Temporal prediction of suicidal ideation in an ecological momentary assessment study with recurrent neural networks.

INTRODUCTION: Ecological Momentary Assessment (EMA) holds promise for providing insights into daily life experiences when studying mental health phenomena. However, commonly used mixed-effects linear statistical models do not fully utilize the richness of the ultidimensional time-varying data that EMA yields. Recurrent Neural Networks (RNNs) provide an alternative data analytic method to leverage more information and potentially improve prediction, particularly for non-normally distributed outcomes. METHODS: As part of a broader research study of suicidal thoughts and behavior in people with borderline personality disorder (BPD), eighty-four participants engaged in EMA data collection over one week, answering questions multiple times each day about suicidal ideation (SI), stressful events, coping strategy use, and affect. RNNs and mixed-effects linear regression models (MEMs) were trained and used to predict SI. Root mean squared error (RMSE), mean absolute percent error (MAPE), and a pseudo-R2 accuracy metric were used to compare SI prediction accuracy between the two modeling methods. RESULTS: RNNs had superior accuracy metrics (full model: RMSE = 3.41, MAPE = 42 %, pseudo-R2 = 26 %) compared with MEMs (full model: RMSE = 3.84, MAPE = 56 %, pseudo-R2 = 16 %). Importantly, RNNs showed significantly more accurate prediction at higher values of SI. Additionally, RNNs predicted, with significantly higher accuracy, the SI scores of participants with depression diagnoses and of participants with higher depression scores at baseline. CONCLUSION: In this EMA study with a moderately sized sample, RNNs were better able to learn and predict daily SI compared with mixed-effects models. RNNs should be considered as an option for EMA analysis.

Stress Response in Suicide Attempters with Borderline Personality Disorder: The Role of Behavioral Problems in Childhood.

Objective: Suicidal individuals are a heterogeneous population and may differ in systematic ways in their responsiveness to stress. The primary aim of the present study was to identify whether a different pattern of physiological stress response exists among adult suicide attempters with a history of behavioral problems during childhood and adolescence, which earlier studies have related to both decreased activity of the HPA axis and to suicidal behaviors. Method: Seventy-eight participants with Borderline Personality Disorder were assessed using the SCID-II, and completed self-report measures assessing their history of suicide attempts, history of aggressive behaviors, depressive symptoms, history of lifetime abuse and demographics. Participants' cortisol reactivity was assessed using the Trier Social Stress Test. Results: Analyses indicated that suicide attempters with a history of behavioral problems in youth (n = 30) had a significantly lower response to stress than both suicide attempters without such a history (n = 26) and non-attempters (n = 22), when controlling for lifetime history of abuse. The groups did not differ in basal cortisol. Conclusions: These findings suggest a unique subtype of suicide attempter among those with Borderline Personality Disorder, characterized by a blunted physiological stress response.

Variability in Suicidal Ideation is Associated with Affective Instability in Suicide Attempters with Borderline Personality Disorder.

Objective: Suicidal ideation (SI) is heterogeneous with different patterns and risk factors. SI can be persistent with stable severity, but may also fluctuate rapidly over a short period of time. The latter pattern is likely associated with affective instability and may consist of activation of SI at times of stress, that then subside. Although affective instability is a hallmark of borderline personality disorder (BPD), little is known about SI variability in BPD. We hypothesized that SI variability would be associated with affective instability in BPD suicide attempters. Method: Sample included 38 females with BPD and history of suicidal behavior. SI was assessed over 1 week using ecological momentary assessment (EMA) at six epochs daily. The relationship between SI variability (i.e., change of SI from one epoch to another) and SI severity (i.e., average scores across epochs), and affective instability, assessed using the Affective Lability Scale (ALS), were examined. Possible confounding effects of depression severity and impulsiveness were tested. Results: Participants demonstrated high ALS scores and wide range of SI variability. ALS scores predicted SI variability, even after controlling for depression severity. Although ALS also predicted SI severity, this association was driven by depression severity. ALS did not correlate with impulsiveness score. Conclusions: Affective instability may predict SI variability in BPD suicide attempters independent of depression severity. This supports our model of suicidal subgroups with different constellations of clinical aspects and risk factors. Future studies could examine these associations in larger samples and different populations to determine implications for suicide prevention.

Perceptions of Adjunctive Mindfulness-Based Cognitive Therapy to Prevent Suicidal Behavior Among High Suicide-Risk Outpatient Participants.

BACKGROUND: Few investigations of patient perceptions of suicide prevention interventions exist, limiting our understanding of the processes and components of treatment that may be engaging and effective for high suicide-risk patients. AIMS: Building on promising quantitative data that showed that adjunct mindfulness-based cognitive therapy to prevent suicidal behavior (MBCT-S) reduced suicidal thinking and depression among high suicide-risk patients, we subjected MBCT-S to qualitative inspection by patient participants. METHOD: Data were provided by 15 patients who completed MBCT-S during a focus group and/or via a survey. Qualitative data were coded using thematic analysis. Themes were summarized using descriptive analysis. RESULTS: Most patients viewed the intervention as acceptable and feasible. Patients attributed MBCT-S treatment engagement and clinical improvement to improved emotion regulation. A minority of patients indicated that factors related to the group treatment modality were helpful. A small percentage of patients found that aspects of the treatment increased emotional distress and triggered suicidal thinking. These experiences, however, were described as fleeting and were not linked to suicidal behavior. LIMITATIONS: The sample size was small. CONCLUSION: Information gathered from this study may assist in refining MBCT-S and treatments to prevent suicidal behavior among high suicide-risk patients generally.

The Zero Suicide Model: Applying Evidence-Based Suicide Prevention Practices to Clinical Care.

Suicide is reaching epidemic proportions, with over 44,000 deaths by suicide in the US, and 800,000 worldwide in 2015. This, despite research and development of evidence-based interventions that target suicidal behavior directly. Suicide prevention efforts need a comprehensive approach, and research must lead to effective implementation across public and mental health systems. A 10-year systematic review of evidence-based findings in suicide prevention summarized the areas necessary for translating research into practice. These include risk assessment, means restriction, evidence-based treatments, population screening combined with chain of care, monitoring, and follow-up. In this article, we review how suicide prevention research informs implementation in clinical settings where those most at risk present for care. Evidence-based and best practices address the fluctuating nature of suicide risk, which requires ongoing risk assessment, direct intervention and monitoring. In the US, the National Action Alliance for Suicide Prevention has put forth the Zero Suicide (ZS) Model, a framework to coordinate a multilevel approach to implementing evidence-based practices. We present the Assess, Intervene and Monitor for Suicide Prevention model (AIM-SP) as a guide for implementation of ZS evidence-based and best practices in clinical settings. Ten basic steps for clinical management model will be described and illustrated through case vignette. These steps are designed to be easily incorporated into standard clinical practice to enhance suicide risk assessment, brief interventions to increase safety and teach coping strategies and to improve ongoing contact and monitoring of high-risk individuals during transitions in care and high risk periods.

Teaching Dialectical Behavior Therapy to Psychiatry Residents: The Columbia Psychiatry Residency DBT Curriculum.

OBJECTIVE: Dialectical behavior therapy (DBT) is an evidence-based psychosocial treatment with efficacy in reducing self-harm behaviors in borderline personality disorder (BPD). This study describes and evaluates a clinical curriculum to teach DBT to psychiatry residents, developed at a large urban university hospital. The curriculum objectives are to (1) have psychiatry residents achieve basic understanding of DBT theory and clinical skill, (2) increase residents' ability and confidence in treating self-harm behaviors (both suicidal behavior and non-suicidal self-injury), and (3) enhance residents' willingness to treat individuals with BPD. METHODS: In addition to a 6-week didactic course on DBT offered to all residents (n = 62), 25 elected to enroll in a year-long DBT clinical training curriculum over the course of a 5-year period. The DBT clinical training consisted of 15 h of additional didactics, ongoing conduct of individual therapy and group DBT skills training, videotaping of individual therapy sessions, and weekly supervision meetings utilizing videotape to provide feedback. Residents participating in the clinical training program videotaped baseline and later sessions, which were rated for DBT adherence. All 62 graduates of the program were surveyed regarding the impact of the training on their practice of psychiatry. RESULTS: Upon graduation, a high percentage (87 % in the curriculum and 70 % in the didactic course only) reported incorporating DBT into their psychiatry practice, as well as willingness and confidence in treating BPD and self-harm behaviors. Residents participating in the clinical training demonstrated significant improvement in their ability to utilize DBT interventions, particularly in structuring sessions, problem assessment, problem solving, and using validation and dialectical strategies. CONCLUSION: This DBT curriculum was effective in preparing psychiatrists-in-training to incorporate evidence-based practices for effective treatment of BPD and self-harm behaviors and can serve as a model for teaching DBT during psychiatry residency training. Limitations include a small sample size and lack of baseline survey measurement of attitudes for pre- and post-curriculum comparison.

Early Childhood Environment and Genetic Interactions: the Diathesis for Suicidal Behavior.

Adverse childhood experiences are associated with higher risk for suicide and suicidal behavior later in life. There are known associations between childhood trauma, particularly sexual abuse, and higher rates of suicide, non-lethal suicide attempts, and non-suicidal self-injurious behaviors in adolescence and adulthood. Emotional abuse/neglect, disrupted parental attachment, and cumulative effect of multiple forms of maltreatment, also increase risk. Yet, the causal relationship remains unclear. The diathesis-stress model provides a framework for understanding how early life adverse experiences contribute to suicide vulnerability. Current findings from the fields of biology, neurology, and genetics shed new light on mediating variables and possible causal links between early childhood trauma and suicide. In this paper, we review recent advances, particularly regarding the interaction of early life environmental adverse events with genetics factors, that increase the diathesis for psychological traits are associated with subsequent deliberate self-harm behaviors.

Affective lability and difficulties with regulation are differentially associated with amygdala and prefrontal response in women with Borderline Personality Disorder.

The present neuroimaging study investigated two aspects of difficulties with emotion associated with Borderline Personality Disorder (BPD): affective lability and difficulty regulating emotion. While these two characteristics have been previously linked to BPD symptomology, it remains unknown whether individual differences in affective lability and emotion regulation difficulties are subserved by distinct neural substrates within a BPD sample. To address this issue, sixty women diagnosed with BPD were scanned while completing a task that assessed baseline emotional reactivity as well as top-down emotion regulation. More affective instability, as measured by the Affective Lability Scale (ALS), positively correlated with greater amygdala responses on trials assessing emotional reactivity. Greater difficulties with regulating emotion, as measured by the Difficulties with Emotion Regulation Scale (DERS), was negatively correlated with left Inferior Frontal Gyrus (IFG) recruitment on trials assessing regulatory ability. These findings suggest that, within a sample of individuals with BPD, greater bottom-up amygdala activity is associated with heightened affective lability. By contrast, difficulties with emotion regulation are related to reduced IFG recruitment during emotion regulation. These results point to distinct neural mechanisms for different aspects of BPD symptomology.

Suicide attempters with Borderline Personality Disorder show differential orbitofrontal and parietal recruitment when reflecting on aversive memories.

Suicidal behavior and difficulty regulating emotions are hallmarks of Borderline Personality Disorder (BPD). This study examined neural links between emotion regulation and suicide risk in BPD. 60 individuals with BPD (all female, mean age = 28.9 years), 46 of whom had attempted suicide, completed a fMRI task involving recalling aversive personal memories. Distance trials assessed the ability to regulate emotion by recalling memories from a third-person, objective viewpoint. Immerse trials assessed emotional reactivity and involved recalling memories from a first-person perspective. Behaviorally, both groups reported less negative affect on Distance as compared to Immerse trials. Neurally, two sets of findings were obtained. The first reflected differences between attempters and non-attempters. When immersing and distancing, attempters showed elevated recruitment of lateral orbitofrontal cortex, a brain region implicated in using negative cues to guide behavior. When distancing, attempters showed diminished recruitment of the precuneus, a region implicated in memory recall and perspective taking. The second set of findings related to individual differences in regulation success - the degree to which individuals used distancing to reduce negative affect. Here, we observed that attempters who successfully regulated exhibited precuneus recruitment that was more similar to non-attempters. These data provide insight into mechanisms underlying suicide attempts in BPD. Future work may examine if these findings generalize to other diagnoses and also whether prior findings in BPD differ across attempters and non-attempters.

Improvements in Executive Attention, Rumination, Cognitive Reactivity, and Mindfulness Among High-Suicide Risk Patients Participating in Adjunct Mindfulness-Based Cognitive Therapy: Preliminary Findings.

OBJECTIVE: To test changes to cognitive functioning among high-suicide risk outpatients participating in an adjunct mindfulness-based intervention combining mindfulness-based cognitive therapy and safety planning (MBCT-S). DESIGN: Ten outpatients with a 6-month history of suicide attempt or active suicidal ideation plus suicidal ideation at study entry received 9 weeks of adjunct group-based MBCT-S. Executive attention, sustained attention, visual memory, and semantic memory encoding were measured by neuropsychological assessment. Rumination, mindfulness, cognitive reactivity (defined as the tendency towards depressogenic information processing and thought content in response to mild mood deterioration), and self-compassion were assessed using self-report measures. Changes in pre- to post-treatment functioning on these constructs were analyzed by using dependent t-tests. Where significant improvements were found, correlations between changes to cognitive functioning and depression and suicidal ideation during treatment were calculated. RESULTS: Executive attention improved with MBCT-S in high-suicide risk outpatients (Stroop interference effect = 0.39 [standard deviation (SD), 27] at baseline and 0.27 (SD, 0.15) at post-treatment, t[9] = 2.35, p = 0.04, d = 0.75). One mindfulness skill, acting with awareness, increased with MBCT-S (average change in Five Facet Mindfulness Questionnaire-acting with awareness subscale score with treatment, 3.3 [SD, 3.0], t[9] = 3.46, p < 0.01, d = 1.1). Self-reported rumination and cognitive reactivity to suicidality and hopelessness decreased among participants (Ruminative Responses Brooding subscale score change, -3.4 [SD, 1.1], t[9] = 10, p < 0.001, d = 3.2; Leiden Index of Depression Sensitivity-Revised-Hopelessness/Suicidality subscale score change, -3 [SD, 2.7], t[9] = 3.56, p < 0.01, d = 1.1). None of these changes were related to improvements in depression or reductions in suicidal ideation during treatment. CONCLUSIONS: Findings from the present pilot study suggest that treatment with MBCT-S may improve cognitive deficits specific to suicide ideators and attempters among depressed patients. Future controlled trials using follow-up assessments are needed to determine the specificity of these improvements in cognitive functioning to MBCT-S and their durability and to formally test whether the observed improvements in cognitive functioning explain MBCT-S treatment gains.

Familial transmission of parental mood disorders: unipolar and bipolar disorders in offspring.

OBJECTIVES: Offspring of depressed parents are at increased risk for psychiatric disorders. Although bipolar disorder (BD) and major depressive disorder (MDD) are both found in the same families, it is not clear whether transmission to offspring of BD or MDD tends to occur from parents with the same mood disorder subtype. Our primary hypothesis was that the offspring of parents with BD would be at increased risk for BD and other comorbid disorders common to BD, such as anxiety and substance use, relative to the offspring of parents with MDD. The offspring of parents with BD versus those with MDD were also hypothesized to be at greater risk for externalizing disorders (i.e., conduct disorder, attention-deficit hyperactivity disorder, or antisocial personality disorder). METHODS: Parents (n = 320) with mood disorders and their offspring (n = 679) were studied. Adult offspring were administered the Structured Clinical Interview for DSM-IV Axis I Disorders to establish the presence of psychopathology. Offspring aged 10-18 years were assessed using the School Aged Schedule for Affective Disorders and Schizophrenia, Present and Lifetime version, and parents of children under the age of ten completed the Child Behavioral Checklist. Data were examined using Cox proportional hazard regression. RESULTS: There was no difference in hazard of mood disorders in the offspring of parents with BD as compared to the offspring of parents with MDD. However, a number of other parent and offspring characteristics increased the risk of mood, anxiety, externalizing, and substance use disorders in the offspring, including self-reported childhood abuse in the parent or offspring, offspring impulsive aggression, and the age at onset of parental mood disorder. CONCLUSIONS: Mood disorders are highly familial, a finding that appears independent of whether the parent's condition is unipolar or bipolar, suggesting considerable overlap in the heritability of MDD and BD. Although parental characteristics had a limited influence on the risk of offspring psychopathology, reported childhood adversity, be it in the parent or child, is a harbinger of negative outcomes. These risk factors extend previous findings, and are consistent with diathesis-stress conceptualizations.

Higher executive control and visual memory performance predict treatment completion in borderline personality disorder.

BACKGROUND: Non-completion of a prescribed course of treatment occurs in 20-60% of individuals diagnosed with borderline personality disorder (BPD). While symptom severity, personality traits and environmental factors have been implicated as predictors of treatment non-completion (TNC), there have been no studies of neuropsychological predictors in this population. METHODS: From a randomized controlled trial, a subsample of 31, unmedicated outpatients diagnosed with BPD with recent self-injurious behavior was assessed on 5 neuropsychological domains. Patients were also assessed for general IQ, demographic and other salient clinical variables. Patients were randomized to one of four treatment conditions, which lasted up to 1 year. Number of weeks in treatment (WIT) up to 1 year was utilized as the index of TNC. RESULTS: Thirty-three percent of the subsample (n = 12) did not complete 1 year of treatment. However, more WIT were predicted by better baseline executive control (Trails B; p < 0.01) and visual memory performance (Benton visual retention; p < 0.001); other neuropsychological domains did not predict WIT. CONCLUSION: In the treatment of outpatients with BPD, better executive control and visual memory performance predict more WIT. Assessing and addressing these neurocognitive factors in treatment may reduce TNC in this high-risk population.

Familial transmission of suicidal behavior: factors mediating the relationship between childhood abuse and offspring suicide attempts.

BACKGROUND: Self-reported childhood sexual abuse is associated with major depression and with suicidal behavior. The current study investigates the relationship between reported childhood abuse and the familial transmission of suicidal behavior and other related risk factors. METHOD: 507 offspring of 271 parent probands with DSM-IV major depressive disorder were compared according to the reported childhood abuse history on demographic, diagnostic, and clinical variables related to risk for suicidal behavior. Both self-report and clinical interview measures assessed history of childhood physical and sexual abuse. The study was conducted from May 1997 to February 2004. RESULTS: Reported childhood sexual abuse, but not physical abuse, in the proband correlated with suicide attempts, posttraumatic stress disorder, earlier onset of major depressive disorder, higher levels of impulsivity, and greater likelihood of childhood sexual abuse in the offspring and was rarely perpetrated by the affected parent. A reported history of childhood physical abuse was related to more lifetime aggression in the offspring. CONCLUSIONS: Reported childhood sexual abuse is a risk factor for suicidal behavior in parent and offspring. Transmission of suicide risk across generations is related to the familial transmission of sexual abuse and impulsivity. Sexual abuse is not directly transmitted by the victim to the next generation and may be related to family dynamics related to sexual abuse.

Adverse childhood experiences and suicidal behavior.

Early experiences of physical and sexual abuse and parental neglect are risk factors for suicidal behavior in adolescence and adulthood. This article reviews the correlational, retrospective findings, emphasizing the more recent prospective and familial transmission studies that explore the factors mediating the relationship between childhood abuse/neglect and suicidal behavior. Related areas of research such as protective factors and the personality traits that are possible risk factors that mediate this relationship are reviewed. Research on the neurobiologic correlates of trauma that might have implications for understanding suicidal behavior is discussed, and several models for the study of the relationship between childhood adverse experiences and suicidal behavior are described.

Classification trees distinguish suicide attempters in major psychiatric disorders: a model of clinical decision making.

OBJECTIVE: Determining risk for a suicide attempt in psychiatric patients requires assessment of multiple risk factors and knowledge of their relative importance. Classification and regression tree (CART) analysis generates decision trees that select the variables that perform best in identifying the group of interest and model clinical decision making. Hypothetical decision trees to identify recent and remote suicide attempters, weighted to increase sensitivity, were generated for psychiatric patients using correlates of past suicidal behavior. METHOD: Correlates of past suicide attempts were identified in 408 patients with mood, schizophrenia spectrum, or personality disorders (DSM-IV). Correlated variables were entered into recursive partitioning statistical models to generate equally weighted and unequally weighted hypothetical decision trees for distinguishing recent ( 250 days prior to study) suicide attempters from nonattempters. The study was conducted from December 1989 to November 1998. RESULTS: In equally weighted trees, a recent past suicide attempt was best predicted by current suicidal ideation (sensitivity = 56%, specificity = 91%, positive predictive value = 69%), and no adequate model was found for remote attempts. In unequally weighted models, recent attempters were identified by suicidal ideation and comorbid borderline personality disorder (sensitivity = 73%, specificity = 80%, positive predictive value = 58%). Remote attempters were identified by lifetime aggression and current subjective depression (sensitivity = 89%, specificity = 36%, positive predictive value = 44%). CONCLUSION: Current suicidal ideation is the best indicator of a recent suicide attempt in psychiatric patients. Indicators of a remote attempt are aggressive traits and current depression. Weighted decision trees can improve sensitivity and miss fewer attempters but with a cost in specificity.

Borderline personality disorder, stigma, and treatment implications.

Borderline personality disorder (BPD) is often viewed in negative terms by mental health practitioners and the public. The disorder may have a stigma associated with it that goes beyond those associated with other mental illnesses. The stigma associated with BPD may affect how practitioners tolerate the actions, thoughts, and emotional reactions of these individuals. It may also lead to minimizing symptoms and overlooking strengths. In society, people tend to distance themselves from stigmatized populations, and there is evidence that some clinicians may emotionally distance themselves from individuals with BPD. This distancing may be especially problematic in treating patients with BPD; in addition to being unusually sensitive to rejection and abandonment, they may react negatively (e.g., by harming themselves or withdrawing from treatment) if they perceive such distancing and rejection. Clinicians' reactivity may be self-protective in response to actual behavior associated with the pathology. As a consequence, however, the very behaviors that make it difficult to work with these individuals contribute to the stigma of BPD. In a dialectical relationship, that stigma can influence the clinician's reactivity, thereby exacerbating those same negative behaviors. The result is a self-fulfilling prophecy and a cycle of stigmatization to which both patient and therapist contribute. The extent to which therapist distancing is influenced by stigma is an important question that highlights the possibility that the stigma associated with BPD can have an independent contribution to poor outcome with this population. A final issue concerns the available means for identifying and limiting the impact of stigmatization on the treatment of individuals with BPD.

Interpersonal precipitants and suicide attempts in borderline personality disorder.

Borderline personality disorder (BPD) is often characterized by multiple low lethality suicide attempts triggered by seemingly minor incidents, and less commonly by high lethality attempts that are attributed to impulsiveness or comorbid major depression. The relationships among life events, impulsiveness, and type of suicidal behavior has hardly been studied in BPD and mood disorders. This study compared depressed attempters with and without BPD to identify specific suicide precipitants and risk factors in BPD and their relationship to severity of suicidal behavior. Attempters with comorbid BPD and major depressive disorder (MDD) had a higher number of lifetime suicide attempts; made their first attempt at a younger age; reported more interpersonal triggers; and had higher levels of lifetime aggression, hostility, and impulsivity, compared with attempters with major depression only. Environmental triggers of attempts in BPD are more likely to be interpersonal stressors. Lethality of attempts in BPD plus MDD is equal to that in MDD only, indicating that the seriousness of precipitants is unrelated to the lethality of the suicidal behavior. The differences between groups suggest that risk assessment and treatment should target both depression and personality disorder in those with combined illness.

Clinical impact of a 2-week psychotropic medication washout in unipolar depressed inpatients.

BACKGROUND: Short-term discontinuation of psychiatric medications is required in many types of research studies. Yet there are few studies of the clinical impact of psychotropic discontinuation. We studied the impact of a short-term medication washout in unipolar depressed patients consecutively admitted to hospital for neuroimaging and cerebrospinal fluid (CSF) studies. METHOD: Patients (n=51) with unipolar depression who were taking antidepressant or mood stabilizing medication at or within 1 week of admission, and who had not been responding satisfactorily, were assessed for severity of psychopathology within 1 week of hospital admission and 41 of the group were reassessed following an approximately 2-week medication washout. RESULTS: On average, patients remained stable during the washout or improved on clinical measures. No serious adverse clinical changes were observed. LIMITATIONS: Potential sample bias, small sample size. CONCLUSION: The results suggest that similar studies can be conducted without causing undue worsening of symptoms. The benefit of medication washout may be related to the fact that many of the patients had been responding poorly to the medication they were taking. There is a need for further research on the effects of medication washout, for example in outpatients or those who are responding well to treatment, but have intolerable side-effects.

Prolactin response to fenfluramine administration in patients with unipolar and bipolar depression and healthy controls.

The hormonal response to the serotonin releasing agent/uptake inhibitor fenfluramine has been used as an indicator of central serotonin system function. The serotonergic system plays an important role in the etiology and pathogenesis of mood disorders. We compared the prolactin response to fenfluramine administration in unipolar depressed patients (major depressive disorder), depressed patients with bipolar disorder, and healthy controls. We found a trend towards a blunted prolactin response in depressed patients compared to healthy controls, after controlling for sex, family history, family history-by-gender interaction, and baseline levels. There was no significant difference between unipolar and bipolar patients in the baseline prolactin levels or the response to the fenfluramine administration. We also found a negative correlation between aggression and impulsivity scores and prolactin responses in subgroup with unipolar but not bipolar depression. Female patients with unipolar depression who had first-degree relatives with unipolar depression and normal controls had significantly higher prolactin responses than female patients with unipolar depression who did not have first-degree relatives with unipolar depression. The lack of difference in the response to fenfluramine administration between unipolar and bipolar depressed patients may indicate that overall serotonergic function in unipolar and bipolar depressed patients is similarly impaired.

Association of comorbid posttraumatic stress disorder and major depression with greater risk for suicidal behavior.

OBJECTIVE: Posttraumatic stress disorder (PTSD) increases the risk of suicidal behavior; a major depressive episode also increases the risk for suicidal behavior. The authors' goal was to examine the effect of comorbid PTSD and major depressive episode on suicidal behavior. METHOD: Inpatients with a diagnosis of major depressive episode (N=156) were assessed for PTSD, suicidal behavior, and clinical risk factors for suicidal acts. RESULTS: Patients with comorbid major depressive episode and PTSD were more likely to have attempted suicide, and women with both disorders were more likely to have attempted suicide than men with both disorders. Cluster B personality disorder and PTSD were independently related to history of suicide attempts. CONCLUSIONS: The greater rate of suicide attempts among patients with comorbid PTSD and major depressive episode was not due to differences in substance use, childhood abuse, or cluster B personality disorders.