate treatment delivery., Affiliation: Johanne Renaud & Claude Marquette : CHU Ste-Justine, Université de Montréal

Objective: Our study was designed to explore additional outcome variables of a suicide case–control study to determine the association between sexual orientation and gender identity in suicide completion in children and adolescents. Method: Fifty-five child and adolescent suicide victims and 55 community control subjects were assessed using semi-structured, proxy-based interviews and questionnaires regarding sexual orientation and gender issues, psychopathological diagnoses, and service use. Results: In our sample, no significant differences between suicide victims and control subjects were found regarding same-sex sexual orientation nor intimidation related to same-sex sexual orientation. Suicide victims with same-sex sexual orientation were more likely than suicide victims without same-sex sexual orientation, to meet criteria for anxiety disorders. Within the month preceding their deaths, these youth were more likely to have consulted a health professional, a psychiatrist, as well as having been hospitalized, and were more likely to have consulted a psychiatrist in the last year. Conclusions: In our sample, same-sex sexual orientation and gender identity issues do not appear to be more prevalent among youth who die by suicide, compared with youth recruited from the general population, nor for same-sex sexual-related intimidation. While exhibiting comparable levels of general psychopathological diagnoses associated with suicide, suicide victims with same-sex sexual orientation were more likely to meet criteria for anxiety disorders and to have consulted mental health professionals before their deaths.