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Biomedical subjects

Leo Sher

Publications and source records attributed to Leo Sher.

At least 37 records · Page 2Linked to original sources
PubMed2006

Aggression and substance abuse in bipolar disorder.

OBJECTIVES: The goal of this retrospective study was to examine factors differentiating persons with bipolar disorder who did or did not have comorbid lifetime substance use disorders (SUD) at an index assessment. We also explored the chronology of onset of mood and SUD. METHODS: We studied 146 subjects with DSM-defined bipolar disorder. Subgroups with and without lifetime SUD were compared on demographic and clinical measures. RESULTS: Substance abuse disorders in this bipolar sample were associated with male sex, impulsive-aggressive traits, comorbid conduct and Cluster B personality disorders, number of suicide attempts and earlier age at onset of a first mood episode. In a multivariable logistic regression analysis, male sex and aggression and possibly earlier age at mood disorder onset were associated with SUD. In those with or without SUD, the first mood episode tended to be depressive and to precede the onset of SUD. CONCLUSIONS: In persons with bipolar disorder, an earlier age of onset and aggressive traits appear to be factors associated with later development of comorbid SUD.

Adolescent↗
PubMed2006

A comparison of the medical lethality of suicide attempts in bipolar and major depressive disorders.

OBJECTIVES: Among mood disorders, bipolar disorder (BPD) is often noted to involve the highest rates of suicide attempts and possibly of completion. This study sought to determine whether suicide attempters with BPD exhibit suicide attempts with higher lethality than attempters with major depressive disorder (MDD) and to explore differences in clinical features associated with suicidal acts. METHODS: Mood disordered suicide attempters were interviewed about Axis I and II diagnoses, lifetime history of suicide attempts, suicidal intent, suicidal ideation, the medical lethality of their most severe suicide attempt, severity of depression, hopelessness, lifetime aggression, and impulsivity. RESULTS: The maximum lethality of suicidal acts tended to be higher among BPD attempters compared with those with MDD. However, there were no differences in the number of suicide attempts, intent to die or suicidal ideation. Suicide attempters with BPD reported higher levels of aggression and impulsivity but less hopelessness compared with MDD attempters. These differences could not be explained by Cluster B personality disorder comorbidity. Of note, within the BPD group, but not the MDD group, males reported suicidal acts with higher lethality. Multivariate analyses suggested that risk for more lethal suicide attempts is associated with BPD and male sex and that bipolar males appear to be especially vulnerable to these behaviors. CONCLUSIONS: Males with BPD make more lethal suicide attempts than females with BPD, an effect not observed among the MDD sample. Our findings suggest that higher rates of suicidal behavior in BPD may be due to a specific effect of BPD on males, leading to more dangerous suicidal behaviors. This effect, together with the larger proportion of males in the BPD group compared with the MDD group may lead to higher rates of reported attempted and completed suicide.

Adult↗
PubMed2005

Lower cerebrospinal fluid homovanillic acid levels in depressed suicide attempters.

BACKGROUND: Studies suggest that the dopaminergic system is involved in the pathogenesis of major depression, Axis II disorders, and suicidal behavior. Depressed suicide attempters constitute a heterogenous group and important differences may exist between depressed suicide attempters with or without Axis II disorders. Therefore, we compared demographic and clinical parameters, and cerebrospinal fluid (CSF) homovanillic acid (HVA) levels in depressed suicide attempters without comorbid Axis II disorders, depressed non-attempters without comorbid Axis II disorders, and normal controls. METHODS: Thirty-one depressed subjects with a history of a suicide attempt, 27 depressed subjects without a history of a suicide attempt, and 50 healthy controls were included in the study. Subjects with comorbid Axis II disorders were excluded. Demographic and clinical parameters, and CSF HVA levels were examined. RESULTS: The two depressed groups did not differ with regard to depression, aggression, hopelessness, and total hostility scale scores. Depressed suicide attempters had higher current suicidal ideation scores compared to depressed non-attempters. Depressed suicide attempters had lower CSF HVA levels compared to depressed non-attempters (t = 4.4, df = 56, p < 0.0001) and to controls (t = -4.09, df = 79, p < 0.0001). There was no difference in CSF HVA levels between depressed non-attempters and controls (t < 1, df = 75, NS). CONCLUSIONS: Dopaminergic abnormalities are associated with suicidality but not with depression. The variability in the rates of comorbid Axis II disorders and in the prevalence of suicide attempters in different patient populations may affect both clinical and biological results of studies of mood disorders.

Adult↗
PubMed2005

Alcohol use and suicide rates.

Alcohol use and abuse substantially influence suicide rates. Suicide is a cause of death for a substantial percentage of individuals with alcoholism. However, the results of epidemiological studies of the relation between alcohol use and suicide have been inconsistent. Studies conducted in one nation are not always applicable to other nations. Many different factors including prevalence of various psychiatric and medical disorders, quality of psychiatric and medical care, unemployment and divorce rates and other psychosocial and demographic factors determine suicide rates in a certain region or a country. There may be a broad-based social characteristic related to social stress which is associated with high rates of a variety of stress-related behaviors, including heavy alcohol use and suicide.

Alcohol Drinking↗
PubMed2005

Plasma serotonin levels and suicidal behavior in adolescents.

To evaluate the relationship between plasma serotonin (p5-HT) levels and psychometric measures in suicidal adolescents vs. controls, 211 adolescents from three sites in Israel were divided into four groups: suicidal psychiatric inpatients (n=35); non-suicidal psychiatric inpatients (n=30); adolescents referred to the emergency room (ER) due to a suicide attempt (n=51); and a community-based control group from 4 high schools in the same catchment areas (n=95). All were interviewed and assessed for violence, aggression, depression, impulsivity, anger, anxiety, and p5-HT. p5-HT levels were significantly lower in the control group compared to all other groups. A significant negative correlation was found between p5-HT level and suicidal behavior severity among the suicidal inpatients. p5-HT did not discriminate between the psychiatric diagnostic categories and was significantly lower in ER violent compared to non-violent subjects. Gender, depression, and anger were associated with suicidal behavior in all four groups. Beck Depression Inventory (BDI) scores together with p5-HT levels discriminated between healthy controls and other groups. p5-HT level in combination with some of the psychometric scales may serve as a safe and inexpensive peripheral marker of psychopathology, and may help to differentiate between sub-populations of suicidal adolescents. The biological mechanism behind the serotonin dysregulation in suicidal adolescents requires further investigation.

Adolescent↗
PubMed2005

Higher cerebrospinal fluid homovanillic acid levels in depressed patients with comorbid posttraumatic stress disorder.

Major depression and posttraumatic stress disorder (PTSD) are often comorbid, resulting in more impairment compared than with either diagnosis alone. Both major depression and PTSD are thought to be associated with monoamine transmitter abnormalities. This study compared clinical features and cerebrospinal fluid (CSF) monoamine metabolites in drug-free depressed subjects with a current major depressive episode (MDE) without comorbid PTSD, subjects with a current MDE and comorbid PTSD, and healthy volunteers. Depressed subjects with comorbid PTSD had higher CSF homovanillic acid (HVA) levels compared with depressed subjects without comorbid PTSD or healthy volunteers. Higher HVA was present after adjustment for sex, lifetime aggression severity and depression scores, alcoholism, tobacco smoking, comorbid cluster B personality disorder, reported childhood abuse, and psychosis. We found no group difference in CSF 5-hydroxyindolacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) levels. Higher dopaminergic activity may contribute to alterations in memory and other cognitive functions, anhedonia, and hypervigilance observed in PTSD.

Adult↗
PubMed2005

The concept of post-traumatic mood disorder.

Post-traumatic stress disorder (PTSD) is frequently comorbid with depression. A number of studies have been conducted to compare individuals suffering from comorbid PTSD and depression with individuals suffering from PTSD alone or depression alone. Comorbidity of PTSD and depression is associated with more severe symptoms as well as higher levels of disability compared to individuals with PTSD alone. A severity of overall symptoms is three to fivefold greater in subjects with comorbid PTSD and depression compared to those with PTSD alone. The comorbid group is five times more likely to manifest functional impairment compared to those diagnosed with PTSD alone. Patients with comorbid PTSD and depression have higher depression, impulsivity, and hostility scores and are significantly more likely to make a suicide attempt compared to subjects with depression alone. Depressed subjects with comorbid PTSD tend towards earlier age of first hospitalization and a higher number of hospitalizations compared to depressed individuals without comorbid PTSD. Lower affinity of alpha-2 adrenoreceptors and higher plasma tyrosine availability to the brain are associated with comorbid PTSD and depression, but not with PTSD alone. Individuals with comorbid PTSD and depression do not exhibit the classic rapid eye movement sleep architectural modifications associated with depression, despite the fact that several other psychophysiological indices of dysphoria are detectable in their sleep. In fenfluramine challenge studies, depressed patients with comorbid PTSD have lower plasma cortisol compared to depressed patients without comorbid PTSD. Cortisol levels increase with age and the number of previous major depressive episodes is a predictor of the cortisol response to fenfluramine administration in depressed patients without PTSD, but not in depressed patients with comorbid PTSD. Depressed subjects with comorbid PTSD have higher cerebrospinal fluid homovanillic acid levels compared with depressed subjects without comorbid PTSD. Thus, studies suggest that patients suffering from comorbid PTSD and depression differ clinically and biologically from individuals with PTSD alone or depression alone. It is possible that some or all individuals diagnosed with comorbid PTSD and depression have a separate psychobiological condition that can be termed "post-traumatic mood disorder". Future clinical and neurobiological studies may not only advance our understanding of the role of environmental and genetic factors in the etiology and pathogenesis of stress-related disorders, but also be useful in refining conceptions of stress-related disorders themselves and possible approaches to the treatment of these conditions.

Comorbidity↗
PubMed2005

Higher cortisol levels in spring and fall in patients with major depression.

BACKGROUND: Multiple lines of evidence suggest that there are seasonal effects on mood and behavior, and that these effects are related to serotonergic and hypothalamic-pituitary-adrenal (HPA) function. This study sought to determine whether there is a seasonal effect on clinical parameters, baseline cortisol and prolactin levels, and cortisol and prolactin responses to fenfluramine administration in subjects with major depression. METHODS: In all, 136 subjects with major depression entered the study. Sixty-two subjects who had a major depressive episode (MDE) in Spring or in Fall (the Spring/Fall group) were compared to 74 subjects who had MDE in Winter or in Summer (the Winter/Summer group). Demographic and clinical parameters were assessed and recorded. Clinical parameters included depression, aggression, impulsivity, hopelessness, hostility, and current suicide ideation rating scales, suicide attempt status, and number and maximum lethality of suicide attempts. Cortisol and prolactin levels were drawn before fenfluramine administration and hourly for 5 h thereafter. Cortisol and prolactin levels were computed as the area under the curve of hourly cortisol measurements. RESULTS: Baseline cortisol levels were significantly higher in the Spring/Fall group compared to the Winter/Summer group (14.1+/-4.5 ng/ml vs. 12.5+/-4.4 ng/ml, df=132, t=2.16, p=0.03). There were no seasonal effects on baseline prolactin levels, or post-challenge cortisol and prolactin levels. CONCLUSIONS: The Spring/Fall group and the Winter/Summer group may represent different subtypes of major depression. Future studies need to both confirm our results and elucidate the mechanism of the circannual effect on biological function in depressed patients. The results of our study underline the importance of considering seasonality in psychobiology.

Adult↗
PubMed2004

The relationship of aggression to suicidal behavior in depressed patients with a history of alcoholism.

BACKGROUND: Alcoholism and depression are often comorbid. Studies suggest that depressed subjects with alcoholism have more chronic impairment and suicidal behavior than individuals with either diagnosis alone. The reason for higher rate of suicide and suicide attempts in comorbid subjects is uncertain. We explored clinical characteristics that may be associated with this increased suicidality. METHODS: In all, 219 depressed subjects (n=62 males and n=157 females) without a history of any alcohol or substance use disorder and 129 (n=49 males and n=80 females) depressed individuals with a prior history of alcohol use disorder participated in the study. Demographic and clinical parameters were assessed and recorded. RESULTS: Depressed subjects with a history of alcoholism had higher lifetime aggression and impulsivity, and were more likely to report a history of childhood abuse, suicide attempts, and tobacco smoking. Depressed suicide ideators with a history of alcoholism had higher suicide ideation scores than depressed suicide ideators without a history of alcoholism. Subjects with a history of alcoholism were younger at the time of the first depressive episode and first hospitalization than those without a history of alcoholism. Logistic regression analysis indicated that alcoholism was significantly associated with smoking and aggression. Suicidal behavior and higher suicidal ideation in depressed subjects with a history of alcoholism might be attributed to higher aggression scores in this group. CONCLUSION: The greater frequency of suicidal behavior and severity of suicidal ideation in major depression with comorbid alcoholism appears related to associated aggressive traits. Alcoholism, aggression, smoking, and suicide may have a common biological causal substrate.

Adult↗
PubMed2004

Age effects on cortisol levels in depressed patients with and without comorbid post-traumatic stress disorder, and healthy volunteers.

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.

Adult↗
PubMed2004

Etiology, pathogenesis, and treatment of seasonal and non-seasonal mood disorders: possible role of circadian rhythm abnormalities related to developmental alcohol exposure.

Developmental alcohol exposure adversely influences the developing brain. Alcohol exposure during rapid brain growth causes cell loss, alters connections between brain regions, and lowers the production of biological substances responsible for the communication among neurons. It is reasonable to suggest that alcohol may adversely affect the development of suprachiasmatic nuclei (SCN), the master circadian pacemaker. Multiple research reports suggest that abnormalities in circadian rhythms are involved in the etiopathogenesis of seasonal affective disorder (SAD), a syndrome in which depression develops during autumn or winter and remits the following spring or summer. Several lines of evidence suggest that changes in the circadian system are also involved in the development of nonseasonal mood disorders, such as major depression and bipolar disorder. Thus, developmental alcohol exposure produces subtle abnormalities in circadian rhythms that may contribute to the development of seasonal and nonseasonal mood disorders. Pharmacological, psychological, and light treatments of mood disorders have multiple effects on circadian function. The state of the circadian system may affect a response to treatment. Circadian rhythms have been reported for neurotransmitters, receptors, enzymes, and the second messenger system in the brain that are involved in the effects of treatments. Some of these rhythms have amplitudes as large as several 100%. Effects of many psychotropic medications depend on the time of administration in relation to body rhythmicity. Therefore, subtle circadian rhythm abnormalities related to developmental alcohol exposure may affect treatment response in patients with mood disorders.

Alcohol Drinking↗
PubMed2004

Daily hassles, cortisol, and the pathogenesis of depression.

Daily hassles and/or ongoing stress are associated with increased cortisol secretion in healthy individuals. Hassles are also associated with increased cortisol levels in depressed patients. Considerable evidence suggests that hypercortisolism is involved in the pathogenesis of depressive disorders. Over the past decade, there has been a shift from viewing excessive hypothalamic-pituitary-adrenal (HPA) activity in depression as an epiphenomenon to its having specific effects on symptom formation. The author suggests that increased cortisol secretion caused by daily hassles and/or ongoing stress contributes to the development of depressive disorders. Minor stressful events may lead to depression in vulnerable individuals. Genetic factors interact with environmental factors to influence the vulnerability to stress and mood disorders. The author also proposes that elevated cortisol levels associated with stressful daily events may worsen the condition of depressed patients. The author notes that one of the goals of prevention of stress-related disorders is to help individuals be more competent in managing their behavior and emotions in reaction to negative aspects of their environment, and briefly discusses stress management methods and techniques. The risk of developing depression is determined by a complex interplay between genetic susceptibility, environmental exposures, and aging. These influences also account for long term changes in the regulation of HPA function. Further studies of HPA function may not only advance our understanding of the role of the HPA system in the etiology and pathogenesis of psychiatric disorders, but also be useful in refining conceptions of psychiatric disorders themselves and possible approaches to the treatment of these conditions.

Depression↗