Kevin M. Malone

Suicidal behavior in bipolar mood disorder: clinical characteristics of attempters and nonattempters

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.

Major depression and the risk of attempted suicide

We examined the risk of attempted suicide in 100 inpatients during a major depressive episode. We hypothesized that patients who attempt suicide have a vulnerability for suicidal behavior independent of severity or duration of depression, manifested by suicide attempts early in the course of a depressive episode. The first 3 months after the onset of an MDE and the first 5 years after the lifetime onset of major depressive disorder represented the highest-risk period for attempted suicide, independent of the severity or duration of depression. Familial, genetic, early-life loss experiences and comorbid alcoholism may be causal factors.

Cerebrospinal fluid amines and higher-lethality suicide attempts in depressed inpatients

Previous studies have found that not all suicide attempters with major depression have reduced serotonergic activity based on low cerebrospinal fluid 5-hydroxyindoleacetic acid (CSF- 5-HIAA) levels. In this study we hypothesized that serotonergic function is lower in depressed patients who have carried out high-lethality suicide attempts resulting in more medical damage, which might explain differences in serotonergic activity among depressed suicide attempters. We assessed the relationship of CSF 5-HIAA and other amine metabolites to the most lethal lifetime suicide attempt in 22 drug-free inpatients with major depression. CSF 5-HIAA levels were lower in depressed patients with a history of a high-lethality or well-planned suicide attempt compared to depressed patients with a history of only low-lethality suicide attempt(s). Other CSF monoamine metabolites did not correlate with suicidal behavior. Low serotonergic activity may correlate with a predisposition to more lethal suicide attempts in major depression.

Aggressivity, suicide attempts, and depression: relationship to cerebrospinal fluid monoamine metabolite levels

BACKGROUND We have proposed a stress-diathesis model for suicidal behavior, in which major depression is a stressor and the diathesis is shared with aggression. Neurotransmitter correlates of the stress or diathesis have not been adequately evaluated by previous studies, because they did not simultaneously examine the relationship of multiple neurotransmitters to all three psychopathologies in the same population. In the present study we investigated the relationship of monoamine metabolites to aggressivity, suicidal behavior, and depression in patients with mood disorders. METHODS Ninety-three drug-free subjects with a major depressive episode underwent lumbar puncture and psychiatric evaluation. Cerebrospinal fluid CSF levels of 5hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA) and methoxy-hydroxy-phenylglycol (MHPG) were assayed. The relationships between monoamine metabolites and clinical variables were statistically evaluated. RESULTS Higher lifetime aggressivity correlated significantly with lower CSF 5-HIAA. Lower CSF 5-HIAA and greater suicidal intent were found in high-lethality suicide attempters compared with low-lethality suicide attempters. Low-lethality attempters did not differ biologically from nonattempters. No correlation between CSF HVA and any of the psychopathological variables was found. Only aggression showed a trend statistically in correlating positively with CSF MHPG levels. CONCLUSIONS Lower CSF 5-HIAA concentration was independently associated with severity of lifetime aggressivity and a history of a higher lethality suicide attempt and may be part of the diathesis for these behaviors. The dopamine and norepinephrine systems do not appear to be as significantly involved in suicidal acts, aggression, or depression. The biological correlates of suicide intent warrant further study.

Mindfulness-based cognitive therapy for residual depressive symptoms

OBJECTIVES Mindfulness-based cognitive therapy (MBCT) is a new group-based intervention for prevention of relapse in recurrent depression which has not been scientifically evaluated regarding its clinical effectiveness for ameliorating residual depressive symptoms following a depressive episode. The aim of this study was to assess the efficacy of MBCT in reducing residual depressive symptoms in psychiatric outpatients with recurrent depression, and to particularly explore the effects of mindfulness techniques on rumination. DESIGN The design of this study was a mixed model complex design. Design 1 consisted of a consecutive series of patients. They were assigned to either MBCT or TAU. The independent variables were time and group allocation, and dependent variables were Beck Depression Inventory (BDI) and Rumination Scale. In Design 2, the TAU group proceeded to complete an MBCT group, and the BDI and Rumination Scale results of the two groups were collapsed. METHOD Nineteen patients with residual depressive symptoms following a depressive episode, and who were attending outpatient clinic, were assigned to either MBCT or treatment as usual (TAU), with the TAU group then proceeding to complete an MBCT group. Depressive and ruminative symptoms were assessed before, during, and after treatment, and at one-month follow-up. RESULTS A significant reduction in depressive symptoms was found at the end of MBCT, with a further reduction at one-month follow-up. A trend towards a reduction in rumination scores was also observed. CONCLUSIONS Group MBCT has a marked effect on residual depressive symptoms, which may be mediated through the mindfulness-based cognitive approach towards excessive negative ruminations in patients with residual depressive symptoms following a depressive episode.

Attempted suicide characteristics and cerebrospinal fluid amine metabolites in depressed inpatients.

Background: Serotonin abnormalities have been reported in the brain of suicide victims. Evidence of a serotonin deficiency in suicide attempters is less consistent. We hypothesized that a serotonin deficiency may be present in suicide attempters whose attempt behavior more closely approximates completed suicide. Method: Sixty-seven (67) drug-free depressed inpatients (46 suicide attempters, 21 nonattempters) underwent research clinical assessments and a lumbar puncture. Cerebrospinal fluid (CSF) monoamine metabolites were assayed. Degree of medical damage and intent of the most recent suicide attempt were rated. Results: CSF amine metabolites did not differentiate suicide attempters as a group from nonattempters. However, reduced serotonergic activity, as indicated by lower levels of CSF 5-hydroxyindoleacetic acid (5-HIAA) was associated with a history of planned suicide attempts and with suicide attempts that resulted in greater medical damage. Other monoamine metabolites did not correlate with seriousness of suicidal behavior, except for low CSF homovanillic acid and higher medical damage. No correlation was found with violent method. Conclusions: Planned and more medically damaging suicide attempts appear to be associated specifically with low serotonergic activity and, therefore, resemble completed suicide both behaviorally and biochemically. It remains to be determined whether low levels of CSF 5-HIAA can predict greater medical damage in future suicide attempts.

Blunted Serotonergic Responsivity in Depressed Inpatients

We found a 38% lower maximal prolactin response to an oral challenge dose of 60 mg of dl-fenfluramine relative to placebo in younger (<30 years) depressed inpatients compared with the response in age-matched healthy controls (p <. 03). Severity of depression did not correlate with prolactin response. Prolactin responses in older depressed patients (⩾30 years) did not differ from older controls. Younger depressed patients differed from older depressed patients in terms of earlier age of onset of first lifetime episode of major depression, greater degree of suicidal intent during a recent suicide attempt, double the level of hopelessness on admission to hospital, and a higher rate of comorbid borderline personality disorder. A blunted prolactin response to fenfluramine may be interpreted as evidence for reduced serotonergic function in younger depressed patients and may underlie their observed greater suicidality and hopelessness.

Clinical anxiety, cortisol and interleukin-6: evidence for specificity in emotion-biology relationships.

Anxiety confers increased risk for inflammatory diseases, and elevated inflammatory activity in anxious individuals may contribute to this increased risk. One complication, however, is that anxiety could be associated with inflammatory activity either through a specific anxiety pathway or through a more general negative emotionality pathway. To investigate, we measured levels of the stress hormone cortisol, the pro-inflammatory cytokine interleukin-6 (IL-6), and the systemic inflammatory marker C-reactive protein (CRP), as well as depression and neuroticism, in clinically anxious and non-anxious adults. Compared with non-anxious participants, clinically anxious participants exhibited significantly lower levels of morning cortisol and significantly higher levels of IL-6, independent of age, sex, and depressive symptoms. These group differences were robust when controlling for neuroticism. Conversely, the groups had equivalent levels of CRP in all analyses. Results are indicative of anxiety-specific effects on inflammatory activity, and highlight a pathway by which anxiety may increase risk for inflammatory diseases.

Substance abuse disorder and major depression are associated with the human 5-HT1B receptor gene (HTR1B) G861C polymorphism.

The 5-HT1B receptor has been implicated in several psychopathologies, including pathological aggression, alcoholism and suicide. To test these and related potential genetic relationships in a single population, the human 5-HT1B receptor (h5-HTR1B) genotype for the G861C polymorphism was determined in 394 psychiatric patients and 96 healthy volunteers. Structured clinical interviews generated DSM III-R diagnoses. No significant association of the genotype or allele frequencies of the h5-HTR1B G861C locus was observed with diagnoses of alcoholism, bipolar disorder, schizophrenia or a history of a suicide attempt. Exploratory analyses indicated an association of the genotype and allele frequencies of the h5-HTR1B G861C locus with a history of substance abuse disorder (χ2=9.51, df=2, p=0.009; χ2=7.31, df=1, p=0.007, respectively) and with a diagnosis of a major depressive episode (χ2=6.83, df=2, p=0.033; χ2=5.81, df=1, p=0.016, respectively). Significant gene dose effects on the risk for substance abuse disorder and a major depressive episode were observed with the 861C allele (Armitage linearity tendency test: χ2=7.20, df=1, p=0.008; χ2=6.80, df=1, p=0.009, respectively). Substance abuse disorder and major depression appear to be associated with the h5-HTR1B G861C locus in the patient population, but other psychopathologies such as bipolar disorder, schizophrenia, alcoholism, and suicide attempts were not found to be associated with this polymorphism. This preliminary result will need replication, given the limitations of association studies.

Suicidal behavior in patients with major depression and comorbid personality disorders

We investigated the relationship of DSM-III-R personality disorder (PD) diagnoses and traits to suicidal behavior in patients with Major Depressive Disorder (MDD). Axis I and Axis II criteria and suicidal behavior were assessed using structured interviews of 102 psychiatric inpatients. Subjects with comorbid MDD and Borderline PD (BPD: n = 30) were more likely than other patients to have a history of multiple suicide attempts, and were equally likely to have made a highly lethal attempt. Number of BPD and other Cluster B (dramatic/erratic) criteria were better predictors of past suicidal behavior than were depressive symptoms. We conclude that patients with BPD symptomatology are at risk for serious suicide attempts. Moreover, severity of comorbid Cluster B PD psychopathology should be considered when assessing suicide risk in MDD patients even in those without a PD diagnosis.