The serotonin transporter gene and alcoholism: the two pathways to suicidal behavior.
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Alcoholism↗
Biomedical subjects
Leo Sher
Publications and source records attributed to Leo Sher.
Testing the self-medication hypothesis of depression and aggression in cannabis-dependent subjects.
BACKGROUND: A self-medication hypothesis has been proposed to explain the association between cannabis use and psychiatric and behavioral problems. However, little is known about the reasons for use and reactions while intoxicated in cannabis users who suffer from depression or problems controlling violent behavior. METHOD: We assessed 119 cannabis-dependent subjects using the Schedules of Clinical Assessment in Neuropsychiatry (SCAN), parts of the Addiction Severity Index (ASI), and questionnaires on reasons for cannabis use and reactions to cannabis use while intoxicated. Participants with lifetime depression and problems controlling violent behavior were compared to subjects without such problems. Validity of the groupings was corroborated by use of a psychiatric treatment register, previous use of psychotropic medication and convictions for violence. RESULTS: Subjects with lifetime depression used cannabis for the same reasons as others. While under the influence of cannabis, they more often experienced depression, sadness, anxiety and paranoia, and they were less likely to report happiness or euphoria. Participants reporting problems controlling violent behavior more often used cannabis to decrease aggression, decrease suspiciousness, and for relaxation; while intoxicated they more often reacted with aggression. CONCLUSIONS: Subjects with prior depression do not use cannabis as a mean of self-medication. They are more likely to experience specific increases of adverse symptoms while under the influence of cannabis, and are less likely to experience specific symptom relief. There is some evidence that cannabis is used as a means of self-medication for problems controlling aggression.
Adolescent↗
Combined dexamethasone suppression-corticotropin-releasing hormone stimulation test in studies of depression, alcoholism, and suicidal behavior.
The hypothalamic-pituitary-adrenal (HPA) axis controls the secretion of corticotropin-releasing hormone (CRH), corticotropin (adrenocorticotropic hormone, ACTH), and cortisol. The dexamethasone suppression test (DST) is the most frequently used test to assess HPA system function in psychiatric disorders. Patients who have failed to suppress plasma cortisol secretion, i.e., who escape from the suppressive effect of dexamethasone, have a blunted glucocorticoid receptor response. After CRH became available for clinical studies, the DST was combined with CRH administration. The resulting combined dexamethasone suppression-corticotropin-releasing hormone stimulation (DST-CRH) test proved to be more sensitive in detecting HPA system changes than the DST. There is a growing interest in the use of the DEX-CRH test for psychiatric research. The DEX-CRH test has been used to study different psychiatric conditions. Major depression, alcoholism, and suicidal behavior are public health problems around the world. Considerable evidence suggests that HPA dysregulation is involved in the pathogenesis of depressive disorders, alcoholism, and suicidal behavior. Over the past 2 decades, there has been a shift from viewing excessive HPA activity in depression as an epiphenomenon to its having specific effects on symptom formation and cognition. The study of HPA function in depression, alcoholism, and suicidal behavior may yield new understanding of the pathophysiology of these conditions, and suggest new approaches for therapeutic interventions. The combined DEX-CRH test may become a useful neuroendocrinological tool for evaluating psychiatric patients.
Alcoholism↗
Risk and protective factors for suicide in patients with alcoholism.
Alcoholism is associated with a high risk for suicidal behavior. Up to 40% of persons with alcoholism attempt suicide at some time and 7% end their lives by committing suicide. Risk factors include being male, older than 50 years of age, living alone, being unemployed, poor social support, interpersonal losses, continued drinking, consumption of a greater amount of alcohol when drinking, a recent alcohol binge, previous alcohol treatment, a family history of alcoholism, a history of comorbid substance abuse (especially cocaine), a major depressive episode, serious medical illness, suicidal communication, and prior suicidal behavior. Suicidal behavior is especially frequent in patients with comorbid alcoholism and major depression. However, all patients with alcoholism should be evaluated for suicide risk. Understanding of risk and vulnerability to suicidal behavior in alcoholism still outweighs our knowledge of protective factors and resilience. Knowledge of protective factors for suicide may help to prevent and/or predict suicidal behavior. Protective factors for suicide in alcoholism are quite varied and include an individual's biological and behavioral characteristics, as well as attributes of the environment and culture. Protective factors include effective clinical care for psychiatric (including alcoholism and drug abuse) and physical disorders, easy access to a variety of clinical interventions and support for seeking help, restricted access to highly lethal means of suicide, strong connections to family and community support, skills in problem solving and conflict resolution, cultural and religious beliefs that discourage suicide and support self-preservation. Future studies are necessary to determine which interventions may reduce suicidal behavior in alcoholism.
Age Factors↗
A 10-year retrospective study of inpatient adolescents with schizophrenia/schizoaffective disorder and substance use.
The comorbidity of schizophrenia/schizoaffective disorder and substance use is a major psychiatric concern that is associated with aggressive and suicidal behavior. This study investigated the clinical correlates and characterizes adolescent psychotic inpatients with and without comorbid substance use. We performed a retrospective study of 188 adolescent inpatients who were admitted between the years 1994 and 2004 to the inpatient unit of Geha Mental Health Center and who were diagnosed as suffering from either schizophrenia or schizoaffective disorder. The substance-using psychotic inpatients were found to have more relatives with substance-related disorders, fewer comorbid anxiety disorders, lower scores on the Brief Psychiatric Rating Scale and Hamilton Scale for Depression, higher scores on the Overt Aggression Scale, and they were more suicidal than the nonsubstance using inpatients. Adolescent inpatients with schizophrenia and schizoaffective who use substances possess differential clinical characteristics and particular correlates that justify adopting a specific approach to this high-risk clinical subgroup.
Adolescent↗
Alcohol and suicide: neurobiological and clinical aspects.
Alcohol, primarily in the form of ethyl alcohol (ethanol), has occupied an important place in the history of humankind for at least 8,000 years. In most Western societies, at least 90% of people consume alcohol at some time during their lives, and 30% or more of drinkers develop alcohol-related problems. Severe alcohol-related life impairment, alcohol dependence (alcoholism), is observed at some time during their lives in about 10% of men and 3-5% of women. An additional 5-10% of each sex develops persistent, but less intense, problems that are diagnosed as alcohol abuse. It this review, neurobiological aspects of suicidal behavior in alcoholism is discussed. In individuals with comorbid depression and alcoholism, greater serotonergic impairment may be associated with higher risk of completed suicide. Dopaminergic dysfunction may play an important role in the pathophysiology of suicidal behavior in alcoholism. Brain damage and neurobehavioral deficits are associated with alcohol use disorders and may contribute to suicidal behavior in persons with alcohol dependence or abuse. Aggression/impulsivity and alcoholism severity affect risk for suicide among individuals with alcoholism. Major depressive episodes and stressful life events particularly, partner-relationship disruptions, may precipitate suicidal behavior in individuals with alcohol use disorders. Alcohol misuse and psychosocial adversity can combine to increase stress on the person, and, thereby, potentially, increase the risk for suicidal behavior. The management of suicidal patients with alcohol use disorders is also discussed. It is to be hoped that the efforts of clinicians will reduce morbidity and mortality associated with alcohol misuse.
Aggression↗
CSF monoamine metabolites and lethality of suicide attempts in depressed patients with alcohol dependence.
BACKGROUND: Alcohol dependence (alcoholism) and major depressive disorder are frequently comorbid and are risk factors for suicidal behavior. Monoaminergic abnormalities have been implicated in the pathophysiology of depression, alcohol dependence, and suicidal behavior. Lower cerebrospinal fluid (CSF) 5-hydroxyindolacetic acid (5-HIAA) levels are associated with higher lethality of suicide attempts in major depression and predict a higher rate of future suicide. We sought to study the relationship of CSF monoamine metabolites to lethality of suicidal acts in depressed subjects with comorbid alcoholism. METHODS: We compared 16 high- and 16 low-lethality drug-free depressed suicide attempters with comorbid alcoholism. Subjects were free from any substance use disorder for at least two months. Demographic and clinical parameters, and CSF 5-HIAA, homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) levels were examined. RESULTS: The two groups did not differ with regard to the demographic characteristics. CSF 5-HIAA levels were lower in high-lethality attempters compared to low-lethality attempters. There were no group difference in CSF HVA or MHPG levels. CONCLUSION: Higher lethality of suicidal behavior in depressed patients with alcoholism is related to lower serotonergic activity.
Adult↗
Are BPI and BPII suicide attempters distinct neuropsychologically?
UNLABELLED: 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.
Adolescent↗
Relation between rates of geriatric suicide and consumption of alcohol beverages in European countries.
Among older adults, suicide is a significant and persistent health problem. The highest suicide rate is found among white men aged 65 years and older. The causes of elder suicide are multifaceted. Although no predominate factor precipitates or explains geriatric suicide, alcohol is strongly linked to suicide attempts and completions. This study examined the relationship between rates of suicide in 65- to 74-year-olds and per capita consumption of alcoholic beverages in European countries. Data on suicide rates in 65- to 74-year-olds and per capita consumption of alcoholic beverages were obtained from the World Health Organization databases. Correlations were computed to examine relationships between suicide rates in 65- to 74-year-old males and females and per capita consumption of beer, wine, and spirits in the general population in 34 European countries. There was a positive correlation between suicide rates in 65- to 74-year-old males and per capita consumption of spirits. No correlations between suicide rates in 65- to 74-year-old males and per capita consumption of beer or wine were found. We also found no correlations between rates of suicide in 65- to 74-year-old females and per capita consumption of beer, wine, or spirits. The results of this study are consistent with reports that consumption of spirits is associated with suicide events. It is to be hoped that this paper will stimulate further studies that are necessary to clarify the relation between suicide rates in different age groups and consumption of alcoholic beverages, and attract more attention to the problem of geriatric suicide.
Aged↗
Combined dexamethasone suppression/corticotropin-releasing hormone stimulation test and antidepressants: different antidepressants may produce different effects.
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Antidepressive Agents↗
Sunshine and suicide: bright light may lead to serotonin-driven behavioural activation without improvement in depressive cognitive deficits.
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Behavior↗
Clinical characteristics of inpatient adolescents with severe obsessive-compulsive disorder.
Obsessive-compulsive disorder (OCD) is a common disorder in adolescents, usually treated in the outpatient setting. Our aim in this study was to evaluate the clinical characteristics of adolescents with severe OCD that required hospitalization. A total of 342 patients consecutively admitted to a psychiatric adolescent inpatient unit and 87 healthy volunteers were assessed by a semistructured interview for clinical diagnosis, suicide risk factors, aggression, ego defense mechanisms, and intelligence. Patients with OCD (n=40) were compared to other four diagnostic patient groups with psychotic, affective, conduct, and eating disorders, as well as to normal controls. Adolescent inpatients with OCD experienced less separation anxiety than all the other psychiatric groups (P < .01) and were less impulsive than controls (P < .001). They differed in aggressive/impulsive traits and hospital-related behaviors from other diagnostic groups. Adolescent inpatients with OCD consist of a unique subgroup in the inpatient unit in terms of their clinical characteristics and risk factors for suicide. These characteristics should be taken into account when developing a treatment plan for these difficult-to-treat inpatients.
Adolescent↗
Dopamine and the pathophysiology of suicidal behavior in alcoholism.
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Aggression↗
Tryptophan depletion and alcoholism research.
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Alcoholism↗
Substance use, suicidality, and adolescent-onset schizophrenia: an Israeli 10-year retrospective study.
OBJECTIVE: The aim of this study was to investigate the link between the use of specific types of substances and suicidality in adolescent inpatients with schizophrenia and schizoaffective disorder. METHODS: We performed a 10-year naturalistic retrospective study of 178 adolescent inpatients diagnosed as suffering from either schizophrenia or schizoaffective disorder. A comparison was made between the suicide-attempting adolescent inpatients and the non-attempting subjects, by the use of specific types of substances, measurements of psychotic, depressive, and aggressive symptoms, and clinical data reported during their hospitalization. RESULTS: The suicide attempters reported considerably greater usage of inhalants and lysergic acid diethylamide (LSD). Alcohol and methylene-dioxy-methylamphetamine (MDMA) were also used significantly more by this group. However, no differences were found in the usage of cannabis, amphetamines, cocaine, and opiates. The suicide-attempting patients were found to have had more previous psychiatric admissions, a greater level of deliberate self-harm behavior, and a higher level of suicide ideation, but a decreased severity of psychotic symptoms. CONCLUSIONS: This study is the first report of the association between specific types of substances and suicidality in the high-risk population of adolescent psychotic inpatients. The strong association between inhalants, LSD, alcohol, and MDMA with suicidality is relevant to suicide prevention and intervention programs in adolescent-onset schizophrenia.
Adolescent↗
Correlates of suicide attempt history in bipolar disorder: a stress-diathesis perspective.
OBJECTIVES: Distinguishing clinical characteristics of bipolar patients who have made a suicide attempt may help to identify at-risk individuals. We sought to identify such factors and to consider them within a stress-diathesis model of suicidal behavior. METHODS: Patients with bipolar disorder (N = 96) were compared with respect to the presence or absence at baseline evaluation of a history of suicide attempt. We used multiple logistic regression analysis to assess the unique associations of independent variables to history of a past suicide attempt. RESULTS: The regression analysis showed that a history of suicide attempt in bipolar disorder was associated with greater recent suicidal ideation, more psychiatric hospitalizations, lifetime aggressive traits and an earlier age at onset of a first mood episode. CONCLUSIONS: Aggressive traits and early treatment of mood disorders, especially major depressive episodes, are potential targets for suicide prevention in bipolar disorder.
Adult↗
A prospective study of the association of cerebrospinal fluid monoamine metabolite levels with lethality of suicide attempts in patients with bipolar disorder.
OBJECTIVES: Bipolar disorder is a severe illness that is associated with suicidal behavior. A biological predictor of highly lethal suicide attempts in patients with bipolar disorder would be valuable. We hypothesized that cerebrospinal fluid (CSF) monoamine metabolite levels are related to lethality of suicide attempts in bipolar patients and examined the relation between CSF 5-hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and maximum lethality of suicide attempts at baseline and during a 2-year follow up. METHODS: Twenty-seven bipolar depressed patients participated in the study. Demographic and clinical parameters were examined and recorded. Lumbar punctures were performed and CSF 5-HIAA, HVA, and MHPG were assayed by high-performance liquid chromatography with electrochemical detection. Following discharge, patients were evaluated after 3 months, 1 year, and 2 years. Each follow-up interview included an in-depth assessment of suicidal behavior during the intervening time period. RESULTS: Six subjects made suicide attempts during the 2-year follow-up. Bipolar patients who attempted suicide during the follow-up period had higher aggression and hostility scale scores compared to bipolar subjects who did not make a suicide attempt during the follow-up period. CSF 5-HIAA, HVA, and MHPG levels were negatively correlated with the maximum lethality of suicide attempts during the 2-year follow-up period. CONCLUSIONS: Our finding is the first observation that CSF monoamine metabolite levels may be predictors of lethality of suicide attempts in patients with bipolar disorder. Further studies are necessary to answer the question whether CSF monoamine metabolite levels are clinically useful biochemical predictors of highly lethal suicide attempts or completed suicides.
Adult↗
Clinical predictors of suicidal acts after major depression in bipolar disorder: a prospective study.
OBJECTIVE: This study determined the clinical predictors of suicidal behavior during a 2-year follow-up of patients with bipolar disorder presenting with a major depressive episode (MDE). METHOD: Sixty four patients with DSM-III-R bipolar disorder were assessed at presentation for treatment of an MDE. Correlates of past suicidal behavior were determined by comparing patients with and without a history of suicide attempts using a t-test, Wilcoxon test or chi-squared test of independence on individual explanatory variables. Putative predictors of attempts during the follow-up period were tested separately using Cox proportional hazards regression analysis. RESULTS: Twelve of 64 patients had at least one suicide attempt in the follow-up period, five of them attempted in the first 2 months and seven around or shortly after the 1-year follow-up visit. All attempters had a history of past suicide attempts. Most predictors of future suicidal behavior were correlates of past suicidal behavior. Family history of suicide acts and comorbid borderline personality disorder predicted early attempts, while younger age, high hostility scores, number of past attempts, subjective pessimism as reflected in depression and suicidal ideation, and few reported reasons for living predicted suicidal acts during the whole period. CONCLUSION: In this data set of bipolar patients we noted an intriguing picture of two clusters of suicide attempts. Hostility was the strongest risk factor. These findings may have implications in both the identification of at-risk patients and the timing of clinical interventions including aggressive pharmacotherapeutic prophylaxis to prevent relapse or recurrence of depressive symptomatology.
Adult↗