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Abstract Background Clinicians often report that their own anxiety and low self-efficacy inhibit their use of evidence-based suicide prevention practices, including gold-standard screening and brief interventions. Exposure therapy to reduce clinician maladaptive anxiety and bolster self-efficacy use is a compelling but untested approach to improving the implementation of suicide prevention evidence-based practices (EBPs). This project brings together an interdisciplinary team to leverage decades of research on behavior change from exposure theory to design and pilot test an exposure-based implementation strategy (EBIS) to target clinician anxiety to improve suicide prevention EBP implementation. Methods We will develop, iteratively refine, and pilot test an EBIS paired with implementation as usual (IAU; didactic training and consultation) in preparation for a larger study of the effect of this strategy on reducing clinician anxiety, improving self-efficacy, and increasing use of the Columbia Suicide Severity Rating Scale and the Safety Planning Intervention in outpatient mental health settings. Aim 1 of this study is to use participatory design methods to develop and refine the EBIS in collaboration with a stakeholder advisory board. Aim 2 is to iteratively refine the EBIS with up to 15 clinicians in a pilot field test using rapid cycle prototyping. Aim 3 is to test the refined EBIS in a pilot implementation trial. Forty community mental health clinicians will be randomized 1:1 to receive either IAU or IAU + EBIS for 12 weeks. Our primary outcomes are EBIS acceptability and feasibility, measured through questionnaires, interviews, and recruitment and retention statistics. Secondary outcomes are the engagement of target implementation mechanisms (clinician anxiety and self-efficacy related to implementation) and preliminary effectiveness of EBIS on implementation outcomes (adoption and fidelity) assessed via mixed methods (questionnaires, chart-stimulated recall, observer-coded role plays, and interviews). Discussion Outcomes from this study will yield insight into the feasibility and utility of directly targeting clinician anxiety and self-efficacy as mechanistic processes informing the implementation of suicide prevention EBPs. Results will inform a fully powered hybrid effectiveness-implementation trial to test EBIS’ effect on implementation and patient outcomes. Trial registration Clinical Trials Registration Number: NCT05172609 . Registered on 12/29/2021.

Abstract Introduction Lower adherence to antiretroviral treatment (ART) has been found among people with HIV (PWH) who have comorbid mental disorders like depression and alcohol use in Sub-Saharan African. However, there has been less exploration with regards to other mental disorders. Methods This study assessed the association of multiple mental disorders and adherence to ART based on the data from primary/tertiary health care facilities in Maputo and Nampula, Mozambique. We administered a sociodemographic questionnaire, Mini International Neuropsychiatric Interview (MINI) Plus 4.0.0 adapted for use in Mozambique to assess mental conditions, and a 3-item self-report to measure ART adherence. Results 395 HIV-positive (self-report) participants on ART, with an average age of 36.7 years (SD = 9.8), and 30.4% were male. The most common mental disorders were major depressive disorder (27.34%) followed by psychosis (22.03%), suicidal ideation/behavior (15.44%), and alcohol-use disorder (8.35%). Higher odds of missing at least one dose in the last 30 days (OR = 1.45, 95% CI: 1.01, 2.10) were found in participants with any mental disorder compared to those without a mental disorder. The highest levels of non-adherence were observed among those with drug use disorders and panic disorder. Conclusions In Mozambique, PWH with any co-occurring mental conditions had a lower probability of ART adherence. Integrating comprehensive mental health assessment and treatment and ART adherence interventions tailored to PWH with co-occurring mental disorders is necessary to attain optimal ART adherence and reach the UNAIDS ART target.

Abstract Background This study assessed the prevalence of suicidal behavior and associated risk factors in public primary health care in Mozambique. Methods The Mini International Neuropsychiatric Interview was used to evaluate suicidal behavior among 502 adults attending three Primary Health Care (PHC) settings. Results In the past month, 13% (n = 63) of PHC attendees expressed suicidal ideation, 8% (n = 40) had made a suicide plan, 4% (n = 20) had made a suicide attempt, and 5% (n = 25) reported a lifetime suicide attempt. Females had 2.8-fold increased odds of suicide plan (95% CI: 1.5, 5.5) and 3.3-fold increased odds of suicide attempt in the past month (95% CI: 1.2, 9.1). Each 10-year increase in age was associated with 0.61-fold the odds of suicide plan (95% CI: 0.38, 0.98) and 0.09-fold the odds of suicide attempt (95% CI: 0.01, 0.69) in the past month. People living with HIV (PLWHA) had 2.2-fold increased adjusted odds of past month suicide attempt (CI: 1.1, 4.1). Conclusion Suicidal behaviors are common among adults attending PHC clinics in Mozambique. Screening and linkage to effective preventive interventions are urgently needed in PHC settings. Females, younger individuals, and PLWHA are at elevated risk for suicidal behavior in PHC.

Abstract Backgroud Globally, women have been shown to have high rates of common mental disorders (CMDs). In low and middle-income countries (LMICs), women face significant challenges related to maternity. However, no study has compared mental health problems among pregnant/post-partum women, childless women of childbearing age, and women with children in a low-income country. We sought to compare the frequency of CMD and suicide risk in a sample of women presenting or accompanying patients in primary care in two Mozambican semi-urban settings. Methods We administered the MINI International Neuropsychiatric Interview to 853 women, of whom 220 (25.8%) were pregnant/post-partum, 177 (20.8%) were non-pregnant and childless, and 456 (53.5%) were non-pregnant and with children more than 1-year-old. Logistic regression models compared the likelihood of a psychiatric disorder across groups, adjusting for sociodemographic and chronic-illness covariates. Results We found a high frequency of CMD and suicide risk among all women in this low-income context sample. In adjusted models, no differences in rates of depression, anxiety, or panic disorder were observed among groups. However, suicide risk was higher in women without children than pregnant/post-partum women. Conclusion The frequency of CMD among women of childbearing age in our study was higher than documented rates in high-income countries and other LMIC. Additionally, we found that motherhood was not protective and that pregnancy and the postpartum period were not stages of increased risk for most disorders. This highlights the need to expand mental health services not only for perinatal women but all women of childbearing age in this and possibly similar settings.

Abstract Brain targets to lower the high risk of suicide in Bipolar Disorder (BD) are needed. Neuroimaging studies employing analyses dependent on regional assumptions could miss hubs of dysfunction critical to the pathophysiology of suicide behaviors and their prevention. This study applied intrinsic connectivity distribution (ICD), a whole brain graph‐theoretical approach, to identify hubs of functional connectivity (FC) disturbances associated with suicide attempts in BD. ICD, from functional magnetic resonance imaging data acquired while performing a task involving implicit emotion regulation processes important in BD and suicide behaviors, was compared across 40 adults with BD with prior suicide attempts (SAs), 49 with BD with no prior attempts (NSAs) and 51 healthy volunteers (HVs). Areas of significant group differences were used as seeds to identify regional FC differences and explore associations with suicide risk-related measures. ICD was significantly lower in SAs than in NSAs and HVs in bilateral ventromedial prefrontal cortex (vmPFC) and right anterior insula (RaIns). Seed connectivity revealed altered FC from vmPFC to bilateral anteromedial orbitofrontal cortex, left ventrolateral PFC (vlPFC) and cerebellum, and from RaIns to right vlPFC and temporopolar cortices. VmPFC and RaIns ICD were negatively associated with suicidal ideation severity, and vmPFC ICD with hopelessness and attempt lethality severity. The findings suggest that SAs with BD have vmPFC and RaIns hubs of dysfunction associated with altered FC to other ventral frontal, temporopolar and cerebellar cortices, and with suicidal ideation, hopelessness, and attempt lethality. These hubs may be targets for novel therapeutics to reduce suicide risk in BD.

Abstract Background Reported childhood adversity (CA) is associated with development of depression in adulthood and predicts a more severe course of illness. Although elevated serotonin 1A receptor (5-HT1AR) binding potential, especially in the raphe nuclei, has been shown to be a trait associated with major depression, we did not replicate this finding in an independent sample using the partial agonist positron emission tomography tracer [11C]CUMI-101. Evidence suggests that CA can induce long-lasting changes in expression of 5-HT1AR, and thus, a history of CA may explain the disparate findings. Methods Following up on our initial report, 28 unmedicated participants in a current depressive episode (bipolar n = 16, unipolar n = 12) and 19 non-depressed healthy volunteers (HVs) underwent [11C]CUMI-101 imaging to quantify 5-HT1AR binding potential. Participants in a depressive episode were stratified into mild/moderate and severe CA groups via the Childhood Trauma Questionnaire. We hypothesized higher hippocampal and raphe nuclei 5-HT1AR with severe CA compared with mild/moderate CA and HVs. Results There was a group-by-region effect (p = 0.011) when considering HV, depressive episode mild/moderate CA, and depressive episode severe CA groups, driven by significantly higher hippocampal 5-HT1AR binding potential in participants in a depressive episode with severe CA relative to HVs (p = 0.019). Contrary to our hypothesis, no significant binding potential differences were detected in the raphe nuclei (p -value s > 0.05). Conclusions With replication in larger samples, elevated hippocampal 5-HT1AR binding potential may serve as a promising biomarker through which to investigate the neurobiological link between CA and depression.

Abstract Preclinical studies have implicated kappa opioid receptors (KORs) in stress responses and depression-related behaviors, but evidence from human studies is limited. Here we present results of a secondary analysis of data acquired using positron emission tomography (PET) with the KOR radiotracer [11C]GR103545 in 10 unmedicated, currently depressed individuals with major depressive disorder (MDD; 32.6 ± 6.5 years, 5 women) and 13 healthy volunteers (34.8 ± 10 years, 6 women). Independent component analysis was performed to identify spatial patterns of coherent variance in KOR binding (tracer volume of distribution, V T) across all subjects. Expression of each component was compared between groups and relationships to symptoms were explored using the 17-item Hamilton Depression Rating Scale (HDRS). Three components of variation in KOR availability across ROIs were identified, spatially characterized by [11C]GR103545 V T in (1) bilateral frontal lobe; (2) occipital and parietal cortices, right hippocampus, and putamen; and (3) right anterior cingulate, right superior frontal gyrus and insula, coupled to negative loading in left middle cingulate. In MDD patients, component 3 was negatively associated with symptom severity on the HDRS (r = −0.85, p = 0.0021). There were no group-wise differences in expression of any component between patients and controls. These preliminary findings suggest that KOR signaling in cortical regions relevant to depression, particularly right anterior cingulate, could reflect MDD pathophysiology.

IntroductionDepression is the most common mental disorder among people living with HIV/AIDS and has a negative impact on HIV treatment outcomes. Training lay HIV counselors to identify and manage depression may contribute to improved patient access and adherence to treatment, and reduce stigma and discrimination among lay health workers toward both HIV and depression. The purpose of this study was to assess the current knowledge and attitudes of lay HIV counselors toward managing depression in primary care in Mozambique.MethodsWe conducted a mixed-methods cross-sectional study to assess depression-related knowledge and attitudes among lay HIV counselors in 13 primary healthcare facilities in Mozambique. We used the quantitative Depression Attitude Questionnaire (DAQ) scale, followed by open-ended questions to further explore three key DAQ domains: the nature of depression, treatment preferences, and professional attitudes or reactions.ResultsThe sample included 107 participants (77.6% female, mean age: 32.3 years, sd = 7.4). Most (82.2%) had less than a high/technical school education. Findings suggested that some HIV counselors had knowledge of depression and described it as a cluster of psychological symptoms (e.g., deep sadness, anguish, apathy, isolation, and low self-esteem) sometimes leading to suicidal thoughts, or as a consequence of life stressors such as loss of a loved one, abuse, unemployment or physical illness, including being diagnosed with HIV infection. HIV counselors identified talking to trusted people about their problems, including family and/or counseling with a psychotherapist, as the best way for patients to deal with depression. While acknowledging challenges, counselors found working with patients with depression to be rewarding.ConclusionLay health counselors identified HIV and psychosocial issues as key risk factors for depression. They believed that the treatment approach should focus on social support and psychotherapy.

Environment (E) is pivotal in explaining variability in brain and behavior development, including suicidal ideation (SI) and behavior. It is therefore critical to systematically study relationships among environmental exposures (i.e., exposome) and suicidal phenotypes. Here, we evaluated the role of individual-level adversity and neighborhood environment and their interaction (E x E) in association with youth SI. Sample included youth (N = 7,054, ages 11–21) from the Philadelphia Neurodevelopmental Cohort, which investigated clinical phenotypes in a diverse US community population. We examined cross-sectional associations of environmental exposures with lifetime history of SI (n = 671), focusing on interactions between individual-level exposures to assaultive trauma (n = 917) and neighborhood-level socioeconomic status (SES) quantified using geocoded Census data. Models included potential confounds and overall psychopathology. Results showed that assaultive trauma was strongly associated with SI (OR = 3.3, 95%CI 2.7–4, p

Lipid microdomains (‘lipid rafts’) are plasma membrane subregions, enriched in cholesterol and glycosphingolipids, which participate dynamically in cell signaling and molecular trafficking operations. One strategy for the study of the physicochemical properties of lipid rafts in model membrane systems has been the use of nuclear magnetic resonance (NMR), but until now this spectroscopic method has not been considered a clinically relevant tool. We performed a proof-of-concept study to test the feasibility of using NMR to study lipid rafts in human tissues. Platelets were selected as a cost-effective and minimally invasive model system in which lipid rafts have previously been studied using other approaches. Platelets were isolated from plasma of medication-free adult research participants (n=13) and lysed with homogenization and sonication. Lipid-enriched fractions were obtained using a discontinuous sucrose gradient. Association of lipid fractions with GM1 ganglioside was tested using HRP-conjugated cholera toxin B subunit dot blot assays. 1H high resolution magic-angle spinning nuclear magnetic resonance (HRMAS NMR) spectra obtained with single-pulse Bloch decay experiments yielded spectral linewidths and intensities as a function of temperature. Rates of lipid lateral diffusion that reported on raft size were measured with a two-dimensional stimulated echo longitudinal encode-decode NMR experiment. We found that lipid fractions at 10–35% sucrose density associated with GM1 ganglioside, a marker for lipid rafts. NMR spectra of the membrane phospholipids featured a prominent ‘centerband’ peak associated with the hydrocarbon chain methylene resonance at 1.3 ppm; the linewidth (full width at half-maximum intensity) of this ‘centerband’ peak, together with the ratio of intensities between the centerband and ‘spinning sideband’ peaks, agreed well with values reported previously for lipid rafts in model membranes. Decreasing temperature produced decreases in the 1.3 ppm peak intensity and a discontinuity at ~18 °C, for which the simplest explanation is a phase transition from Ld to Lo phases indicative of raft formation. Rates of lateral diffusion of the acyl chain lipid signal at 1.3 ppm, a quantitative measure of microdomain size, were consistent with lipid molecules organized in rafts. These results show that HRMAS NMR can characterize lipid microdomains in human platelets, a methodological advance that could be extended to other tissues in which membrane biochemistry may have physiological and pathophysiological relevance.

Antidepressant medications are commonly used to treat depression, but only about 30% of patients reach remission with any single first-step antidepressant. If the first-step treatment fails, response and remission rates at subsequent steps are even more limited. The literature on biomarkers for treatment response is largely based on secondary analyses of studies designed to answer primary questions of efficacy, rather than on a planned systematic evaluation of biomarkers for treatment decision. The lack of evidence-based knowledge to guide treatment decisions for patients with depression has lead to the recognition that specially designed studies with the primary objective being to discover biosignatures for optimizing treatment decisions are necessary. Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) is one such discovery study. Stage 1 of EMBARC is a randomized placebo controlled clinical trial of 8 week duration. A wide array of patient characteristics is collected at baseline, including assessments of brain structure, function and connectivity along with electrophysiological, biological, behavioral and clinical features. This paper reports on the data analytic strategy for discovering biosignatures for treatment response based on Stage 1 of EMBARC.

Abstract Background Suicide is the primary cause of unnatural death in Spain, and suicide re-attempts a major economic burden worldwide. The risk factors for re-attempt and suicide after an index suicide attempt are different. This study aims to investigate risk factors for re-attempt and suicide after an index suicide attempt. Methods This observational study is part of a one-year telephone management program. We included all first-time suicide attempters evaluated in the emergency department at Parc Taulí-University Hospital (n = 1241) recruited over a five-year period (January 2008 to December 2012). Suicide attempters were evaluated at baseline using standardized instruments. Bivariate logistic regression models were used to identify risk factors. Kaplan-Meier curves were used to compare the time to re-attempt between categorical variables. Comparisons were performed using Log-Rank and Wilcoxon tests. Variables with a p-value lower than 0.2 were included in a multivariate Cox regression model. Bivariate logistic regression models were considered to identify risk factors for suicide. The significance level was set to 0.05. Results Suicide re-attempters were more likely diagnosed with cluster B personality disorders (36.8% vs. 16.6%; p

Background: Neuropsychiatric disorders are the leading cause of disability worldwide, accounting for 22.7% of all years lived with disability. Despite this global burden, fewer than 25% of affected individuals ever access mental health treatment; in low-income settings, access is much lower, although nonallopathic interventions through traditional healers are common in many venues. Three main barriers to reducing the gap between individuals who need mental health treatment and those who have access to it include stigma and lack of awareness, limited material and human resources, and insufficient research capacity. We argue that investment in dissemination and implementation research is critical to face these barriers. Dissemination and implementation research can improve mental health care in low-income settings by facilitating the adaptation of effective treatment interventions to new settings, particularly when adapting specialist-led interventions developed in high-resource countries to settings with few, if any, mental health professionals. Emerging evidence from other low-income settings suggests that lay providers can be trained to detect mental disorders and deliver basic psychotherapeutic and psychopharmacological interventions when supervised by an expert. Objectives: We describe a new North-South and South-South research partnership between Universidade Eduardo Mondlane (Mozambique), Columbia University (United States), Vanderbilt University (United States), and Universidade Federal de São Paulo (Brazil), to build research capacity in Mozambique and other Portuguese-speaking African countries. Conclusions: Mozambique has both the political commitment and available resources for mental health, but inadequate research capacity and workforce limits the country’s ability to assess local needs, adapt and test interventions, and identify implementation strategies that can be used to effectively bring evidence-based mental health interventions to scale within the public sector. Global training and research partnerships are critical to building capacity, promoting bilateral learning between and among low- and high-income settings, ultimately reducing the mental health treatment gap worldwide.

OBJECTIVE: This article reviews the evidence for the major risk factors associated with suicidal behavior in bipolar disorder. METHOD: Review of the literature studies on bipolar disorder, suicidal behavior and suicidal ideation. RESULTS: Bipolar disorder is strongly associated with suicide ideation and suicide attempts. In clinical samples between 14-59% of the patients have suicide ideation and 25-56% present at least one suicide attempt during lifetime. Approximately 15% to 19% of patients with bipolar disorder die from suicide. The causes of suicidal behavior are multiple and complex. Some strong predictors of suicidal behavior have emerged in the literature such as current mood state, severity of depression, anxiety, aggressiveness, hostility, hopelessness, comorbidity with others Axis I and Axis II disorders, lifetime history of mixed states, and history of physical or sexual abuse. CONCLUSION: Bipolar disorder is the psychiatric condition associated with highest lifetime risk for suicide attempts and suicide completion. Thus it is important to clinicians to understand the major risk factors for suicidal behavior in order to choose better strategies to deal with this complex behavior.OBJETIVO: O artigo revisa as evidências relacionadas aos principais fatores de risco associados ao comportamento suicida no transtorno bipolar. MÉTODO: Revisão de artigos da literatura em transtorno bipolar, tentativa de suicídio e ideação suicida. RESULTADOS: O transtorno bipolar está fortemente associado à presença de ideação suicida e a tentativas de suicídio. Em amostras clínicas, entre 14% e 59% dos pacientes apresentam ideação suicida e entre 25% e 56% têm pelo menos uma tentativa de suicídio ao longo da vida. Aproximadamente 15% a 19% dos pacientes com transtorno afetivo bipolar morrem por suicídio. As causas do comportamento suicida são múltiplas e complexas. Alguns preditores de comportamento suicida vêm sendo demonstrados consistentemente na literatura, tais como estado de humor atual, gravidade da depressão, ansiedade, agressividade, hostilidade, presença de comorbidades com outros transtornos do eixo I e eixo II, presença de estados mistos ao longo do curso da doença e história de abuso físico ou sexual. CONCLUSÃO: O transtorno bipolar é o transtorno psiquiátrico com maior risco ao longo da vida para tentativas de suicídio e suicídio completo. Sendo assim é importante para o clínico identificar os principais fatores de risco para comportamento suicida visando a escolha das melhores estratégias para lidar com esse comportamento complexo.

Objectives. To define different subgroups of suicide attempters according to age at onset of suicide attempts. Methods. Participants were 229 suicide attempters (147 females; 82 males) admitted to a general hospital in Madrid, Spain. We used admixture analysis to determine the best-fitting model for the age at onset of suicide attempts separated by sex. Results. The best fitted model for the age at onset of suicide attempts was a mixture of two gaussian distributions. Females showed an earlier age at onset of suicide attempts in both Gaussian distributions (mean ± S.D.) (26.98 ± 5.69 and 47.98 ± 14.13) than males (32.77 ± 8.11 and 61.31 ± 14.61). Early-onset female attempters were more likely to show borderline personality disorder than late-onset female attempters (OR = 11.11; 95% CI = 2.43–50.0). Conclusions. Age at onset of suicide attempts characterizes different subpopulations of suicide attempters.

Background. Impulsiveness, hostility and aggressiveness are traits associated with suicidal behavior, but also with borderline personality disorder (BPD). The presence of large numbers of BPD subjects in past attempter samples may distort the relative importance of each of these traits to predicting suicidal behavior, and lead to prospective, biological and genetic models that systematically misclassify certain subpopulations of suicidal individuals.Method. Two hundred and seventy-five subjects with major depressive disorder (MDD), including 87 with co-morbid BPD (69 past suicide attempters, 18 non-attempters) and 188 without BPD (76 attempters, 112 non-attempters) completed standard impulsiveness, hostility and aggressiveness ratings. Differences between past suicide attempters and non-attempters were examined with the sample stratified by BPD status.Results. As expected, BPD subjects scored significantly higher than non-BPD subjects on all three trait measures. Stratifying by BPD status, however, eliminated attempter/non-attempter differences in impulsiveness and hostility in both patient subgroups. Past suicide attempters in each of the two subgroups of patients were only distinguished by higher levels of aggressiveness.Conclusions. Once BPD is accounted for, a history of aggressive behavior appears to be the distinguishing trait characteristic of suicide attempters with major depression, rather than global personality dimensions such as impulsiveness or hostility. Aggressiveness, and not these related traits, may be the ideal target for behavioral, genetic and biological research on suicidal behavior, as well as for the clinical assessment of suicide risk. [ABSTRACT FROM AUTHOR]

Polyunsaturated fatty acid (PUFA) status has been associated with neuropsychiatric disorders, including depression and risk of suicide. Long-chain PUFAs (LC-PUFAs) are obtained in the diet or produced by sequential desaturation and elongation of shorter-chain precursor fatty acids linoleic acid (LA, 18:2n-6) and α-linolenic acid (ALA, 18:3n-3). We compared DNA methylation patterns in genes involved in LC-PUFA biosynthesis in major depressive disorder (MDD) with (n=22) and without (n=39) history of suicide attempt, and age- and sex-matched healthy volunteers (n=59). Plasma levels of selected PUFAs along the LC-PUFA biosynthesis pathway were determined by transesterification and gas chromatography. CpG methylation levels for the main human LC-PUFA biosynthetic genes, fatty acid desaturases 1 (Fads1) and 2 (Fads2), and elongation of very long chain fatty acids protein 5 (Elovl5), were assayed by bisulfite pyrosequencing. Associations between PUFA levels and diagnosis or suicide attempt status did not survive correction for multiple testing. However, MDD diagnosis and suicide attempts were significantly associated with DNA methylation in Elovl5 gene regulatory regions. Also the relative roles of PUFA levels and DNA methylation with respect to diagnostic and suicide attempt status were determined by least absolute shrinkage and selection operator (LASSO) logistic regression analyses. We found that PUFA associations with suicide attempt status were explained by effects of Elovl5 DNA methylation within the regulatory regions. The observed link between plasma PUFA levels, DNA methylation, and suicide risk may have implications for modulation of disease-associated epigenetic marks by nutritional intervention.

Suicide and suicide attempts are complex behaviors that result from the interaction of different factors, including genetic variants that increase the predisposition to suicidal behaviors. Copy number variations (CNVs) are deletions or duplications of a segment of DNA usually larger than one kilobase. These structural genetic changes, although quite rare, have been associated with genetic liability to mental disorders, such as autism, schizophrenia, and bipolar disorder. No genome-wide level studies have been published investigating the potential role of CNVs in suicidal behaviors. Based on single-nucleotide polymorphism array data, we followed the Penn-CNV standards to detect CNVs in 1,608 subjects, comprising 475 suicide and suicide attempt cases and 1,133 controls. Although the initial algorithms determined the presence of CNVs on chromosomes 6 and 12 in seven and eight cases, respectively, compared with none of the controls, visual inspection of the raw data did not support this finding. Furthermore we were unable to validate these findings by CNV-specific real-time polymerase chain reaction. Additionally, rare CNV burden analysis did not find an association between the frequency or length of rare CNVs and suicidal behavior in our sample population. Although our findings suggest CNVs do not play an important role in the etiology of suicidal behaviors, they are not inconsistent with the strong evidence from the literature suggesting that other genetic variants account for a portion of the total phenotypic variability in suicidal behavior.

Longitudinal investigation of the neural correlates of reward processing in depression may represent an important step in defining effective biomarkers for antidepressant treatment outcome prediction, but the reliability of reward-related activation is not well understood. Thirty-seven healthy control participants were scanned using fMRI while performing a reward-related guessing task on two occasions, approximately one week apart. Two main contrasts were examined: right ventral striatum (VS) activation fMRI BOLD signal related to signed prediction errors (PE) and reward expectancy (RE). We also examined bilateral visual cortex activation coupled to outcome anticipation. Significant VS PE-related activity was observed at the first testing session, but at the second testing session, VS PE-related activation was significantly reduced. Conversely, significant VS RE-related activity was observed at time 2 but not time 1. Increases in VS RE-related activity from time 1 to time 2 were significantly associated with decreases in VS PE-related activity from time 1 to time 2 across participants. Intraclass correlations (ICCs) in VS were very low. By contrast, visual cortex activation had much larger ICCs, particularly in individuals with high quality data. Dynamic changes in brain activation are widely predicted, and failure to account for these changes could lead to inaccurate evaluations of the reliability of functional MRI signals. Conventional measures of reliability cannot distinguish between changes specified by algorithmic models of neural function and noisy signal. Here, we provide evidence for the former possibility: reward-related VS activations follow the pattern predicted by temporal difference models of reward learning but have low ICCs.