Suicidal behavior across a broad range of psychiatric disorders.

Suicide is a leading cause of death worldwide. In 2020, some 12.2 million Americans seriously contemplated suicide, 3.2 million planned suicide attempts, and 1.2 million attempted suicide. Traditionally, the approach to treating suicidal behavior (SB) has been to treat the "underlying" psychiatric disorder. However, the number of diagnoses associated with SB is considerable. We could find no studies describing the range of disorders reported to be comorbid with SB. This narrative review summarizes literature documenting the occurrence of SB across the lifespan and the full range of psychiatric diagnoses, not only BPD and those that comprise MDE, It also describes the relevance of these observations to clinical practice, research, and nosology. The literature searches contained the terms "suicid*" and each individual psychiatric diagnosis and identified 587 studies. We did not include case reports, case series, studies only addressing suicidal ideation or non-suicidal self-injury (NSSI), studies on self-harm, not distinguishing between SB and NSSI and studies that did not include any individuals that met criteria for a specific DSM-5 diagnosis (n = 366). We found that SB (suicide and/or suicide attempt) was reported to be associated with 72 out of 145 diagnoses, although data quality varied. Thus, SB is not exclusively germane to Major Depressive Episode (MDE) and Borderline Personality Disorder (BPD), the only conditions for which it is a diagnostic criterion. That SB co-occurs with so many diagnoses reinforces the need to assess current and past SB regardless of diagnosis, and supports the addition of charting codes to the DSM-5 to indicate current or past SB. It also comports with new data that specific genes are associated with SB independent of psychiatric diagnoses, and suggests that SB should be managed with specific suicide prevention interventions in addition to treatments indicated for co-occurring diagnoses. SB diagnostic codes would help researchers and clinicians document and measure SB's trajectory and response to treatment over time, and, ultimately, help develop secondary and tertiary prevention strategies. As a separate diagnosis, SB would preclude situations in which a potentially life-threatening behavior is not accounted for by a diagnosis, a problem that is particularly salient when no mental disorder is present, as is sometimes the case.

Cognitive, Disability, and Treatment Outcome Implications of Symptom-Based Phenotyping in Late-Life Depression.

OBJECTIVE: Late-life depression is associated with substantial heterogeneity in clinical presentation, disability, and response to antidepressant treatment. We examined whether self-report of severity of common symptoms, including anhedonia, apathy, rumination, worry, insomnia, and fatigue were associated with differences in presentation and response to treatment. We also examined whether these symptoms improved during treatment with escitalopram. DESIGN: Eighty-nine older adults completed baseline assessments, neuropsychological testing and providing self-reported symptom and disability scales. They then entered an 8-week, placebo-controlled randomized trial of escitalopram, and self-report scales were repeated at the trial's end. Raw symptom scale scores were combined into three standardized symptom phenotypes and models examined how symptom phenotype severity was associated with baseline measures and depression improvement over the trial. RESULTS: While rumination/worry appeared independent, severity of apathy/anhedonia and fatigue/insomnia were associated with one another and with greater self-reported disability. Greater fatigue/insomnia was also associated with slower processing speed, while rumination/worry was associated with poorer episodic memory. No symptom phenotype severity score predicted a poorer overall response to escitalopram. In secondary analyses, escitalopram did not improve most phenotypic symptoms more than placebo, aside for greater reductions in worry and total rumination severity. CONCLUSION: Deeper symptom phenotype characterization may highlight differences in the clinical presentation of late-life depression. However, when compared to placebo, escitalopram did not improve many of the symptoms assessed. Further work is needed to determine whether symptom phenotypes inform longer-term course of illness, and which treatments may best benefit specific symptoms.

Biomarkers of Suicide Attempt Behavior: Towards a Biological Model of Risk.

PURPOSE OF REVIEW: The rising suicide rate in the USA will not be reversed without improved risk assessment and prevention practices. To date, the best method for clinicians to assess a patient's risk for suicide is screening for past suicide attempts in the patient and their family. However, neuroimaging, genomic, and biochemical studies have generated a body of findings that allow description of an initial heuristic biological model for suicidal behavior that may have predictive value. RECENT FINDINGS: We review studies from the past 3 years examining potential biological predictors of suicide attempt behavior. We divide findings into two major categories: (1) structural and functional brain imaging findings and (2) biochemical and genomic findings encompassing several systems, including major neurotransmitters (serotonin, catecholamines, GABA, and glutamate), the hypothalamic pituitary adrenal (HPA) axis, the inflammasome, lipids, and neuroplasticity. The biomarkers that appear promising for assessing suicide risk in clinical settings include indices of serotonergic function, inflammation, neuronal plasticity, and lipids.

Toward a biosignature for suicide.

OBJECTIVE: Suicide, a major cause of death worldwide, has distinct biological underpinnings. The authors review and synthesize the research literature on biomarkers of suicide, with the aim of using the findings of these studies to develop a coherent model for the biological diathesis for suicide. METHOD: The authors examined studies covering a large range of neurobiological systems implicated in suicide. They provide succinct descriptions of each system to provide a context for interpreting the meaning of findings in suicide. RESULTS: Several lines of evidence implicate dysregulation in stress response systems, especially the hypothalamic-pituitary-adrenal axis, as a diathesis for suicide. Additional findings related to neuroinflammatory indices, glutamatergic function, and neuronal plasticity at the cellular and circuitry level may reflect downstream effects of such dysregulation. Whether serotonergic abnormalities observed in individuals who have died by suicide are independent of stress response abnormalities is an unresolved question. CONCLUSIONS: The most compelling biomarkers for suicide are linked to altered stress responses and their downstream effects, and to abnormalities in the serotonergic system. Studying these systems in parallel and in the same populations may elucidate the role of each and their interplay, possibly leading to identification of new treatment targets and biological predictors.

SSRI versus bupropion effects on symptom clusters in suicidal depression: post hoc analysis of a randomized clinical trial.

OBJECTIVE: Identifying the depression symptoms most closely associated with suicidal thoughts and which medications provide the fastest depression relief may help suicide prevention. METHOD: Post hoc analysis of data from a randomized, double-blind, 8-week clinical trial of the selective serotonin reuptake inhibitor paroxetine controlled release (n = 36) versus the norepinephrine-dopamine reuptake inhibitor bupropion extended release (n = 38) was conducted in patients with DSM-IV major depressive disorder and past suicide attempt or current suicidal thoughts. Treatment effects on Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory symptom clusters were compared. We hypothesized that paroxetine would demonstrate a superior effect on nonsuicidal, affective/cognitive depression symptom clusters that our prior work found to be associated with suicidal thoughts and attempts. Data were collected from February 2005 to January 2010. RESULTS: There was a treatment main effect on HDRS psychic depression (depressed mood, guilt, retardation, helpless, hopeless, worthless) (estimate = -2.2; 95% CI, -3.2 to -1.1; t67.16 = -4.01; P < .001), one of the clusters most strongly correlated to suicidal ideation. The net drug effect demonstrated that mean psychic depression score was 2.2 points lower after 1 week of paroxetine compared to bupropion treatment. The significance level of this effect was P < .001 at weeks 1 and 2, P = .012 at week 3 and P = .051 at week 4. Results for other depression scale factors were nonsignificant (P > .05). CONCLUSIONS: The results require replication but suggest a pathway by which selective serotonin reuptake inhibitor treatment may exert a stronger effect compared with norepinephrine-dopamine reuptake inhibitor treatment on reduction of suicidal thoughts during initial weeks of pharmacotherapy in these higher risk patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00429169.