Beth S. Brodsky

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.

Human 5-HT1A receptor C(−1019)G polymorphism and psychopathology

Dysfunction of the serotonin (5-HT1A) receptor (5-HTR1A) has been implicated in mood disorders, anxiety disorders, psychosis and the action of antidepressants. A common C(-1018)G [C(-1019)G] functional polymorphism in the promoter region of the human 5-HT1A receptor gene has been reported, which may be useful in identifying psychopathology associated with altered function of the human 5-HT1A receptor. We studied the relationship of this polymorphism to psychopathology and 5-HT1A binding in prefrontal cortex. The 5-HT1A receptor genotype for the C(-1019)G polymorphism was typed in 696 unrelated psychiatric subjects, 107 unrelated healthy volunteers, and in post-mortem brain samples from 241 cases. 5-HT1A receptor binding was assayed in post-mortem prefrontal cortex using [3H]8-OH-DPAT, and specific binding determined by 1 microM 5-HT. An association of genotype distribution and allele frequency of the 5-HTR1A C(-1019)G locus was observed in schizophrenia (chi2=9.51, d.f.=2, p=0.009; chi2=9.52, d.f.=1, p=0.002; Armitages trend test: chi2=9.07, d.f.=1, p=0.003), in substance use disorder (chi2=8.41, d.f.=2, p=0.015; chi2=8.35, d.f.=1, p=0.004; Armitages trend test: chi2=6.27, d.f.=1, p=0.0012), and in panic attack (chi2=6.31, d.f.=2, p=0.043; chi2=6.14, d.f.=1, p=0.013; Armitages trend test: chi2=6.27, d.f.=1, p=0.012). An association of the 5-HTR1A C(-1019)G locus with schizophrenia, substance use disorder, and panic attack was suggested by our results. In post-mortem brain samples, 5-HT1A receptor binding in prefrontal cortex and suicide were not associated with genotype. The relationship does not appear to be explained by binding differences, although we cannot rule out altered receptor affinity and transduction.

Adverse childhood experiences and suicidal behavior

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

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.

Aggressiveness, not impulsiveness or hostility, distinguishes suicide attempters with major depression

BACKGROUND Impulsiveness, hostility and aggressiveness are traits associated with suicidal behavior, but also with borderline personality disorder (BPD). The presence of large numbers of BPD subjects in past attempter samples may distort the relative importance of each of these traits to predicting suicidal behavior, and lead to prospective, biological and genetic models that systematically misclassify certain subpopulations of suicidal individuals. METHOD Two hundred and seventy-five subjects with major depressive disorder (MDD), including 87 with co-morbid BPD (69 past suicide attempters, 18 non-attempters) and 188 without BPD (76 attempters, 112 non-attempters) completed standard impulsiveness, hostility and aggressiveness ratings. Differences between past suicide attempters and non-attempters were examined with the sample stratified by BPD status. RESULTS As expected, BPD subjects scored significantly higher than non-BPD subjects on all three trait measures. Stratifying by BPD status, however, eliminated attempter/non-attempter differences in impulsiveness and hostility in both patient subgroups. Past suicide attempters in each of the two subgroups of patients were only distinguished by higher levels of aggressiveness. CONCLUSIONS Once BPD is accounted for, a history of aggressive behavior appears to be the distinguishing trait characteristic of suicide attempters with major depression, rather than global personality dimensions such as impulsiveness or hostility. Aggressiveness, and not these related traits, may be the ideal target for behavioral, genetic and biological research on suicidal behavior, as well as for the clinical assessment of suicide risk.

Early childhood sexual abuse increases suicidal intent

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.

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

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

Developmental effects on suicidal behavior: the role of abuse in childhood

Abstract Early childhood experiences of physical and sexual abuse and parental neglect are risk factors for suicidal behavior in adulthood. However, little is known about the mechanisms by which trauma in childhood trauma results in self-destructive behavior later in life. This article reviews the empirical evidence of the relationship between childhood abuse and suicidal behavior. Related areas of research, such as the relationship of abuse history to borderline personality disorder, trait impulsivity and aggression as possible risk factors, as well as protective factors, are also reviewed. Research on the neurobiological correlates of trauma that might have implications for understanding suicidal behavior is also discussed. Several models for the study of the relationship between childhood abuse and suicidal behavior will be described. Recommendations are made for theoretical and methodological approaches to future research.

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

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).

Is there circannual variation of human platelet 5-HT2A binding in depression?

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.