Narcolepsy associated with other central nervous system disorders.

The authors identified patients with the coexistence of narcolepsy and another CNS disorder seen between 1975 and 1998 at their institution. Eighteen patients were identified, nine with narcolepsy commencing within 1 year before or after the other disorder. Seven patients (39%) had hypothalamic-pituitary syndromes. When they occur together, narcolepsy and other CNS disorders frequently emerge at about the same time, suggesting a causative relationship. Hypothalamic-pituitary pathology was the most common association.

Voltage-gated calcium channel gamma 2 subunit gene is not deleted in velo-cardio-facial syndrome.

Velo-cardio-facial syndrome (VCFS) has been associated with schizophrenic symptoms in some patients and is caused by a deletion of 22q11.21--q11.23. The voltage-gated calcium channel (VGCC) gamma 2 subunit is located on chromosome 22 and is telemeric to the most commonly observed VCFS deletion region but is near a putative marker for schizophrenia (D22S278). Metaphase spreads of four controls, four patients with VCFS, and one patient with VCFS and schizophrenia were evaluated for the VCFS deletion using the VCFS-diagnostic probe, TUPLE 1, and for deletion of VGCC gamma 2 subunit gene using probes for that gene's exon 1 and exons 3 and 4. All of the VCFS patients had deletion of the TUPLE 1 probe on one chromosome of the chromosome 22 pair. None showed deletion of the gamma 2 subunit exons studied. The location of the gamma 2 subunit gene at 22q13.1 was confirmed by FISH in all cases. This study did not show a deletion of the gamma 2 subunit gene as a distinguishing feature of our patient with VCFS and schizophrenia.

Prolonged inhibition of presynaptic catecholamine synthesis with alpha-methyl-para-tyrosine attenuates the circadian rhythm of human TSH secretion.

OBJECTIVE: Originating from the pituitary gland, TSH secretion is regulated predominantly by thyroid-releasing hormone (TRH) neurons located in the hypothalamus. Norepinephrine and dopamine have important effects in modulation of TSH secretion. An inhibitor of catecholamine synthesis, alpha-methyl-para-tyrosine (AMPT) has been used in several studies of the regulation of human TSH secretion. The short-term effects (<8 hours) of low doses of AMPT include stimulation of pituitary TSH secretion by selective lowering of brain dopamine levels. After prolonged administration of AMPT (>24 hours), theoretically both dopamine and norepinephrine levels are lowered significantly in the brain, although this has not been reported previously. METHODS: Nine subjects (five women and four men) received a total of five 1-g doses of AMPT or five 50-mg doses of promethazine (active placebo) over 28 hours in a randomized, double-blind, placebo-controlled crossover design in which the active and control tests were separated by 4-6 weeks. Blood samples were obtained over 24 hours (18 time points) on day 2 of each condition. RESULTS: Changes in prolactin secretion and 6-hydroxymelatonin sulfate excretion indirectly showed the effects of AMPT on dopamine and norepinephrine. The typical circadian rhythm of TSH secretion was blunted by AMPT throughout the night; at ten time points, the difference between the two groups was statistically significant (P <.01). The long-term effects of repeated doses of AMPT were inhibition of TSH secretion and significant attenuation of the circadian rhythm of TSH. Additionally, AMPT induced low norepinephrine levels, which counteracted the stimulatory effect of low dopamine levels on TSH. CONCLUSION: Through its inhibitory effect on TRH, norepinephrine appeared to be involved in the regulation of TSH.

Treating fibromyalgia with a brief interdisciplinary program: initial outcomes and predictors of response.

OBJECTIVES: To evaluate the efficacy of a brief, intense treatment program for fibromyalgia and to determine which patient characteristics are associated with a better treatment response. PATIENTS AND METHODS: Two self-report measures, the Fibromyalgia Impact Questionnaire (FIQ) and the Multidimensional Pain Inventory (MPI), were administered before patients completed treatment and 1 month after participating in the program. The main outcome measure was the difference in FIQ score and MPI scale before and after program participation. RESULTS: Of 139 patients who met the American College of Rheumatology criteria for fibromyalgia, 100 chose to participate in the 1 1/2-day Fibromyalgia Treatment Program at the Mayo Clinic, Rochester, Minn. Of these 100 patients, 74 completed the follow-up surveys. Patients were less affected by fibromyalgia after participation in the treatment program. This was demonstrated by a posttreatment improvement in the total FIQ score (P<.001), the MPI pain severity score (P<.001), and the MPI interference score (P=.01). The 1 patient characteristic found to be significantly associated (P<.001) with a better response to treatment was a high pretreatment level of impairment from fibromyalgia, as measured by the pretreatment FIQ score. CONCLUSIONS: A brief interdisciplinary program for treating fibromyalgia reduced some associated symptoms. Patients more severely affected by fibromyalgia may benefit most from this approach. Clinicians may apply these findings to develop beneficial and convenient treatment programs for patients with fibromyalgia.

Electroconvulsive therapy and cardiovascular complications in patients taking trazodone for insomnia.

BACKGROUND: Trazodone has been used widely to treat insomnia in depressed patients. When used in combination with electroconvulsive therapy (ECT), trazodone has been suspected to cause cardiovascular side effects. METHOD: A retrospective study was done of 100 patients who received ECT with concurrent trazodone. One patient was excluded because permission to review the patient's records had not been given. The remaining 99 patients were matched with control ECT patients. RESULTS: No statistically significant between-group differences were identified in cardiovascular side effects, although a trend toward more orthostatic hypotension was observed in patients taking trazodone. CONCLUSION: Administering low-dose trazodone for insomnia in conjunction with ECT does not appear to increase cardiovascular complications. The true incidence of adverse cardiac events was not higher than 3.66% at a 95% confidence level.

Narcolepsy: new understanding of irresistible sleep.

Recently, low levels of a newly identified neuropeptide, hypocretin 1, were described in the cerebrospinal fluid of patients with narcolepsy. This neurochemical finding furthers our understanding of this enigmatic sleep disorder typically characterized by excessive daytime sleepiness, cataplexy, sleep paralysis, and hypnagogic hallucinations. Narcolepsy appears to be fundamentally related to abnormally regulated rapid eye movement sleep. The diagnosis of this disorder remains challenging because of multiple other conditions that can cause daytime sleepiness and the difficulties in recognizing cataplexy based on patient report. The role of hypocretins in narcolepsy is unclear but intriguing because the cell bodies are restricted to the lateral hypothalamus, a brain region long associated with sleep regulation, with neuronal widespread projections to areas including the locus ceruleus, ventral tegmental area, amygdala, and dorsal raphe. Hypocretins potentially modulate the activity of monoamines and acetylcholine, and therefore their absence leads to the multiple symptoms of narcolepsy. This article reviews the current understanding of the diagnosis and treatment of narcolepsy and discusses the possible implications of the hypocretin discovery.

The effects of antidepressants on sleep: a review.

Sleep disturbances are a frequent complication of depressive disorders and their treatment. Familiarity with the interaction among sleep, depression, and antidepressant medications may assist the clinician in selecting agents to suit the needs of individual patients. The authors review the current knowledge of changes in sleep architecture associated with particular antidepressant agents and with depressive illness, as well as the theoretical relevance of such changes to the antidepressant effect. Articles for review were found through a Medline search on the terms "polysomnography," "sleep," "antidepressants," and "insomnia" in English-language papers published from 1966 through March 2000. Additional articles were found in the reference lists of relevant papers.

The effects of electroconvulsive therapy on melatonin.

Although several studies have investigated the impact of various antidepressant medications on melatonin, there are no published reports addressing the effects of electroconvulsive therapy (ECT). Melatonin's major urinary metabolite, 6-sulfatoxymelatonin (6MT), was measured before and after an acute course of ECT. Fourteen subjects diagnosed with major depression who had failed prior pharmacologic therapy were enrolled. 6MT excretion was measured using an enzyme-linked immunosorbent assay test in 24 hour samples separated into daytime and nighttime components. Hamilton Rating Scale for Depression scores showed a significant improvement (p < 0.0001). Data analysis using the Wilcoxon signed rank test demonstrated a significant decrease in 24 hour 6MT post-ECT (p < 0.016) and daytime 6MT (p < 0.008). These results demonstrate an association between a therapeutic response to ECT and decrease in endogenous melatonin production.

ECT post eye surgery: two cases and a review of the literature.

Little is known about the safety of electroconvulsive therapy (ECT) following any surgical procedure. We present two cases of elderly patients who required treatment with ECT shortly after eye surgery. One patient received ECT 12 days post cataract surgery. The other patient received ECT 1 week post vitrectomy on one eye, and then a few years after that she received ECT 2.5 weeks post cataract surgery on the other eye. There were no complications or adverse events for either patient. We review the existing literature on the effects of ECT on intraocular pressure and discuss the implications on patients who have recently undergone ophthalmic surgery.

The effect of presynaptic catecholamine depletion on 6-hydroxymelatonin sulfate: a double blind study of alpha-methyl-para-tyrosine.

Because it is a competitive inhibitor of tyrosine hydroxylase, alpha-methyl-para-tyrosine (AMPT) is used to study psychiatric disorders. Melatonin serves as a biological marker of catecholamine function since its secretion is regulated by noradrenergic neurons via beta-adrenergic receptors in the pineal gland. Ten healthy volunteers were administered AMPT in a double-blind placebo controlled study. When subjects received AMPT, nocturnal 6-hydroxymelatonin sulfate (6-SM) decreased significantly as compared with promethazine (night 1 P=0.002; and night 2 P=0.001). Urinary MHPG also decreased on both study days (DF1,9 F=9.82, GG=0.0121). Nocturnal 6-SM excretion and melatonin secretion correlated highly (r=0.91, P=0.0007). Behavioral ratings did not reveal a difference in symptomatology and did not correlate with changes in 6-SM or MHPG. This study demonstrates in healthy controls that 6-SM reliably reflects presynaptic catecholamine depletion induced by AMPT without the emergence of behavioral symptoms.

Patient satisfaction with electroconvulsive therapy.

OBJECTIVE: To determine whether patients who have electroconvulsive therapy (ECT) are satisfied with their treatment and demonstrate more favorable attitudes about ECT compared with controls. PATIENTS AND METHODS: We developed a 44-item survey measuring ECT treatment satisfaction and attitudes. The survey was administered to 24 psychiatric inpatients near the end of ECT treatment and 2 weeks later. A modified survey was administered to 24 outpatient controls who had never received ECT and who were recruited from a psychiatry clinic waiting room. RESULTS: Patients who received ECT had positive attitudes about it. For example, 21 (91%) of 24 patient respondents endorsed the statement, "I am glad that I received ECT." Attitude score was significantly higher for the ECT group compared with controls. A higher degree of satisfaction was associated with a higher level of education and younger age. CONCLUSIONS: Patients who received ECT were satisfied with their treatment and had more favorable attitudes about it than patients who did not receive this treatment.

Childhood-onset schizophrenia associated with parkinsonism in a patient with a microdeletion of chromosome 22.

The deletion of a gene or genes on chromosome 22q11 is responsible for the velocardiofacial syndrome (VCFS), which is associated with cardiac anomalies, short stature, palate abnormalities, learning disabilities, and developmental delay. Herein we describe a 30-year-old man with VCFS in whom a chronic psychotic disorder originated during childhood. A 10% rate of psychotic disorders has been reported in association with this genetic syndrome. In our patient, the clinical manifestation was complicated by extrapyramidal symptoms that predated the onset of psychotic symptoms. To our knowledge, extrapyramidal symptoms have not previously been reported in a patient with VCFS. The diagnosis of VCFS was confirmed with the fluorescence in situ hybridization probe for VCFS. The role of the atypical antipsychotic drug clozapine is discussed with respect to treating this patient who has severe psychotic symptoms coexisting with extrapyramidal symptoms and seizures. In light of the observation that patients with VCFS have an unexpectedly high rate of psychotic disorders, issues concerning the genetics of schizophrenia are intriguing.

Major depression in medically ill patients.

Major depression is one of the most common psychiatric problems complicating the treatment and prognosis of patients with active medical illness. Recognizing and treating major depressive conditions in this population can often be challenging, even for the most seasoned clinicians. This article reviews the medical and neurologic conditions that have been associated with the high prevalence rates of major depression. Highlights of the evaluation process that help confirm this suspected diagnosis are addressed, and management issues are discussed. Brief reviews of supportive psychotherapeutic tools that the clinician may find helpful are included, as well as current advances in pharmacologic interventions.

Hypokalemia leading to torsades de pointes. Munchausen's disorder or bulimia nervosa?

A 45-year-old woman traveled over 1000 miles from a major metropolitan area to obtain another opinion for medically refractory diarrhea. She had an extremely complicated medical history with no outside records or family members accompanying her to give collateral history. She had multiple previous diagnostic evaluations including 13 surgical procedures and many therapeutic trials of various medications. She acknowledged a preoccupation with weight and appearance, described previous attempts to diet, and repetitively denied purging, including laxative abuse. During her hospitalization she had two episodes of torsades de pointes requiring cardiac defibrillation. Laboratory testing revealed hypokalemia at the time of these events, and a toxicology screen was positive for bisacodyl, confirming laxative abuse. When confronted by a combined team of cardiology, gastroenterology, and psychiatry specialist, she admitted her laxative abuse and surrendered her supply of Dulcolax tablets. The discussion addresses the procedures employed to detect her surreptitious medication use, the near lethal cardiac complications, and the appropriate psychiatric diagnosis.

Adverse cutaneous reactions to psychotropic drugs.

Psychotropic drugs are frequently used in both psychiatric and general medical practice. Familiarity with common side effects and their management may assist psychiatrists in the selection of agents to suit individual patient needs. The authors describe the morphologic features and pathologic basis of cutaneous reactions to drugs and discuss the common and reported cutaneous side effects of psychotropic drugs. Although most dermatologic reactions to drugs follow a benign course after drug discontinuation, more serious effects are known to occur with certain agents. An overview of the diagnosis and management of these adverse drug reactions is provided.