Evidence that COMT genotype and proline interact on negative-symptom outcomes in schizophrenia and bipolar disorder.

Elevated peripheral proline is associated with psychiatric disorders, and there is evidence that proline is a neuromodulator. The proline dehydrogenase (PRODH) gene, which encodes the enzyme that catalyzes proline catabolism, maps to human chromosome 22q11.2, a region conferring risk of schizophrenia. In the Prodh-null mouse, an interaction between elevated peripheral proline and another 22q11.2 gene, catechol-O-methyltransferase (COMT), on neurotransmission and behavior has been reported. We explored the relationship between fasting plasma proline levels and COMT Val(158)Met genotype on symptoms (positive, negative and total) in schizophrenia patients. In an exploratory study we also examined symptom change in patients with bipolar disorder. There was a significant interaction between peripheral proline and COMT on negative symptoms in schizophrenia (P<0.0001, n=95). In COMT Val/Val patients, high proline was associated with low Scale for the Assessment of Negative Symptom (SANS) scores. In contrast, high proline was associated with high SANS scores in patients carrying a Met allele. The relationship between proline and COMT also appears to modify negative symptoms across psychiatric illness. In bipolar disorder, a significant interaction was also observed on negative-symptom change (P=0.007, n=43). Negative symptoms are intractable and largely unaddressed by current medications. These data indicate a significant interaction between peripheral proline and COMT genotype, influencing negative symptoms in schizophrenia and bipolar disorder. That high proline has converse effects on symptoms by COMT genotype, may have implications for therapeutic decisions.

Phenylalanine kinetics are associated with tardive dyskinesia in men but not in women.

RATIONALE: An association between tardive dyskinesia (TD) and severely impaired metabolism of the large neutral amino acid (LNAA), phenylalanine (Phe) was defined in a group of mentally retarded patients. Subsequently, an altered kinetics of Phe was associated with TD in men with schizophrenia based on plasma analyses subsequent to the ingestion of a protein meal. METHODS: In the present study, a standardized oral challenge of pure Phe (100 mg/kg in 170 ml orange juice) was administered to psychiatric patients of both sexes (n = 312), with and without TD after an overnight fast. Plasma LNAA levels were assayed both fasting and 2 h subsequent to the ingestion of the challenge. The extent of the increase in plasma Phe levels 2 h following a standardized challenge is determined by the sum of the kinetic processes of plasma absorption, tissue distribution, metabolism and elimination. RESULTS: The study hypothesis, that TD would be associated with significantly higher post-challenge plasma Phe indices of an absolute plasma Phe level and plasma Phe/LNAA ratio (a brain availability measure), was verified for the study men (n = 209), but not for the study women (n = 103). CONCLUSIONS: The demonstrated altered kinetics of Phe in men with TD indicates a greater availability of Phe to the brain in these men. We suggest that the disorder may be related to the effects of this greater availability. Such effects could be the direct neurotoxic effects of Phe and its metabolites and/or the modulating effects of these compounds on the synthesis of the monoamine neurotransmitters. The fact that TD (Yes/No) group differences in post-challenge plasma Phe indices were not seen for the study women suggests the possibility of a sex difference in the biology of TD that we propose may be reflective of the young age of the study sample.

Branched chain amino acids decrease tardive dyskinesia symptoms.

RATIONALE: Prior studies had suggested (a) that a lessened ability to clear ingested forms of the large neutral amino acid (LNAA), phenylalanine (Phe), was associated with having tardive dyskinesia (TD), and (b) that greater availability of a group of LNAA, the branched chain amino acids (BCAA), concomitant with the lower availability of Phe to the brain are associated with a decrease in TD symptoms. The present study was then conducted to test whether increasing the daily intake of the BCAA would decrease the symptoms of TD. METHODS: A 2-week trial of a BCAA medical food administered three times a day was conducted in nine men with long neuroleptic treatment histories. Frequency counts of TD movements were collected by videotape throughout the trial and these tapes were analyzed in blind random sequence for both patient and time for TD symptom level changes subsequent to completion of the trial. Plasma levels of the LNAA were also collected throughout the trial. RESULTS: A statistically significant decrease in the level of TD symptoms was observed for the sample. The symptom changes were also clinically significant in that six of the nine subjects had symptom decreases of at least 58%, with all subjects having a decrease of at least 38%. BCAA administration increased plasma BCAA concentrations and BCAA/LNAA ratios and decreased plasma Phe concentrations and the Phe/LNAA ratio. Analyses indicated a strong significant correlation between the percent increase in the plasma BCAA values at the first administration and the percent improvement in TD over the trial in eight of the nine subjects. CONCLUSIONS: The BCAA show promise as a treatment for TD. The decrease in TD symptoms seen in the trial may have been modulated by the BCAA treatment-induced increased availability of the BCAA and decreased availability of Phe to the brain.

Weight change among registered nurses in a self-help smoking cessation program.

Abstract Weight-related beliefs, attitudes, and patterns of weight change were analyzed for 144 registered nurses followed for one year in a self-help smoking cessation study. Smoking history and outcome status, physical descriptors, weight orientation, and use of self-help smoking cessation materials were examined in relation to weight change. A multiple regression analysis which included all subjects yielded three predictors of weight gain: continuous abstainer smoking status, lower body mass index, and greater fear of weight gain. A logistic regression confirmed the influence of smoking status at outcome on weight change. Abstinence was associated with weight gain; continuous abstainers were more likely to gain weight (88.2%) than noncontinuous abstainers (50%) and never quitters (35.9%). Weight variables were found to be interrelated, forming an "eating orientation" linked to smoking behavior.

Ethnic variations in the prevalence of smoking among registered nurses.

A survey of smoking behavior was conducted on 1,569 registered nurses in six unrelated acute care hospitals in Los Angeles in 1984-1985. Smoking prevalence, higher than for other health professionals but lower than for women in the United States or in other recently surveyed samples of nurses, was closely linked to the ethnicity and the age distribution of the nurses surveyed. Patterns for black and white nurses, who account for the majority of nurses nationally, were similar to those found in other recent studies of registered nurses. Among Asian nurses, however, prevalence was lower, age of initiation was higher, and the mean number of cigarettes smoked daily was lower than for other nurses. Smoking prevalence for younger nurses was lower than for other nurses, and these nurses were more likely to report themselves as never having smoked. Smoking patterns among nurses remain a significant public health concern.

Evaluation of a worksite self-help smoking cessation program for registered nurses.

Cigarette smoking among nurses remains a public health concern despite a recent decline in current smoking prevalence. We recruited 149 registered nurses into a no-cost, targeted, self-help smoking cessation program supplemented by a supportive worksite environmental module. The study was designed to expand understanding of nurses' smoking and to measure program effectiveness. Follow-ups were conducted at one, six and 12 months post-intervention to assess self-reported smoking status (92% objectively validated) and predictors of cessation. Point prevalence abstinence at these time points (22.5%, 21.5% and 19.5%), continuous abstinence (12.7%), and an ever-quit rate of 57% (i.e., quit for at least 48 hours), compare favorably to population quit rates and to rates reported for other self-help programs. Logistic regression analyses were utilized to identify predictors of short-term cessation [time before needing a cigarette, concern regarding the health hazards of smoking, working in a critical care setting, use of targeted weight manual] and long-term cessation [dosage (inverse relationship), use of standard American Lung Association maintenance manual, working with dying patients, and M.D.s' opposition to upgrading nursing service (inverse relationship)].

Nicotine gum in smoking cessation: a placebo-controlled, double-blind trial.

Sixty subjects were run in a study comparing the use of nicotine gum with placebo gum during cessation from smoking. Subjects were given clinic support and chewed the gum ad libitum. A survival analysis showed the two groups differed significantly in successful abstinence over time (p less than .03). Differences between groups appeared early (within weeks) and, at six months, a 28% superiority of nicotine over placebo gum was demonstrated with mean success rates of 48% and 20%, respectively. Between six months and one year, relapse in the nicotine group accounted for the 30% vs. 20% success rates for nicotine and placebo observed at one year. In a pilot study ("dispensary") testing the efficacy of the two gums when intervention was minimal, subjects in both groups resumed smoking within the first two weeks. The enhanced short-term success rates with nicotine gum in the clinic study are attributed to an effective interaction between use of the active preparation and clinic support. Long-term cessation may require extended maintenance procedures and/or an identification of optimal gum use.