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During adolescence, suicide risk increases; effective treatments are needed to reduce risk.Databases were searched (1995-2020) for randomized controlled trials (RCTs) concerning psychosocial treatments for suicide prevention in adolescents (10-18 yrs). Data were extracted from the timepoint closest to 6 months. Cohen's ds were estimated for reducing suicidal ideation (SI), self-harming behaviors (SHB) excluding strictly non-suicidal self-injury, and suicide attempts (SA) and analyzed using generalized least square regression. Meta-analytic innovations included within-person correlations to reflect trait suicidality; annualization to control for exposure; estimated lifetime risk based on ages; and modeling inclusion/exclusion criteria. Alternate approaches included relative risk and comparison of intervention and control treatments to baseline.Of 30 RCTs, 6 assessing SHB (4 measuring SA), and 7 assessing SI demonstrated treatment effectiveness. Overall, interventions decreased SI (n = 25) with low effect size (d = 0.08, p = 0.01), non-significant after controlling for publication bias (d = 0.05, p = 0.1); interventions were non-significant for SHB (n = 25, d = 0.001, p = 0.97) or SA (n = 18, d = 0.03, p = 0.52). To prevent one SHB, the number needed to treat (NNT) was 45[26,156]; for SA, NNT=42[24,149]. Non-superiority may relate to effectiveness of control treatments. Thus, experimental and control treatments also were compared to baseline: both reduced SI (p 0.0001), and effectiveness improved for SHB (NNT=12) and SA (NNT=11).Study heterogeneity and inconsistent statistical reporting limited meta-analysis.Psychosocial interventions for suicide risk in adolescents showed little effectiveness compared with control treatments; suicide outcomes improved in both groups compared to baseline. Different approaches may be needed, including precision medicine methodologies and standardized statistical reporting criteria.

OBJECTIVE: To identify risk factors for preadolescent onset suicidal behavior compared with adolescent/young adult onset suicidal behavior in a longitudinal sample of youth with parental history of mood disorders. METHODS: The sample includes 545 youth who were age 21 years or less at the time of their baseline assessment. Participants underwent baseline and yearly study assessments. Observations were censored at the time point closest to the first episode of suicidal behavior for youth with suicidal behavior and at the time of last observation for youth without suicidal behavior. Youth were categorized into 3 groups: first onset of suicidal behavior before the age of 13 (n=32), first onset of suicidal behavior between the ages of 13–21 (n=51) and those without suicide related behaviors (n=462). ANOVA, Chi-square, Fisher’s exact test and multinomial regression were used to test the hypotheses. RESULTS: Significant predictors of preadolescent onset suicidal behavior were diagnosis of depressive disorder (RRR=11.41, p

It has been argued that unipolar major depressive disorder (MDD) and bipolar disorder (BD) exist on a continuous spectrum, given their overlapping symptomatology and genetic diatheses. The Bipolarity Index (BI) is a scale that considers bipolarity as a continuous construct and was developed to assess confidence in bipolar diagnosis. Here we investigated whether BI scores correlate with gray matter volume (GMV) in a sample of unmedicated unipolar and bipolar depressed individuals.158 subjects (139 with MDD, 19 with BD) in a major depressive episode at time of scan were assigned BI scores. T1-weighted Magnetic Resonance Imaging scans were obtained and processed with Voxel-Based Morphometry using SPM12 (CAT12 toolbox) to assess GMV. Regression was performed at the voxel level to identify clusters of voxels whose GMV was associated with BI score, (p0.001, family-wise error-corrected cluster-level p0.05), with age, sex and total intracranial volume as covariates.GMV was inversely correlated with BI score in four clusters located in left lateral occipital cortex, bilateral angular gyri and right frontal pole. Clusters were no longer significant after controlling for diagnosis. GMV was not correlated with BI score within the MDD cohort alone.Incomplete clinical data required use of a modified BI scale.BI scores were inversely correlated with GMV in unmedicated subjects with MDD and BD, but these correlations appeared driven by categorical diagnosis. Future work will examine other imaging modalities and focus on elements of the BI scale most likely to be related to brain structure and function.

Background Smaller hippocampal volumes are reported in adults with major depressive disorder (MDD) and in reported childhood abuse. The hippocampus is a complex structure with distinct functional subfields. We sought to examine the effect of MDD diagnosis and childhood abuse on hippocampal subfields. Methods Forty-one MDD participants (17 reported abuse and 24 did not) and 46 healthy volunteers (HV) (2 reported abuse) underwent T1- weighted structural magnetic resonance imaging (MRI) and clinical characterization in a retrospective design. A subfield segmentation program was used to measure the whole and subfield hippocampal volumes. Linear mixed-effects models were fitted for group comparisons. Results No main effect of diagnosis interaction effect between diagnosis and subfield region was observed. However, a comparison of abused MDD vs. HVs showed a group by region interaction. A significant interaction between childhood abuse and region was observed. Effects were confined to the left side of the brain, and post hoc, exploratory region-specific tests indicated smaller left CA1 volume in abused MDD compared with non-abused MDD. In addition, smaller amygdala volume was found in all MDD compared with HVs. Limitations We did not have a sample of healthy volunteers with reported childhood abuse. Conclusions The diagnosis of pure MDD may not be sufficient to exert effects on hippocampal volumes, indicating the importance of taking into account childhood trauma in studies on psychopathological mechanisms. Left CA1 might be the hippocampal subfield most relevant to reported childhood abuse. Smaller amygdala volume may be related to MDD diagnosis independent of childhood abuse.

Background Our lab has previously found that structural integrity in tracts from the raphe nucleus (RN) to the amygdala, measured by fractional anisotropy (FA), predicts remission to selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder (MDD). This could potentially serve as a biomarker for remission that can guide clinical decision-making. To enhance repeatability and reproducibility, we replicated our study in a larger, more representative multi-site sample. Methods 64 direction DTI was collected in 144 medication-free patients with MDD from the Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) study. We performed probabilistic tractography between the RN and bilateral amygdala and hippocampus and calculated weighted FA in these tracts. Patients were treated with either sertraline or placebo, and their change in Hamilton Depression Rating Scale (HDRS) score reported. Pretreatment weighted FA was compared between remitters and nonremitters, and correlation between FA and percent change in HDRS score was assessed. Exploratory moderator and voxel analyses were also performed. Results Contrary to our hypotheses, FA was greater in nonremitters than in remitters in RN-left and right amygdala tracts (p = 0.02 and 0.01, respectively). Pretreatment FA between the raphe and left amygdala correlated with greater, not reduced, HDRS (r = 0.18, p = 0.04). This finding was found to be greater in the placebo group. Moderator and voxel analyses yielded no significant findings. Conclusions We found greater FA in nonremitters between the RN and amygdala than in remitters, and a correlation between FA and symptom worsening, particularly with placebo. These findings may help reveal more about the nature of MDD, as well as guide research methods involving placebo response.

Background Findings regarding brain circuitry abnormalities in suicide attempters (SAs) converge across bipolar disorder (BD) and major depressive disorder (MDD), the most common disorders observed in suicides. These abnormalities appear to be present during adolescence/young adulthood when suicide rates increase steeply, and suicide is a leading cause of death in this age group. Identification of brain circuitry common to adolescent/young adult SAs with BD and MDD is important for generating widely effective early prevention strategies. We examined brain circuitry in SAs in adolescents/young adults across these two disorders. Methods Eighty-three participants (ages 14–25 years), 46 with BD (21 SAs) and 37 with MDD (19 SAs), underwent structural and diffusion-weighted magnetic resonance scanning. Whole-brain analyses compared gray matter (GM) volume and white matter (WM) fractional anisotropy (FA) between SAs and non-suicide attempters (NSAs) across and within BD and MDD (p Results Across and within BD and MDD, SAs showed differences compared to NSAs in ventral prefrontal cortex (PFC) GM volume and fronto-limbic (including uncinate fasciculus (UF)) WM FA. Exploratory analyses showed additional within-disorder differences for BD SAs in dorsolateral PFC (dlPFC) and hippocampus GM volume and UF FA, and for MDD SAs dorsomedial and dlPFC GM and dorsal frontal WM. However, there was no significant interaction between suicide attempt status and diagnosis. Limitations Modest sample size. Conclusions Common fronto-limbic gray and white matter alterations in adolescent/young adult SAs are potential targets for suicide prevention strategies across mood disorders. Preliminary findings of disorder-specific regional findings could suggest diagnostic-specific optimal targets may exist.

BACKGROUND: Mood disorders are major risk factors for suicidal behavior. While cross-sectional studies implicate frontal systems, data to aid prediction of suicide-related behavior in mood disorders are limited. Longitudinal research on neuroanatomical mechanisms underlying suicide risk may assist in developing targeted interventions. Therefore, we conducted a preliminary study investigating baseline gray and white matter structure and longitudinal structural changes associated with future suicide attempts. METHODS: High-resolution structural magnetic resonance imaging, diffusion tensor imaging, and suicide-related behavioral assessment data for 46 adolescents and young adults with mood disorders [baseline age(mean)=18 years; 61% female] were collected at baseline and at follow-up (interval(mean)=3 years). Differences in baseline and longitudinal changes in gray matter volume and white matter fractional anisotropy in frontal systems that distinguished the participants who made future attempts from those who did not were investigated. RESULTS: Seventeen (37%) of participants attempted suicide within the follow-up period. Future attempters (those attempting suicide between their baseline and follow-up assessment), compared to those who did not, showed lower baseline ventral and rostral prefrontal gray matter volume and dorsomedial frontal, anterior limb of the internal capsule, and dorsal cingulum fractional anisotropy, as well as greater decreases over time in ventral and dorsal frontal fractional anisotropy (p

Background Neurocognitive deficits are common in depression, but most prior studies have not found strong associations between standard measures of symptom severity and the extent of these neurocognitive deficits. Diagnostic heterogeneity, or the lack of specific questions about neurocognition in these measures, may be undermining these associations. Method Neuropsychological performance was assessed via 10 tasks in a sample of 262 unmedicated patients with Major Depressive Disorder (MDD) and compared to that in healthy volunteers (n = 140), then correlated with (1) standard measures of depression severity including the Hamilton Depression Rating Scale and Beck Depression Inventory, (2) previously established, factor-analytically derived symptom factors that characterize the heterogeneity of these scales, and (3) a separate measure of cognitive complaint (Cognitive Failures Questionnaire) that was included to address the absence of specific questions about cognition in standard rating scales. Results Neurocognitive performance in these unmedicated MDD patients was not significantly associated with either total scores on the depression severity measures, any of their derived symptom factors, or the degree of subjective cognitive complaint – which itself was most strongly associated with mood disturbance. Limitations Depressed patients with the most prominent neurovegetative symptoms may be underrepresented in this sample. Conclusions Neurocognitive deficits were only weakly associated with standard depression symptom ratings, and not captured by self-report ratings of cognitive complaint. Neurocognitive deficits appear to be a separate symptom dimension that cannot be inferred from overall depression severity and require their own assessment, given that they have prognostic value for functional outcomes, suicide risk, and differential therapeutics.

Background Smartphone monitoring could contribute to the elucidation of the correlates of suicidal thoughts and behaviors (STB). In this study, we employ smartphone monitoring and machine learning techniques to explore the association of wish to die (passive suicidal ideation) with disturbed sleep, altered appetite and negative feelings. Methods This is a prospective cohort study carried out among adult psychiatric outpatients with a history of STB. A daily questionnaire was administered through the MEmind smartphone application. Participants were followed-up for a median of 89.8 days, resulting in 9,878 person-days. Data analysis employed a machine learning technique called Indian Buffet Process. Results 165 patients were recruited, 139 had the MEmind mobile application installed on their smartphone, and 110 answered questions regularly enough to be included in the final analysis. We found that the combination of wish to die and sleep problems was one of the most relevant latent features found across the sample, showing that these variables tend to be present during the same time frame (96 hours). Conclusions Disturbed sleep emerges as a potential clinical marker for passive suicidal ideation. Our findings stress the importance of evaluating sleep as part of the screening for suicidal behavior. Compared to previous smartphone monitoring studies on suicidal behavior, this study includes a long follow-up period and a large sample.

Background Major depressive disorder (MDD) is associated with impaired attention control and alterations in frontal-subcortical connectivity. We hypothesized that attention control as assessed by Stroop task interference depends on white matter integrity in fronto-cingulate regions and assessed this relationship using diffusion tensor imaging (DTI) in MDD and healthy volunteers (HV). Methods DTI images and Stroop task were acquired in 29 unmedicated MDD patients and 16 HVs, aged 18–65 years. The relationship between Stroop interference and fractional anisotropy (FA) was examined using region-of-interest (ROI) and tract-based spatial statistics (TBSS) analyses. Results ROI analysis revealed that Stroop interference correlated positively with FA in left caudal anterior cingulate cortex (cACC) in HVs (r = 0.62, p = 0.01), but not in MDD (r = −0.05, p= 0.79) even after controlling for depression severity. The left cACC was among 4 ROIs in fronto-cingulate network where FA was lower in MDD relative to HVs (F(1,41) = 8.87, p = 0.005). Additionally, TBSS showed the same group interaction of differences and correlations, although only at a statistical trend level. Limitations The modest sample size limits the generalizability of the findings. Conclusions Structural connectivity of white matter network of cACC correlated with magnitude of Stroop interference in HVs, but not MDD. The cACC-frontal network, sub-serving attention control, may be disrupted in MDD. Less cognitive control may include enhanced effects of salience in HVs, or less effective response inhibition in MDD. Further studies of salience and inhibition components of executive function may better elucidate the relationship between brain white matter changes and executive dysfunction in MDD.

BACKGROUND Serotonin transporter (5-HTT) binding and polyunsaturated fatty acids (PUFAs) are implicated in major depressive disorder (MDD). Links between the two systems in animal models have not been investigated in humans. METHODS Using positron emission tomography (PET) and [ 11 C]DASB, we studied relationships between 5-HTT binding potential and plasma levels of PUFAs docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (AA) in medication-free MDD patients ( n =21). PUFAs were quantified using transesterification and gas chromatography. Binding potential BP P , and alternative outcome measures BP F and BP ND , were determined for [ 11 C]DASB in six a priori brain regions of interest (ROIs) using likelihood estimation in graphical analysis (LEGA) to calculate radioligand total distribution volume (V T ), and a validated hybrid deconvolution approach (HYDECA) that estimates radioligand non-displaceable distribution volume (V ND ) without a reference region. Linear mixed models used PUFA levels as predictors and binding potential measures as outcomes across the specified ROIs; age and sex as fixed effects; and subject as random effect to account for across-region binding correlations. As nonlinear relationships were observed, a quadratic term was added to final models. RESULTS AA predicted both 5-HTT BP P and depression severity nonlinearly, described by an inverted U-shaped curve. 5-HTT binding potential mediated the relationship between AA and depression severity. LIMITATIONS Given the small sample and multiple comparisons, results require replication. CONCLUSIONS Our findings suggest that AA status may impact depression pathophysiology through effects on serotonin transport. Future studies should examine whether these relationships explain therapeutic effects of PUFAs in the treatment of MDD.

Background The lower-expressing (S′) alleles of the serotonin transporter (5-HTT) gene promoter polymorphism (5-HTTLPR) are linked to mood and anxiety related psychopathology. However, the specific neural mechanism through which these alleles may influence emotional and cognitive processing remains unknown. We examined the relationship between both 5-HTTLPR genotype and in vivo 5-HTT binding quantified via PET with amygdala reactivity to emotionally negative stimuli. We hypothesized that 5-HTT binding in both raphe nuclei (RN) and amygdala would be inversely correlated with amygdala reactivity, and that number of S′ alleles would correlate positively with amygdala reactivity. Methods In medication-free patients with current major depressive disorder (MDD; N =21), we determined 5-HTTLPR genotype, employed functional magnetic resonance imaging (fMRI) to examine amygdala responses to negative emotional stimuli, and used positron emission tomography with [ 11 C]DASB to examine 5-HTT binding. Results [ 11 C]DASB binding in RN and amygdala was inversely correlated with amygdala response to negative stimuli. 5-HTTLPR S′ alleles were not associated with amygdala response to negative emotional stimuli. Limitations Primary limitations are small sample size and lack of control group. Conclusions Consistent with findings in healthy volunteers, 5-HTT binding is associated with amygdala reactivity to emotional stimuli in MDD. 5-HTT binding may be a stronger predictor of emotional processing in MDD as compared with 5-HTTLPR genotype.

Background Suicide is a heterogeneous phenomenon, and thus defining more homogeneous subgroups may help in understanding its underlying biology and ultimately in its prevention. Suicidal ideation is far more common than suicidal behavior and predicts future suicide attempts. Hypothalamic–pituitary–adrenal (HPA)-axis reactivity has been implicated in individuals with suicidal ideation but findings are mixed with some studies showing increased and others demonstrating decreased reactivity. This suggests that dysregulation of HPA-axis is related to a specific character of suicidal ideation. We hypothesized that individuals with brief suicidal ideation are more stress responsive than those with longer/continuous ideation. Methods Thirty-five individuals with major depressive disorder (MDD) and 23 healthy volunteers (HVs), aged 18–65 years, underwent the Trier Social Stress Test (TSST). Salivary cortisol was measured at 6 time-points before and during TSST. Total severity and duration of current suicidal ideation were assessed using the Beck Scale for Suicidal Ideation (SSI). Brief suicidal ideators (N = 18), longer/continuous ideators (N = 17) and HVs were compared regarding cortisol response, baseline cortisol and total output. Results Participants with brief suicidal ideation had greater cortisol response compared to those with longer/continuous ideation and HVs, even after controlling for relevant covariates. However, total SSI score was not associated with cortisol response. Baseline cortisol and total output were not related to overall severity or duration of suicidal ideation. Limitations The cross-sectional design and modest sample limit generalizability of the results. Conclusions Hyper-responsiveness of HPA-axis to social stress is associated with brief suicidal ideation, possibly defining a pathway for exploring the biological subtyping of suicidal individuals.

An estimated 350 million people live with depression worldwide. In Mozambique, there are no national data quantifying the burden of mental illnesses. With the sixth highest suicide rate in the world, there is strong evidence of an unmet mental health need. We conducted a survey to measure the prevalence of depression among female heads of household and assess individual, social, and cultural risk factors associated with a positive depression screening.This survey was conducted across 14 rural districts in central Mozambique in 2014. We gathered information from 3543 female heads of household (100% response rate) on500 variables, including a depression screening tool (PHQ-8). Weighted percentages of survey responses are reported.Among female heads of household, 14% screened positive for depression (PHQ-8 score ≥ 10). Our adjusted models show increased odds of depression per additional year of age (aOR: 1.02 [1.01, 1.04]; p = 0.002), additional year of education (aOR: 1.06 [1.02, 1.11]; p = 0.006), and additional kilometer from the nearest clinic (aOR: 1.05 [1.02, 1.07]; p =0.001). Experiencing food insecurity (aOR: 1.05 [1.02, 1.08]; p = 0.003) was associated with increased odds of depression. Being single (aOR: 0.42 [0.29, 0.60]) or divorced/widowed/separated (aOR: 0.57 [0.34, 0.98]; p0.001) vs. married was protective against depression, as was a perceived "sufficient" household income (aOR: 0.37 [0.19, 0.69]; p = 0.008).Social desirability bias may have led women to underreport feelings of depression.The association of more education and marriage with increased odds of depression may reflect a frustration with limited opportunity for success experienced by some women in rural Mozambique.

Background Suicidal ideation appears to be more strongly associated with subjective rather than neurovegetative symptoms of depression. Effective treatment, then, should produce reductions in suicidal ideation to the degree that these subjective symptoms are alleviated relative to treatment effects on other symptoms. Methods In a randomized clinical trial comparing paroxetine and bupropion for treatment of depression in patients with either suicidal ideation or past attempt, depression severity and suicidal ideation were assessed weekly during the 8-week study. Depression rating scales - the 24-item Hamilton Depression Rating Scale [HDRS] and the Beck Depression Scale [BDI] - were decomposed into symptom clusters based on our published factor analyses, and their change over time compared to changes on the Beck Scale for Suicidal Ideation [SSI]. Results Improvement in factor scores associated with subjective symptoms of depression - HDRS Psychic Depression, BDI Subjective Depression, and BDI Self-Blame - were the best predictors of declining scores on the SSI regardless of type of drug treatment. BDI Subjective Depression was the best single predictor in the context of all other significant univariate predictors, accounting for 31.4% of the variance in the change in SSI. The three factors together accounted for 35.3%. Limitations This is a secondary analysis of clinical trial data, with fixed treatments. Conclusions Effective treatments to reduce suicidal ideation are associated with the reduction of the subjective symptoms of depression, which may not always decline in synchrony with improvement in neurovegetative symptoms. This asynchrony may result in a period of elevated risk after the initiation of therapy. Data indicate that subjective depression symptoms should be a primary target in the treatment of depressed suicidal patients.

Considerable evidence suggests that testosterone may play a role in the pathophysiology of mood disorders in females. This is the first prospective study to examine whether blood testosterone levels predict suicide attempts in females with bipolar disorder.Females with a DSM-IV diagnosis of a bipolar disorder in a depressive or mixed episode with at least one past suicide attempt were enrolled. Demographic and clinical parameters were assessed and recorded. Plasma testosterone was assayed using a double antibody radioimmunoassay procedure. Patients were followed up prospectively for up to 2.5 years.At baseline, testosterone levels positively correlated with the number of previous major depressive episodes and suicide attempts. Cox proportional hazards regression analysis found that higher baseline testosterone levels predicted suicide attempts during the follow-up period.A limitation of the study is that the sample size is modest. Another limitation is that we did not have a bipolar nonattempter or healthy volunteer control group for comparison.Testosterone levels may predict suicidal behavior in women with bipolar disorder.

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.

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.

Background Desire for death is not generally considered a harbinger of more severe suicidal behavior and is not routinely included in suicide research and assessment interviews. We aimed to compare desire for death and suicidal ideation as clinical markers for suicide attempts. Methods Using data from two nationally representative surveys (n = 42,862 and n = 43,093 respectively), we examined whether desire for death predicts suicide attempts. We compared the odds ratio (OR) and “Number Needed to be Exposed for one additional person to be Harmed” [NNEH] for lifetime suicide attempts among those with desire for death but no suicidal ideation; those with suicidal ideation but no desire for death, and those with both desire for death and suicidal ideation, compared to those with neither desire for death nor suicidal ideation. Results The risk for lifetime suicide attempt was similar among those with lifetime desire for death with no suicidal ideation and those with lifetime suicidal ideation with no desire for death. Respondents with both lifetime desire for death and suicidal ideation had the highest risk for lifetime suicide attempts. Limitations Cross-sectional design and self-reported suicidal ideation/attempts are viewed as limitations of this study. Conclusions Querying individuals on desire for death has the same value as assessing suicidal ideation to examine risk for suicide attempt. A combination of desire for death and suicidal ideation is the best predictor for suicide attempts. This is of high clinical relevance since we suggest that desire for death should be included as a potential clinical marker of suicidality in clinical assessments.

We compared brain-map correlations of relative cerebral glucose metabolism (rCMRglu) with psychopathologic factors derived from the self-rated Beck Depression Inventory (BDI) and factors from the clinician-rated Hamilton Depression Rating Scale (HDRS) factors, seeking an anatomic basis for differences in self and clinician ratings.[(18)F]-FDG Positron Emission Tomography generated rCMRglu, SPM-estimated, voxel-level, brain correlation maps with BDI factor scores and HDRS factor scores in medication-free major depressive disorder.Regional brain correlates of BDI are more extensive than HDRS, even when adjusting for variance accounted for by the HDRS. Factors comprising the BDI were associated with distinct cortical and subcortical regions. The degree of overlap in factor correlation brain maps is explained by the variance shared by BDI and HDRS factor scores.Self and clinician-rated aspects of depression have common and distinct neuroanatomic correlates that reflect correlations between rating scales, but correlations between glucose metabolism and self-rated depression were anatomically more extensive in this sample. Findings highlight the importance and biological underpinnings of these subjective features of major depression.

We aimed to examine the adequacy of antidepressant treatment and compliance with treatment in bipolar patients with and without alcohol use disorders (AUD). We hypothesize that the adequacy of antidepressant treatment and the compliance with treatment for those with AUD are lower than for those without AUD.Subjects were 97 patients with current bipolar major depressive episode, 39 (40.2%) with lifetime history of AUD and 58 (59.8%) without AUD. Adequacy of antidepressant medication treatment in the 3 previous months was assessed using the Antidepressant Treatment History Form. Compliance rates were estimated.Rates of inadequate treatment were high in all patients. Bipolar patients with AUD (74.3%) showed higher rates of inadequate antidepressant treatment than those without AUD (67.3%). The proportion of intensive treatment was higher in bipolars without AUD (15.5%) than in those with AUD (2.6%). Median compliance was similar in bipolars with and without AUD.We lack serum medication levels to assess the compliance. We do not have data to address the possibility that the presence of AUD adversely affected prescribing practices.Bipolars with AUD had lower rates of adequate treatment than those without AUD, but the two groups were not different in terms of self-reported treatment adherence. The finding that bipolar patients with or without comorbid AUD did not receive adequate treatment is of considerable clinical relevance. It raises the question as to whether inadequate treatment of depression contributes to the high rates of morbidity, and attempted and completed suicides in bipolar patient populations.

A number of studies have compared clinical diagnostic and suicide assessments to standardized schedules to determine the level of agreement. At best there is only moderate diagnostic agreement, but most often it is fair. There are only a few reports comparing clinical assessments for suicidal behavior with standardized schedules. We present the data from 201 inpatient admissions for major depression that had both clinical diagnostic and suicide evaluations by PGYII resident physicians under supervision from an attending psychiatrist and research evaluations using standardized schedules for diagnosis and suicide by at least masters' level clinicians. There was moderate agreement for diagnosis and suicide attempt history but only fair agreement for the presence of suicidal ideation using Cohen's kappa statistic. In regards to suicide attempt history a cross-tabulation demonstrated that 18.7% of those patients identified by a research schedule as having a past suicide attempt were not identified as such by the clinicians. A cross-tabulation demonstrated that 29.7% of those patients identified by structured interview as having suicidal ideation were not identified as such by the clinician. There was a statistically significant difference in the level of agreement for suicide attempt history between clinical and research assessments for attempts within a year of admission and those beyond a year. These findings suggest the importance of adding a structured diagnostic and suicide assessment to routine clinical care to improve the reliability and validity of clinical evaluations and to inform treatment planning to benefit our patients.

Background Assessment of suicide plans is standard in acute psychiatric care, but there is a limited evidence base to guide this routine clinical practice. The purpose of this study was to investigate clinical correlates of suicide planning in depressed patients. Methods 151 patients with major depressive disorder and a lifetime history of suicide attempt were studied. Subjects received a comprehensive evaluation including structured diagnostic interview for Axis I and II disorders, current symptoms, impulsivity, and systematic assessment of suicide planning prior to the most recent suicide attempt. Results Seriousness of suicide attempt planning correlated with lethality of suicidal acts. Comorbid anxiety disorder and anxiety correlated with less suicide planning. Specifically, this negative correlation was with comorbid panic disorder. Planning did not correlate with severity of depression or aggressive/impulsive traits. Limitations Cross-sectional design, retrospective recall of suicide planning data, limited applicability to completed suicide or other psychiatric disorders. Conclusions In major depression, comorbid panic disorder appears protective against more carefully planned, higher lethality suicide attempts. Surprisingly, severity of depression and aggressive impulsive traits do not predict planning or lethality of suicide attempts. We have previously reported that anxiety severity protects against the probability of a suicide attempt and now extend that observation to show there is protection against lethality of a suicide attempt. Treatment of anxiety without directly treating major depression may place patients at greater risk of suicidal behavior.

Background Bipolar disorder (BD) is associated with a high prevalence of suicide attempt and completion. Family history of suicidal behavior and personal history of childhood abuse are reported risk factors for suicide among BD subjects. Methods BD individuals with family history of suicidal behavior and personal history of childhood abuse (BD-BOTH), BD individuals with family history of suicidal behavior or personal history of childhood abuse (BD-ONE), and BD individuals with neither of these two risk factors (BD-NONE) were compared with regard to demographic variables and clinical measures. Results Almost 70% of the sample had a history of a previous suicide attempt. There were significantly higher rates of previous suicide attempts in the BD-BOTH and BD-ONE relative to the BD-NONE group. BD-BOTH were significantly younger at the time of their first suicide attempt and had higher number of suicide attempts compared with BD-NONE. BD-BOTH were significantly younger at the time of their first episode of mood disorder and first psychiatric hospitalization and had significantly higher rates of substance use and borderline personality disorders compared to BD-NONE. Limitations Retrospective study. Use of semi-structured interview for the assessment of risk factors. Conclusions BD individuals with a familial liability for suicidal behavior and exposed to physical and/or sexual abuse during childhood are at a greater risk to have a more impaired course of bipolar illness and greater suicidality compared to those subjects with either only one or none of these risk factors. Prospective studies are needed to confirm these findings.

Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in serotonin synthesis. TPH2 is a recently discovered isoform that is expressed predominantly in serotonin neurons. Associations are reported of TPH2 polymorphisms with MDD, bipolar disorder and suicidal behavior. This study examines a single nucleotide polymorphism in the putative promoter region of the TPH2 gene.One hundred nine bipolar, 324 major depressive disorder, and 130 healthy volunteers were genotyped for the rs4131347 (-C8347G) promoter SNP. Association was assessed with diagnosis, suicide attempt status, severity of psychopathology and cerebrospinal fluid monoamine metabolite levels of 5-HIAA, HVA, and MHPG. General linear models and logistic regression tested the effect of genotype*childhood abuse interactions on psychopathology severity and suicide attempt.There was no association between genotype and either mood disorder, suicide attempt status, psychopathology severity or CSF monoamine metabolite levels.No association was detected between the rs4131347 (-C8347G) SNP in the promoter region of the TPH2 gene and mood disorders, suicidal behavior or monoamine function.

Background There are limited data on depressive symptoms and antidepressant use in ethnically diverse, urban elderly. Methods Analysis of depressive symptom and antidepressant use data from an epidemiological survey of dementia in an ethnically diverse, urban, elderly community. Results 21.5% ( N = 566) reported clinically significant depressive symptoms. Severity was inversely associated with socioeconomic status. 7.5% ( N = 194) reported antidepressant medication use. Multiple logistic regression analysis adjusting for severity and other covariates showed that men and African Americans had nearly half the odds of using antidepressants. Antidepressant use was more frequent among Hispanics, those with more severe depression and more medical illness. Limitations Combined sample; CES-D not validated in Hispanics and inner-city African Americans; depressive symptoms assessed at one time-point; lack of complete income data; geographically restricted. Conclusions In this elder sample, taking into account depressive symptom severity and other confounds, antidepressant use is nearly half as likely among men and African Americans.

Background Defining bipolar disorder (BD) subtypes with increased risk of suicidal behavior may help clinical management. We tested the hypothesis that the polarity of a patient's first mood episode would be a marker for BD subtypes with differential risk for suicidality. Methods One hundred thirteen subjects with DSM-IV defined BD were classified based on whether their first reported episode was manic/hypomanic (FM) or depressed (FD). They were compared on demographic and clinical variables. Logistic regression adjusting for potential confounds tested the association between first episode polarity and history of suicide attempt. Results Multiple logistic regression analysis showed that FD group membership was associated with eightfold odds of a past suicide attempt, adjusting for years ill and total number of lifetime major depressive episodes. Limitations Sample size, retrospective design, recall bias, assessment during a mood episode, and imprecise recall of hypomania. Conclusions Polarity of patients' first reported mood episode suggested a depression-prone subtype with a greater probability of past suicide attempt. The FM group had more alcoholism and psychosis, but less likelihood of past suicide attempt. Validation of these putative subtypes requires prospective study.

Background: Comorbid personality disorders may predispose patients with mood disorders to suicide attempts (SAs), but factors mediating this effect are not well known. Methods: Altogether 597 patients from three prospective cohort studies (Vantaa Depression Study, Jorvi Bipolar Study, and Vantaa Primary Care Depression Study) were interviewed at baseline, at 18 months, and in VDS and PC-VDS at 5 years. Personality disorders (PDs) at baseline, number of previous SAs, life-charted time spent in major depressive episodes (MDEs), and precise timing of SAs during follow-up were determined and investigated. Results: Overall, 219 (36.7%) patients had a total of 718 lifetime SAs; 88 (14.7%) patients had 242 SAs during the prospective follow-up. Having any PD diagnosis increased the SA rate, both lifetime and prospectively evaluated, by 90% and 102%, respectively. All PD clusters increased the rate of new SAs, although cluster C PDs more than the others. After adjusting for time spent in MDEs, only cluster C further increased the SA rate (by 52%). Mediation analyses of PD effects on prospectively ascertained SAs indicated significant mediated effects through time at risk in MDEs, but also some direct effects. Limitations: Findings generalizable only to patients with mood disorders. Conclusions: Among mood disorder patients, comorbid PDs increase the risk of SAs to approximately two-fold. The excess risk is mostly due to patients with comorbid PDs spending more time in depressive episodes than those without. Consequently, risk appears highest for PDs that most predispose to chronicity and recurrences. However, also direct risk-modifying effects of PDs exist. (C) 2015 Elsevier B.V. All rights reserved.

Background Many, but not all studies of suicide attempters' cortisol response to stress-either social stress or pharmacological challenge-report an exaggerated response. Recent studies of resting baseline cortisol in past suicide attempters, however, have found lower baseline levels. Methods In this study, baseline salivary cortisols were obtained prior to a stress procedure from adults with lifetime diagnoses of a mood disorder ( N =69), 31.9% of whom had made a prior suicide attempt. Data were collected during the piloting of this stress procedure, at various times of day and with/without an additional confederate in the room. Results Adjusting for procedural, demographic and clinical variables that affect salivary cortisol levels-including time of day of sampling, order of procedure with respect to other assessments, past alcohol abuse, current medication use, and bipolar diagnosis-past suicide attempters had lower baseline cortisol levels compared to non-attempters. Limitations This is a pilot study with modest sample sizes using statistical, rather than experimental control of numerous variables affecting salivary cortisol levels. Conclusions Results confirm previous studies. Low baseline cortisol levels have been associated with childhood adversity and externalizing disorders, suggesting a potential role in reducing inhibitions for risky and dangerous behaviors. Further research is needed to more fully characterize these associations and their role in suicidal behavior risk.

It is not clear if bipolar disorder I (BPI) and bipolar disorder II (BPII) represent the same disorder on a continuum of severity or two distinct syndromes. Neuropsychological functioning is a means of understanding similarities and differences between diagnostic groups. Objective To compare the neuropsychological functioning of depressed suicide attempters with BPI or BPII and healthy controls. Methods Fifty-one individuals with bipolar disorder (BPI n = 32, BPII n = 19) and a history of suicide attempt were compared with 58 healthy controls with respect to neuropsychological functioning in the following domains: motor functioning, psychomotor performance, attention, memory, working memory, impulsiveness and language fluency. Results Participants with BPI and BPII performed significantly more poorly than healthy controls on tests of Digit Symbol Test of psychomotor functioning, the N Back Test of working memory and the Go-No-Go Test of impulsiveness. Participants with BPI were significantly worse than controls but not those with BPII on the Test of Verbal Fluency. Participants with BPII performed significantly worse than either controls or those with BPI on the Simple Reaction Time Motor Test and the Stroop Test of attention. Conclusion While participants with both BPI and BPII performed more poorly than healthy controls, individuals with BPII also performed more poorly than those with BPI on some tests suggesting that they may have a unique syndrome. The findings have implications for assessment and treatment in bipolar disorder.

Background : Post-traumatic stress disorder (PTSD) and major depression are frequently comorbid. Age and major depression are associated with higher cortisol levels and dexamethasone resistance, whereas PTSD is associated with lower cortisol and dexamethasone supersensitivity. Therefore, we examined the effect of age on the hypothalamic–pituitary–adrenal (HPA) system in depressed patients with and without PTSD. Methods : Thirty-one depressed patients without PTSD, 12 depressed patients with PTSD, and 23 healthy volunteers were studied on 2 days. Subjects received single-blind placebo on day 1 and fenfluramine on day 2. Cortisol levels were drawn before challenge and for 5 h thereafter. Results : Cortisol levels increase with age in depressed patients without PTSD but not in depressed patients with PTSD or in healthy volunteers. Number of previous major depressive episodes was a predictor of the cortisol response to fenfluramine administration in depressed patients without PTSD. Conclusions : The results of our study highlight the importance of considering age in psychobiology. Further research is needed to fully delineate the role of age in abnormalities of the HPA axis found in major depression and PTSD.

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.

Objective: Bipolar Disorder is associated with a higher frequency of attempted suicide than most other psychiatric disorders. The reasons are unknown. This study compared bipolar subjects with a history of a suicide attempt to those without such a history, assessing suicidal behavior qualitatively and quantitatively, and examining possible demographic, psychopathologic and familial risk factors. Methods: Patients (ages 18 to 75) with a DSM III-R Bipolar Disorder (n=44) diagnosis determined by a structured interview for Axis I disorders were enrolled. Acute psychopathology, hopelessness, protective factors, and traits of aggression and impulsivity were measured. The number, method and degree of medical damage was assessed for suicide attempts, life-time. Results: Bipolar suicide attempters had more life-time episodes of major depression, and twice as many were in a current depressive or mixed episode, compared to bipolar nonattempters. Attempters reported more suicidal ideation immediately prior to admission, and fewer reasons for living even when the most recent suicide attempt preceded the index hospitalization by more than six months. Attempters had more lifetime aggression and were more likely to be male. However, attempters did not differ from nonattempters on lifetime impulsivity. Limitations: The generalizability of the results is limited because this is a study of inpatients with a history of suicide attempts. Patients with Bipolar I and NOS Disorders were pooled and a larger sample is needed to look at differences. We could not assess psychopathology immediately prior to the suicide attempt because, only half of the suicide attempters had made attempts in the six months prior to admission. Patients with current comorbid substance abuse were excluded. No suicide completers were studied. Conclusions: Bipolar subjects with a history of suicide attempt experience more episodes of depression, and react to them by having severe suicidal ideation. Their diathesis for acting on feelings of anger or suicidal ideation is suggested by a higher level of lifetime aggression and a pattern of repeated suicide attempts.

Background Whether suicide attempters and completers represent the same population evaluated at different points along a progression towards suicide death, overlapping populations, or completely different populations is a problem still unresolved. Methods 446 Adult suicide attempters and knowledgeable collateral informants for 190 adult suicide probands were interviewed. Sociodemographic and clinical data was collected for both groups using semi-structured interviews and structured assessments. Univariate analyses and logistic regression models were conducted to explore the similarities and differences between suicide attempters and completers. Results Univariate analyses yielded significant differences in sociodemographics, recent life events, impulsivity, suicide intent, and distribution of Axis I and II disorders. A logistic regression model aimed at distinguishing suicide completers from attempters properly classified 90% of subjects. The most significant variables that distinguished suicide from attempted suicide were the presence of narcissistic personality disorder (OR=21.4; 95% CI=6.8–67.7), health problems (OR=20.6; 95% CI=5.6–75.9), male sex (OR=9.6; 95% CI=4.42–20.9), and alcohol abuse (OR=5.5; 95% CI=2.3–14.2). Limitations Our study shares the limitations of studies comparing suicide attempters and completers, namely that information from attempters can be obtained from the subject himself, whereas the assessment of completers depends on information from close family or friends. Furthermore, different semi-structured instruments assessed Axis I and Axis II disorders in suicide attempters and completers. Finally, we have no data on inter-rater reliability data. Conclusions Suicide completers are more likely to be male and suffer from alcohol abuse, health problems (e.g. somatic illness), and narcissistic personality disorder. The findings emphasize the importance of implementing suicide prevention programs tailored to suicide attempters and completers.

Background Suicidal ideation is common in depression, but only moderately related to depression severity — in part because certain clusters of symptoms, such as those related to core mood disturbance, have a differential relationship to suicidal thinking. Methods 400 medication free participants with current major depression were assessed with either or both the Hamilton Depression Rating Scale (HDRS, n = 396) and Beck Depression Inventory (BDI, n = 366), and the Scale for Suicide Ideation (SSI). Depression rating scales were decomposed into symptoms clusters previously reported (Grunebaum et al., 2005), in order to evaluate their association to suicidal thinking. Results Correlations between overall depression severity ratings and the measure of suicidal ideation were modest, and reduced when specific items assessing suicidal thinking on these depression scales were removed. Symptom clusters assessing Psychic Depression (HDRS), Subjective Depression (BDI), and Self-Blame (BDI) were the strongest correlates of suicidal ideation; other somatic and vegetative symptoms had little or no association to suicidal ideation. Severity of these symptom clusters effectively discriminated those with (SSI > 0) and without (SSI = 0) ideation; severity of these symptom clusters was less strongly associated with the severity of ideation once ideation was present. Limitations This is a cross-sectional study, and the dynamic relationship between changes in the severity of various depressive symptoms and change in suicidal thinking remains to be explored. Conclusions Depression severity is moderately associated with suicidal ideation, and accounted for primarily by core mood disturbance symptoms and self-punitive thinking. These associations may explain why suicide risk might remain high during treatment even though somatic and vegetative symptoms improve.

Desire for death is not generally considered a harbinger of more severe suicidal behavior and is not routinely included in suicide research and assessment interviews. We aimed to compare desire for death and suicidal ideation as clinical markers for suicide attempts.Using data from two nationally representative surveys (n=42,862 and n=43,093 respectively), we examined whether desire for death predicts suicide attempts. We compared the odds ratio (OR) and "Number Needed to be Exposed for one additional person to be Harmed" [NNEH] for lifetime suicide attempts among those with desire for death but no suicidal ideation; those with suicidal ideation but no desire for death, and those with both desire for death and suicidal ideation, compared to those with neither desire for death nor suicidal ideation.The risk for lifetime suicide attempt was similar among those with lifetime desire for death with no suicidal ideation and those with lifetime suicidal ideation with no desire for death. Respondents with both lifetime desire for death and suicidal ideation had the highest risk for lifetime suicide attempts.Cross-sectional design and self-reported suicidal ideation/attempts are viewed as limitations of this study.Querying individuals on desire for death has the same value as assessing suicidal ideation to examine risk for suicide attempt. A combination of desire for death and suicidal ideation is the best predictor for suicide attempts. This is of high clinical relevance since we suggest that desire for death should be included as a potential clinical marker of suicidality in clinical assessments.

The tryptophan hydroxylase 1 (TPH1) gene is reported to be associated with suicidal behavior. This has not been confirmed by prospective studies of suicide and clinical or biological mediators of this genetic risk have not been identified.343 subjects (Caucasian, African-American, Hispanic) presenting with a Major Depressive Episode were genotyped for polymorphisms A218C in intron 7 and A-6526G in the promoter region of TPH1, and monitored for suicide attempts for up to one year. Clinical correlates of suicidal behavior and CSF-HIAA, HVA and MHPG levels were explored as possible mediators of genetic risk. Analyses were adjusted for ethnicity.The AA genotype on intron 7 and the AA genotype on the promoter (both more prevalent in Caucasians) predicted suicide attempts during the 1 year follow-up, and were associated with past attempts of high medical lethality, regardless of ethnicity. The intron 7 genotype was associated with fewer reported reasons for living, and lower impulsivity. Haplotype analysis indicated significant increase in risk of suicide attempts for subjects with four risk alleles. TPH1 genotype was not associated with CSF metabolite levels.The TPH1 gene is likely one of several genes associated with suicidal behavior. Power to detect differential genotype effects by ethnicity is low.Polymorphisms of TPH1 may assist in identifying a subgroup of mood disorder patients that is at higher risk for suicidal behavior.

Background Mood disorders exhibit familial transmission due to both environmental and genetic risk factors. Mood disorders are more common in women, yet the role of gender in the familial transmission of mood disorders is unclear. This study examines rates of mood disorder transmission to offspring based on the sex of affected parent, sex of offspring and role of clinical factors, such as childhood abuse history, comorbid psychiatric disorders, and traits of aggression and impulsivity. Methods Risk of transmission of mood disorder to offspring from females and males was compared in a sample of 272 probands with a major mood disorder using generalized estimating equations (GEE). Demographic and clinical characteristics of all male and female probands were compared. Characteristics that differed in probands were entered into the model to obtain an unbiased test of gender differences in transmission rate. Multivariate GEE models, one for male probands and one for female probands, were used to test for risk factors in transmission of mood disorder. Results Familial transmission rate of mood disorders from female probands was almost double that of males. There was no difference in transmission to male or female offspring. For male probands, offspring mood disorder was independently associated with earlier age of proband mood disorder onset, greater number of proband years ill, and proband history of childhood abuse. For female probands, offspring mood disorder was associated with higher aggression scores in probands. Limitations We did not directly interview offspring and also had limited data on psychopathology in co-parents. This is a cross-sectional study and cannot account for emergence of illness in offspring in the future. Conclusions The two-fold higher rate of maternal transmission of mood disorder may reflect differences in regulation of maternal and paternal transmission of mood disorder. Future studies need to determine the relative contribution of genetic and non-genetic factors and identify the factors responsible for higher rates of transmission of mood disorders by females with a mood disorder.

Background Global severity on depression scales may obscure associations between specific symptoms and suicidal behavior. Methods We studied 298 persons with major depressive disorder. Factor analysis of the 24-item Hamilton Depression Rating Scale (HDRS) and the Beck Depression Inventory (BDI) was used to compare symptom clusters between past suicide attempters and non-attempters. Results Factor analyses extracted five HDRS and three BDI factors. Suicide attempters had significantly lower scores on an HDRS anxiety factor and higher scores on a BDI self-blame factor. The factor scores correlated with total number of suicide attempts and with known risk factors for suicidal behavior. Limitations The differences in factor scores between suicide attempters and non-attempters were significant but modest and may be most relevant in suggesting areas for further clinical studies. Structured diagnostic interviews in this study may have limited the detection of Bipolar II or milder bipolar spectrum disorders. Conclusions Depressed suicide attempters exhibit comparably severe mood and neuro-vegetative symptoms, but less anxiety and more intense self-blame than non-attempters. This clinical profile may help guide studies of biological correlates and of treatments to reduce suicide risk.

Background : Positron Emission Tomography (PET) studies have reported altered resting regional brain glucose metabolism in mood disorders. This study examines the relationship of such changes to serotonin system abnormalities associated with depression. Methods : Thirteen male medication free subjects who were inpatients with a DSM-IIIR major depressive disorder and seven healthy male subjects underwent an [ 18 F]-fluorodeoxyglucose ( 18 FDG) PET scan on consecutive days. Three hours prior to 18 FDG subjects received single blind placebo or fenfluramine. Comparisons of voxel level regional glucose metabolic rate responses (rCMRglu) between groups in the two states were performed with SPM99. Results : Unlike healthy male subjects who have significant increases in rCMRglu in prefrontal and parietal cortical regions after receiving fenfluramine, depressed male subjects have no significant increases in rCMRglu. Conclusions : Blunted increases in rCMRglu in response to fenfluramine in prefrontal and parietal cortex are consistent with our previous pilot study and the indoleamine hypothesis of depression. Differences in specific brain regions affected between this study and previous studies may be attributable to gender differences.

Background : Seasonal variations in onset of mood disorders and in serotonergic function are reported, but their relationship is unclear. Methods : Circannual variation in platelet 5-HT 2A binding was measured in 68 healthy subjects and 121 patients with a major depressive episode. In 73 patients the current episode began during Spring or Fall. Results : Significant, but different, circannual variations were found in patients compared with controls. Controls had two peaks of B max , one in Spring and another in Fall. Fall and Winter K D was 41% lower compared with Spring and Summer K D . Patients had a peak of B max in early Spring and a lesser one in late Fall. B max during Spring and Fall was 12% higher compared with Winter and Summer. K D was higher during October through February compared with the rest of the year. B max in patients was higher compared with controls in March. The opposite difference was observed in September–December. These differences from controls were mostly due to patients with an onset of the current major depressive episode during Spring or Fall. Conclusions : Patients with a major depressive episode differed from controls in circannual variation of platelet 5-HT 2A binding. This may reflect a vulnerability to seasonal effects in patients with mood disorders.