Cerebrospinal fluid corticotropin-releasing factor concentrations in patients with anxiety disorders and normal comparison subjects.

Cerebrospinal fluid (CSF) concentrations of corticotropin-releasing factor (CRF) were measured in a group of patients with anxiety disorders and normal comparison subjects (NC) to explore the hypothesis that abnormalities in CRF neuronal regulation occur in patients with anxiety disorders. Analysis of variance (ANOVA) revealed no differences in CSF CRF concentrations between the four diagnostic categories: panic disorder (PD), generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), and NCs. Male OCD patients had higher CSF CRF concentrations than men with PD and GAD and male NCs. CSF CRF concentration was positively correlated with age in women but not in men. These findings suggest that central neuronal CRF regulation may be affected by both age and gender.

Chronicity of symptoms in combat veterans with PTSD treated by the VA mental health system.

Self-report questionnaire data, collected at two stages of treatment, are presented for a group of 40 combat veterans with PTSD treated within the VA mental health system. Patients completed the Beck Depression Inventory, Mississippi Scale, and Dissociative Experiences Scale prior to treatment at a PTSD outpatient clinic and at midtreatment follow-up. Patients' symptom reports at follow-up were not correlated with length of time in treatment. Further, results suggest that patients' self-reported symptoms on these measures do not show evidence of improvement after entry into the VA mental health system. Explanations for this apparent chronicity of symptoms are discussed.

Clonazepam-related sexual dysfunction in male veterans with PTSD.

Medication-induced sexual dysfunction can significantly interfere with patients' quality of life and lead to poor compliance. This retrospective study examined the records of 100 male veterans with post-traumatic stress disorder (PTSD) selected in alphabetical order from an active treatment file of 230 patients. Forty-two patients had received clonazepam (mean maximum dose: 3.4 +/- 1.6 mg/day) at some point during their treatment. Of these, 18 (42.9%) complained of significant sexual dysfunction (primarily erectile dysfunction). Eighty-four patients received diazepam (mean maximum dose: 52.1 +/- 29.7 mg/day), nine received alprazolam (mean maximum dose: 5.2 +/- 2.8 mg/day) and eight received lorazepam (mean maximum dose: 3.8 +/- 2.4 mg/day). None of these patients complained of sexual dysfunction during treatment with these three other benzodiazepines. Our findings suggest that benzodiazepines, particularly clonazepam in the current study, can be a cause of sexual dysfunction in many male patients. Prospective studies comparing the overall clinical utility of various benzodiazepines are indicated in this and other clinic populations.

CSF cholecystokinin octapeptide in patients with bulimia nervosa and in normal comparison subjects.

Cholecystokinin octapeptide (CCK-8) appears to modulate appetitive behavior, and in rodents, anxiety-related behavior. The authors studied CCK-8 in patients with bulimia nervosa. CSF concentrations of CCK-8 were measured in 11 drug-free female patients with DSM-III-R-defined bulimia nervosa and in 16 normal subjects. The bulimic patients had significantly lower levels of CCK-8 than the comparison subjects. CCK-8 concentrations were inversely correlated with scores on the anger-hostility, anxiety, and interpersonal sensitivity subscales of the SCL-90-R. They were not significantly correlated with age, percentage of standardized average body weight, or mean weekly frequency of binge eating or vomiting. The results indicate that central CCK-8 abnormalities may play a role in the pathophysiology of bulimia nervosa.

Prevalence of psychiatric disorders in patients with irritable bowel syndrome.

Thirty-five patients with irritable bowel syndrome were referred from the gastroenterology service and underwent structured psychiatric interviews to assess the prevalence of psychiatric illness. Thirty-three (94%) of 35 patients were found to have a lifetime prevalence of any Axis I disorder; the predominant diagnoses were mood and anxiety disorders. Theoretical and practical implications of these findings are discussed.

Cerebrospinal fluid thyrotropin-releasing hormone concentrations in patients with anxiety disorders.

In a study of 45 patients with anxiety disorders and 11 control subjects, mean cerebrospinal fluid (CSF) concentrations of thyrotropin-releasing hormone (TRH) were not significantly different between nonpsychiatric control subjects and those with panic disorder, generalized anxiety disorder, or obsessive-compulsive disorder. Male subjects, regardless of diagnosis, had significantly higher mean CSF concentrations of TRH than females.

CSF diazepam-binding inhibitor concentrations in panic disorder.

Diazepam-binding inhibitor (DBI) is a neuropeptide that has been detected in the brain and cerebrospinal fluid (CSF). Previous studies have suggested the possible role of DBI as a potential endogenous anxiogenic ligand modulating GABAergic transmission at the benzodiazepine-GABA receptor complex. The measurement of DBI immunoreactivity (DBI-IR) in CSF of panic-disorder patients and normal controls was undertaken to assess whether there were differences in the CSF concentration of this peptide to assess possible relationships with other monoamines and peptides. Lumbar CSF was obtained from 18 panic patients (4 men, 14 women) and 9 controls (5 men, 4 women). As a group, no significant differences were found between panic patients' CSF concentration of DBI-IR (1.12 +/- 0.27 pmol/mL) and normal volunteers (1.23 +/- 0.27 pmol/mL). No gender differences were demonstrated. However, we did find a positive correlation between CSF levels of DBI and CSF corticotropin releasing hormone (CRH) in our panic patients.

CSF cholecystokinin concentrations in patients with panic disorder and in normal comparison subjects.

Cholecystokinin concentrations in the CSF of 25 patients with panic disorder and 16 normal comparison subjects were ascertained by radioimmunoassay. The patients with panic disorder had significantly lower CSF concentrations of cholecystokinin, which may reflect increased CNS cholecystokinin receptor sensitivity, reduced numbers of receptors, or a compensatory reduction in cholecystokinin octapeptide secondary to theoretically increased central cholecystokinin tetrapeptide activity.

Dopamine blocking activity of clomipramine in patients with obsessive-compulsive disorder.

While many data suggest that Obsessive-Compulsive Disorder (OCD) is an illness accompanied by dysregulation of the serotonergic system, interesting clinical evidence and animal studies also suggest possible dysregulation of the dopaminergic (DA) system. In order to determine whether clomipramine (CMI), an antiobsessional agent, is capable of altering DA function, we performed a neuroleptic radioreceptor assay (NRRA) on plasma samples from OCD patients before and after treatment in a double-blind, placebo controlled trial of CMI. CMI produced mild but significant DA D-2 receptor binding activity in an in vitro assay. The degree of dopamine binding activity did not correlate with clinical response to clomipramine. Because it has been suggested that another drug with antiobsessional efficacy, fluoxetine, may also have dopamine blocking properties, it may be speculated that antidopaminergic activity in combination with serotonergic effects is involved in antiobsessional activity of effective agents for some patients.

Panic and phobic disorders in patients with obsessive compulsive disorder.

Obsessive compulsive disorder shares numerous clinical features with other anxiety disorders. To study the relationship between OCD and other anxiety disorders, the authors administered the Structured Clinical Interview for DSM-III to 36 OCD patients. Thirty-nine percent (14) of patients reported a lifetime history of panic attacks, and 14% (5) met DSM-III-R criteria for panic disorder at the time of interview. Fourteen percent (5) met criteria for social phobias, and 19% (7) met criteria for simple phobias. Eighteen patients were treated with clomipramine in doses of at least 100 mg/day for 3 months. Patients with a history of other anxiety disorders responded significantly better to clomipramine.

CSF monoamine levels in normal-weight bulimia: evidence for abnormal noradrenergic activity.

Normal-weight bulimic patients have disturbed appetite, mood, and neuroendocrine function and often respond to antidepressants. Since these findings suggest abnormalities in brain monoaminergic pathways, the authors measured CSF monoamine concentrations in 27 normal-weight bulimic patients and 14 volunteers. Bulimic patients had a significantly lower mean CSF norepinephrine concentration. Levels of CSF 5-HIAA, the major serotonin metabolite, and CSF HVA, the major dopamine metabolite, were normal, although more frequent binge-eating in bulimic subjects was associated with a significantly lower CSF HVA level. Whether trait- or state-related, monoaminergic disturbances are part of this disorder's neurobiological syndrome. The lower CSF norepinephrine concentration suggests bulimia is not simply a variant of affective disorders.

Anxiety and the gastrointestinal system.

There is a growing recognition that a link exists between anxiety and the gastrointestinal tract. This is evident in studies examining the effects of stress on gastrointestinal function and also in studies assessing psychopathology in patients with functional gastrointestinal disorders which demonstrate a high prevalence of anxiety disorders and depression in these individuals. The recent conceptualization of anxiety as resulting from dysfunction in separable subsystems of the brain as well as experimental evidence linking the brain with the GI tract may allow for testing hypotheses that the high prevalence of anxiety in patients with functional GI disorders may be due to common or interacting pathophysiology. The similarity between the ENS and the CNS may also be a plausible explanation for this association. The high prevalence of anxiety disorders in functional GI patients suggests that medications useful in the treatment of anxiety disorders (anxiolytics and antidepressants) may be useful in the treatment of functional GI disorders especially refractory cases, but further treatment studies are needed.

Phenelzine treatment of panic disorder: lack of effect on pyridoxal phosphate levels.

Earlier reports indicated that phenelzine treatment may result in clinically significant reductions of vitamin B6 in some individuals. Sixteen subjects, ages 21-59 years (seven men, nine women) with panic disorder with or without agoraphobia were treated with an average of phenelzine 53.5 mg/day for an average of 10 weeks in an open treatment study. No significant effects on plasma levels of pyridoxal phosphate, the active form of vitamin B6, were discernible in this group, nor was there any clear relationship between pyridoxal phosphate levels and symptoms in the subgroup of five patients who did develop deficiency-type symptoms. Pyridoxine replacement had unclear effects in symptomatic patients.