Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

d-Fenfluramine (dF) (15 mg twice daily) has been studied in controlled trials in human obesity and has been shown to increase adherence to diet, to enhance its efficacy, and most importantly, to prevent weight regain when continued over 1 y. Few side effects, mostly transient, have been observed. A long-term use of dF in the management of some obese patients could be foreseen. Additionally, evidence that dF improves eating symptoms and dysphoric impairments in obese cravers, premenstrual syndrome, seasonal affective disorder, and smoking withdrawal syndrome has been presented.
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PMID:Clinical studies with d-fenfluramine. 172 29

Common to repetitive episodes of weight gain or failures to succeed on weight loss regimens is the excessive consumption of carbohydrate-rich foods in association with dysphoria. The brain neurotransmitter, serotonin, seems to be involved in the abnormal regulation of mood and food intake that underlies diet failures or weight gain in individuals who suffer from carbohydrate craving obesity (CCO), premenstrual syndrome (PMS) and seasonal affective disorder (SAD). All 3 syndromes are characterized by episodic bouts of increased carbohydrate consumption and depressed mood. Studies with dietary treatment or drugs that enhance serotoninergic neurotransmission have found that increased serotonin neurotransmission is associated with normalised food intake and mood. These results suggest that periodic intervention with dietary or drug treatment that increases serotonin availability may help sustain weight or assist in weight loss.
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PMID:Carbohydrate craving. Relationship between carbohydrate intake and disorders of mood. 219 75

Seasonal affective disorder (SAD) appears to be a disturbance of circadian rhythm caused by desynchronization between the solar clock and the human biologic clock during seasons of short photoperiods. The supplemental bright light of phototherapy resynchronizes the disturbed rhythm; however, a comprehensive theory to explain the mechanism of phototherapy is lacking. Future research on the action of melatonin and serotonin and the photochemical effect of light in relation to possible circadian rhythm disorders should help us to better understand and treat not only SAD but other conditions such as jet lag, premenstrual syndrome, eating disorder, and carbohydrate-craving obesity.
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PMID:Seasonal affective disorder. Shedding light on a dark subject. 267 72

Current findings on the relationship between excessive appetite for carbohydrate-rich foods and mood disorders may explain repetitive weight gain or the inability to lose weight among some obese individuals. Obese individuals who crave carbohydrates, exhibit positive changes in mood after carbohydrate intake; individuals suffering from Seasonal Affective Disorder experience a craving for carbohydrate-rich foods in association with their mood disturbances. Brain serotonin may be involved in these disorders of affect and appetite; thus therapies that mimic the effect of carbohydrate intake on the synthesis and release of this neurotransmitter may be useful in treating obesity arising from these causes.
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PMID:Carbohydrate cravings: a disorder of food intake and mood. 305 12

The pharmacology, pharmacokinetics, efficacy, and adverse effects of dexfenfluramine hydrochloride are reviewed. Dexfenfluramine, the dextrorotatory isomer of fenfluramine, is indicated for use in the management of obesity in patients with a body mass index of > or = 30 kg/m2, or > or = 27 kg/m2 in the presence of other risk factors. Unlike fenfluramine, dexfenfluramine is a pure serotonin agonist. Dexfenfluramine may mimic the effect of carbohydrate intake. Systemic bioavailability is about 68%, and the drug is metabolized in the liver. In randomized, placebo-controlled trials, dexfenfluramine was effective in reducing weight in obese patients given the drug for three or six months. In trials lasting one year, the statistically significant weight loss occurred during months 4 to 6. Dexfenfluramine reduces blood pressure, percent glycosylated hemoglobin, and concentrations of blood glucose and blood lipids, but these benefits may be indirect. Dexfenfluramine may also be of some value in controlling eating habits in diabetic patients, preventing weight gain after smoking cessation, and treating bulimia, seasonal affective disorder, neuroleptic-induced obesity, and premenstrual syndrome. Dexfenfluramine's most frequent adverse effects are insomnia, diarrhea, and headache; it has also been associated with primary pulmonary hypertension. The drug should not be combined with other serotonergic agonists because of the risk of serotonin syndrome. The recommended dosage is 15 mg twice daily. Dexfenfluramine is effective in the treatment of obesity in selected patients. Because its efficacy is lost after six months of continuous treatment, it should be viewed primarily as an adjunct to diet and exercise.
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PMID:Dexfenfluramine hydrochloride: an anorexigenic agent. 937 5

There is significant evidence that altered dopamine activity plays a role in seasonal affective disorder (SAD). The current study examined three separate genetic hypotheses for SAD related to the 7-repeat allele (7R) of the dopamine-4 receptor gene (DRD4), a variant associated with decreased affinity for dopamine. We examined the possible contribution of 7R to the overall expression of SAD, attention deficit disorder (ADD) comorbidity, and body weight regulation. As part of an ongoing genetic study of increased eating behavior and mood in female subjects, 108 women with winter SAD and carbohydrate craving/weight gain were administered the Wender-Utah Rating Scale to measure childhood ADD symptomatology, and a questionnaire to assess maximal lifetime body mass index (BMI). To test for an association between 7R and the categorical diagnosis of SAD, the transmission disequilibrium test (TDT) was used in a subsample of probands providing familial DNA. Standard parametric tests were used to compare childhood ADD symptoms and maximal lifetime BMI across the two genotypic groups defined by the presence or absence of 7R. The TDT found no initial evidence for an association between 7R and the categorical diagnosis of SAD. However, 7R carriers reported significantly greater inattention and dysphoria in childhood (p=0.01 and 0.001, respectively) and a higher maximal lifetime BMI (p=0.007) than did probands without this allele. Furthermore, excluding probands with extreme obesity (maximal BMI >40), a strong correlation was found linking childhood inattentive symptoms and maximal lifetime BMI (r=0.35, p=0.001). In overeating women with SAD, the 7R allele of DRD4 may be associated with a unique developmental trajectory characterized by attentional deficits and dysphoria in childhood and mild to moderate obesity in adulthood. This developmental course may reflect different manifestations of the same underlying vulnerability related to central dopamine dysfunction. Given the possibility of population stratification when studying genotype/phenotype relationships, future use of genomic controls and replication of our findings in other overeating and/or ADD populations are needed to confirm these initial results.
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PMID:Childhood inattention and dysphoria and adult obesity associated with the dopamine D4 receptor gene in overeating women with seasonal affective disorder. 1456 Mar 22

While depression is common in Cushing's syndrome from whatever cause (pituitary, adrenal, or ectopic adrenocorticotropic hormone-secreting tumor or hyperplasia, or exogenous administration of glucocorticoids) and hypercortisolemia is prevalent in major depression, any association between seasonal affective disorder and Cushing's syndrome is unknown. We present a case of seasonal bipolar disorder, gradually worsening for more than 9 years (1985-1994), accompanied by increasing osteoporosis, mild weight gain, and slight truncal obesity in a middle-aged woman. In January 1991, her seasonal affective disorder was successfully treated with light therapy, but in the following year, bipolar mood swings with a seasonal pattern emerged, which were refractory to light therapy and antidepressants but responsive to lithium. In August 1992, she became depressed despite a 1500-mg lithium daily dosage along with light therapy, and, in 1993, a diagnosis of Cushing's disease (Cushing's syndrome as a result of a pituitary adrenocorticotropic hormone-secreting tumor) was made. The pituitary tumor was removed in February 1994, and pituitary function was fully restored by 1996. While the symptoms of Cushing's syndrome subsided, her bipolar illness continued to require maintenance treatment with low doses of lithium but did not require light therapy.
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PMID:A case of seasonal bipolar disorder exacerbated by Cushing's disease. 1572 34

Melatonin, or N-acetyl 5-methoxytryptamine, a neurohormone produced in the pineal gland during periods of darkness, plays a key role in the regulation of circadian and seasonal biological rhythms. In mammals, specific MT1 and MT2 receptors are located in the central nervous system, mainly in suprachiasmatic nuclei, and also in a number of peripheral sites. Besides its chronobiotic action on light-dependant functions, such as sleep/waking alternance or seasonal depression, melatonin exerts modulatory effects on immune, endocrine and metabolic functions. However, its short half-life and extensive metabolism lead to a poor bioavailability. This prompted to search for metabolically stable analogs displaying new and innovative properties. The S 20098 compound, a melatoninergic agonist, has proven potent antidepressive and anxiolytic actions. The S 20928 compound, a melatonin antagonist, was shown to enhance basal metabolism and reduce weight gain. Thus, both of these melatonin derivatives open perspectives for the development of innovative therapeutic agents in the fields of depression and obesity.
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PMID:[Melatoninergic receptor agonists and antagonists: pharmacological aspects and therapeutic perspective]. 1629 32

We have recently described an association between the hypofunctional 7-repeat allele (7R) of the dopamine-4 receptor gene (DRD4), weight gain, and obesity in women with seasonal affective disorder (SAD). In the current study, we examined whether season-of-birth might interact with the 7R allele to influence body weight regulation in SAD. In 182 female probands with SAD, we performed an analysis of covariance predicting maximum lifetime body mass index (BMI) with both the exon-3 variable number of tandem repeat polymorphism of DRD4 and season-of-birth as independent variables, and age as the covariate. The overall model was highly significant (F = 4.42, df = 8, 173, p < 0.0001) with season-of-birth predicting maximal lifetime BMI both on its own and in its interaction with the 7R allele. The latter finding was attributable to 7-repeat carriers born in the spring (N = 17), who had a mean maximal lifetime BMI of 33.7 kg/m2 (SD 8.6), compared to 26.7 kg/m2 (SD 5.4) for all other probands combined (N = 165) (F = 20.01, df = 1, 179, p < 0.0001). The lifetime rate of obesity (maximal BMI > 30 kg/m2) was also significantly higher in the 7R/spring birth group (9/17=52.9% vs 32/165=19.4%; chi2 = 9.94, df = 1, p = 0.002; odds ratio = 4.68, 95% CI = 1.67-13.07). These data may reflect a novel gene-environment interaction, during early brain development, which establishes an increased risk for obesity in women with SAD. Although the mechanism for season-of-birth effects in psychiatric disorders is unknown, a characteristic pattern of melatonin exposure during the second and third trimesters may be of particular relevance in this study population. We speculate that these data may reflect the vestigial expression of a seasonal thrifty phenotype that contributed to the positive selection of the 7R allele over the past 40,000 years.
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PMID:A birth-season/DRD4 gene interaction predicts weight gain and obesity in women with seasonal affective disorder: A seasonal thrifty phenotype hypothesis. 1676 Sep 22

Bupropion, a noradrenaline and dopamine re-uptake inhibitor, has long been indicated for the treatment of depression. Recent studies have demonstrated additional benefits in depression, including: prevention of the recurrence of seasonal affective disorder in depressive subtypes with decreased energy, pleasure and interest; in major depression with concomitant anxiety; in elderly depressed patients; for non-response to initial serotonin re-uptake inhibitor therapy or augmentation of partial efficacy with serotonin re-uptake inhibitors; and in bipolar depression. Efficacy in other conditions has also been shown in studies of attention deficit hyperactivity disorder, nicotine dependence, obesity and hypoactive sexual desire disorder. Thus, bupropion has proven effective across a broad spectrum of depressive conditions, subtypes and comorbidities.
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PMID:Extended-release bupropion: an antidepressant with a broad spectrum of therapeutic activity? 1730 40


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