Resting-state neural mechanisms of capability for suicide and their interaction with pain - A CAN-BIND-05 Study.

BACKGROUND: Suicidal ideation is highly prevalent in Major Depressive Disorder (MDD). However, the factors determining who will transition from ideation to attempt are not established. Emerging research points to suicide capability (SC), which reflects fearlessness of death and increased pain tolerance, as a construct mediating this transition. This Canadian Biomarker Integration Network in Depression study (CANBIND-5) aimed to identify the neural basis of SC and its interaction with pain as a marker of suicide attempt. METHODS: MDD patients (n = 20) with suicide risk and healthy controls (n = 21) completed a self-report SC scale and a cold pressor task measuring pain threshold, tolerance, endurance, and intensity at threshold and tolerance. All participants underwent a resting-state brain scan and functional connectivity was examined for 4 regions: anterior insula (aIC), posterior insula (pIC), anterior mid-cingulate cortex (aMCC) and subgenual anterior cingulate cortex (sgACC). RESULTS: In MDD, SC correlated positively with pain endurance and negatively with threshold intensity. Furthermore, SC correlated with the connectivity of aIC to the supramarginal gyrus, pIC to the paracingulate gyrus, aMCC to the paracingulate gyrus, and sgACC to the dorsolateral prefrontal cortex. These correlations were stronger in MDD compared to controls. Only threshold intensity mediated the correlation between SC and connectivity strength. LIMITATIONS: Resting-state scans provided an indirect assessment of SC and the pain network. CONCLUSIONS: These findings highlight point to a neural network underlying SC that is associated with pain processing. This supports the potential clinical utility of pain response measurement as a method to investigate markers of suicide risk.

Using a Safety Planning Mobile App to Address Suicidality in Young People Attending Community Mental Health Services in Ireland: Protocol for a Pilot Randomized Controlled Trial.

BACKGROUND: Over 700,000 people die by suicide annually, making it the fourth leading cause of death among those aged 15-29 years globally. Safety planning is recommended best practice when individuals at risk of suicide present to health services. A safety plan, developed in collaboration with a health care practitioner, details the steps to be taken in an emotional crisis. SafePlan, a safety planning mobile app, was designed to support young people experiencing suicidal thoughts and behaviors and to record their plan in a way that is accessible immediately and in situ. OBJECTIVE: The aim of this study is to assess the feasibility and acceptability of the SafePlan mobile app for patients experiencing suicidal thoughts and behaviors and their clinicians within Irish community mental health services, examine the feasibility of study procedures for both patients and clinicians, and determine if the SafePlan condition yields superior outcomes when compared with the control condition. METHODS: A total of 80 participants aged 16-35 years accessing Irish mental health services will be randomized (1:1) to receive the SafePlan app plus treatment as usual or treatment as usual plus a paper-based safety plan. The feasibility and acceptability of the SafePlan app and study procedures will be evaluated using both qualitative and quantitative methodologies. The primary outcomes are feasibility outcomes and include the acceptability of the app to participants and clinicians, the feasibility of delivery in this setting, recruitment, retention, and app use. The feasibility and acceptability of the following measures in a full randomized controlled trial will also be assessed: the Beck Scale for Suicide Ideation, Columbia Suicide Severity Rating Scale, Coping Self-Efficacy Scale, Interpersonal Needs Questionnaire, and Client Service Receipt Inventory. A repeated measures design with outcome data collected at baseline, post intervention (8 weeks), and at 6-month follow-up will be used to compare changes in suicidal ideation for the intervention condition relative to the waitlist control condition. A cost-outcome description will also be undertaken. Thematic analyses will be used to analyze the qualitative data gathered through semistructured interviews with patients and clinicians. RESULTS: As of January 2023, funding and ethics approval have been acquired, and clinician champions across mental health service sites have been established. Data collection is expected to commence by April 2023. The submission of completed manuscript is expected by April 2025. CONCLUSIONS: The framework for Decision-making after Pilot and feasibility Trials will inform the decision to progress to a full trial. The results will inform patients, researchers, clinicians, and health services of the feasibility and acceptability of the SafePlan app in community mental health services. The findings will have implications for further research and policy regarding the broader integration of safety planning apps. TRIAL REGISTRATION: OSF Registries osf.io/3y54m; https://osf.io/3y54m. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/44205.

Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Report: A Systematic Review and Recommendations of Cannabis use in Bipolar Disorder and Major Depressive Disorder.

BACKGROUND: Given the increasing acceptability and legalization of cannabis in some jurisdictions, clinicians need to improve their understanding of the effect of cannabis use on mood disorders. OBJECTIVE: The purpose of this task force report is to examine the association between cannabis use and incidence, presentation, course and treatment of bipolar disorder and major depressive disorder, and the treatment of comorbid cannabis use disorder. METHODS: We conducted a systematic literature review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching PubMed, Embase, PsycINFO, CINAHL and Cochrane Central Register of Controlled Trials from inception to October 2020 focusing on cannabis use and bipolar disorder or major depressive disorder, and treatment of comorbid cannabis use disorder. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach was used to evaluate the quality of evidence and clinical considerations were integrated to generate Canadian Network for Mood and Anxiety Treatments recommendations. RESULTS: Of 12,691 publications, 56 met the criteria: 23 on bipolar disorder, 21 on major depressive disorder, 11 on both diagnoses and 1 on treatment of comorbid cannabis use disorder and major depressive disorder. Of 2,479,640 participants, 12,502 were comparison participants, 73,891 had bipolar disorder and 408,223 major depressive disorder without cannabis use. Of those with cannabis use, 2,761 had bipolar disorder and 5,044 major depressive disorder. The lifetime prevalence of cannabis use was 52%-71% and 6%-50% in bipolar disorder and major depressive disorder, respectively. Cannabis use was associated with worsening course and symptoms of both mood disorders, with more consistent associations in bipolar disorder than major depressive disorder: increased severity of depressive, manic and psychotic symptoms in bipolar disorder and depressive symptoms in major depressive disorder. Cannabis use was associated with increased suicidality and decreased functioning in both bipolar disorder and major depressive disorder. Treatment of comorbid cannabis use disorder and major depressive disorder did not show significant results. CONCLUSION: The data indicate that cannabis use is associated with worsened course and functioning of bipolar disorder and major depressive disorder. Future studies should include more accurate determinations of type, amount and frequency of cannabis use and select comparison groups which allow to control for underlying common factors.

Acute and chronic stress predict anti-depressant treatment outcome and naturalistic course of major depression: A CAN-BIND report.

BACKGROUND: In treatment studies of major depressive disorder (MDD), exposure to major life events predicts less symptom improvement and greater likelihood of relapse. In contrast, the impact of minor life events has received less attention. We hypothesized that the impact of minor events on symptom improvement and risk of relapse would be heightened in the presence of concurrent chronic stress. We also hypothesized that major events would predict less symptom improvement and greater risk of relapse independently of chronic stress. METHODS: Adult patients experiencing an episode of MDD were enrolled into a 16-week trial with antidepressant treatments (n = 156). Forty-three fully remitted patients agreed to participate in a naturalistic 18-month follow-up, and 30 had full data for analyses. Life events and chronic stressors were assessed using a contextual life stress interview. RESULTS: Greater exposure to minor events predicted greater improvement in symptoms during acute treatment, but this relation was specific to those who reported greater severity of chronic stress. During follow-up, however, major life events predicted increased risk of relapse, and this effect was not moderated by chronic stress. LIMITATION: High attrition rates led to a small sample size for the follow-up analyses. CONCLUSIONS: Exposure to minor events may provide an opportunity to practice problem-solving skills, thereby facilitating symptom improvement. Nevertheless, acute treatment did not protect patients from relapse when they subsequently faced major events during follow-up. Therefore, adjunctive strategies may be needed to enhance outcomes during pharmacotherapy, consolidating benefits from acute treatment and providing skills to prevent relapse.

Association between discrepancy in objective and subjective cognitive abilities and treatment response in patients with major depressive disorder: A CAN-BIND-1 study report.

BACKGROUND: Major Depressive Disorder (MDD) is characterized by objective and subjective cognitive deficits. Discrepancies between objective and subjective cognitive performance can reflect under- to over-estimations of cognitive abilities, and these discrepancies are referred to as cognitive self-appraisals. Despite evidence that low self-appraisals are associated with depression, the modifiability of self-appraisals and their association with treatment outcome remains unclear. The current study examined whether self-appraisals change following antidepressant treatment. Furthermore, we investigated the association of self-appraisals with treatment outcome. METHODS: As part of the CAN-BIND-1 clinical trial, 154 patients with MDD completed measures of objective and subjective cognitive abilities, depressive symptoms, and functional outcomes (work productivity, psychosocial functioning, and quality of life) at baseline and post-escitalopram treatment. Self-appraisals were calculated based on discrepancies between objective and subjective cognitive abilities, with higher scores indicating overestimation of cognitive abilities. RESULTS: Baseline self-appraisals were not predictive of treatment outcomes. However, self-appraisals increased from pre- to post-treatment. Moreover, pre-post treatment increases in self-appraisals were associated with positive treatment response and remission, decreases in depressive symptoms, and improvements in work productivity, psychosocial functioning, and quality of life. LIMITATIONS: The pre-post intervention design precluded examining the temporal precedence of change in self-appraisals versus depressive symptoms and functional outcomes. CONCLUSIONS: Findings are the first to demonstrate that self-appraisals are treatment-sensitive and are associated with treatment outcomes and recovery from MDD. Cognitive self-appraisals may represent a key marker of treatment response and a valuable target for assessment and intervention, as well as a potential mechanism underlying risk and recovery.

Exploring the experiences of mental health professionals engaged in the adoption of mobile health technology in Irish mental health services.

BACKGROUND: The World Health Organization report that an estimated 793,000 people died by suicide in 2016 globally. The use of digital technology has been found to be beneficial in the delivery of Web-based suicide prevention interventions. Research on the integration of digital technology within mental health services has indicated that despite the proliferation of technology, engagement by patients and professionals in adopting such technology can be poor. OBJECTIVES: The current study aims to explore the experiences of 15 mental health professionals involved in integrating mobile health technology into their practice. A secondary aim was to identify the drivers and barriers to the adoption of such technology by mental health professionals, and to consider what theoretical models could best account for the data. METHODS: Semi-structured interviews, conducted from July to October 2019, were used to explore the experiences of mental health professionals engaged in the adoption of mobile health technology within mental health services. Mental Health professionals and clinician managers working in HSE Child and Adolescent Mental Health, Adult Mental Health, and Primary Care Psychology services were recruited for the study. Qualitative interview data was transcribed and analysed using NVivo. Thematic Analysis was used to identify themes. RESULTS: Four major themes were identified: Accessibility, 'Transitional Object', Integration, and Trust. Within these 4 major themes, a total of 9 subthemes were identified: Service Accessibility, Immediate Access, Client Engagement, Adjunct-to-therapy, Therapeutic Relationship, Infrastructural Support, Enhancing Treatment, Trust in the Technology, Trust in the Organisation. CONCLUSIONS: Overall, Diffusion of Innovation Theory provides a useful theoretical framework which is consistent with and can adequately account for many of the Major and Subthemes identified in the data. In addition, 'Transitional Objects', a key concept within Object Relations Theory, could offer a means of better understanding how patients and professionals engage with digital technology within mental health services particularly.

Predictors of Quality of Life Improvement with Escitalopram and Adjunctive Aripiprazole in Patients with Major Depressive Disorder: A CAN-BIND Study Report.

BACKGROUND: Non-response to first-line treatment for major depressive disorder (MDD) is common; for such individuals, quality of life (QoL) impairments can be severe. Identifying predictors of QoL changes may support the management of cases with persistent depressive symptoms despite adequate initial pharmacological/psychological treatment. OBJECTIVE: The present study aimed to explore predictors of domain-specific QoL improvement following adjunctive aripiprazole treatment for inadequate response to initial antidepressant therapy. METHODS: We evaluated secondary QoL outcomes from a CAN-BIND (Canadian Biomarker Integration Network in Depression) study in patients with MDD who did not respond to an initial 8 weeks of escitalopram and received a further 8 weeks of adjunctive aripiprazole (n = 96). Physical, psychological, social, and environmental QoL domains were assessed using the World Health Organization QoL Scale Brief Version (WHOQOL-BREF). Clinician-rated depressive symptoms were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). Functioning was measured with the Sheehan Disability Scale (SDS). Satisfaction with medication was assessed with a single item from the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). Exploratory t-tests were used to describe domain score changes. A hierarchical linear regression was used to explore demographic, clinical, and treatment-related predictors of improvement. RESULTS: Across domains, QoL improved with adjunctive aripiprazole treatment. Satisfaction with medication and MADRS and SDS scores similarly improved. Symptom reduction was a predictor for positive change to physical and psychological QoL; functioning improvements were predictive of increases to all QoL domains. Satisfaction with medication predicted improvements to physical and psychological domains, whereas number of medication trials was a predictor of worsening QoL in the physical domain. CONCLUSION: The final model explained the most variance in psychological (68%) and physical (67%) QoL. Less variance was explained for environmental (43%) and social QoL (33%), highlighting a need for further exploration of predictors in these domains. Strategies such as functional remediation may have potential to support QoL for individuals with persistent depressive symptoms. CLINICAL TRIALS REGISTRY: ClinicalTrials.gov identifier: NCT016557.

How do delirium motor subtypes differ in phenomenology and contributory aetiology? a cross-sectional, multisite study of liaison psychiatry and palliative care patients.

OBJECTIVES: To investigate whether delirium motor subtypes differ in terms of phenomenology and contributory aetiology. DESIGN: Cross-sectional study. SETTING: International study incorporating data from Ireland and India across palliative care, old age liaison psychiatry and general adult liaison psychiatry settings. PARTICIPANTS: 1757 patients diagnosed with delirium using criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth edition (DSM IV). PRIMARY AND SECONDARY OUTCOME MEASURES: Hyperactive, mixed and hypoactive delirium subtypes were identified using the abbreviated version of the Delirium Motor Subtype Scale. Phenomenology was assessed using the Delirium Rating Scale Revised. Contributory aetiologies were assessed using the Delirium Aetiology Checklist (DEC), with a score >2 indicating that the aetiology was likely or definitely contributory. RESULTS: Hypoactive delirium was associated with dementia, cerebrovascular and systemic infection aetiologies (p<0.001) and had a lower overall burden of delirium symptoms than the other motor subtypes. Hyperactive delirium was associated with younger age, drug withdrawal and the DEC category other systemic aetiologies (p<0.001). Mixed delirium showed the greatest symptom burden and was more often associated with drug intoxication and metabolic disturbance (p<0.001). All three delirium motor subtypes had similar levels of impairment in attention and visuospatial functioning but differed significantly when compared with no subtype (p<0.001). CONCLUSIONS: This study indicates a pattern of aetiology and symptomatology of delirium motor subtypes across a large international sample that had previously been lacking. It serves to improve our understanding of this complex condition and has implications in terms of early detection and management of delirium.

Cognitive Outcomes with Sequential Escitalopram Monotherapy and Adjunctive Aripiprazole Treatment in Major Depressive Disorder: A Canadian Biomarker Integration Network in Depression (CAN-BIND-1) Report.

BACKGROUND: Cognitive deficits are detectable in major depressive disorder (MDD). The cognitive impact of antidepressants remains unclear, as does the cognitive effects of aripiprazole in MDD, a commonly used adjunct with putative pro-cognitive properties. OBJECTIVES: In this multi-centre, open-label study, cognitive changes associated with escitalopram monotherapy and adjunctive aripiprazole were examined. METHODS: Acutely depressed participants with MDD (n = 209) received 8 weeks of escitalopram. Non-responders received an additional 8 weeks of adjunctive aripiprazole (ESC-ARI, n = 88), while responders (ESC-CONT, n = 82) continued escitalopram monotherapy (n = 39 lost to attrition). ESC-ARI, ESC-CONT and matched healthy participants (n = 112) completed the Central Nervous System Vital Signs cognitive battery at baseline, 8 and 16 weeks. Linear mixed models compared participants with MDD cognitive trajectories with healthy participants. RESULTS: Participants with MDD displayed poorer baseline global cognition (assessed via the Neurocognitive Index), composite memory and psychomotor speed vs healthy participants. There were no statistically significant changes in participants with MDD receiving escitalopram monotherapy from baseline to week 8 in the neurocognitive index, reaction time, complex attention, cognitive flexibility, memory or psychomotor speed. Overall symptom severity changes were not associated with cognitive changes. The ESC-CONT group displayed no significant cognitive changes from weeks 8 to 16; reaction time worsened in the ESC-ARI group (p = 0.008) from weeks 8 to 16, independent of symptom change. CONCLUSIONS: Escitalopram monotherapy in acute MDD did not result in significant cognitive improvements. We provide novel evidence that escitalopram continuation in responders does not adversely affect cognition, but adjunctive aripiprazole in escitalopram non-responders worsens reaction time. Treatments targeting cognitive dysfunction are needed in MDD. CLINICALTRIALS. GOV IDENTIFIER: NCT01655706; 2 August, 2012.

Treatment-resistant major depressive disorder: Canadian expert consensus on definition and assessment.

BACKGROUND: Treatment-resistant depression (TRD) is a debilitating chronic mental illness that confers increased morbidity and mortality, decreases the quality of life, impairs occupational, social, and offspring development, and translates into increased costs on the healthcare system. The goal of this study is to reach an agreement on the concept, definition, staging model, and assessment of TRD. METHODS: This study involved a review of the literature and a modified Delphi process for consensus agreement. The Appraisal of Guidelines for Research & Evaluation II guidelines were followed for the literature appraisal. Literature was assessed for quality and strength of evidence using the grading, assessment, development, and evaluations system. Canadian national experts in depression were invited for the modified Delphi process based on their prior clinical and research expertize. Survey items were considered to have reached a consensus if 80% or more of the experts supported the statement. RESULTS: Fourteen Canadian experts were recruited for three rounds of surveys to reach a consensus on a total of 27 items. Experts agreed that a dimensional definition for treatment resistance was a useful concept to describe the heterogeneity of this illness. The use of staging models and clinical scales was recommended in evaluating depression. Risk factors and comorbidities were identified as potential predictors for treatment resistance. CONCLUSIONS: TRD is a meaningful concept both for clinical practice and research. An operational definition for TRD will allow for opportunities to improve the validity of predictors and therapeutic options for these patients.

Alexithymia in People With Recurrent Suicide Attempts.

Background: Alexithymia, an inability to identify or describe emotions, is associated with suicidality yet the correlation with single or repeated suicide attempts is less clear. Aims: We aimed to assess the modifiability of alexithymia following a group psychosocial intervention focused on improving emotional literacy in those with a history of recurrent suicide attempts (RSA). Method: A total of 169 participants with self-reported RSA completed pre- and postgroup assessments of a 20-week group therapy intervention. Questionnaires assessed alexithymia, depression, impulsivity, and hopelessness; the Toronto Alexithymia Scale (TAS-20) was the primary outcome. Data were analyzed using multiple imputation. Results: Participants had on average 7.8 lifetime suicide attempts, 73% were female, and 16.6% had a >13-point reduction in TAS-20 scores after 20 weeks. Directed acyclic graph (DAG) analysis demonstrated significant relationships between alexithymia, depression, hopelessness, problem-solving, and satisfaction with life. Age of onset of suicidality was the only factor predictive of postintervention TAS-20 score in univariate linear regression. Limitations: The study limitations were its sample size, insufficient resources, and missing data. Conclusion: A change in TAS scores indicated that alexithymia can be a modifiable treatment target. Being able to identify and describe feelings may lead to improvement in depression, hopelessness, problem-solving, and satisfaction with life in this population.

Cognition and Its Association with Psychosocial and Occupational Functioning during Treatment with Escitalopram in Patients with Major Depressive Disorder: A CAN-BIND-1 Report: La Cognition Et Son Association Avec Le Fonctionnement Psychosocial Et Professionnel Durant Le Traitement Par Escitalopram Chez Des Patients Souffrant De Trouble Dépressif Majeur: Une Étude Can-Bind-1.

OBJECTIVES: Major depressive disorder (MDD) is associated with impairments in both cognition and functioning. However, whether cognitive deficits significantly contribute to impaired psychosocial and occupational functioning, independent of other depressive symptoms, is not well established. We examined the relationship between cognitive performance and functioning in depressed patients before and after antidepressant treatment using secondary data from the first Canadian Biomarker Integration Network in Depression-1 study. METHODS: Cognition was assessed at baseline in unmedicated, depressed participants with MDD (n = 207) using the Central Nervous System Vital Signs computerized battery, psychosocial functioning with the Sheehan Disability Scale (SDS), and occupational functioning with the Lam Employment Absence and Productivity Scale (LEAPS). Cognition (n = 181), SDS (n = 175), and LEAPS (n = 118) were reassessed after participants received 8 weeks of open-label escitalopram monotherapy. A series of linear regressions were conducted to determine (1) whether cognitive functioning was associated with psychosocial and occupational functioning prior to treatment, after adjusting for overall depressive symptom severity and (2) whether changes in cognitive functioning after an 8-week treatment phase were associated with changes in psychosocial and occupational functioning, after adjusting for changes in overall symptom severity. RESULTS: Baseline global cognitive functioning, after adjusting for depression symptom severity and demographic variables, was associated with the SDS work/study subscale (ß = -0.17; P = 0.03) and LEAPS productivity subscale (ß = -0.17; P = 0.05), but not SDS total (ß = 0.19; P = 0.12) or LEAPS total (ß = 0.41; P = 0.17) scores. Although LEAPS and SDS scores showed significant improvements after 8 weeks of treatment (P < 0.001), there were no significant associations between changes in cognitive domain scores and functional improvements. CONCLUSION: Cognition was associated with occupational functioning at baseline, but changes in cognition were not associated with psychosocial or occupational functional improvements following escitalopram treatment. We recommend the use of more comprehensive functional assessments to determine the impact of cognitive change on functional outcomes in future research.

Progression of neuroanatomical abnormalities after first-episode of psychosis: A 3-year longitudinal sMRI study.

The location, extent and progression of longitudinal morphometric changes after first-episode of psychosis (FEP) remains unclear. We investigated ventricular and cortico-subcortical regions over a 3-year period in FEP patients compared with healthy controls. High resolution 1.5T T1-weighted MR images were obtained at baseline from 28 FEP patients at presentation and 28 controls, and again after 3-years. The longitudinal FreeSurfer pipeline (v.5.3.0) was used for regional volumetric and cortical reconstruction image analyses. Repeated-measures ANCOVA and vertex-wise linear regression analyses compared progressive changes between groups in subcortical structures and cortical thickness respectively. Compared with controls, patients displayed progressively reduced volume of the caudate [F (1,51)=5.86, p=0.02, Hedges' g=0.66], putamen [F (1,51)=6.06, p=0.02, g=0.67], thalamus [F (1,51)=6.99, p=0.01, g=0.72] and increased right lateral ventricular volume [F (1, 51)=4.03, p=0.05], and significantly increased rate of cortical thinning [F (1,52)=5.11, p=0.028)] at a mean difference of 0.84% [95% CI (0.10, 1.59)] in the left lateral orbitofrontal region over the 3-year period. In patients, greater reduction in putamen volume over time was associated with lower cumulative antipsychotic medication dose (r=0.49, p=0.01), and increasing lateral ventricular volume over time was associated with worsening negative symptoms (r=0.41, p=0.04) and poorer global functioning (r= -0.41, p=0.04). This study demonstrates localised progressive structural abnormalities in the cortico-striato-thalamo-cortical circuit after the onset of psychosis, with increasing ventricular volume noted as a neuroanatomical marker of poorer clinical and functional outcome.

Procognitive Effects of Antidepressants and Other Therapeutic Agents in Major Depressive Disorder: A Systematic Review.

OBJECTIVE: To review the efficacy of antidepressants and other therapeutic agents for the treatment of cognitive impairment in adults with major depressive disorder (MDD). DATA SOURCES: We conducted a database search of MEDLINE, PsycINFO, and Embase through Ovid on May 7, 2019. The year of publication was not restricted. The search terms "Major Depressive Disorder," "depress*," "cognit*," and "therapeutics" were used. STUDY SELECTION: The studies included in this review were clinical trials of antidepressants and other therapeutic agents in MDD populations. Participants were aged between 18 and 65 years and had a DSM-III, -IV, or -5 diagnosis of MDD. In total, 2,045 research papers were screened, 53 full-text articles were assessed, and 26 articles were eligible to be included in this systematic review. DATA EXTRACTION: The data and quality of research papers were assessed and screened by 2 independent reviewers. Discrepancies were resolved through a third reviewer. RESULTS: Overall, studies demonstrated that tricyclic antidepressants do not have procognitive effects, while vortioxetine and bupropion have demonstrated procognitive effects in MDD populations relative to selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. Several non-antidepressant agents, such as modafinil, amphetamines, and erythropoietin, have also demonstrated significant positive effects on cognition in depression. CONCLUSIONS: Present-day antidepressants and other agents have demonstrated procognitive effects in MDD, but the findings between various agents are mixed. Further research looking at objective measures of cognitive performance would be helpful to obtain more definitive results regarding the efficacy of therapeutics for cognitive impairment in MDD.

Cognitive and Clinical Predictors of Prefrontal Cortical Thickness Change Following First-Episode of Psychosis.

The association of neuroanatomical progression with cognitive and clinical deterioration after first-episode of psychosis remains uncertain. This longitudinal study aims to assess whether i)impaired executive functioning and emotional intelligence at first presentation are associated with progressive prefrontal and orbitofrontal cortical thinning ii)negative symptom severity is linked to progressive prefrontal cortical thinning. 1.5T MRI images were acquired at baseline and after 3.5 years for 20 individuals with first-episode psychosis and 18 controls. The longitudinal pipeline of Freesurfer was employed to parcellate prefrontal cortex at two time points. Baseline cognitive performance was compared between diagnostic groups using MANCOVA. Partial correlations investigated relationships between cognition and negative symptoms at baseline and cortical thickness change over time. Patients displayed poorer performance than controls at baseline in working memory, reasoning/problem solving and emotional intelligence. In patients, loss of prefrontal and orbitofrontal thickness over time was predicted by impaired working memory and emotional intelligence respectively at baseline. Moreover, exploratory analyses revealed that the worsening of negative symptoms over time was significantly related to prefrontal cortical thinning. Results indicate that specific cognitive deficits at the onset of psychotic illness are markers of progressive neuroanatomical deficits and that worsening of negative symptoms occurs with prefrontal thickness reduction as the illness progresses.

Alexithymia and self-harm: A review of nonsuicidal self-injury, suicidal ideation, and suicide attempts.

INTRODUCTION: Suicide attempts are a significant global public health concern. Research into non-traditional factors, such as the presence of alexithymia, may shed light on the prediction of suicidal behaviours, which can aid intervention and prevention strategies. To ascertain whether alexithymia is a unique risk factor for suicide attempts, this article reviews the evidence on alexithymia related to suicidal ideation, attempts, and non-suicidal self-injury (NSSI). METHODS: A literature search was conducted for original articles examining the general and psychiatric populations. RESULTS: There is consistent evidence linking alexithymia with suicidal ideation and NSSI, but inconsistent evidence linking it to suicide attempts. CONCLUSION: The relationship between alexithymia and suicidality seems to differ based on whether the research focuses on suicidal ideation, suicide attempts, or NSSI. The relationship between alexithymia and suicidality can be understood within the context of multiple code theory and childhood trauma. Future research should explore the whether alexithymia can reliably distinguish between those with a single attempt and those with multiple suicide attempts as well as alexithymia levels pre- and post-intervention with suicide-related behavior as outcomes in treatment studies.

Examining suicide-related presentations to the emergency department.

OBJECTIVE: Although the Emergency Department (ED) is a frequent point of contact for individuals with suicide-related behaviour (SRB) or ideation, there is limited literature specifically examining presentations to the ED for SRB. This review examines the international literature published in North America, the United Kingdom and Australia relating to presentations to the ED for SRB, with focus on high-risk groups, screening tools used in the ED, and difficulties in classifying ED presentations of SRB. METHOD: The database PubMed was searched using relevant terms, and national health care administrative data were reviewed. RESULTS: Psychiatric history, substance use, and lower socioeconomic status were all found to be associated with higher rates of ED presentations for SRB. Limited research exists around ED presentations of SRB by particular high-risk groups, including lesbian, gay, bisexual, and transgender populations and Indigenous peoples. Individuals who present to EDs for SRB are often chronic users of EDs and have a high rate of repeat self-harm and death by suicide. CONCLUSION: These findings suggest that EDs could serve as a focal point for suicide treatment interventions. Deepening our understanding of ED presentations for SRB could inform further development and implementation of interventions to reduce death by suicide.

Childhood maltreatment and cognitive functioning in patients with major depressive disorder: a CAN-BIND-1 report.

BACKGROUND: Patients with major depressive disorder (MDD) display cognitive deficits in acutely depressed and remitted states. Childhood maltreatment is associated with cognitive dysfunction in adults, but its impact on cognition and treatment related cognitive outcomes in adult MDD has received little consideration. We investigate whether, compared to patients without maltreatment and healthy participants, adult MDD patients with childhood maltreatment display greater cognitive deficits in acute depression, lower treatment-associated cognitive improvements, and lower cognitive performance in remission. METHODS: Healthy and acutely depressed MDD participants were enrolled in a multi-center MDD predictive marker discovery trial. MDD participants received 16 weeks of standardized antidepressant treatment. Maltreatment and cognition were assessed with the Childhood Experience of Care and Abuse interview and the CNS Vital Signs battery, respectively. Cognitive scores and change from baseline to week 16 were compared amongst MDD participants with (DM+, n = 93) and without maltreatment (DM-, n = 90), and healthy participants with (HM+, n = 22) and without maltreatment (HM-, n = 80). Separate analyses in MDD participants who remitted were conducted. RESULTS: DM+ had lower baseline global cognition, processing speed, and memory v. HM-, with no significant baseline differences amongst DM-, HM+, and HM- groups. There were no significant between-group differences in cognitive change over 16 weeks. Post-treatment remitted DM+, but not remitted DM-, scored significantly lower than HM- in working memory and processing speed. CONCLUSIONS: Childhood maltreatment was associated with cognitive deficits in depressed and remitted adults with MDD. Maltreatment may be a risk factor for more severe and persistent cognitive deficits in adult MDD.

The Potential Procognitive Effects of Modafinil in Major Depressive Disorder: A Systematic Review.

OBJECTIVE: To assess the efficacy of modafinil, a wakefulness-promoting drug, in major depressive disorder (MDD), with a specific focus on the putative procognitive effects of modafinil. DATA SOURCES: A database search of MEDLINE, PsycINFO, and Embase was conducted. No date limits were applied (the end date of the search was October 26, 2018), and only articles in English were included. The following search terms were used: modafinil, depression, depress*, major depressive disorder, cognition, cognitive dysfunction, and cogniti*. STUDY SELECTION: Studies included were placebo-controlled or open-label trials of modafinil in MDD populations. Participants had to be diagnosed with MDD via DSM-IV or DSM-5 criteria, and no other interventions other than standard antidepressant treatment could be used in the trial. Overall, 540 articles were screened, 22 full-text research articles for inclusion criteria were assessed, and 12 studies were included in this review. DATA EXTRACTION: Two independent reviewers extracted data and assessed the quality of publications. RESULTS: Modafinil was associated with improvements in executive functioning after 4 weeks of open-label adjunctive treatment in currently depressed participants. Furthermore, in a placebo-controlled study of remitted MDD participants, modafinil led to rapid improvements in episodic and working memory after a single dose. There were contradictory findings on the subjective effects of modafinil on concentration. CONCLUSIONS: Modafinil shows preliminary evidence of alleviating specific cognitive symptoms in MDD patients, especially in the short term. However, more research using placebo-controlled longitudinal designs is needed to assess the benefits of modafinil, as there are very few studies addressing modafinil and cognition in MDD.