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Biomedical subjects

J J Mann

Publications and source records attributed to J J Mann.

At least 19 recordsLinked to original sources
PubMed1992

Platelet and whole blood serotonin content in depressed inpatients: correlations with acute and life-time psychopathology.

Platelet or whole blood serotonin content did not differ significantly in patients with major depression compared to healthy controls, but within the patient group, platelet serotonin levels correlated negatively with severity of depression (r = -0.49, p = 0.007). Levels were 39% lower in patients who had made a suicide attempt compared to nonattempter patients (47.2 +/- 27.3 versus 77.6 +/- 41.7 ng/10(8) platelets, p = 0.04). Conversely, comorbid borderline personality disorder (85.3 +/- 41.5 ng/10(8) platelets) was associated with 31% greater platelet serotonin content than nonborderline patients (58.9 +/- 31.1 ng/10(8) platelets) and 27% greater than healthy controls (62.4 +/- 19.8 ng/10(8) platelets). A pronounced seasonal variation in whole blood and platelet serotonin content was found in both patients and controls, largely due to lower levels in summer. Excluding cases tested in the summer abolished the statistically significant differences in patients with and without comorbid borderline personality disorder (BPD). Nevertheless, BPD attempters had lower serotonin levels than BPD nonattempters but higher serotonin levels than non-BPD attempters. Current hostility and a life-time history of aggression were positively correlated with platelet serotonin content (r = 0.44, p = 0.04 and r = 0.41, p = 0.06). This study provides evidence for an association between lower platelet serotonin content and depression and suicidal behavior, and association of higher platelet serotonin content and comorbid borderline personality disorder and behavior traits such as aggressivity.

Adult↗
PubMed1992

Role of the dopaminergic system in depression.

A hypothesis implicating dopamine in depression was proposed over 15 years ago (Randrup et al 1975). The identification of multiple new subtypes of dopamine receptors and evolving views regarding the function of the dopamine systems in the brain require a reexamination of this hypothesis. Results from studies in depression, Parkinson's disease, and animal models of depression suggest a deficiency of dopamine in depression. Dopamine precursors, dopamine agonists, and dopamine reuptake inhibitors show therapeutic efficacy in depression. Electroconvulsive therapy (ECT) and standard pharmacological antidepressants enhance dopamine function. Studies using receptor-specific drugs in clinical trials and neuroimaging studies are needed to further clarify the role of dopamine in depression.

Animals↗
PubMed1992

Neuroendocrine and behavioral responses to challenge with the indirect serotonin agonist dl-fenfluramine in adults with obsessive-compulsive disorder.

Neuroendocrine and behavioral responses to a single 60-mg oral dose of the indirect serotonin agonist dl-fenfluramine were assessed in unmedicated adults with obsessive-compulsive disorder (OCD) and neuroendocrine results contrasted with those in normal control subjects. Net fenfluramine-induced prolactin release did not differ significantly between OCD patients and normal controls. Prolactin responses in the OCD group were not significantly correlated with baseline Yale-Brown Obsessive Compulsive Scale scores for either obsessions or compulsions, but were positively correlated with the baseline Hamilton Depression Scale score and Hamilton Anxiety Scale score. No clear difference in the severity of patients' obsessions or compulsions was found following challenge with fenfluramine versus placebo. Although the present study does not demonstrate a serotonergic abnormality in OCD, this may be more a reflection of limitations of the test procedures than evidence that central nervous system (CNS) serotonergic function is normal in the disorder.

Adult↗
PubMed1992

Relationship between central and peripheral serotonin indexes in depressed and suicidal psychiatric inpatients.

Serious suicidal behavior, affective disorders, and a variety of other psychopathologic behaviors and syndromes have been found to correlate with measures of the serotonin system. Clinical studies have employed a range of serotonin indexes, including the cerebrospinal fluid level of 5-hydroxyindoleacetic acid, the prolactin response to serotonin agonists, such as fenfluramine hydrochloride, and platelet serotonin-related proteins or serotonin content. Many of these indexes are correlated with suicidal behavior, but the interrelationship of these biologic measures has been uncertain. We studied the relationship of a series of serotonin indexes in patients in whom these measures were correlated with suicidal behavior. A positive correlation was found between cerebrospinal fluid 5-hydroxyindoleacetic acid and the maximal prolactin response to fenfluramine but not with platelet serotonin2 receptor indexes. The fenfluramine-stimulated maximal prolactin response correlated with platelet serotonin2 receptor number, particularly in older patients. We conclude that cerebrospinal fluid 5-hydroxyindoleacetic acid measurements cannot be replaced but can be complemented by less invasive procedures, such as a fenfluramine challenge test or platelet serotonin2 measures, in the study of the relationship of the serotonin system to psychiatric disorders.

Adult↗
PubMed1992

The effect of access to lethal methods of injury on suicide rates.

The relationship between the availability of lethal methods of injury and suicide rates is an important, but unresolved question. We investigated this relationship by prospectively classifying lethal methods according to their accessibility in the five counties of New York City. These counties have both similarities and differences in the proportion of their populations with access to specific lethal means. We then compared the age- and gender-adjusted method-specific suicide rates of these counties. There were marked differences in overall crude suicide rates among the five counties. The counties had similar suicide rates involving methods that were equally accessible to all persons in each county (eg, hanging, laceration, suffocation, and burns) as well as methods that were accessible to a smaller, but similar proportion of the population in each county (eg, firearms and drowning in waterways). Virtually all of the differences in overall suicide risk among counties were explained by differences in rates involving methods that were differentially available in the counties, principally fall from height, overdose of prescription medications, and carbon monoxide poisoning. We conclude that differences in suicide rates between communities are, in large part, due to differences in accessibility to lethal methods of injury. Therefore, systematic studies should evaluate the effect of reducing accessibility to specific lethal means on suicide rates.

Age Factors↗
PubMed1992

Simultaneous effects of the platelet 5-HT2 and alpha 2-adrenergic receptor populations on phosphoinositide hydrolysis.

The interaction of multiple receptor populations on a common second messenger system is a critical aspect of cell function and may be involved in pathology. We studied the interactions of the 5-HT2, alpha 2-adrenergic and prostaglandin (PGI2) receptors on phosphoinositide (PI) turnover in human platelets. Serotonin and epinephrine (EPI) stimulated PI hydrolysis in a dose-dependent manner. The PI turnover response to serotonin was mediated by the 5-HT2 receptor. The PI response to EPI was mediated by alpha 2-adrenergic receptors. An additive PI turnover response was generated by the combination of 5-HT and EPI. The sum of the maximal responses to 5-HT (72.5 +/- 4.9%) and EPI (56.0 +/- 4.2%) approximated the maximal response (129.3 +/- 9.5) to the combination. Prostacyclin (PGI2) at 1 microgram/mL reduced PI turnover by 21.8 +/- 1.1%. The PI response to 5-HT and EPI was not significantly altered once the reduction in the baseline PI turnover by PGI2 is taken into account. Similarly, PGI2 did not reduce PI hydrolysis stimulated by a combination of 5-HT (0.2 mM) and EPI (0.1 mM) once the decrease in baseline was taken into account (p greater than 0.20). The summation of serotonin stimulation of PI turnover by a combination of both epinephrine and serotonin was blocked by either yohimbine or ketanserin. These studies indicate: (1) the pool of phospholipases appears to exceed the maximal capacity of the individual alpha 2-adrenergic and 5-HT2 receptor populations to activate this second messenger system. (2) inhibition of serotonin or epinephrine-stimulated PI turnover by prostacyclin is due to a lowering of basal PI turnover. Future studies should examine other cell systems to assess the generalizability of these findings regarding the differences in effects on a second messenger system when activated by one receptor population as opposed to two different receptor types.

Blood Platelets↗
PubMed1992

Regulation of cortical blood flow by the dorsal raphe nucleus: topographic organization of cerebrovascular regulatory regions.

We examined in rat: (1) the time-course and magnitude of change in cortical blood flow (CoBF) following electrical stimulation of the dorsal raphe nucleus (DRN) and (2) whether DRN lesions affect resting CoBF or the cerebrovascular response to CO2. Animals were anesthetized (chloralose), paralyzed, and artificially ventilated. The effect of stimulus frequency (1-200 Hz) and intensity (10-100 microA) on arterial pressure, heart rate, and CoBF was examined; lesions were made electrolytically. CoBF was measured using a laser-Doppler flowmeter with the probe placed extradurally over the parietal sensorimotor cortex. The DRN was computer reconstructed in three dimensions from Nissl stained coronal sections for localization of electrode placements. Brief stimuli (8 s; n = 6) elicited frequency and intensity-dependent increases in arterial pressure, heart rate, and CoBF. Sustained intermittent trains of stimuli of rostral DRN (200 Hz; 1 s on/1 s off; 70 microA) elicited a decrease (85 +/- 12% of baseline; n = 9) in CoBF (p less than 0.05) while stimulation in caudal DRN resulted in increased CBF (126 +/- 13% of baseline; n = 9). Phenylephrine infusion (0.1-1 microgram; i.v.; n = 8) increased arterial pressure and CoBF less than that elicited by brief DRN stimulation (p less than 0.05). DRN lesions did not affect resting CoBF (140 +/- 25 perfusion units (PU) before; 127 +/- 16 PU after DRN lesion; p greater than 0.05, n = 5) or mean arterial pressure (127 +/- 13 before; 120 +/- 11 after); nor did it affect the cerebrovascular response to change in arterial PCO2. Sustained intermittent stimulation of the DRN can evoke either increases or decreases in CoBF depending on the anatomical sublocalization. The DRN does not tonically maintain resting CoBF, nor participate in the cerebrovascular response to change in PCO2.

Animals↗
PubMed1992

Self-mutilation in personality disorders: psychological and biological correlates.

OBJECTIVE: The goal of this study was to determine whether self-mutilators with personality disorders differ from nonmutilators with personality disorders in impulsivity, aggression, and other psychopathology and whether serotonergic dysfunction contributes to self-mutilation. METHOD: Twenty-six self-mutilators with personality disorders were matched to 26 control subjects with personality disorders for gender, age, education, axis I diagnosis of affective disorder, and axis II diagnosis of personality disorder. Numerous indexes of psychopathology as well as CSF 5-hydroxyindoleacetic acid (5-HIAA) levels and platelet imipramine binding sites (Bmax) and affinity (Kd) were determined. RESULTS: Self-mutilators had significantly more severe character pathology, had greater lifetime aggression, and were more antisocial than the control subjects. The self-mutilators scored higher on the Hamilton Rating Scale for Depression but not on the Beck Depression Inventory or the Beck Hopelessness Scale. The two groups did not differ on the Buss-Durkee Hostility and Guilt Inventory or on the Sensation Seeking Scale. The degree of self-mutilation was significantly correlated with impulsivity, chronic anger, and somatic anxiety. Both self-mutilation and impulsivity showed significant negative correlations with Bmax, although the two groups did not differ in CSF 5-HIAA levels or in platelet imipramine binding. CONCLUSIONS: The results demonstrate the contribution of severe character pathology, aggression, impulsivity, anxiety, and anger to self-mutilation and provide preliminary support for the hypothesis of underlying serotonergic dysfunction facilitating self-mutilation.

Humans↗
PubMed1992

Prevalence of cocaine use among residents of New York City who committed suicide during a one-year period.

OBJECTIVE: In the mid-1980s the form of cocaine called "crack" became widely available in New York City. The authors sought to determine the prevalence of cocaine metabolites detected at autopsy in persons who committed suicide in New York City during this period. METHOD: Individual reviews of the autopsy and toxicological records of all persons under the age of 61 who had committed suicide in the city during a 1-year period were conducted to determine demographic characteristics, suicide methods, and cocaine and alcohol use at the time of death. RESULTS: In one of every five cases studied, the person who committed suicide had used cocaine within days of his or her death. The prevalence of cocaine use among young Hispanic males who committed suicide was 45%. Persons who were young, black, or Hispanic and who had used alcohol immediately before the fatal injury were most likely to have been recent cocaine users. After controlling for demographic variables and ethanol use, the investigators found that individuals who committed suicide with firearms were twice as likely to have used cocaine as those who used other methods. CONCLUSIONS: In contrast to the results of regional and household surveys during this period, which suggested that the current prevalence of cocaine use in New York City was 3%-5%, these results suggest a high prevalence of cocaine use in the days immediately preceding death by young persons who commit suicide. Additional studies are needed to determine how cocaine may act as a risk factor for suicide.

Adolescent↗
PubMed1992

Alterations in monoamine receptors in the brain of suicide victims.

Suicide has been linked to alterations in the serotonergic and noradrenergic systems. Using in vitro quantitative receptor autoradiography, we compared the binding of 125I-lysergic acid diethylamide (5-hydroxytryptamine-2 sites) and 125I-pindolol (beta-adrenergic sites) with slide-mounted sections from the prefrontal and the temporal cortex of a group of suicide victims, matched to control specimens on postmortem interval, age, sex, and race. A specific laminar distribution of 5-hydroxytryptamine-2 binding was found in both groups, with layers III and IV having the highest level of binding, but beta-adrenergic binding did not differ across cortical layers. Binding to both 125I-lysergic acid diethylamide and 125I-pindolol was increased in the prefrontal cortex of the suicide victims, whereas only beta-adrenergic binding was increased in the temporal cortex of the suicide group.

Adolescent↗
PubMed1992

Integration of neurobiology and psychopathology in a unified model of suicidal behavior.

Suicidal behavior is the result of a combination of factors that span the domains of psychopathology, genetics, early life experience, family interactions, social stress, physical illness, and neurobiology. To develop predictive and explanatory models of suicidal behavior it is necessary to consider all of these domains. A stress-diathesis model is proposed that classifies risk factors for suicidal behavior into those that are trait-dependent and those that are state-dependent. The timing of suicidal behavior is determined by state-dependent factors. The relationship of psychopathologic factors such as severity of depression or anxiety to suicide will be discussed. Biologic changes that correlate with suicide may be either state- or trait-dependent. Particular emphasis will be given to changes in the serotonin system and how these may represent a constitutional risk factor as opposed to a state-dependent risk factor for suicidal behavior.

Brain↗
PubMed1992

Biology of elderly suicide.

Most studies of suicide in younger patients have demonstrated significant alterations in the serotonin system. Although a high percentage of completed suicides occur in late-life, to date very few studies of the biology of suicide have focused on this age group. This chapter describes age-related changes in the central nervous system pertinent to the biology of suicide, then reviews post-mortem biological studies of the brains of suicides and suicide attempters. As suicide attempts in the elderly are characterized by the use of violent means, biologic studies of impulsive violence are discussed. Finally we describe data on the effect of degenerative diseases on the serotonin system and the possible link to increased suicidal behavior in affected patients. This review underscores the need for further study of the biology of suicide in the geriatric age group.

Age Factors↗
PubMed1990

Effects of age and gender on CNS serotonergic responsivity in normal adults.

The effects of age and gender on central nervous system (CNS) serotonergic responsivity were assessed with a neuroendocrine challenge test in 30 normal adults. Subjects greater than or equal to 30 years of age, compared with younger subjects, exhibited decreased prolactin secretion in response to a 60-mg oral dose of dl-fenfluramine hydrochloride, an indirect serotonin agonist. Furthermore, women had greater prolactin responses than men. As prolactin secretory capacity appears to be stable through midlife, the age-associated decrease in fenfluramine-induced prolactin release suggests a decline in CNS serotonergic responsivity. In contrast, the finding of greater prolactin release in women than in men probably reflects the effects of nonserotonergic modulatory influences at the level of the lactotroph. Age and gender effects must be considered in studies of the CNS serotonergic system.

Adult↗
PubMed1990

Demonstration of high- and low-affinity beta-adrenergic receptors in slide-mounted sections of rat and human brain.

Studies using isolated cell membranes have shown that beta-adrenergic receptors exist in two interconvertible conformations, one with high affinity for agonists and the other with low affinity. Guanine nucleotides and sodium shift high-affinity receptor sites into low-affinity sites. We sought to demonstrate affinity states of the beta-adrenergic receptor in slide-mounted sections of rat and human postmortem brain, and to determine using quantitative receptor autoradiography the regional distribution in the brain of high-affinity receptors relative to the total population of beta-adrenergic receptors. The beta-adrenergic agonist isoproterenol inhibited the binding of 125I-iodopindolol to slide-mounted sections of rat forebrain and human premotor cortex in a biphasic manner. Approximately 80% of the beta-receptor sites in both rat and human brain showed high-affinity for isoproterenol (7-14 nM). Treatment with 0.1 mM non-hydrolyzable guanine nucleotide 5'-guanylylimidodiphosphate and 25 mM NaCl abolished high-affinity binding in rat brain sections and reduced it in human brain sections. These findings were confirmed by membrane studies using similar tissue samples. For autoradiographic studies, 17 nM isoproterenol displaced 71% of the high-affinity sites without affecting low-affinity beta-adrenergic receptors. Digital subtraction was used to selectively visualize beta-receptors in the high-affinity conformation. The proportion of beta-adrenergic receptors in the high-affinity conformation differed significantly across rat brain regions and across human cortical layers. We conclude that beta-adrenergic affinity states, presumably reflecting the interaction of the receptor with a G-protein, occur in slide-mounted sections of rat brain and persist in human postmortem material.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗