Biomedical subjects

K M Malone

Publications and source records attributed to K M Malone.

At least 19 recordsLinked to original sources

PubMed2002

Lower cortisol levels in depressed patients with comorbid post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is often comorbid with major depressive episodes (MDEs) and both conditions carry a higher rate of suicidal behavior. Hypothalamic-pituitary-adrenal (HPA) axis and serotonin abnormalities are associated with both conditions and suicidal behavior, but their inter-relation is not known. We determined cortisol response to placebo or fenfluramine in MDE, MDE and PTSD (MDE+PTSD), and healthy volunteers (HVs) and examined the relation of cortisol responses to suicidal behavior. A total of 58 medication-free patients with MDE (13 had MDE+PTSD) and 24 HVs were studied. They received placebo on the first day and fenfluramine on the second day. Cortisol levels were drawn before challenge and for 5 h thereafter. The MDE+PTSD group had the lowest plasma cortisol, the MDE group had the highest, and HVs had intermediate levels. There were no group differences in cortisol response to fenfluramine. Suicidal behavior, sex, and childhood history of abuse were not predictors of baseline or postchallenge plasma cortisol. Cortisol levels increased with age. This study finds elevated cortisol levels in MDE and is the first report of lower cortisol levels in MDE+PTSD. The findings underscore the impact of comorbidity of PTSD with MDE and highlight the importance of considering comorbidity in psychobiology.

Adult↗

PubMed2001

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.

Adult↗

PubMed2001

Prolactin response to dl-fenfluramine challenge before and after treatment with paroxetine.

The prolactin response to dl-fenfluramine (an indirect central serotonin agonist) challenge has been used to assess serotonergic function and appears to be blunted in depressed patients. We used this method to determine whether the serotonergic deficit in depressed patients is corrected by treatment with paroxetine. Prior to treatment with paroxetine sixteen depressed patients received a placebo challenge followed by a dl-fenfluramine challenge the next day. The same two challenges were repeated after treatment. Prolactin baseline levels were measured before pill administration, and then hourly for 5 hours. Fenfluramine/norfenfluramine levels were assayed at each time point after drug administration. Treatment with paroxetine significantly increased the baseline prolactin level independently of treatment response but positively correlated with paroxetine dose. We found that pre-treatment prolactin response to dl-fenfluramine challenge did not predict clinical response to paroxetine, nor did the prolactin response change significantly after treatment. There was no significant difference in the post-treatment prolactin response between treatment responders and treatment non-responders. We found evidence of increased prolactin levels that may reflect effects of paroxetine in enhancing serotonin levels. Acute release of serotonin as measured by the prolactin response to fenfluramine is not altered by paroxetine treatment.

Aged↗

PubMed2001

Ethnic and sex differences in suicide rates relative to major depression in the United States.

OBJECTIVE: Suicide rates differ between ethnic groups in the United States. Since suicide is commonly associated with a mood disorder, the authors compared suicide rates relative to depression rates in five ethnic groups in the United States. METHOD: Rates of major depression were generated from the Epidemiologic Catchment Area study and the Hispanic Health and Nutrition Epidemiologic Survey. Sociodemographic effects were determined by examining depression rates for respondents who were separated or divorced, earning low incomes, or not working for pay. The survey data were analyzed with age and sex standardization to generate 1-year prevalence rates of major depression. The depression rates of the different ethnic groups were compared and were examined in relation to suicide rates. RESULTS: The 1-year prevalence rates of major depression were 3.6% for whites, 3.5% for blacks, 2.8% for Mexican Americans, 2.5% for Cuban Americans, and 6.9% for Puerto Ricans. Compared to the rate for whites, the rate of depression was significantly higher in Puerto Ricans and significantly lower in Mexican Americans. Relative to the depression rates, the annual suicide rates were higher for males than for females. Mexican American and Puerto Rican males had lower relative suicide rates than white males. CONCLUSIONS: Identifying reasons for differences in suicide rates relative to depression among ethnic groups and between males and females may suggest interventions to reduce suicide rates. Some possibilities are that depression differs in form or severity or that unidentified factors protect against suicide in different subgroups.

Adult↗

PubMed2001

The relationship of childhood abuse to impulsivity and suicidal behavior in adults with major depression.

OBJECTIVE: This study investigated whether a higher frequency of reported childhood trauma would be found in depressed adults with higher levels of trait impulsivity, aggression, and suicidal behavior. METHOD: In 136 depressed adult inpatients, the authors assessed trait impulsivity, aggression history, and number of lifetime suicide attempts as well as the medical lethality and the intent to die associated with the most lethal attempt. These variables were then compared between those with and those without a reported history of childhood physical or sexual abuse. RESULTS: Subjects who reported an abuse history were more likely to have made a suicide attempt and had significantly higher impulsivity and aggression scores than those who did not report an abuse history. Impulsivity and aggression scores were significantly higher in subjects with a history of at least one suicide attempt. A logistic regression analysis revealed that abuse history remained significantly associated with suicide attempt status after adjustment for impulsivity, aggression history, and presence of borderline personality disorder. Among those who attempted suicide, there were no significant differences in severity of suicidal behavior between those with and without a childhood history of abuse. CONCLUSIONS: Abuse in childhood may constitute an environmental risk factor for the development of trait impulsivity and aggression as well as suicide attempts in depressed adults. Alternatively, impulsivity and aggression may be inherited traits underlying both childhood abuse and suicidal behavior in adulthood disorders. Additional research is needed to estimate the relative contributions of heredity and environmental experience to the development of impulsivity, aggression, and suicidal behavior.

Adult↗

PubMed2001

Decreased regional brain metabolism after ect.

OBJECTIVE: The antidepressant action of ECT may be related to its anticonvulsant properties. Positron emission tomography (PET) studies of regional cerebral metabolic rate for glucose were used to test this hypothesis. METHOD: Ten patients with major depression were studied with PET before and approximately 5 days after a course of bilateral ECT. Statistical parametric mapping was used to identify regions of decreased cerebral glucose metabolism. RESULTS: Widespread regions of decreased regional cerebral glucose metabolism were identified after ECT, especially in the frontal and parietal cortex, anterior and posterior cingulate gyrus, and left temporal cortex. A region-of-interest analysis similarly indicated post-ECT reductions in regional cerebral glucose metabolism. CONCLUSIONS: ECT reduces neuronal activity in selected cortical regions, a potential anticonvulsant and antidepressant effect.

Brain↗

PubMed2001

Neuropsychological dysfunction in depressed suicide attempters.

OBJECTIVE: Neuropsychological deficits in the context of psychiatric disease may be associated with suicide risk. In this study, neuropsychological performance was compared among depressed patients with at least one prior suicide attempt of high lethality, depressed patients with low-lethality prior attempts, depressed patients with no prior suicide attempts, and nonpatients. METHOD: Fifty unmedicated patients in a major depressive episode (21 with no history of suicide attempts and 14 and 15 patients with previous attempts of low and high lethality, respectively) and 22 nonpatients were assessed. Groups were comparable in age, education, occupational level, and estimated premorbid intelligence. The neuropsychological battery produced scores within five composite domains: general intellectual functioning (current), motor functioning, attention, memory, and executive functioning. RESULTS: Patients whose prior suicide attempts were of high lethality performed significantly worse than all groups on tests of executive functioning and were the only group to perform significantly worse than nonpatients on tests of general intellectual functioning, attention, and memory. A discriminant function analysis revealed two prominent dimensions in the data: one that discriminated high-lethality suicide attempters from all other groups (primarily associated with performance on tests of executive functioning) and another that discriminated all depressed patient groups from nonpatients (associated with performance on measures of attention and memory). For the patients with high-lethality prior suicide attempts, deficits did not appear to reflect diffuse brain damage from past attempts, since the results of tests commonly affected by diffuse injury were not selectively impaired. CONCLUSIONS: Neuropsychological deficits in depressed patients with high-lethality prior suicide attempts suggest impairment of executive functioning beyond that typically found in major depression. This more extensive neuropsychological impairment in the context of depression may be a risk factor for severe suicide attempts.

Adult↗

PubMed2001

Delusions and suicidality.

OBJECTIVE: Delusions have been considered a risk factor for suicidal behavior. To determine whether specific delusion types are related to suicidal behaviors, the authors compared the clinical characteristics of patients with mood disorders and schizophrenia who did and did not have a history of suicide attempts. METHOD: After admission for inpatient or outpatient psychiatric treatment, 429 patients (ages 14-72 years; 47.1% male; and 73.0% Caucasian) were assessed with a structured clinical interview that generated axis I and II diagnoses. In addition, their psychiatric symptoms, history of suicide attempts, and overall functioning were rated. RESULTS: Data for three diagnostic subgroups (223 patients with major depression, 150 with schizophrenia, and 56 with bipolar disorder) were analyzed separately. Multivariate analyses did not find evidence of a relationship between delusions and history of suicidal ideation or suicide attempts in any of the diagnostic groups. CONCLUSIONS: This study did not find evidence that the presence of delusions distinguished persons with or without a history of suicide attempt.

Adolescent↗

PubMed2000

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.

Adult↗

PubMed2000

Anxiety in major depression: relationship to suicide attempts.

OBJECTIVE: This study was an examination of the relationship of lifetime panic disorder and anxiety symptoms at index hospitalization to a history of a suicide attempt in patients with a major depressive episode. METHOD: A total of 272 inpatients with at least one major depressive episode, with or without a history of a suicide attempt, were entered into the study. They were given structured diagnostic interviews for axis I and axis II disorders. Suicide attempt history, current psychopathology, and traits of aggression and impulsivity were also assessed. RESULTS: The rates of panic disorder did not differ in the suicide attempters and nonattempters. Agitation, psychic anxiety, and hypochondriasis were more severe in the nonattempter group. A multivariate analysis confirmed that this effect was independent of aggression and impulsivity. CONCLUSIONS: Comorbid panic disorder in patients with major depression does not seem to increase the risk for lifetime suicide attempt. The presence of greater anxiety in the nonattempters warrants further investigation.

Adolescent↗

PubMed2000

Characteristics of suicide attempts of patients with major depressive episode and borderline personality disorder: a comparative study.

OBJECTIVE: Suicidal behavior is highly prevalent in borderline personality disorder and major depressive episode, although the characteristics of suicide attempts in the two disorders are believed to differ. Comorbidity of borderline personality disorder and major depressive episode may obscure characteristics of suicide attempts that are uniquely related to the psychopathology of each disorder. We compared suicidal behavior in patients with borderline personality disorder, major depressive episode, and borderline personality disorder plus major depressive episode to determine whether characteristics of suicide attempts differed between groups and if aspects of core psychopathology predicted specific attempt characteristics. METHOD: Eighty-one inpatients with borderline personality disorder, including 49 patients with borderline personality disorder plus major depressive episode, were compared to 77 inpatients with major depressive episode alone on measures of depressed mood, hopelessness, impulsive aggression, and suicidal behavior, including lifetime number of attempts, degree of lethal intent, objective planning, medical damage, and degree of violence of suicide methods. RESULTS: No significant differences were found in the characteristics of suicide attempts between patients with borderline personality disorder and those with major depressive episode. However, patients with both disorders had the greatest number of suicide attempts and the highest level of objective planning. An increase in either impulsive aggression or hopelessness or a diagnosis of borderline personality disorder predicted a greater number of attempts. Hopelessness predicted lethal intent in all three groups and predicted objective planning in the group with both disorders. Medical damage resulting from the most serious lifetime suicide attempt was predicted by number of attempts. CONCLUSIONS: Comorbidity of borderline personality disorder with major depressive episode increases the number and seriousness of suicide attempts. Hopelessness and impulsive aggression independently increase the risk of suicidal behavior in patients with borderline personality disorder and in patients with major depressive episode.

Adolescent↗

PubMed2000

Protective factors against suicidal acts in major depression: reasons for living.

OBJECTIVE: Over 30,000 people a year commit suicide in the United States. Prior attempted suicide and hopelessness are the most powerful clinical predictors of future completed suicide. The authors hypothesized that "reasons for living" might protect or restrain patients with major depression from making a suicide attempt. METHOD: Inpatients with DSM-III-R major depression were assessed for depression, general psychopathology, suicide history, reasons for living, and hopelessness. Of the 84 patients, 45 had attempted suicide and 39 had not. RESULTS: The depressed patients who had not attempted suicide expressed more feelings of responsibility toward family, more fear of social disapproval, more moral objections to suicide, greater survival and coping skills, and a greater fear of suicide than the depressed patients who had attempted suicide. Scores for hopelessness, subjective depression, and suicidal ideation were significantly higher for the suicide attempters. Reasons for living correlated inversely with the combined score on these measures, considered an indicator of "clinical suicidality." Neither objective severity of depression nor quantity of recent life events differed between the two groups. CONCLUSIONS: During a depressive episode, the subjective perception of stressful life events may be more germane to suicidal expression than the objective quantity of such events. A more optimistic perceptual set, despite equivalent objective severity of depression, may modify hopelessness and may protect against suicidal behavior during periods of risk, such as major depression. Assessment of reasons for living should be included in the evaluation of suicidal patients.

Adaptation, Psychological↗

PubMed1999

Toward a clinical model of suicidal behavior in psychiatric patients.

OBJECTIVE: Risk factors for suicide attempts have rarely been studied comprehensively in more than one psychiatric disorder, preventing estimation of the relative importance and the generalizability of different putative risk factors across psychiatric diagnoses. The authors conducted a study of suicide attempts in patients with mood disorders, psychoses, and other diagnoses. Their goal was to determine the generalizability and relative importance of risk factors for suicidal acts across diagnostic boundaries and to develop a hypothetical, explanatory, and predictive model of suicidal behavior that can subsequently be tested in a prospective study. METHOD: Following admission to a university psychiatric hospital, 347 consecutive patients who were 14-72 years old (51% were male and 68% were Caucasian) were recruited for study. Structured clinical interviews generated axis I and axis II diagnoses. Lifetime suicidal acts, traits of aggression and impulsivity, objective and subjective severity of acute psychopathology, developmental and family history, and past substance abuse or alcoholism were assessed. RESULTS: Objective severity of current depression or psychosis did not distinguish the 184 patients who had attempted suicide from those who had never attempted suicide. However, higher scores on subjective depression, higher scores on suicidal ideation, and fewer reasons for living were reported by suicide attempters. Rates of lifetime aggression and impulsivity were also greater in attempters. Comorbid borderline personality disorder, smoking, past substance use disorder or alcoholism, family history of suicidal acts, head injury, and childhood abuse history were more frequent in suicide attempters. CONCLUSIONS: The authors propose a stress-diathesis model in which the risk for suicidal acts is determined not merely by a psychiatric illness (the stressor) but also by a diathesis. This diathesis may be reflected in tendencies to experience more suicidal ideation and to be more impulsive and, therefore, more likely to act on suicidal feelings. Prospective studies are proposed to test this model.

Adolescent↗

PubMed1999

Inadequacy of antidepressant treatment for patients with major depression who are at risk for suicidal behavior.

OBJECTIVE: The authors' goal was to determine whether suicide attempters with major depression received more intensive antidepressant treatment than depressed patients who had not attempted suicide. METHOD: One hundred eighty inpatients who met DSM-III-R criteria for a major depressive episode according to the Structured Clinical Interview for DSM-III-R were enrolled in the study. All patients were assessed for lifetime history of suicide attempts. Depressive symptoms at the index hospitalization were assessed with the Hamilton Depression Rating Scale and the Beck Depression Inventory. Strength of antidepressant treatment over the 90 days preceding the hospitalization was scored by using the Antidepressant Treatment History Form. RESULTS: A large majority of the depressed patients with a history of suicide attempts, who were at higher risk for future suicide and suicide attempts, received inadequate treatment. Similarly, most of the depressed patients at lower risk for suicide attempts also received inadequate treatment. CONCLUSIONS: Major depression is undertreated pharmacologically, regardless of history of suicide attempt. Some suicide attempts may be preventable if the problem of underdiagnosis and undertreatment of depression can be overcome by psychoeducation for health professionals and the public.

Adult↗

PubMed1997

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.

Adult↗

PubMed1997

Pharmacotherapy of affectively ill suicidal patients.

The development of psychopharmacologic strategies for ameliorating the symptoms associated with major psychiatric disorders is relatively recent in the history of medicine. Regarding depression, the past 30 years have seen the advent of several clinically therapeutic antidepressant medication classes. With the advent of these newer and safer antidepressants, more primary care practitioners are prescribing these drugs, and as a result, more people are being prescribed antidepressant medication than ever before. This article reviews this psychopharmacologic revolution that has emerged as a consequence of a greater understanding of the neurochemical perturbations underlying major affective disorders.

Antidepressive Agents↗

PubMed1997

Possible association of a polymorphism of the tryptophan hydroxylase gene with suicidal behavior in depressed patients.

OBJECTIVE: This study was designed to test the hypothesis that serotonin-system-related genes may be correlated with suicide risk. METHOD: Fifty-one unrelated Caucasian inpatients with major depression, with or without a history of suicidal acts, were genotyped for a biallelic polymorphism at the tryptophan hydroxylase locus. RESULTS: The less common tryptophan hydroxylase U allele occurred with greater frequency in the patients who had attempted suicide. A logistic regression analysis confirmed an association between tryptophan hydroxylase genotype and lifetime history of suicide attempts. CONCLUSIONS: Serotonergic-system-related genes may influence the risk of suicide in persons with major depression.

Adult↗

PubMed1997

Characteristics of borderline personality disorder associated with suicidal behavior.

OBJECTIVE: This study examined the relationship between characteristics of borderline personality disorder and suicidal behavior. The authors hypothesized that a specific feature of borderline personality disorder, impulsivity, and childhood trauma, a possible etiological factor in the development of impulsivity, would be associated with suicidal behavior. METHOD: Information on lifetime history of suicidal behavior was obtained from 214 inpatients diagnosed with borderline personality disorder by structured clinical interview. The authors examined the relationship between DSM-III-R criteria met and the following measures of suicidal behavior: presence or absence of a previous suicide attempt, number of previous attempts, and lethality and intent to die associated with the most lethal lifetime attempt. RESULTS: Impulsivity was the only characteristic of borderline personality disorder (excluding the self-destructive criterion) that was associated with a higher number of previous suicide attempts after control for lifetime diagnoses of depression and substance abuse. Global severity of pathology of borderline personality disorder was not associated with suicidal behavior. History of childhood abuse correlated significantly with number of lifetime suicide attempts. CONCLUSIONS: The trait of impulsivity is associated with number of lifetime suicide attempts and may therefore be a putative risk factor for a future suicide attempt. If so, impulsivity is a potential target therapeutically for prevention of future suicide attempts. The association between childhood abuse and number of lifetime suicide attempts is consistent with the hypothesis that childhood abuse is an etiological factor in the development of self-destructive behaviors.

Adolescent↗