Search

Few studies have examined white matter abnormalities in suicide attempters using diffusion tensor imaging (DTI). This study sought to identify white matter regions altered in individuals with a prior suicide attempt.DTI scans were acquired in 13 suicide attempters with major depressive disorder (MDD), 39 non-attempters with MDD, and 46 healthy participants (HP). Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were determined in the brain using two methods: region of interest (ROI) and tract-based spatial statistics (TBSS). ROIs were limited a priori to white matter adjacent to the caudal anterior cingulate cortex, rostral anterior cingulate cortex, dorsomedial prefrontal cortex, and medial orbitofrontal cortex.Using the ROI approach, suicide attempters had lower FA than MDD non-attempters and HP in the dorsomedial prefrontal cortex. Uncorrected TBSS results confirmed a significant cluster within the right dorsomedial prefrontal cortex indicating lower FA in suicide attempters compared to non-attempters. There were no differences in ADC when comparing suicide attempters, non-attempters and HP groups using ROI or TBSS methods.Low FA in the dorsomedial prefrontal cortex was associated with a suicide attempt history. Converging findings from other imaging modalities support this finding, making this region of potential interest in determining the diathesis for suicidal behavior.

While prominent models of suicidal behavior emphasize the hypothalamic- pituitary-adrenal (HPA) axis dysregulation, studies examining its role have yielded contradictory results. One possible explanation is that suicide attempters are a heterogeneous group and HPA axis dysregulation plays a more important role only in a subset of suicidal individuals. HPA axis dysregulation also plays a role in impulsivity and aggression. We hypothesize subgroups of attempters, based on levels of impulsivity and aggression, will differ in HPA axis dysregulation. We examined baseline cortisol, total cortisol output, and cortisol reactivity in mood disordered suicide attempters (N = 35) and non-attempters (N = 37) during the Trier Social Stress Test. Suicide attempters were divided into four subgroups: low aggression/low impulsivity, high aggression/low impulsivity, low aggression/high impulsivity, and high aggression/high impulsivity. As hypothesized, attempters and non-attempters did not differ in any cortisol measures while stress response differed based on impulsivity/aggression levels in suicide attempters, and when compared to non-attempters. Specifically, attempters with high impulsive aggression had a more pronounced cortisol response compared with other groups. This is the first study to examine the relationship between cortisol response and suicidal behavior in impulsive aggressive subgroups of attempters. These findings may help to identify a stress responsive suicidal subtype of individuals.

Significance The primary finding in this study was the dramatic primary association of brain resting-state network (RSN) connectivity abnormalities with a history of childhood trauma in major depressive disorder (MDD). Even though participants in this study were not selected for a history of trauma and the brain imaging took place decades after trauma occurrence, the scar of prior trauma was evident in functional dysconnectivity. In addition to childhood trauma, dimensions of MDD symptoms were related to abnormal network connectivity. Further, we found that a network model of MDD described within- and between-network connectivity differences from controls in multiple RSNs, including the default mode network, frontoparietal network, and attention and sensory systems., Patients with major depressive disorder (MDD) present with heterogeneous symptom profiles, while neurobiological mechanisms are still largely unknown. Brain network studies consistently report disruptions of resting-state networks (RSNs) in patients with MDD, including hypoconnectivity in the frontoparietal network (FPN), hyperconnectivity in the default mode network (DMN), and increased connection between the DMN and FPN. Using a large, multisite fMRI dataset (n = 189 patients with MDD, n = 39 controls), we investigated network connectivity differences within and between RSNs in patients with MDD and healthy controls. We found that MDD could be characterized by a network model with the following abnormalities relative to controls: (i) lower within-network connectivity in three task-positive RSNs [FPN, dorsal attention network (DAN), and cingulo-opercular network (CON)], (ii) higher within-network connectivity in two intrinsic networks [DMN and salience network (SAN)], and (iii) higher within-network connectivity in two sensory networks [sensorimotor network (SMN) and visual network (VIS)]. Furthermore, we found significant alterations in connectivity between a number of these networks. Among patients with MDD, a history of childhood trauma and current symptoms quantified by clinical assessments were associated with a multivariate pattern of seven different within- and between-network connectivities involving the DAN, FPN, CON, subcortical regions, ventral attention network (VAN), auditory network (AUD), VIS, and SMN. Overall, our study showed that traumatic childhood experiences and dimensional symptoms are linked to abnormal network architecture in MDD. Our results suggest that RSN connectivity may explain underlying neurobiological mechanisms of MDD symptoms and has the potential to serve as an effective diagnostic biomarker.

IMPORTANCE: Predicting suicidal behavior continues to be among the most challenging tasks in psychiatry. OBJECTIVES: To examine the trajectories of clinical predictors of suicide attempt (specifically, depression symptoms, hopelessness, impulsivity, aggression, impulsive aggression, and irritability) for their ability to predict suicide attempt and to compute a risk score for suicide attempts. DESIGN, SETTING, AND PARTICIPANTS: This is a longitudinal study of the offspring of parents (or probands) with mood disorders who were recruited from inpatient units at Western Psychiatric Institute and Clinic (Pittsburgh) and New York State Psychiatric Institute. Participants were recruited from July 15, 1997, to September 6, 2005, and were followed up through January 21, 2014. Probands and offspring (n = 663) were interviewed at baseline and at yearly follow-ups for 12 years. Lifetime and current psychiatric disorders were assessed, and self-reported questionnaires were administered. Model evaluation used 10-fold cross-validation, which split the entire data set into 10 equal parts, fit the model to 90% of the data (training set), and assessed it on the remaining 10% (test set) and repeated that process 10 times. Preliminary analyses were performed from July 20, 2015, to October 5, 2016. Additional analyses were conducted from July 26, 2017, to July 24, 2018. MAIN OUTCOMES AND MEASURES: The broad definition of suicide attempt included actual, interrupted, and aborted attempts as well as suicidal ideation that prompted emergency referrals during the study. The narrow definition referred to actual attempt only. RESULTS: The sample of offspring (n = 663) was almost equally distributed by sex (316 female [47.7%]) and had a mean (SD) age of 23.8 (8.5) years at the time of censored observations. Among the 663 offspring, 71 (10.7%) had suicide attempts over the course of the study. The trajectory of depression symptoms with the highest mean scores and variability over time was the only trajectory to predict suicide attempt (odds ratio [OR], 4.72; 95% CI, 1.47-15.21; P = .01). In addition, we identified the following predictors: younger age (OR, 0.82; 95% CI, 0.74-0.90; P

Objective We have previously reported higher brain serotonin 1A (5-HT1A ) autoreceptor binding in antidepressant-naive patients with Major Depressive Disorder (MDD) compared with healthy volunteers, and a decrease in binding in MDD after selective serotonin reuptake inhibitor (SSRI) treatment. This SSRI effect is also present in rodents administered SSRIs chronically. We therefore sought to determine the duration of antidepressant medication effects on 5-HT1A receptor binding after medication discontinuation. Methods Positron emission tomography (PET) imaging with the 5-HT1A receptor radioligand [11 C]WAY-100635 was performed in 66 individuals with current DSM-IV MDD to examine relationships between 5-HT1A binding and time since most recent antidepressant treatment. All subjects were medication-free for at least 2 weeks prior to scanning. Thirty-two additional MDD comparison subjects were antidepressant naive. Results No differences in [11 C]WAY-100635 binding were observed between antidepressant naive and antidepressant exposed MDD groups in 13 a priori cortical and subcortical regions of interest, including raphe autoreceptors, assessed simultaneously in linear mixed effects models. Furthermore, [11 C]WAY-100635 binding did not correlate with time off antidepressants in the antidepressant exposed patients considering these ROIs. The same results were observed when effects of treatment discontinuation of any psychotropic medication used to treat their depression was examined. Conclusion These results indicate that any antidepressant-associated downregulation of 5-HT1A autoreceptor binding reverses within 2 weeks of medication discontinuation. Since this effect is hypothesized to mediate the antidepressant action of SSRIs, and perhaps other antidepressants, it suggests that patients who need ongoing treatment may relapse rapidly when medication is discontinued. Moreover, 2 weeks appears to be a sufficiently long washout of antidepressant medications for a reliable measure of illness-related binding levels.

Background The hypothalamic–pituitary–adrenal (HPA) axis is dysfunctional in a subgroup of mood disorders. Methods We compared cortisol and adrenocorticotropic hormone (ACTH) responses in major depression and healthy volunteers to the combined dexamethasone suppression–corticotrophin-releasing hormone stimulation (DEX–CRH) test. Unlike other published studies, the study patients were medication-free and the healthy volunteers did not have first-degree relatives with a mood or psychotic disorder. Demographics, DSM-IV diagnoses and other clinical parameters were evaluated in major depressive disorder (MDD) and healthy control groups. Participants received an oral dose of 1.5 mg dexamethasone at 11 pm the day before CRH administration. On the following day, at 3 pm, 100 µg of ovine CRH was infused. Blood samples for determination of cortisol and ACTH were collected every 15 min from 3 pm to 4:15 pm. Cortisol and ACTH responses were calculated as areas under the curve. Results Controlling for age, baseline (i.e., post-dexamethasone) ACTH levels were higher in depressed patients compared to controls ( p =0.01). There was a trend for higher ACTH responses in depressed patients compared to the control group ( p =0.08). In depressed patients, cortisol and ACTH responses correlated positively with age, duration of illness and number of hospitalizations. Limitations Because of the cross-sectional study design we can only evaluate the nature of potential HPA axis disturbances that were present in patients when they are acutely depressed. Conclusions Feedback inhibition of ACTH secretion by cortisol is compromised in MDD, and this is independent of an age effect on the HPA axis function.

Bipolar patients (BP) are at high risk of suicide. Causal factors underlying suicidal behavior are still unclear. However, it has been shown that lithium has antisuicidal properties. Genes involved in its putative mechanism of action such as the phosphoinositol and the Wnt/β-catenine pathways could be considered candidates for suicidal behavior (SB). Our aim was to investigate the association of the IMPA1 and 2, INPP1, GSK3α and β genes with suicidal behavior in BP. 199 BP were recruited. Polymorphisms at the IMPA1 (rs915, rs1058401 and rs2268432) and IMPA2 (rs66938, rs1020294, rs1250171 and rs630110), INPP1 (rs3791809, rs4853694 and 909270), GSK3α (rs3745233) and GSK3β (rs334558, rs1732170 and rs11921360) genes were genotyped. All patients were grouped and compared according to the presence or not of history of SB (defined as the presence of at least one previous suicidal attempt). Single SNP analyses showed that suicide attempters had higher frequencies of AA genotype of the rs669838-IMPA2 and GG genotype of the rs4853694-INPP1gene compared to non-attempters. Results also revealed that T-allele carriers of the rs1732170-GSK3β gene and A-allele carriers of the rs11921360-GSK3β gene had a higher risk for attempting suicide. Haplotype analysis showed that attempters had lower frequencies of A:A haplotype (rs4853694:rs909270) at the INPP1 gene. Higher frequencies of the C:A haplotype and lower frequencies of the A:C haplotype at the GSK-3β gene (rs1732170:rs11921360) were also found to be associated to SB in BP. Therefore, our results suggest that genetic variability at IMPA2, INPP1 and GSK3β genes is associated with the emergence of SB in BP.

Background We previously reported higher serotonin 1A receptor (5-HT1A) binding in subjects with major depressive disorder (MDD) during a major depressive episode using positron emission tomography imaging with [ 11 C]WAY-100635. 5-HT1A receptor binding is also associated with treatment outcome after nonstandardized antidepressant treatment. We examined whether pretreatment 5-HT1A binding is associated with treatment outcome following standardized escitalopram treatment in MDD. We also compared 5-HT1A binding between all MDD subjects in this cohort and a sample of healthy control subjects. Methods Twenty-four MDD subjects in a current major depressive episode and 51 previously studied healthy control subjects underwent positron emission tomography scanning with [ 11 C]WAY-100635, acquiring a metabolite-corrected arterial input function and free-fraction measurement to estimate 5-HT1A binding potential (BP F = B max /K D , where B max = available receptors and K D = dissociation constant). Major depressive disorder subjects then received 8 weeks of treatment with escitalopram; remission was defined as a posttreatment 24-item Hamilton Depression Rating Scale Results Remitters to escitalopram had 33% higher baseline 5-HT1A binding in the raphe nuclei than nonremitters ( p = .047). Across 12 cortical and subcortical regions, 5-HT1A binding did not differ between remitters and nonremitters ( p = .86). Serotonin 1A receptor binding was higher in MDD than control subjects across all regions ( p = .0003). Remitters did not differ from nonremitters in several relevant clinical measures. Conclusions Elevated 5-HT1A binding in raphe nuclei is associated with subsequent remission with the selective serotonin reuptake inhibitor escitalopram; this is consistent with data from a separate cohort receiving naturalistic antidepressant treatment. We confirmed our previous findings of higher 5-HT1A binding in current MDD compared with control subjects.

The Institute of Medicine’s (IOM) report on psychosocial interventions challenges us to think not only about the way we study and deliver these important treatments, but also the way we teach and implement them. The report’s emphasis on protecting consumers by ensuring that effective psychosocial interventions are delivered in forms that closely approximate the ones for which the evidence exists has major implications for recruitment and training of faculty, didactic and supervisory teaching methods, competency standards held by national accreditation organizations, and research training. We briefly outline each of these issues below. Perhaps, the real game-changing suggestion of the report is that psychosocial interventions be delivered, taught, and researched using an “elements approach.” In its most radical form, this model, which is somewhat analogous to dimensional model of psychopathology taken by the NIMH’s Research Domain Criteria (RDoC), identifies elements that are both effective and common to multiple types of psychotherapy so that these elements can be studied, taught, and delivered a la carte. This is an exciting and challenging way to conceptualize psychosocial interventions that would require an entirely new approach to training. Curricula would cease to consist of separate courses and supervisors for each type of treatment, instead of employing a single “psychosocial interventions” course that would teach each of the effective elements and how and when to use them. Faculty trained in each of the psychotherapies would have to be retrained in the elements approach, with new or harmonized terminology and an “un-silo-ing” of their approach to assessment, treatment, and formulation. This could be difficult, as loyal practitioners of different psychotherapies often mix as well as oil and water. Even if psychotherapies continued to be delivered and taught in their extant forms, beginning to think about the effective elements of these interventions could prompt new and innovative ways to teach these common elements, much as we teach factors such as therapeutic alliance, empathic listening, and maintaining frame/boundaries as being common to all forms of therapy. The elements approach would also require new directions for psychotherapy research training, with requisite reframing for established psychotherapy research mentors. Beyond the discussion of the elements approach, the major thrust of the report is the importance of delivering psychosocial interventions that maintain fidelity to the effective form for which evidence exists. Sadly, much is often lost in translation, leading to less than ideal health care delivery. Changing this for psychosocial interventions will require increased attention to quality measures, as well as altering training in the following domains.

Suicidal behavior is often conceptualized as a response to overwhelming stress. Our model posits that given a propensity for acting on suicidal urges, stressors such as life events or major depressive episodes (MDEs) determine the timing of suicidal acts. Depressed patients (n=415) were assessed prospectively for suicide attempts and suicide, life events and MDE over 2 years. Longitudinal data were divided into 1-month intervals characterized by MDE (yes/no), suicidal behavior (yes/no) and life event scores. Marginal logistic regression models were fit, with suicidal behavior as the response variable and MDE and life event score in either the same or previous month, respectively, as time-varying covariates. Among 7843 person-months, 33% had MDE and 73% had life events. MDE increased the risk for suicidal behavior (odds ratio (OR)=4.83, P⩽0.0001). Life event scores were unrelated to the timing of suicidal behavior (OR=1.06 per 100 point increase, P=0.32), even during a MDE (OR=1.12, P=0.15). However, among those without borderline personality disorder (BPD), both health- and work-related life events were key precipitants, as was recurrent MDE, with a 13-fold effect. The relationship of life events to suicidal behavior among those with BPD was more complex. Recurrent MDE was a robust precipitant for suicidal behavior, regardless of BPD comorbidity. The specific nature of life events is key to understanding the timing of suicidal behavior. Given unanticipated results regarding the role of BPD and study limitations, these findings require replication. Of note, that MDE, a treatable risk factor, strongly predicts suicidal behaviors is cause for hope.

This study compared regional cerebral metabolic rates of glucose (rCMRglu) determined by [(18)F]-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) in suicide attempters and non-attempters. Medication-free patients with major depression (n = 29) had FDG-PET after single-blind administration of placebo (day 1) and fenfluramine (day 2). Suicide attempt history was obtained before scanning and at assessments over 2 subsequent years. Statistical parametric mapping evaluated associations between attempt status and rCMRglu, controlling for age. The study included 13 patients with and 16 without a history of suicide attempt within 2 years before or after scanning. After placebo, rCMRglu in attempters was lower in right dorsolateral prefrontal regions and higher in ventromedial regions than in non-attempters. After fenfluramine, relatively hypometabolic areas enlarged, and no hypermetabolic areas were detected. Distinct rCMRglu patterns may be serotonin-sensitive biomarkers of suicide risk.

Growing awareness of health and health care disparities highlights the importance of including information about race, ethnicity, and culture (REC) in health research. Reporting of REC factors in research publications, however, is notoriously imprecise and unsystematic. This article describes the development of a checklist to assess the comprehensiveness and the applicability of REC factor reporting in psychiatric research publications. The 16-item GAP-REACH checklist was developed through a rigorous process of expert consensus, empirical content analysis in a sample of publications (N = 1205), and interrater reliability (IRR) assessment (N = 30). The items assess each section in the conventional structure of a health research article. Data from the assessment may be considered on an item-by-item basis or as a total score ranging from 0% to 100%. The final checklist has excellent IRR (κ = 0.91). The GAP-REACH may be used by multiple research stakeholders to assess the scope of REC reporting in a research article.

Identifying the depression symptoms most closely associated with suicidal thoughts and which medications provide the fastest depression relief may help suicide prevention.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.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).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.ClinicalTrials.gov identifier: NCT00429169.

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. Language: en

Background Several lines of evidence implicate abnormal serotonergic function in suicidal behavior and completed suicide, including low serotonin transporter binding in postmortem studies of completed suicide. We have also reported low in vivo serotonin transporter binding in major depressive disorder (MDD) during a major depressive episode using positron emission tomography (PET) with [ 11 C]McN5652. We quantified regional brain serotonin transporter binding in vivo in depressed suicide attempters, depressed nonattempters, and healthy controls using PET and a superior radiotracer, [ 11 C]DASB. Methods Fifty-one subjects with DSM-IV current MDD, 15 of whom were past suicide attempters, and 32 healthy control subjects underwent PET scanning with [ 11 C]DASB to quantify in vivo regional brain serotonin transporter binding. Metabolite-corrected arterial input functions and plasma free-fraction were acquired to improve quantification. Results Depressed suicide attempters had lower serotonin transporter binding in midbrain compared with depressed nonattempters ( p = .031) and control subjects ( p = .0093). There was no difference in serotonin transporter binding comparing all depressed subjects with healthy control subjects considering six a priori regions of interest simultaneously ( p = .41). Conclusions Low midbrain serotonin transporter binding appears to be related to the pathophysiology of suicidal behavior rather than of major depressive disorder. This is consistent with postmortem work showing low midbrain serotonin transporter binding capacity in depressed suicides and may partially explain discrepant in vivo findings quantifying serotonin transporter in depression. Future studies should investigate midbrain serotonin transporter binding as a predictor of suicidal behavior in MDD and determine the cause of low binding.

Background Although lower levels of omega-3 polyunsaturated fatty acids (PUFAs) are found in major depressive disorder, less is known about PUFA status and anxiety disorders. Method Medication-free participants with DSM-IV-defined major depressive disorder (MDD), with (n = 18) and without (n = 41) comorbid DSM-IV anxiety disorders, and healthy volunteers (n = 62) were recruited from October 2006 to May 2010 for mood disorder studies at the New York State Psychiatric Institute. Participants were 18-73 years of age (mean age, 35.8 ± 12.6 years). Depression and anxiety severity was assessed using depression and anxiety subscales from the 17-item Hamilton Depression Rating Scale. Plasma PUFAs eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) and the ratio of arachidonic acid (AA; 22:4n-6) to EPA (AA:EPA) were quantified. This secondary analysis employed analysis of variance with a priori planned contrasts to test for diagnostic group differences in log-transformed PUFA levels (logDHA, logEPA, and logAA:EPA). Results Plasma levels of logDHA (F(2,118) = 4.923, P = .009), logEPA (F(2,118) = 6.442, P = .002), and logAA:EPA (F(2,118) = 3.806, P = .025) differed across groups. Participants with MDD had lower logDHA (t(118) = 2.324, P = .022) and logEPA (t(118) = 3.175, P = .002) levels and higher logAA:EPA levels (t(118) = -2.099, P = .038) compared with healthy volunteers. Lower logDHA (t(118) = 2.692, P = .008) and logEPA (t(118) = 2.524, P = .013) levels and higher logAA:EPA levels (t(118) = -2.322, P = .022) distinguished anxious from nonanxious MDD. Depression severity was not associated with PUFA plasma levels; however, anxiety severity across the entire sample correlated negatively with logDHA (r(p) = -0.22, P = .015) and logEPA (r(p) = -0.25, P = .005) levels and positively with logAA:EPA levels (r(p) = 0.18, P = .043). Conclusions The presence and severity of comorbid anxiety were associated with the lowest EPA and DHA levels. Further studies are needed to elucidate whether omega-3 PUFA supplementation may preferentially alleviate MDD with more severe anxiety.

Childhood sexual abuse has been consistently associated with suicidal behavior. We studied suicide attempt features in depressed individuals sexually abused as children. On average, sexual abuse started before age 9. It frequently coexisted with physical abuse. Suicide attempters more often had personality disorders and had endured abuse for longer, but did not differ in terms of other clinical characteristics from non-attempters. Earlier onset of sexual abuse and its duration were associated with more suicide attempts. However, when personality disorders were included in the regression model, only these disorders predicted number of attempts. The severity of sexual abuse and the coexistence of physical abuse were correlated with age at first suicide attempt. However, only severity of sexual abuse was marginally associated with age at first suicide attempt in the regression model. Finally, the earlier the age of onset of sexual abuse, the higher the intent, even after controlling for age, sex and personality disorders. This suggests that the characteristics of childhood sexual abuse, especially age of onset, should be considered when studying the risk for suicidal behavior in abused populations.

Sexual abuse during childhood is surprisingly common, with estimates in the general population ranging from 15% to 38% (1). It is associated with significant psychiatric sequelae, including the development of major depression and posttraumatic stress disorder (PTSD). These common consequences of exposure to trauma can emerge in the aftermath of natural disasters as well as those in which humans have a hand (2). Some responses, such as suicidal behavior, are not only life-threatening but have multigenerational repercussions, as individuals who report childhood sexual abuse are at risk not only for suicidal behavior themselves but also for transmitting suicidal behavior and mood disorders to their offspring (3). The timing (4) and severity of childhood sexual abuse are also relevant to its consequences (5). Earlier age at onset of childhood sexual abuse is associated with more intent during suicide attempts (6) as well as greater severity of PTSD (7) and depressive symptoms (8). Similarly, the severity of sexual abuse during development is reportedly related to earlier-onset suicidal behavior (6), greater depression severity (9), and more pronounced symptoms among patients with borderline personality disorder (5). Interestingly, other forms of early life stress, such as childhood emotional abuse and neglect, have been found to be stronger predictors of subsequent depression in adulthood than childhood sexual or physical abuse (10). Following the excitement generated by the gene-environment interaction literature, researchers are now exploring the biological substrates that may mediate effects of early traumatic experiences on later psychopathology. Elegant studies in animal models have identified epigenetic mechanisms through which the early environment may induce enduring effects on gene expression and, with it, behavioral phenotypes (11). Reports of environmental effects on biological alterations more proximal to clinical phenotypes are also emerging, including effects on neurocognitive, neuroendocrine, and neuroimmune function. Structural and functional neuroimaging provide powerful tools to explore long-term effects of life experience on neurodevelopment. Most, but not all, structural MRI studies examining neuroanatomical correlates of childhood sexual abuse thus far describe volume reductions in a variety of structures. Decreased volume of the corpus callosum, the left hippocampus, the anterior cingulate, the caudate nucleus, the amygdala, and the visual cortex, as well as more general decreased cerebral volume, have all been reported in survivors of childhood sexual abuse (for reviews, see references 12 and 13). In this issue of the Journal, Heim et al. (14) make use of the burgeoning structural MRI technique of measuring cortical brain thickness to understand neuroplastic responses to childhood trauma. The authors studied 51 medically healthy women, of whom 55% (N=28) reported moderate-to-severe maltreatment, 18% (N=9) had PTSD, and 24% (N=12) had major depression. Cortical thinning was found to be present in the brain areas involved in the perception or processing of behaviors that are specific to the type of abuse experienced. For example, childhood sexual abuse was associated with cortical thinning in the genital representation field of the primary somatosensory cortex, whereas emotional abuse was associated with cortical thinning in regions linked to self-awareness and self-evaluation (15). The authors conclude that cortical adaptation to traumatic events may lead to decreases in the density of dendritic spines, leading to cortical thinning. They suggest that such changes relate to the child’s sensory processing of the abusive experience, which alters cortical representation fields in a regionally specific fashion, based on the nature of the abuse itself. This finding comports with another recent work in which young adults, compared with an unexposed group, who witnessed domestic violence as children had decreased visual cortex gray matter (15), in terms of both volume and cortical thickness, regardless of whether or not they developed psychopathology. In addition, Heim et al. noted that age at onset, although not severity of childhood sexual abuse, was related to cortical thinning in the left temporal pole, the left parietal lobe, the left frontal pole, and the right frontal pole, areas associated with autobiographical memory among other functions. This, they postulate, may serve as the neuroanatomical basis for the observation that victims of childhood sexual abuse often have poor, if any, recollection of the experience and report overgeneralized memories. A question that arises from this finding is whether individuals who experience trauma at a later age, outside the window of peak vulnerability for cortical thinning, develop psychopathology through a mechanism that is distinct from the one responsible for consequences in those who experience trauma during an earlier, critical period. What is the relevance of these neuroanatomical findings to the broader picture? If replicated, these data provide compelling evidence about the enduring structural effects on the brain as a function of early life experience that are not defined on the basis of a specific psychiatric diagnostic context. Given the nature of the environmental stressor and the difficulties in identifying victims at the time sexual abuse is occurring, it is unlikely that we will be able to develop longitudinal studies to more completely test the hypothesis. Nonetheless, this research may pave the way for the characterization of endophenotypes associated with trauma-related effects on the brain. The possible mechanisms the authors invoke to explain the neuroplasticity observed in this study may not be dependent on epigenetic effects and may suggest alternative molecular pathways underlying early life experience effects on neurodevelopment and psychopathology. Moreover, if life experience can have a role in brain restructuring during development, then appropriately timed experiential or behavioral interventions may have utility in mitigating the effects of negative environmental input or genetic deficits. Indeed, at the behavioral level, perceived social support protects against the development of adult depression among victims of childhood abuse (10). Consistent with this finding, murine studies suggest that enriched environments can mitigate the deleterious effects of low maternal licking and grooming behavior early in development (16). Of note, the question of whether the “active ingredient” of such enrichment is simply aerobic exercise (17), which is linked to hippocampal neurogenesis, has been recently raised. Finally, if sensory input in general has the potential to precipitate neuroarchitectural restructuring, then observed dose effects of the environmental insults may be related to multimodal sensory input from the traumatic experience. Although it stands to reason that more severe experiences would have more profound effects on an individual, elucidation of the exact mechanism for this observation may uncover the neurophysiological basis of such a relationship. Studies such as the one by Heim et al. bring us closer to delineating the mechanisms that lead to changes in brain morphology and function, which are so critical to developing effective behavioral and pharmacological interventions. We need to understand the role of several key elements leading to these neurobiological changes—the relative contributions of the severity, timing, and nature of a stressor in the context of genetic endowment. Equally important for future research is to study the role of resilience and its neurobiological underpinning, a sorely neglected area. The more clearly we can delineate a biological pathway from environment to psychopathology, the more likely we are to develop interventions to mitigate, cure, or even prevent what ails our patients.

Deficits in decision-making using the Iowa Gambling Task (IGT) have been found in past suicide attempters, but primarily euthymic and/or medicated patients. This study compared IGT performance among medication-free, currently depressed patients (unipolar and bipolar) with (n=26) and without (n=46) a past history of suicide attempt, and healthy volunteers (n=42). Attempter status, in a sample whose attempts were predominantly non-violent, was not associated with impaired IGT performance even when accounting for sex, mood disorder type, and comorbid Borderline Personality Disorder. A non-significant trend towards poorer performance was found in a small subgroup of past attempters who had used a violent method, consistent with prior studies. Suicide intent and ideation were unrelated to IGT scores. There were no consistent associations between IGT performance and ratings of impulsiveness (Barratt Impulsiveness Scale (BIS)), hostility (Buss-Durkee Hostility Inventory (BDHI)) or aggression (Brown-Goodwin Aggression Inventory (BGAI)). Results suggest that decision-making impairment is related to specific subtypes of suicidal behavior, but may not be universally sensitive to suicide risk in all types of attempters, especially those using non-violent means. Psychometric and conceptual issues surrounding the IGT also appear to affect its utility as a general marker of suicidal behavior risk.

Background Brain serotonin-1A receptors (5-HT1A) are implicated in anxiety. We compared regional brain 5-HT1A binding in medication-free participants with posttraumatic stress disorder (PTSD) and healthy volunteers using fully quantitative positron emission tomography (PET) methods.

Three articles in this issue detail the process and results of reliability tests for proposed DSM-5 diagnoses and cross-diagnosis symptom domains. The editorial highlights the good reliability of borderline personality disorder and relates the questionable reliability of major depressive disorder to its heterogeneity. The editorial is also available in Spanish, Traditional Chinese, and Simplified Chinese.

The relationship of Narcissistic Personality Disorder (NPD) to suicidal behavior is understudied. The modest body of existing research suggests that NPD is protective against low-lethality suicide attempts, but is associated with high lethality attempts. Mood-disordered patients (N = 657) received structured interviews including Axis I and II diagnosis and standardized clinical measures. Following chi-square and t-tests, a logistical regression model was constructed to identify predictors of suicide attempt. While there was no bivariate relationship of NPD on suicide attempt, in the logistic regression patients with NPD were 2.4 times less likely to make a suicide attempt (OR = 0.41; 95% CI = 0.19 - 0.88; p

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

The serotonin neurotransmitter system is modulated in part by the uptake of syn aptically released serotonin (5-HT) by the serotonin transporter (5-HTT), and by specific serotonin autoreceptors such as the somatodendritic 5-HT 1A receptor, which can limit serotonin neuron depolarization. However, little is known about how 5-HTT and 5-HT 1A are related in vivo . To study this question, we reanalyzed positron emission tomography (PET) data obtained earlier in 40 healthy participants (21 females) using [ 11 C]WAY-100635 for quantification of 5-HT 1A binding and [ 11 C](+)-McN-5652 for quantification of 5-HTT binding. We hypothesized negative correlations between 5-HT 1A binding in the raphe nuclei (RN) and 5-HTT binding in RN terminal field regions. Controlling for sex, no significant correlations were found (all p>0.05). Similarly, an exploratory analysis correlating whole-brain voxel-wise 5-HTT binding with 5-HT 1A binding in RN identified no significant clusters meeting our a priori statistical threshold. The lack of correlation between 5-HT 1A and 5-HTT binding observed in the current study may be due to the different temporal responsiveness of regulatory processes controlling the somatodendritic 5-HT 1A receptor and 5-HTT in response to changing availability of intrasynaptic serotonin.

IMPORTANCE: Biomarkers that predict suicidal behavior, especially highly lethal behavior, are urgently needed. In cross-sectional studies, individuals with depression who attempt suicide have lower midbrain serotonin transporter binding potential compared with those who do not attempt suicide, and higher serotonin(1A) binding potential in the raphe nuclei (RN) is associated with greater lethality of past suicide attempts and suicidal intent and ideation. OBJECTIVES: To determine whether serotonin transporter binding potential in the lower midbrain predicts future suicide attempts and whether higher RN serotonin(1A) binding potential predicts future suicidal ideation and intent and lethality of future suicide attempts. DESIGN, SETTING, AND PARTICIPANTS: In this prospective 2-year observational study, a well-characterized cohort of 100 patients presenting for treatment of a major depressive episode of at least moderate severity underwent positron emission tomography using carbon 11-labeled N-(2-(1-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl))-N-(2-pyridyl)-cyclohexanecarboxamide ([(11)C]WAY-100635), a serotonin(1A) antagonist; a subset of 50 patients also underwent imaging with carbon 11-labeled 3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)- benzonitrile ([(11)C]DASB), a serotonin transporter radioligand. Imaging was performed at Columbia University Medical Center from May 3, 1999, to March 11, 2008. Follow-up was completed on May 28, 2010, and data were analyzed from August 1, 2013, to March 1, 2016. EXPOSURES: Patients were treated naturalistically in the community and followed up for 2 years with documentation of suicidal behavior, its lethality, and suicidal ideation and intent. MAIN OUTCOMES AND MEASURES: Suicide attempt or suicide. RESULTS: Of the 100 patients undergoing follow-up for more than 2 years (39 men; 61 women; mean [SD] age, 40.2 [11.2] years), 15 made suicide attempts, including 2 who died by suicide. Higher RN serotonin(1A) binding potential predicted more suicidal ideation at 3 (b = 0.02; t = 3.45; P = .001) and 12 (b = 0.02; t = 3.63; P = .001) months and greater lethality of subsequent suicidal behavior (b = 0.08; t = 2.89; P = .01). Exploratory analyses suggest that the serotonin(1A) binding potential of the insula (t = 2.41; P = .04), anterior cingulate (t = 2.27; P = .04), and dorsolateral prefrontal cortex (t = 2.44; P = .03) were also predictive of lethality. Contrary to our hypotheses, suicidal intent was not predicted by serotonin(1A) binding potential in any brain region (F(1,10) = 0.83; P = .38), and midbrain serotonin transporter binding potential did not predict future attempts (log-rank [Formula: see text]; P = .54), possibly owing to low power. CONCLUSIONS AND RELEVANCE: Greater RN serotonin(1A) binding potential predicted higher suicidal ideation and more lethal suicidal behavior during a 2-year period. This effect may be mediated through less serotonin neuron firing and release, which affects mood and suicidal ideation and thereby decision making.

Social support is thought to protect against the risk of suicidal behavior in young people and late life, but less is known about the role of friendship in adults. We explored the effect of friendship on suicide attempt risk during 1-year follow-up of 132 adults presenting with major depressive episode (MDE). Items from the Social Adjustment Scale-Self-Report were used as an index of frequency and quality of recent friendship contacts. Survival methods tested associations of friendship with risk of suicide attempt, recurrent MDE, and related outcomes during follow-up. Impaired friendship predicted greater risk of suicide attempt in an unadjusted Cox model. This association was stronger for quality (p = .009) than frequency (p = .081) of friendship contacts. In the adjusted model, the effect of friendship on suicide attempts was largely explained by self-reported depression severity. Friendship has a potentially bidirectional relationship with depression, and its effect on suicidal behavior appears to occur through its relationship with depression. Future research should examine the effect of antidepressant treatment on friendship and be designed to test mediation models of relationships between friendship, depression, and suicidal behavior.

Self-rated depression and hopelessness severity are predictors of suicide attempt in major depression. This study evaluated whether: (1) greater self-rated distress relative to severity of clinician-rated depression is a trait; (2) that trait is familial; and (3) that trait is linked to familial transmission of suicidal behavior. A total of 285 mood disorder probands and 457 offspring were assessed twice, at least 1 year apart. Family and subject intra-class correlations for self-report depression and hopelessness, controlling for clinician-rated depression severity, were computed. Mixed general linear models determined offspring-proband correlations. Within-individual intra-class correlation (ICC) for depression-hopelessness was 37.8% (bootstrap 95% CI: 31.0-46.3%). Parent-offspring ICC was 10.7% (bootstrap 95% CI: 3.5-17.8%). Suicide attempt concordant parent-offspring correlation for subjective depression was positive, but negative for attempter parent and nonattempter offspring (p = .0213 for slope interaction). Pessimism was greater in proband or offspring attempters than proband or offspring nonattempters (p

Fatty acid desaturase genes (FADS1-FADS2) encode desaturases participating in the biosynthesis of long-chain polyunsaturated fatty acids. As long-chain polyunsaturated fatty acids are implicated in major depressive disorder (MDD) and suicide risk, and as both are partly heritable, we studied the association of FADS1-FADS2 polymorphisms with MDD (635 cases, 480 controls) and suicide attempt status (291 attempters, 344 MDD nonattempters). Eighteen FADS-related single-nucleotide polymorphisms were genotyped from Caucasians enrolled in Madrid (n=791) or New York City (n=324) and entered as predictors into logistic regression analyses with diagnostic group or suicide attempt history as outcomes and location and sex as covariates. No associations were observed between any single-nucleotide polymorphisms and diagnosis or attempt status. As statistical power was adequate, we conclude that FADS1-FADS2 genetic variants may not be a common determinant of MDD.

Background The amygdala is an integral part of the extrahypothalamic stress-response system, and its volume related to childhood trauma has been studied, but less is known of associations with recent stressful life events. Amygdala volume differences also have been studied in depression, with conflicting results. We hypothesized that effects of stress may be a confound for amygdala volumetric differences in the context of depression. Methods Right-handed participants (n=61) experiencing a major depressive episode during major depressive disorder (n=40) or bipolar depression (n=21) and healthy volunteers (n=60) underwent 1.5 T magnetic resonance imaging (MRI). The amygdala perimeter was manually traced with an electronic mouse, based on anatomical landmarks on consecutive coronal slices, by raters blind to diagnosis. The effects of stress on amygdala volume were examined in linear regression models with self-reported physical/sexual abuse or highest category score on the St. Paul-Ramsey scale of stressful life events within the past 6 months as predictors, testing separately for age, sex, race, and depression status as covariates. Results Diagnostic groups did not differ significantly with respect to mean age (depressed, 37.8±11.8 yrs; healthy, 34.9±13.8 yrs) or proportion of males (depressed, 39%, healthy, 50%). We found no association between physical and/or sexual abuse history and amygdala volume. Life stress within the last six months, however, was associated with smaller left amygdala volume. The association between stress and amygdala volume did not differ by diagnostic group. Limitations Most depressed patients were off medications for at least 2 weeks; however, this may not have been long enough to reverse effects of medications on amygdala structure. Conclusions That life stress of relatively short duration was associated with amygdala size in the entire sample, while temporally distant life stress was not, suggests that amygdala volume changes may occur rapidly and reversibly, and independent of depression status.

White matter abnormalities are implicated in major depressive disorder (MDD). As omega-3 polyunsaturated fatty acids (PUFAs) are low in MDD and affect myelination, we hypothesized that PUFA supplementation may alleviate depression through improving white matter integrity. Acutely depressed MDD patients (n = 16) and healthy volunteers (HV, n = 12) had 25-direction diffusion tensor imaging before and after 6 weeks of fish oil supplementation. Plasma phospholipid omega-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and omega-6 PUFA arachidonic acid (AA) levels were determined before and after supplementation using high-throughput extraction and gas chromatography and expressed as a percentage of total phospholipids (PUFA%). Fractional anisotropy (FA) was computed using a least-squares-fit diffusion tensor with non-linear optimization. Regression analyses were performed with changes in PUFA levels or Hamilton Depression Rating Scale scores as predictors, voxel-wise difference maps of FA as outcome, covariates age and sex, with family-wise correction for multiple comparisons. Increases in plasma phospholipid DHA% (but not EPA% or AA%) after fish oil predicted increases in FA in MDD but not HV, in a cluster including genu and body of the corpus callosum, and anterior corona radiata and cingulum (cluster-level p < 0.001, peak t-score = 8.10, p = 0.002). There was a trend for greater change in FA in MDD responders over nonresponders (t = -1.874, df = 13.56, p = 0.08). Decreased depression severity predicted increased FA in left corticospinal tract and superior longitudinal fasciculus (cluster-level p < 0.001, peak t-score = 5.04, p = 0.0001). Increased FA correlated with increased DHA% and decreased depression severity after fish oil supplementation suggests therapeutic effects of omega-3 PUFAs may be related to improvements in white matter integrity.

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.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.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.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.

To date, the identification of individuals at risk of suicide is based on subjective reports. Given that individuals at risk often do not disclose their suicidal thoughts, the introduction of objective measures – such as biomarkers – of suicide risk might help in predicting which individuals will eventually die by suicide. Biomarkers have a potentially relevant role in the prediction of suicide, as an adjunct to, rather than a substitute for, current clinical practice. Within the context of the stress-diathesis model of suicidal behavior, the most relevant biomarkers for estimating suicide risk are non-suppression in the dexamethasone suppression test (DST) – a biomarker of stress – and reduced concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF), a biomarker of diathesis. Given the multi-determined nature of suicide, a combination of biological, clinical, neuropsychological, and neuroimaging factors might yield a better estimate of suicide risk than using biomarkers alone and help overcome current limitations in the prediction of suicide.

Remission rates for Major Depressive Disorder (MDD) are low and unpredictable for any given antidepressant. No biological or clinical marker has demonstrated sufficient ability to match individuals to efficacious treatment. Biosignatures developed from the systematic exploration of multiple biological markers, which optimize treatment selection for individuals (moderators) and provide early indication of ultimate treatment response (mediators) are needed. The rationale and design of a multi-site, placebo-controlled randomized clinical trial of sertraline examining moderators and mediators of treatment response is described. The target sample is 300 participants with early onset (≤30 years) recurrent MDD. Non-responders to an 8-week trial are switched double blind to either bupropion (for sertraline non-responders) or sertraline (for placebo non-responders) for an additional 8 weeks. Clinical moderators include anxious depression, early trauma, gender, melancholic and atypical depression, anger attacks, Axis II disorder, hypersomnia/fatigue, and chronicity of depression. Biological moderator and mediators include cerebral cortical thickness, task-based fMRI (reward and emotion conflict), resting connectivity, diffusion tensor imaging (DTI), arterial spin labeling (ASL), electroencephalograpy (EEG), cortical evoked potentials, and behavioral/cognitive tasks evaluated at baseline and week 1, except DTI, assessed only at baseline. The study is designed to standardize assessment of biomarkers across multiple sites as well as institute replicable quality control methods, and to use advanced data analytic methods to integrate these markers. A Differential Depression Treatment Response Index (DTRI) will be developed. The data, including biological samples (DNA, RNA, and plasma collected before and during treatment), will become available in a public scientific repository. Clinical trial registration Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC). Identifier: NCT01407094. URL: http://clinicaltrials.gov/show/NCT01407094.

Objective The best known neurobehavioral effects of testosterone are on sexual function and aggression. However, testosterone and other androgens may be involved in the pathophysiology of mood disorders and suicidal behavior. This is the first study to examine whether there is a relation between testosterone levels and clinical parameters in bipolar suicide attempters.

BackgroundExecutive dysfunction, distinct from other cognitive deficits in depression, has been associated with suicidal behavior. However, this dysfunction is not found consistently across samples.MethodMedication-free subjects with DSM-IV major depressive episode (major depressive disorder and bipolar type I disorder) and a past history of suicidal behavior (n = 72) were compared to medication-free depressed subjects with no history of suicidal behavior (n = 80) and healthy volunteers (n = 56) on a battery of tests assessing neuropsychological functions typically affected by depression (motor and psychomotor speed, attention, memory) and executive functions reportedly impaired in suicide attempters (abstract/contingent learning, working memory, language fluency, impulse control).ResultsAll of the depressed subjects performed worse than healthy volunteers on motor, psychomotor and language fluency tasks. Past suicide attempters, in turn, performed worse than depressed non-attempters on attention and memory/working memory tasks [a computerized Stroop task, the Buschke Selective Reminding Task (SRT), the Benton Visual Retention Test (VRT) and an N-back task] but not on other executive function measures, including a task associated with ventral prefrontal function (Object Alternation). Deficits were not accounted for by current suicidal ideation or the lethality of past attempts. A small subsample of those using a violent method in their most lethal attempt showed a pattern of poor executive performance.ConclusionsDeficits in specific components of attention control, memory and working memory were associated with suicidal behavior in a sample where non-violent attempt predominated. Broader executive dysfunction in depression may be associated with specific forms of suicidal behavior, rather than suicidal behavior per se.

Nonsuicidal self-injury is the direct, deliberate infliction of pain and tissue damage by an individual on his or her own body in the absence of suicidal intent, psychosis, mental retardation, or developmental delay.1 A wide variety of self-damaging acts may be classified as nonsuicidal self-injury, the most common of which include cutting or burning one’s own skin.1 Nonsuicidal self-injury is a significant and common public health problem in adolescents, with community studies reporting a prevalence of nonsuicidal self-injury at around 20%2,3 and studies of adolescent psychiatric inpatients reporting rates as high as 82%.4 A number of factors have shown consistent relationships to nonsuicidal self-injury. These include mood disorders,5,6 increased severity of depressive symptoms,5,7 and additional clinical characteristics like impulsivity.8 Family features, particularly a history of child maltreatment, have also been found to be related to nonsuicidal self-injury.9,10 These characteristics may be linked by a common thread of emotional dysregulation, which is frequently observed among individuals with nonsuicidal self-injury.11,12 In fact, the most commonly cited function of nonsuicidal self-injury is to achieve emotional regulation in the face of negative affect.4 Despite many common risk factors, the nature of the relationship between nonsuicidal self-injury and suicide attempts is an ongoing area of controversy. Some suggest that any act of self-injury should be considered part of a spectrum of suicidal behavior,13 while others differentiate nonsuicidal self-injury and suicide attempt based on whether there is intent to die or if the behavior is intended to serve a different function. The latter view is supported by the disparate rates of co-occurrence of nonsuicidal self-injury and suicide attempt, particularly in community samples, in which fewer than 1 in 5 of those who engaged in nonsuicidal self-injury also have a history of a suicide attempt.14,15 In contrast, the behaviors are much more likely to co-occur in clinically referred samples.16,17 This finding suggests that nonsuicidal self-injury and suicide attempt may be unique entities that share some common correlates and risk factors. Greater likelihood and increased severity of these overlapping features would therefore lead to an amplified rate of co-occurrence, as is seen in the psychiatric inpatient setting. Examination of youths who are not themselves clinically referred but who are at risk for the development of a mood disorder could help to clarify the extent to which suicide attempt and nonsuicidal self-injury are distinct entities. Therefore, the aim of this study is to examine the correlates of a history of nonsuicidal self-injury in a sample of individuals who are the offspring of mood-disordered parents. Approximately one-half of the parents had a history of suicide attempt, 20% had a history of nonsuicidal self-injury, and 18% had a history of both. In previous reports, correlates and predictors of suicide attempt in these offspring have been identified. These include parental history of suicide attempt and sexual abuse, as well as offspring sexual abuse and increased impulsive aggression and self-reported depressive symptoms.18,19 In the present study, characteristics of offspring and at least 1 of their parents were examined with respect to the occurrence of nonsuicidal self-injury in the offspring. We hypothesized that the presence and severity of mood disorder would predispose to nonsuicidal self-injury, as would impulsivity and history of abuse. Given prior work with this sample, it was also predicted that family discord and lack of cohesion would predispose to nonsuicidal self-injury. Because we are positing that nonsuicidal self-injury and suicidal behavior are distinct entities, we also hypothesized that a parental history of nonsuicidal self-injury but not suicide attempt would be related to nonsuicidal self-injury in offspring.18,19

Assessment of personality disorders during the acute phase of major depression may be invalidated by the potential distortion of personality traits in depressed mood states. However, few studies have tested this assumption. We examined the stability of personality disorder diagnoses during and then after a major depressive episode (MDE). Subjects with major depression (N = 82) completed the 17-item Hamilton Depression Scale (HAM-17) and the Structured Clinical Interview for Axis II both at baseline during an MDE and at 3-month follow-up. We compared subjects who continued to meet DSM-IV criteria for the same Axis II diagnoses with patients whose diagnosis changed and patients with no DSM-IV personality disorder to determine the relationship to major depression and its severity. Sixty-six percent of subjects met DSM-IV criteria for at least one Axis II diagnosis at baseline and 80% had the same personality disorder diagnoses at follow-up. Thirty-four percent had a full remission of MDE at 3-month follow-up. Instability of Axis II diagnosis was associated with number of Axis II diagnoses at baseline (p = .036) and Hispanic ethnicity (p = .013). HAM-17 score change was unrelated to differences in the number of symptoms of personality disorders from baseline to follow-up, nor was remission from MDE on follow-up. Axis II diagnoses in acutely depressed patients reassessed after 3 months are often stable and not associated with remission of or improvement in major depression.

Among subjects with bipolar disorder (BD), depression is much more prevalent (1, 2) and has stronger effects on mortality and psychosocial impairment than mania or hypomania (3, 4). Recently, the clinical, biological, and treatment characteristics of major depressive episodes (MDE) in BD as compared to major depressive disorder (MDD) have been a focus of attention for researchers and clinicians (5–21). However, specific clinical or biological markers for bipolar depression are still lacking. In current diagnostic systems, the same diagnostic criteria apply to MDE occurring during MDD or during the course of BD (22). In comparisons of MDD and depressed BD patients, atypical features, such as hypersomnia or leaden paralysis (5, 6, 9, 20), psychotic symptoms (13, 16, 17, 19), psychomotor retardation (5, 13, 16), shorter depressive episodes (13, 14), higher number of depressive recurrences (9, 18–20), family history of mood disorders (9, 14), comorbidity with substance abuse (8, 17), and earlier age at onset (7, 9, 18) are reported more frequently in BD; whereas, somatic disturbances (5, 6, 18), anxiety (7, 13), sleep loss (5, 6, 9, 11, 13, 14, 18), and appetite loss (5, 6, 14, 17) are reported more frequently in MDD. However, findings in one sample have seldom been replicated in another, resulting in conflicting results across studies. Most studies report on samples of bipolar I disorder (BD-I) patients or on heterogeneous samples comprising of mostly BD-I patients (5, 6, 13, 14, 16–18); only a few have addressed differences between bipolar II disorder (BD-II) and MDD (9–11, 23); and even fewer have compared BD-I and BD-II with MDD (19, 20). Those studies used clinical samples, which preclude extrapolation of their results to the general population, and did not account for the impact of severity of depression on the clinical presentation and treatment patterns. Current categorical classifications do not rely on specific clinical correlates to discriminate between different mood disorders. In fact, DSM-IV differences between MDD, BD-II, and BD-I are based on lifetime presence of increasing number and duration of manic symptoms (22). This, together with the absence of genetic or other biomarkers supporting boundaries between conditions (21, 24, 25), suggests that dimensional approaches may contribute to describe mood disorders more accurately. We used data from a large national representative survey, the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) (26), to address some of the gaps in previous research. Specifically, among individuals with a lifetime history of MDE, we compared those with lifetime BD-I, BD-II, and MDD on sociodemographic and clinical characteristics, symptoms of MDE, and lifetime treatment patterns, and explored whether the different mood diagnoses arrayed along a dimension. Our aim was to expand the knowledge regarding the differential features of MDE occurring in BD-I, BD-II, and MDD, which could aid in the clinical decision-making and the characterization of mood disorders in DSM-V.