The subjective effects of MDMA and mCPP in moderate MDMA users.

The present study is part of a research program designed to better understand the neurochemical mechanisms underlying the abuse liability of 3,4-methylenedioxymethamphetamine (MDMA) in humans. In these studies, MDMA will be compared to prototypical dopamine (D-amphetamine) and serotonin (meta-chlorophenylpiperazine, mCPP) releasing agents on a variety of measures related to dependence. In order to determine an acceptable dose range (safe but active) of MDMA and mCPP for these studies, moderate MDMA users were administered escalating doses of MDMA (75, 110 and 145 mg/70 kg) and mCPP (17.5, 35 and 52.5 mg/70 kg). Each participant received a single dose under controlled laboratory conditions, i.e. this was a six-group design with a separate group for each dose. There were five participants tested in each group. MDMA increased blood pressure and heart rate whereas mCPP had no effect on these physiological measures. MDMA produced increases in subjective effects indicative of both stimulant (increases in POMS Elation, ARCI Amphetamine, VAS High and Stimulated scale scores) and hallucinogenic effects (increases on five of the six scales of the Hallucinogenic Rating Scale). mCPP produced similar stimulant effects (e.g. increases on POMS Elation, VAS High and Stimulated), as well as hallucinogenic effects (four of the six scales of the Hallucinogenic Rating Scale), which has not been observed in previous studies.

Cognitive impairment and depression predict mortality in medically ill older adults.

BACKGROUND: Depression and cognitive impairment are common in medically ill older adults. Few studies, however, have investigated the roles of both in predicting mortality for medically ill older adults. METHODS: We used a cohort of consecutive patients aged 60 or older admitted to a rehabilitation hospital (N = 667) of whom 455 completed a standardized protocol measuring cognition (Dementia Rating Scale), depression (Geriatric Depression Scale), and disabilities (Functional Independence Measure). Burden of medical illnesses was measured with the Charlson Index. Vital status was assessed one year later. RESULTS: Those subjects who did not complete the screening were more likely to die (24% vs 17%; p = .02) during the one-year follow-up. Of those who completed the screening, male sex (odds ratio [OR] = 1.84), depression (mild OR = 1.64; moderate OR = 2.49), and more severe cognitive impairment (OR = 2.13) predicted mortality independent of age, medical illnesses, or disabilities. No interaction of cognitive impairment and depression was detected. In those subjects cognitively intact, moderate depression (OR = 4.95) and male sex (OR = 3.42) were independent risk factors for dying. In those subjects without depression, male sex (OR = 2.24) and elevated Charlson Index (OR = 1.42) predicted mortality. CONCLUSIONS: Depression and cognitive impairment are independent predictors of one-year mortality in this subgroup of medically ill older adults.

Role of serotonin drugs in the treatment of social phobia.

The use of psychotropic agents (particularly serotonin active drugs) for the treatment of patients suffering from social phobia is reviewed in this report. Several important caveats should be kept in mind when reading this paper. First, the etiology of social phobia is not known; what we currently call social phobia is probably a heterogeneous collection of anxiety syndromes with the common symptomatic theme of interpersonal sensitivity. Second, the mechanism of action of psychotropic medications is not known; drugs which bind at serotonin receptors may, in fact, mediate clinical improvement via an entirely different mechanism. Third, while several agents appear clinically helpful for the treatment of patients suffering from social phobia, there is no drug currently approved by the US Food and Drug Administration for this indication.

Neurobiology of social phobia.

Social phobia is an anxiety disorder that is characterized by excessive fear and/or avoidance of situations in which an individual believes that he or she may be the subject of evaluation or scrutiny while interacting with other people or performing a specific task. This article reviews the available literature on the neurobiology underlying social phobia, including autonomic nervous system effects, neuroimaging findings, pharmacologic challenge studies, and neuroendocrine responsivity and function. Overall, such studies have found few consistently demonstrable differences in neurobiology between patients with social phobia and healthy controls, but further investigations are needed.

A direct-interview family study of generalized social phobia.

OBJECTIVE: The goal of this direct-interview family study was to replicate and extend an earlier finding of a familial liability for social phobia. The authors hypothesized that there would be higher rates of the generalized type of social phobia--but not the nongeneralized (or "discrete") type--among relatives of probands with generalized social phobia. They also hypothesized that rates of avoidant personality disorder, a frequent comorbid condition, would be higher in relatives of probands with generalized social phobia. METHOD: The authors examined rates of three social phobia subtypes defined a priori--discrete, nongeneralized, and generalized--as well as rates of avoidant personality disorder by direct interview of 106 first-degree relatives of 23 patients with generalized social phobia and 74 first-degree relatives of 24 comparison subjects without social phobia. RESULTS: Relative risks for generalized social phobia and avoidant personality disorder were markedly higher (approximately 10-fold) among first-degree relatives of probands with generalized social phobia than among first-degree relatives of comparison probands. In contrast, relative risks for discrete social phobia and nongeneralized social phobia were not significantly different between the two groups of first-degree relatives. CONCLUSIONS: These results confirm earlier findings of a higher rate of social phobia among relatives of probands with generalized social phobia and extend these findings by specifically indicating that it is only the generalized type (and its probable axis II counterpart, avoidant personality disorder) that occurs more often among the families of probands with generalized social phobia. Implications for subsequent genetic studies are discussed.

Short stature, growth hormone deficiency, and social anxiety.

OBJECTIVE: We have reported high rates of social phobia in growth hormone-deficient (GHD) adults who had been treated with growth hormone during childhood. This follow-up study was conducted to determine whether the increased social phobia observed in GHD subjects was secondary to the effects of short stature. METHODS: Twenty-one age- and sex-matched non-GHD short adults were evaluated for social anxiety and compared with the previously studied 21 GHD subjects. RESULTS: Thirty-eight percent (8 of 21) of GHD and 10% (2 of 21) of short subjects met DSM-III-R criteria for social phobia. GHD subjected scored significantly higher than short subjects on the following self-report questionnaires: Fear of Negative Evaluation (p = .03), Fear Questionnaire (p = .01), Social Avoidance and Distress Scale (p = .01), Beck Depression Inventory (p = .007), and the Tridimensional Personality Questionnaire-harm avoidance subscale (p = .0004). CONCLUSIONS: These data suggest that the high prevalence of social phobia in GHD adults is not explained by short stature alone.

Role of serotonin drugs in the treatment of social phobia.

Social phobia is a common anxiety disorder that is underdiagnosed and undertreated. To date, three classes of serotonin drugs have been used to treat patients suffering from social phobia. These include the serotonin selective reuptake inhibitors (SSRIs), the partial 5-HT1A agonist buspirone, and the 5-HT3 antagonist ondansetron. Although none of the serotonin agents have yet been directly compared with the gold standard monoamine oxidase inhibitor phenelzine or the high potency triazolobenzo-diazepines alprazolam or clonazepam, the SSRIs, as a class, appear to be clinically useful agents. Further studies using larger sample sizes and double-blind methodology are needed to clarify the role of serotonin drugs in the treatment of social phobia.

Links between growth hormone deficiency, adaptation and social phobia.

Children referred for growth hormone (GH) treatment have increased school achievement problems, lack appropriate social skills and show several forms of behavior problems. A multicenter study in the United States has revealed that many GH-impaired children exhibit a cluster of behavioral symptoms involving disorders of mood and attention. Anxiety, depression, somatic complaints and attention deficits have been identified. These symptoms decline in frequency over a period of 3 years, beginning shortly after GH replacement therapy is started. Many of the patients who have received GH and had good growth responses show lower than average quality of life in young adulthood after treatment is completed. GH-deficient adults placed on GH therapy report improvement in psychological well-being and health status, suggesting that GH might have a central neuroendocrine action. Among a group of adults who were GH deficient as children, we find a high incidence of social phobia, a psychiatric disorder linked to GH secretion and usually accompanied by poor life quality. An ongoing study of non-GH-deficient short individuals suggests that short stature is not the cause of this outcome. We conclude that the origins of psychiatric comorbidities, such as social phobia and depression, in GH deficient adults are likely to be neuroendocrine as well as psychosocial.

Evidence for social phobia and other psychiatric disorders in adults who were growth hormone deficient during childhood.

We assessed the psychiatric status of 21 growth hormone deficient (GHD) adults who had been treated with growth hormone (GH) for short stature during childhood. Eight individuals (38%) were found to have undiagnosed social phobia. On a psychometric battery, the scores of GHD subjects with social phobia corresponded closely to those of a matched group of psychiatric patients with social phobia. Because these psychiatric symptoms have deleterious effects on quality of life, social function, and productivity, the physician should be alert to obtain psychiatric assessment of patients with GHD.

The impact of an electroconvulsive therapy consultation service on ECT use at a university teaching hospital.

In order to test the hypothesis that the establishment of a centralized electroconvulsive therapy (ECT) consultation service would affect ECT use at a university teaching hospital, we retrospectively reviewed medical records of patients who received ECT during two 12-month periods preceding and following the institution of a comprehensive ECT consultation service. Data regarding ECT usage, including utilization, types of patients treated, and lengths of stay, were obtained. Patients treated after the institution of a comprehensive ECT consultation service received ECT with less delay, were discharged more quickly after the conclusion of ECT treatment, and had shorter lengths of stay compared with patients who received treatment before the initiation of the service. Following the establishment of the ECT service, the absolute number of patients who received ECT increased, although the rate of ECT use did not change. These findings suggest that the establishment of a comprehensive ECT consultation service may lead to more efficient use of this important treatment in university hospitals and to more cost-effective treatment of some patients with major depression. Additional research is necessary to explore the generalizability of these findings to other treatment settings.

Normal urinary free cortisol and postdexamethasone cortisol in social phobia: comparison to normal volunteers.

In primates, social stress is associated with activation of the hypothalamic-pituitary-adrenal (HPA) axis. Social phobia is a common, often disabling, form of pathological anxiety characterized by marked distress in situations involving possible scrutiny or evaluation. Little is known about HPA function in patients with social phobia. We examined 24-hour excretion of urinary free cortisol (UFC) in 54 patients with social phobia and post-dexamethasone cortisol levels in 64 patients with social phobia and found no evidence of HPA-axis overactivity compared to normal controls, despite pathological levels of anxiety.

Neuroendocrine responsivity to monoaminergic system probes in generalized social phobia.

We examined neuroendocrine correlates of central monoamine function in patients with the generalized type of social phobia compared to healthy volunteers in order to test hypotheses of dopaminergic, noradrenergic, and/or serotonergic dysregulation in patients with this disorder. A double-blind, placebo-controlled, neuropharmacological challenge study was performed using probes for the serotonergic (fenfluramine), dopaminergic (levodopa), and noradrenergic (clonidine) systems. Twenty-one patients with DSM-III-R social phobia (generalized type) and 22 "never mentally ill" volunteers participated in the study after providing informed consent. Patients with social phobia had an augmented cortisol response to fenfluramine administration compared to the volunteers. In contrast, we found that neither the prolactin response to fenfluramine, the growth hormone or norepinephrine response to clonidine, nor the prolactin or eye-blink responses to levodopa, differed between patients with social phobia and healthy volunteers. The findings suggest that patients with social phobia may exhibit selective supersensitivity of serotonergic systems, but that dopaminergic and noradrenergic function appear normal. Further challenge studies with more specific serotonin probes before and after treatment may assist in the clarification of the pathophysiology of social phobia.

Neurobiology of social phobia.

The neurobiology of social phobia has been examined using four research strategies employed to investigate the neurobiology of patients with other anxiety or mood disorders--chemical challenge paradigms, psychoneuroendocrine assessments, naturalistic challenges, and neuropharmacologic challenges. This article reviews the studies that used each of the research paradigms in patients with social phobia. The author describes these results in the context of the results of other anxiety disorder studies using these four strategies and discusses implications for future research.

Growth hormone response to intravenous clonidine in social phobia: comparison to patients with panic disorder and healthy volunteers.

The growth hormone (GH) response to intravenous administration of clonidine hydrochloride (2 micrograms/kg) was assessed in 16 patients with DSM-III-R social phobia, 13 patients with DSM-III-R panic disorder, and 31 healthy controls. Compared to the healthy volunteers, both social phobic and panic-disorder patients had significantly blunted GH increments after clonidine. The social phobic patients demonstrated a similar degree of GH "blunting" to clonidine as did the patients with panic disorder.

Blunted growth hormone responses to growth hormone-releasing factor and to clonidine in panic disorder.

Blunted growth hormone (GH) responses to growth hormone-releasing factor (GH-RF) and clonidine have been reported in patients with panic disorder. In this study GH-RF and clonidine were administered to 13 patients with panic disorder and 20 healthy volunteers. Compared to the normal subjects, the patients with panic disorder had significantly blunted GH responses after both GH-RF and clonidine.