Timing of computed tomography in acute diverticulitis

OBJECTIVE: Studies on brain serotonin metabolism in human and nonhuman primates have indicated that dysfunction of serotonin transmission may play a role in the biological vulnerability to dependence on alcohol. Among young men, low sensitivity to alcohol intoxication predicts subsequent alcohol abuse and dependence. METHOD: The authors used single photon emission computed tomography and the radioligand [(I)123]beta-CIT ([(I)123]methyl 3beta-(4-iodophenyl) tropane-2-carboxylate) to measure the availability of serotonin transporters in 11 male rhesus monkeys, and the monkeys were genotyped for a functional polymorphism of the serotonin transporter gene. The 11 monkeys had experienced parental separation after birth; their behavior and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in CSF had been assessed regularly. RESULTS: In the 5-year-old monkeys, there was a significant negative correlation between beta-CIT binding to serotonin transporters in the brainstem and 5-HIAA concentrations in CSF. Animals with greater beta-CIT binding and low CSF 5-HIAA concentrations displayed greater aggressiveness and were less sensitive to alcohol-induced intoxication. The genetic constitution of the serotonin transporter promoter gene did not significantly contribute to the availability of brainstem serotonin transporters as measured by beta-CIT binding. CONCLUSIONS: In adult nonhuman primates who underwent early developmental stress, variables indicating a low serotonin turnover rate were associated with behavior patterns similar to those predisposing to early-onset alcoholism among humans.     

The impact of the central serotonin system on alcoholism and therapeutic consequences]

Several studies support the assumption that the development and/or maintenance of alcoholism is due to a deficit of the central serotonergic system. But it still remains open whether the imbalance in the serotonergic functioning is due to genetic factors or whether it is a result of alcoholism. It has been hypothesised that both mechanisms interact with each other creating a vicious circle. The efficacy of serotonin reuptake inhibitors (SSRIs) in treating alcoholism supports the pathophysiological assumptions. Citalopram (40 mg) and Fluoxetine (60-80 mg) significantly reduce ethanol intake. However, treatment effects disappear after a treatment period of more than 4 weeks in most of the studies. Chronic and heavy alcoholics benefit less from treatment. Better treatment results were obtain in alcoholics with primary depression, especially with a prolonged treatment period. The promising treatment outcome in primary depressed alcoholics suggests an efficacy of SSRIs in alcoholism with primary anxiety disorders, although no data are available. The results of the studies in this field support the following therapeutic consequences: 1. Alcoholics with primary depression should be treated with SSRIs. 2. A short-term treatment with SSRIs in primary alcoholism without comorbid psychiatric diseases can be considered, e.g. to prevent treatment drop-outs or for relapse prevention. 3. So far, treatment in alcoholics with primary anxiety disorders is not supported simply due to a complete lack of data. Studies on this problem are imperative.     

Fluoxetine in depressed alcoholics. A double-blind, placebo-controlled trial

BACKGROUND: The selective serotonergic medication fluoxetine has demonstrated efficacy in the treatment of major depression and has suggested efficacy in the treatment of alcoholism. However, no completed trials with any selective serotonergic medication have been reported in patients who display both major depression and alcoholism, despite previous observations that both depression and alcoholism are associated with low serotonergic functioning. METHODS: Fifty-one patients diagnosed as having comorbid major depressive disorder and alcohol dependence were randomized to receive fluoxetine (n = 25) or placebo (n = 26) in a 12-week, double-blind, parallel-group trial. Weekly ratings of depression and alcohol consumption were obtained throughout the 12-week course of the study. RESULTS: The improvement in depressive symptoms during the medication trial was significantly greater in the fluoxetine group than in the placebo group. Total alcohol consumption during the trial was significantly lower in the fluoxetine group than in the placebo group. CONCLUSIONS: Fluoxetine is effective in reducing the depressive symptoms and the alcohol consumption of patients with comorbid major depressive disorder and alcohol dependence. It is unknown whether these results generalize to the treatment of less depressed and less suicidal alcoholics.     

Overt behavior problems and serotonergic function in middle childhood among male and female offspring of alcoholic fathers

A large body of literature indicates that the serotonergic system is involved in behavioral regulation, as evidenced by the inverse relationship between impulsive aggression and serotonergic function found in adult alcoholics and nonalcoholics. However, studies of this relationship among child and adolescent offspring of alcoholics (COAs) have not previously been done. This study examines the potentially parallel relationship between behavioral dysregulation and low serotonergic function in young COAs. The relationship is of potential interest as a phenotypic marker of biological vulnerability to aggressiveness, which itself has been hypothesized to be a risk factor for later antisocial alcoholism. The present work is part of an ongoing prospective study of the development of risk for alcohol abuse/dependence and other problematic outcomes in a sample of families subtyped by the fathers' alcoholism classification. We examined the relationship between overt behavior problems in middle childhood (mean age = 10.5 +/- 1.7 years) and whole blood serotonin (5-HT) in a subsample of the offspring (N = 32 boys and 12 girls). Using a Child Behavior Checklist (CBCL) index of behavioral undercontrol, we obtained results indicating that high total behavior problem (TBP) children had lower levels of whole blood 5-HT than did low-TBP children (p < 0.01). These results support the hypothesis that there is an inverse relationship between whole blood serotonin levels and behavior problems in young male and female COAs. A father's alcoholism status was not significantly related to his child's 5-HT level, i.e., the child's phenotypic expression of behavioral dysregulation was more reliably connected to serotonergic function than was paternal alcoholism.     

Decreases in dopamine receptors but not in dopamine transporters in alcoholics

It has been hypothesized that ethanol's actions on the dopamine (DA) system may participate in addiction. The purpose of this study was to evaluate the DA system in the brain of alcoholics. We evaluated 10 alcoholics and 17 nonalcoholics using positron emission tomography and [11C]raclopride to measure DA D2 receptors. In addition, in 5 of the alcoholics and 16 of the nonalcoholics, we also measured DA transporters with [11C]d-threo methylphenidate. The ratio of the distribution volumes in striatum to that in cerebellum, which corresponds to Bmax/Kd + 1, was used as model parameter of DA D2 receptor and transporter availability. Dopamine D2 receptor availability (Bmax/Kd) was significantly lower in alcoholics (2.1 +/- 0.5) than in nonalcoholics (2.7 +/- 0.6) (p < 0.05) and was not correlated with days since last alcohol use. Alcoholics showed DA transporter values similar to those in nonalcoholics. The ratio of DA D2 receptor to transporter availability was significantly higher in nonalcoholics (1.4 +/- 0.1) than in alcoholics (1.1 +/- 0.1) (p < 0.005). Alcoholics showed significant reductions in D2 receptors (postsynaptic marker) but not in DA transporter availability (presynaptic marker) when compared with nonalcoholics. Because D2 receptors in striatum are mainly localized in gamma-aminobutyric acid (GABA) cells these results provide evidence of GABAergic involvement in the dopaminergic abnormalities seen in alcoholics.     

The autonomic nervous system and hypoxia: mountain medicine

Subregional distributions of serotonin1A receptors and serotonin transporters within the human dorsal raphe nucleus (DR) were determined by quantitative autoradiographic analyses of radioligand binding in tissue sections. [3H]8-Hydroxy-2-(di-n-propyl)aminotetralin (8-OH-DPAT) and [3H]paroxetine were used to label, respectively, serotonin1A receptors and serotonin transporters in the subnuclei of the DR, which were delineated on the basis of tryptophan hydroxylase (TrpOH) immunoreactivity. [3H]8-OH-DPAT binding was coextensive with the TrpOH-immunoreactive cell bodies and fibers but was distributed unevenly among the subnuclei. In contrast, [3H]paroxetine binding was present throughout the central gray matter, with relatively homogeneous labeling across the subnuclei of the DR. In rostral sections, [3H]8-OH-DPAT binding (fmol/mg protein) in the dorsal subnucleus was lower than that in the ventral or the interfascicular subnucleus. Within the interfascicular subnucleus, [3H]8-OH-DPAT binding decreased progressively in a rostral-to-caudal fashion. The highest levels of [3H]8-OH-DPAT binding were found in the ventrolateral subnucleus at the level of the caudal extent of the trochlear nucleus. The influence of age and postmortem interval on radioligand binding was also examined. These data in the human DR indicate that serotonin1A receptors are differentially distributed among the subnuclei and along the rostro-caudal axis of the midbrain raphe, and serotonin transporters appear to be relatively evenly distributed throughout the DR. Subregional analyses of such serotonergic markers may prove useful in evaluating the role that serotonin may play in depression, schizophrenia, and suicide.     

Serotonin and alcohol intake, abuse, and dependence: findings of animal studies

Despite a relatively large body of literature on the role of the neurotransmitter serotonin (5-hydroxytryptamine, or 5-HT) in the regulation of alcohol intake, the functional significance of serotonergic neurotransmission and its relationship to alcohol intake, abuse, and dependence remains to be fully elucidated. In part two of this review, the experimental (animal) data is summarized along two lines: the effects of serotonergic manipulations on the intake of alcohol, and the effects of acute and chronic alcohol intake, as well as the withdrawal of chronic alcohol, on the serotonergic system. It is concluded that serotonin mediates ethanol intake as a part of its larger role in behavior modulation, such that increases in serotonergic functioning decrease ethanol intake, and decreased serotonergic functioning increases ethanol intake. Ethanol produces transient increases in serotonergic functioning that activate the mesolimbic dopaminergic reward system. The results are discussed in light of recent theories describing the regulatory role of serotonin in general behavior.     

Comparative analysis of ribonuclease P RNA structure in Archaea

The relationship between central serotonergic activities and voluntary alcohol consumption was studied in Sprague-Dawley rats, which normally have low alcohol preference. After initial screening for an evenly matched baseline alcohol preference, selective central serotonergic lesioning was induced by intracisternal injection of the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). Control rats received injections of vehicle only. Both 5,7-DHT and vehicle-treated rats were further divided into two subgroups, which either had continued free access to ethanol (alcohol-drinking) or were deprived of it (alcohol-free). All rats were then tested again for alcohol preference. All rats were then killed, and the levels of monoamines in the brains were determined by high performance liquid chromatography with electrochemical detection. Behavioral results indicated that all 5,7-DHT-treated rats had significantly higher alcohol preference and consumption than the corresponding sham controls. Except in the cerebellum, the 5,7-DHT-treated rats had significantly lower levels of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in most brain regions compared with those in the corresponding sham controls. Treatment with 5,7-DHT also resulted in a decrease in serotonin turnover in all brain regions in the alcohol-free rats, except in the cerebellum. In alcohol-drinking rats, however, 5,7-DHT treatment only reduced serotonin turnover in the pons. The levels of norepinephrine and dopamine in several brain regions were not significantly different. Thus, it appeared that in the Sprague Dawley rats, 5,7-DHT treatment depleted 5-HT and 5-HIAA levels in most brain regions while increasing alcohol consumption. Chronic alcohol-drinking attenuated the increase in alcohol consumption associated with serotonergic lesions. Voluntary alcohol consumption seemed more associated with 5-HT turnover than with tissue 5-HT levels. Our data also suggested that tolerance to alcohol-induced hypothermia was primarily attributable to long-term alcohol drinking rather than serotonergic lesioning.     

Effects of anxiety arousal on the consumption of alcohol by alcoholics and social drinkers.

Tested the hypothesis that the arousal of anxiety would lead to an increase in the alcoholic's consumption of alcohol. 20 male nonabstinent alcoholics and 20 male social drinkers were engaged in an alcohol taste rating task. High and low levels of state anxiety were induced by threatening Ss with either a painful or a nonpainful electric shock. Levels of trait anxiety were also assessed using the Neuroticism scale of the Eysenck Personality Inventory. Alcoholics consumed significantly more alcohol than social drinkers in the tasting task, but the amounts consumed by both groups were unrelated either to the anxiety manipulation factor or trait anxiety scores. Results are discussed in terms of their implications for anxiety-reduction models of alcoholism. (22 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Screening for neuropsychological impairment in alcoholics.

A short self-report instrument that could predict neuropsychological impairment in at-risk patients would be advantageous to clinicians treating alcoholics. Seventy-three Veterans Administration alcoholics and 36 control subjects were administered a 50-item self-report symptom checklist, the Neuropsychological Impairment Scale (NIS); psychological measures of anxiety and depression; and a battery of neuropsychological tests known to be sensitive to brain dysfunction. Alcoholics differed from control subjects on the neuropsychological tests and in their NIS profiles. Multiple regression analyses revealed that select NIS subscales could predict neuropsychological impairment in alcoholic subjects. These subscales, however, were found to be more strongly correlated with standard measures of anxiety and depression than with cognitive performance. The confounding role of affect in predicting neuropsychological impairment from self-report questionnaires is discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Depression in Parkinson's disease: biogenic amines in CSF of "de novo" patients

INTRODUCTION: Etiology of depression in Parkinson's disease (PD) is associated with serotonergic dysfunction. Previous studies, supporting this hypothesis, were performed on patients treated with antiparkinsonian drugs. To eliminate the influence of parkinsonian drug therapy and to elucidate significance of different biochemical pathways in PD associated with depression we determined levels of biogenic amines in cerebrospinal fluid (CSF) of 26 untreated "de novo" Parkinsonian patients. MATERIAL AND METHODS: Patients were scored with the Hamilton depression scale (HD) and subdivided into groups with HD score > or = 18 and HD score < 18. Diagnosis of depression was made according to DSM III R. Both groups were matched for age and motor disability. RESULTS: In both groups no significant differences appeared between CSF levels of dopamine, noradrenaline, 3,4-dihydroxyphenylacetic acid, homovanillic acid, 3-methoxy-4-hydroxyphenylglycol and 5-hydroxyindole acetic acid, determined by high-performance liquid chromatography. DISCUSSION: In contrast to previous studies on treated Parkinsonian patients no sign of altered serotonin metabolism especially in context with severity of depression in early stages of PD was found. Due to our results, we suggest, that biochemical markers of depression in CSF of PD may be influenced by antiparkinsonian therapy and that depression in PD may respond to serotonin reuptake inhibitors mainly in later stages of PD.     

Symptom reduction and sobriety in the male alcoholic

The relationship between subjective symptom reduction and sobriety was studied for 82 male alcoholics who had completed an inpatient Alcoholic Rehabilitation Unit that included six or more biofeedback/relaxation sessions. Specific symptom relief for anxiety was significantly correlated with sobriety. In addition, the reduction of symptoms showed a positive trend with sobriety. The discussion focuses on the relationship of anxiety-related symptoms and alcohol abuse.     

The life-time rates of three major mood disorders and four major anxiety disorders in alcoholics and controls

AIMS: While psychiatric symptoms are common in the general population and even more prevalent in alcoholics, their clinical implications are not clear. The goal of this study was to establish the life-time rates of several independent and concurrent mood and anxiety disorders in alcoholics, controls and their relatives. DESIGN: Structured interviews were administered to alcoholics entering treatment, their relatives, and controls. SETTING: The study was carried out in six different centers in the United States as part of the Collaborative Study on the Genetics of Alcoholism (COGA). PARTICIPANTS: Data were gathered from 2713 alcohol dependent subjects (probands and their alcoholic relatives) and 919 controls. MEASUREMENTS: The timeline-based Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) interview was administered face to face by trained, closely supervised interviewers. The life-time rates for concurrent and independent disorders were determined for three DSM-III-R major mood and four major anxiety disorders. FINDINGS: Some form of independent mood disorder was seen during the life-time in slightly fewer alcoholics than controls (14.0% and 17.1%), but alcoholics did show higher rates of independent bipolar disorder (2.3% vs. 1.0%). The life-time rate for independent anxiety disorders was significantly higher in alcoholics than controls (9.4% vs. 3.7%), with most of the differential related to panic disorder (4.2% vs. 1.0%) and social phobia (3.2% vs. 1.4%), but no significant group differences for agoraphobia or obsessive-compulsive disorder. In general, these findings regarding mood and anxiety disorders were reflected in close relatives. CONCLUSIONS: The large majority of alcohol-dependent men and women in this sample did not have any of the independent mood or anxiety disorders evaluated here. However, there was evidence of enhanced risks among alcoholics for independent bipolar, panic and social phobic disorders. Studies which do not distinguish carefully between independent and concurrent mood and anxiety disorders in alcoholics are likely to report much higher rates of co-morbid psychiatric disorders than those that distinguish between the two types of syndromes.     

Alcohol challenge with sons of alcoholics: A critical review and analysis.

Studies are reviewed in which response to acute administration of alcohol was compared between individuals with and without family histories of alcoholism (FH+, FH–). This research represents a search for a psychobiological marker for alcoholism. A methodological critique of the procedures reported in this literature is then presented. Finally, a conceptual model is suggested in which differences in the response to alcohol between FH+ individuals and FH– individuals must be understood in relation to time after drinking alcohol. This Newtonian differentiator model proposes that sons of alcoholics exhibit acute sensitization as blood alcohol level rises and acute tolerance as blood alcohol level falls, compared with sons of nonalcoholics. Therefore, FH+ Ss find alcohol more rewarding because they accentuate the pleasurable, excitatory aspects of initial intoxication and attenuate the feelings of anxiety and depression that predominate as blood alcohol levels drop. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Adverse neuropsychiatric events associated with dexfenfluramine and fenfluramine

1. There is a large body of evidence indicating that fenfluramines damage brain serotonin neurons in animals. 2. Little is known about potential adverse neuropsychiatric consequences in humans associated with use of fenfluramines that could potentially be related to serotonergic dysfunction. 3. The authors now report numerous cases of severe and, sometimes persistent, neuropsychiatric syndromes associated with fenfluramine use. 4. Thirty one representative cases are presented and summarized in table form. 5. Several of the cases presented suggest long-lasting deleterious effects of fenfluramines on brain serotonin function. 6. Clinicians should be vigilant for disorders of mood, anxiety, cognitive function and impulse control in patients previously exposed to fenfluramines.     

Relation between a dimension of Internal-External Control and the MMPI with an alcoholic population.

Investigated locus of control with the Internal-External Control scale as well as the intercorrelations of this scale with the subscales of the MMPI for 262 alcoholics. Contrary to the initial hypothesis, the alcoholic population scored in the internal control direction. Consistent with the 2nd hypothesis, those alcoholics whose scores were lowest (internal) reported least anxiety, depression, and clinical pathology on the MMPI. Results are discussed in terms of control of reinforcement, i.e., alcohol, and regulation of affective states of distress. (16 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Regional cerebral metabolism in female alcoholics of moderate severity does not differ from that of controls

It is generally believed that women are more vulnerable to alcohol's toxic effects than men. Studies in male alcoholics have consistently shown reductions in brain glucose metabolism. However, such studies have not been done in female alcoholics. The purpose of this study was to evaluate if similar or worse brain metabolic abnormalities occurred in female alcoholics. For this purpose, we measured regional brain metabolism with positron emission tomography and [18F]fluorodeoxyglucose in 10 recently detoxified female alcoholics and compared it with that in 12 age-matched female controls. There were no differences between alcoholics and control females in regional brain glucose metabolism whether we used regions of interest analysis or statistical parameter maps methods. These results do not support a higher toxicity for the effects of alcohol in the female brain, as assessed with regional brain glucose metabolism, because metabolic values in female alcoholics did not differ from those of controls, whereas metabolic values in male alcoholics are generally lower than those in controls. However, this study is confounded by the fact that the severity of alcohol use in these female alcoholics was less than that of the male alcoholics previously investigated in positron emission tomography studies. Future studies in male subjects with alcoholism of moderate severity are required to address gender differences in sensitivity to alcohol effects in brain metabolism.     

The place of oral contraceptives and pregnancy in the aetiology of amenorrhoea, a study of 188 cases of secondary amenorrhoea lasting more than one year (author''s transl)

Platelet function was assessed before and one week after acute alcohol withdrawal in eighteen male alcoholics. Compared to normal male controls, the platelets of the alcoholics were slightly hypoaggregable on admission but became hyperaggregable one week after commencement of alcohol withdrawal therapy. The changes were most noticeable in those patients who were alcoholaemic on admission and when using ADP or adrenaline as aggregating agents. There was no consistent change in platelet counts or in platelet adenine nucleotide levels, both of which were normal.     

Which relapse criteria best predict the mortality risk of treated alcoholics?

We examined which relapse criteria best predict the mortality risk of treated male alcoholics. The subjects were 172 male alcoholics who had previously been hospitalized. Using three criteria which defined relapse as failure to maintain abstinence from alcohol, alcohol abuse, or dependence, the relapse of each subject had been evaluated during a previous 3-year outcome study. Relative mortality risks in the next 3 years classified by the three relapse criteria were compared. The follow-up rate was 93.6% and 31 subjects died. The age-corrected relative mortality risk for subjects failing to maintain abstinence compared with abstainers was 5.32, while the relative mortality risks for the group abusing alcohol and for the group suffering alcohol dependence were 2.23 and 2.56, respectively. These results suggest that relapse defined as failure to maintain abstinence predicts a higher relative mortality risk than do criteria defining in terms of alcohol abuse and alcohol dependence.