Ethanol-like effects of thiopental and ketamine in healthy humans.

The gamma-aminobutyric acid-A (GABA(A)) and N-methyl-D-aspartate (NMDA) receptors mediate aspects of the behavioural effects of alcohol. Prior studies reported drugs that block NMDA receptors or facilitate GABA(A) receptor function produce ethanol-like effects in humans. The purpose of this study was to compare the ethanol-related effects of two pharmacological agents with known NMDA and GABA(A) receptor activity. As part of an ongoing, larger study, 28 subjects (age, 21-30) with no personal or family histories of alcoholism were administered subanesthetic doses of the GABA(A) receptor agonist thiopental, the NMDA receptor antagonist, ketamine and placebo on three separate test days. Various ethanol-related measures were administered. At doses of thiopental and ketamine that produced similar levels of sedation and cognitive effects, both agents produced significant ethanol-like effects and subjective intoxication. However, the intensity of the ethanol-like effects of ketamine was greater than that of thiopental. In addition, ketamine produced alterations in perception that were not produced by thiopental. These data provide further support for a model where GABA(A) receptor facilitation may contribute significantly to ethanol effects associated with social drinking, whereas NMDA receptor antagonism may contribute to relatively greater extent to features of ethanol 'intoxication'.

Avoidant personality disorder and social phobia: distinct enough to be separate disorders?

OBJECTIVE: Existing evidence from anxiety disorder research indicates that social phobics (SP) with avoidant personality disorder (AVPD) experience more anxiety and show more impairment than patients with SP alone. The purpose of this study was to examine whether in patients diagnosed with AVPD, the co-occurrence of SP adds to its severity. We hypothesized that the addition of SP will not add to the severity of AVPD alone. METHOD: Two groups of patients (AVPD=224; AVPD/SP=101) were compared at baseline and 2 years later on multiple demographic and clinical variables. RESULTS: Patients with AVPD and an additional diagnosis of SP differed little from patients with AVPD alone. CONCLUSION: These findings suggest that AVPD and SP may be alternative conceptualizations of the same disorder.

Parameters of grieving in spontaneous abortion.

OBJECTIVE: The study's objective was to determine the quality and severity of grief after spontaneous abortion and to statistically determine the effect of significant demographics and social variables such as age, number of previous losses and the effect of perceived family support on the grief experienced. METHODS: Two hundred and ninety-four women who had experienced a miscarriage within the last year were the participants. One hundred and seventy-five had miscarried three months prior to participation in the study; one hundred and nineteen had miscarried one year previously. Ninety-five percent of women approached consented to participate. Standardized psychometric tests and Likert Scales measured elements of grief such as depression, self-esteem, perceived guilt and stress at two time periods in the first year after loss. RESULTS: Women in both time periods after miscarriage had mean depression scores in the "clinical risk for depression" or "in need of treatment" range, i.e., pharmacotherapy or psychotherapy. A majority of women showed negative emotions like self blame and stress. Younger women with multiple miscarriages showed more depression in the early time period after miscarriage than older women (p < .05). However, at one year younger women had the least depression. Marital and family conflict correlated positively with depressive symptomatology (p < .05). CONCLUSIONS: Women assessed in the first year after spontaneous abortion show grief characterized by perceived stress and high levels of depressive symptoms including self-blame. Marital or family problems increase emotional risk to a woman after miscarriage.

The effects of moclobemide on sexual desire and function in healthy volunteers.

Decreased sexual desire is a recognized symptom of major depression (MD). Disturbances in sexual function, although reported in drug = free patients, have more often been viewed as adverse drug effects during antidepressant treatment with established classes of antidepressants (TCA, MAOI, SSRI). However, it is difficult to draw conclusions about the effects of antidepressants on sexual desire and function for two reasons: lack of standardised assessments for sexual function; inability to distinguish depression-related symptoms from drug-induced sexual disturbances. The purpose of this study was to examine the effects of moclobemide (a RIMA antidepressant) on sexual function in healthy male and female volunteers. Sixty male and female volunteers were randomly assigned to either moclobemide 300 mg or placebo for 3 weeks. They were seen at weekly intervals to assess drug compliance and to complete a 10-item sexual function questionnaire (SFQ). In both men and women there were no differences between moclobemide and placebo on measures of sexual desire and function. However, men and women differed in the levels of reported interest and sexual performance.

Nocturnal melatonin and 24-hour 6-sulphatoxymelatonin levels in various phases of bipolar affective disorder.

Nine bipolar patients (2 men and 7 women) and 12 healthy control subjects completed overnight sampling for serum melatonin (MT) and urinary 6-sulphatoxymelatonin (aMT6s). The patients were investigated during manic, depressed, and/or euthymic states. Although serum MT levels did not differ significantly across the bipolar groups, in all cases serum MT levels were significantly lower than in control subjects. Differences in MT levels were also present between bipolar patients who were in a depressed phase and control subjects. There were no statistically significant differences in urinary aMT6s levels among the patients and control subjects, although in all cases nocturnal aMT6s levels were significantly higher than daytime levels. This study provides tentative evidence for decreased serum MT as a trait but not a state marker in bipolar affective disorder.

Obsessive compulsiveness and physical activity in anorexia nervosa and high-level exercising.

Although excessive physical activity and obsessive compulsiveness are both prevalent in anorexia nervosa (AN), to date, the association between these two factors has not been systematically investigated. The aim of the present study was to investigate the relationship between obsessive compulsiveness and both behavioral and psychological aspects of exercise in women with AN, and to compare them to a nonclinical sample of females classified as either moderate or high-level exercisers. Results indicated that obsessive compulsiveness, weight preoccupation, and pathological aspects of exercise were significantly related to the level of physical activity among the eating disorder patients. For the high-level exercisers, only obsessive compulsiveness was significantly related to the amount of physical activity. The findings are discussed in terms of a model in which physical activity, starvation, and obsessive compulsiveness are reciprocally and dynamically related, with each factor creating a destructive bidirectional loop that is resistant to change and difficult to break. We propose that this self-perpetuating loop may be a significant influence in the development and maintenance of eating disorders in a certain subgroup of women.

The role of personality factors in the reporting of side effect complaints to moclobemide and placebo: a study of healthy male and female volunteers.

Although there is good evidence of a relationship between certain personality factors (viz. neuroticism and hypochondriasis) in the reporting of somatic symptoms-both in clinical and in nonclinical research-the recognition of the moderating role of individual differences in the frequency and intensity of side effect reporting is virtually absent from drug trial research. This study was a double-blind moclobemide-versus-placebo trial, the purpose of which was twofold: to investigate the degree of side effect complaints in a sample of healthy nonclinical men and women and to assess the role of personality in symptom reporting. Although there was no overall difference between the groups with respect to side effect complaints, there was a highly significant neuroticism x group x time interaction. In both groups, we found the expected positive relationship between neuroticism and symptom reporting at baseline. At the end of the study, however, this relationship was close to zero in the moclobemide group and had increased to close to 0.60 in the placebo group. These results were essentially replicated when neuroticism was substituted in the regression model by a psychometric measure of hypochondriasis. Our findings provide a striking demonstration of the role of personality factors in the placebo adverse response. As well, they indicate that adverse reactions to the medication were also linked to personality differences. Taken together, our results underscore the importance of considering individual differences in all aspects of pharmacologic research that involve subjective interpretation on the part of patients and subjects.

Melatonin responses to clonidine and yohimbine challenges.

Melatonin (MT) release from the pineal gland has been used as a marker for central noradrenergic function in major depression. Norepinephrine acts at both alpha and beta adrenergic receptors on the pinealocyte membrane to mediate nocturnal MT release, but in humans the contribution of each receptor class is unclear. In order to explore the effect of alpha 2 receptors on MT release, 10 female subjects were given oral challenges, in separate placebo-controlled trials, of either 10.8 mg of yohimbine, an alpha 2 adrenergic antagonist, or clonidine, a partial alpha 2 adrenergic agonist, at doses of either 200 micrograms or 300 micrograms. Post-challenge serum melatonin was measured from 18:00 h to 22:00 h in both studies as was urinary 6-sulphatoxy-melatonin (aMT6s), the major metabolite of MT (from 18:00 h to 22:00 h, and from 22:00 h to 10:00 h). Growth hormone (GH) was also assayed following the clonidine challenge, and blood pressure, pulse rate, and side effects were monitored after both challenges. Neither yohimbine nor clonidine significantly altered nocturnal serum MT levels compared to placebo. However, there was a significant increase in urinary aMT6s between 18:00 h and 22:00 h following yohimbine ingestion. Yohimbine ingestion produced significant rises in pulse rate and the urge to urinate compared to placebo. Both doses of clonidine resulted in a significant reduction in pulse rate, systolic and diastolic blood pressure, and significant increases in drowsiness and other measures of sedation following ingestion. Only clonidine 300 micrograms produced a significant elevation in GH release. This study highlights the limitations of oral neuroendocrine challenge studies.

Exposure with response prevention treatment of anorexia nervosa-bulimic subtype and bulimia nervosa.

Binge exposure with response-prevention of bingeing (ERP-B) was evaluated in 20 female Ss within an inpatient eating disorders unit over 9 sessions as an adjunct to standard milieu therapy. Subjects met DSM-III-R criteria for either bulimia nervosa (BN) (n = 13) or the bulimic subtype of anorexia nervosa (AN-B) (n = 7). The average age of the Ss in each group was 26.5 (+/- 8.8) and 24.1 +/- 6.0) yr, respectively. Results indicate significant within-session and pre-post treatment effects in self-report measures 'urge to binge', 'lack of control', 'feelings of guilt' and 'tension'. Further analysis revealed that the AN-B subgroup had significantly greater reduction in 'depression' and 'urge to vomit' compared to the BN group. This study provides preliminary evidence that ERP-B deserves further investigation with long-term follow-up in both BN and AN-B patients and may be particularly advantageous in the AN-B subpopulation.

Assessment of personality disorders in anorexia nervosa and bulimia nervosa. A comparison of self-report and structured interview methods.

Interest in assessing Personality Disorders (PDs) in association with anorexia nervosa (AN) and bulimia nervosa (BN) has been accompanied by the development of several structured interview and self-report measures. In an attempt to see how the self-report Millon Clinical Multiaxial Inventory (MCMI-II) compared with the Structured Clinical Interview for DSM-III-R (SCID-II) in the assessment of PDs, we gave both instruments to 43 inpatients with a diagnosis of AN or BN. Correlation coefficient values for both categorical and dimensional comparisons were generally less than .4. Although comparable rates of positive PDs occurred for each of the three clusters (A: 30.2% vs. 34.9%, B: 25.6% vs. 18.6%, and C: 62.8% vs. 81.4% for SCID-II vs. MCMI-II), agreement for individual diagnosis and individual subjects was poor. In conclusion, the MCMI-II did not prove to be a reliable instrument for assessing axis II PDs in patients with AN and BN when compared with the SCID-II.

The effects of growth hormone-releasing factor on food consumption in anorexia nervosa patients and normals.

Current evidence from animal studies indicate that growth hormone-releasing factor (GRF) has direct effects on mechanisms controlling eating behavior. There is also evidence that eating disorder patients have abnormalities in their GRF-growth hormone (GH) axis. The present study investigated the possibility that GRF abnormalities contribute to the expression of abnormal eating patterns in anorexia nervosa (AN) patients, and that GRF has therapeutic potential in this regard. To this end, patients diagnosed with anorexia nervosa or combined anorexia nervosa/bulimia nervosa (AN/BN), as well as normal female subjects, were tested for their eating and GH responses following intravenous infusion of GRF (1 micrograms/kg) or placebo. Results indicated that GRF stimulates food consumption in AN patients and attenuates the elevated food consumption in AN/BN patients. These results are consistent with the notion that GRF abnormalities contribute to abnormal eating behavior, and provide preliminary evidence for the therapeutic potential of GRF in such conditions. The extent to which the present effects of GRF are dependent on nutritional status, GH actions, or direct central actions of GRF, are discussed.

Is there a role for selective monoamine oxidase inhibitor therapy in bulimia nervosa? A placebo-controlled trial of brofaromine.

Pharmacologic and cognitive behavioral therapies have been advocated in the treatment of bulimia nervosa (BN). Brofaromine, a selective and reversible inhibitor of monoamine oxidase-A was selected for a double-blind, placebo-controlled evaluation because of previous demonstrated monoamine oxidase inhibitor efficacy in BN and because of its safer adverse reaction profile. Thirty-six female patients who met DSM-III-R criteria for BN were randomly assigned to the drug group (N = 19) or to the placebo group (N = 17) for an 8-week outpatient trial. Brofaromine produced a significant effect in decreasing episodes of vomiting throughout the trial, although comparable reductions in episodes of binge eating were found in both groups. Also, there were no advantages of drug over placebo on improvements in attitudinal measures and shape or on self-report ratings of depression and anxiety. However, a significant proportion of the subjects on brofaromine lost weight when compared with the placebo group. Methodologic issues including subjective assessment measures, placebo response rates, and the elucidation of responder subgroups are discussed.

The acute effects of starvation on 6-sulphatoxy-melatonin output in subgroups of patients with anorexia nervosa.

Sequential measures of daytime and nighttime sulphatoxy-melatonin (aMT6s) in 10 female patients with anorexia nervosa (AN) and 12 female patients with concurrent AN with bulimic symptoms (AN + BN) were compared with 13 female control subjects. The AN + BN group displayed a significant increase in aMT6s output in the acutely symptomatic state compared with both AN patients and controls. However, there were no subsequent differences after 7 or 14 days between the two patient groups. The AN + BN group also initially demonstrated a significant increase in daytime output of aMT6s compared to nighttime with a trend toward reversing this pattern after 7 and 14 days. Altered melatonin output may influence the course of illness or reflect greater disruption of circadian rhythm in those anorexic patients who also binge and purge compared to restricting anorexics.

A comparison of adinazolam and desipramine in the treatment of major depression.

Thirty-one patients with a DSM-III (R) diagnosis of Major Depression received adinazolam (n = 16) or desipramine (n = 15) during a 6 week double-blind randomized controlled trial. Both groups showed a significant decline in Hamilton Rating Scale for Depression scores (21.8 +/- 4.5 to 10.7 +/- 8.5 for adinazolam and 23.5 +/- 5.5 to 12.9 +/- 8.6) for desipramine. Melancholic and anxiety symptoms were reduced equally by both drugs. Initial sedation was the most common side-effect with adinazolam. Plasma levels of desipramine and hydroxy-desipramine correlated highly with oral dose after 3 weeks of treatment.