Expression patterns of melatonin receptors in chicken ovarian follicles affected by monochromatic light.

Artificial illumination is an important exogenous factor in the control of many physiological and behavioral processes as well as an important environmental factor in the management of laying hens. Melatonin receptors are members of the G protein-coupled receptor family. The hormone melatonin is secreted primarily by the pineal gland, with highest levels occurring during the dark period of a circadian cycle. The aim of this study was to examine the effect of monochromatic light on chicken egg reproduction and expression of melatonin receptors in chicken ovarian follicles. A total of 552 19-week-old hens were randomly divided into 4 groups with 138 birds in each group. Each group was randomly divided into 3 replicates with 46 birds in each replicate. Feed and water were provided for ad libitum. Light treatments were: control cool white (400-760 nm), blue (480 nm), green (560 nm), and red (660 nm). The short wavelength (blue light) group produced a greater total number of eggs at 300 days of age than did the long wavelength (red light) group, and the red light group showed higher melatonin receptor type 1A and melatonin receptor type 1C mRNA and protein expression. These results suggest that the wavelength of light is closely related to chicken egg number at 300 days of age; there is no effect of monochromatic light on melatonin receptor type 1B.

Phenylketonuria: the inadvisability of neuroleptic medication.

The use of neuroleptic medications in two disturbed phenylketonuria patients was studied over a period between 4 to 5 years. The outcome of clinical observation, supported by the neurochemical findings, suggests that most neuroleptic medications may be less than indicated for treating these patients. The observation provides an important example of how an adverse neuroleptic drug response can be predicted by base-line biochemical measures which are closer to the basic pathophysiology of the condition and the site of psychotropic drug action.

Theory and practice of psychopharmacogenetics.

This article attempts to elucidate the theory and practice of psychopharmacogenetics. Eight working models were identified and characterized with a distinct view of risk factors in the host, the pathophysiology of disease, and the strategies for optimum therapy. The biochemical culprits related to adverse drug reaction in each case can be used to identify a risk and thus contribute to prevention research. Since the phenomenology of these uncommon conditions covers a broad spectrum of neuropsychiatric manifestations, the insights they generated might presage a better understanding of the natural history of a wider range of mental disorders associated with genetic vulnerability. The emerging information suggests that psychopharmacogenetics could be defined from clinical perspectives as multidimensional analysis of genes, drugs, and behaviour for the treatment and prevention of psychiatric disorders.

A survey of psychotropic medication in mental retardation facilities.

A survey of psychotropic drug usage by questionnaires was conducted at 5 regional residential centers for the mentally subnormal in Eastern Ontario, Canada. Of the 2238 residents studied, 42% were given psychotropics, 27% anticonvulsants, and 11% a combination of both. Prolonged medication and polypharmacy were observed in all facilities. The therapeutic responses to psychotropic medication were generally poor, especially among the disturbed epileptics who had received psychotropic and anticonvulsant simultaneously. It is estimated that between one-half to two-thirds of those on psychotropics were given the agents too liberally.

Progressive trends in the prevalence of benzodiazepine prescribing in older people in Ontario, Canada.

OBJECTIVES: The extensive use of benzodiazepines has been a concern of healthcare providers and policy makers in Canada and around the world. The purpose of this study was to examine temporal trends in benzodiazepine prescriptions dispensed in older people from 1993-1998. DESIGN: Retrospective population-based cross-sectional study using administrative databases. SETTING: Ontario, Canada. PARTICIPANTS: The over 1 million residents of Ontario age 65 and older covered by the provincial universal drug benefit program. MEASUREMENTS: The main outcome measures were the prevalence, overall and with respect to age and gender, of benzodiazepine prescriptions dispensed and the ratio of the number of people to whom short- versus long-acting benzodiazepine prescriptions were dispensed in each study year. The annual rates of switching to other psychotropic agents were examined for those patients that discontinued filling benzodiazepine prescriptions. RESULTS: The annual prevalence of benzodiazepine prescriptions dispensed decreased consistently over time (25.1% in 1993 to 22.5% in 1998; P < .001). Benzodiazepine dispensing prevalence increased with increasing age (approximately 20% of those age 65 to 69 to approximately 30% of those age > or =85; P < .001) and more females than males received the medication (relative risk = 1.50, 95% confidence interval = 1.49-1.51). The ratio of short- to long-acting benzodiazepine prescriptions filled increased over time (3.6 in 1993 to 5.8 in 1998; P < .001), in line with guideline recommendations. Rates of switching to antidepressants increased over time (8.5% in 1993 to 10.2% in 1998; P < .001), whereas switching to barbiturates was consistently low (0.12%; P = .403). CONCLUSION: The prevalence of benzodiazepine therapy for older people in Ontario has steadily declined between 1993 and 1998. There is a trend of dispensing relatively more short-acting than long-acting benzodiazepines and of replacing benzodiazepines with antidepressants in older people without a remarkable increase in barbiturate consumption. These findings suggest that, without undue regulation, physicians are making progress in the prescribing of benzodiazepine therapy on the basis of current knowledge available.

Psychopharmacogenetic aspects of Prader-Willi syndrome.

The study of genes, drugs, and behavior in three male adolescents with Prader-Willi syndrome (PWS) revealed a clinical profile that raises questions about the indications for neuroleptic and appetite-suppressing medications in this condition. Evidence of the inadvisability of neuroleptic medication and of the pathophysiology of PWS has led to a remarkable control of violent outbursts and hyperphagia by carbamazepine in one patient afflicted with both PWS and Klinefelter's syndrome. Testosterone and behavioral therapy proved to be useful in the management of two patients. The present observations, which are supported by recent advances in the pathophysiology of satiety, suggest that PWS should be understood as a metabolic disorder and subjected to psychopharmacogenetic study.

Psychopharmacogenetic basis of medication-induced movement disorders.

In light of the emerging evidence for genetic vulnerability to adverse drug reactions, this article attempts to elucidate the natural history of medication-induced movement disorders from a psychopharmacogenetic perspective. Studies of the risk factors, neurobiology, and pharmacogenetics are reviewed concurrently. The relevant variables associated with 10 genetically mediated movement disorders are tabulated and compared with those of medication-induced movement disorders without a clear-cut genetic basis. As a result of this integrated analysis, it is evident that there is an intimate genetic and pathophysiological link between neuropsychiatric movement disorders of diverse origins. The emergence of drug-induced movement disorders seems to reflect a spectrum of basal ganglia derangement attributable to genetic predisposition; psychotropic medications only augment the genetic vulnerability to clinical phenotypes. It is proposed that a multidimensional analysis of the interacting variables is essential for understanding the natural history of these conditions, and that the scope of psychopharmacology should be broadened to include psychopharmacogenetics for improving therapeutic objectivity and prevention research.

The Eastern Ontario survey: a study of drug-treated psychiatric problems in the mentally handicapped.

This study surveyed psychiatric problems treated with psychotropic medication among mentally handicapped at five regional centres in Eastern Ontario. Of the 2,158 residents studied, 920 (43%) were identified as problem cases, ranging from 36% to 83% in different institutions. Aggressivity, hyperactivity, and self-injury are the most prevalent conditions among more than thirty problem categories. Analysis of multidimensional contingency tables revealed that each of these three problems is involved with a distinct pattern of interactions with the set of demographic and clinical variables. The diversity of these interaction patterns points out the inadequacy of any unitary hypothesis of the pathogenesis and the inadvisability of adopting over-generalized treatment modalities. It is proposed that rational planning of service should rely on a realistic estimation of individuals' needs and a better understanding of the scope and nature of the problem.

Serotonin metabolism in normal and abnormal infants during the perinatal period.

The concentration of serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) in various body fluids was measured during the perinatal period in two groups of infants born with normal and pathological conditions, respectively. Evidence was obtained showing that fetal blood 5-HT level was relatively stable, uninfluenced by maternal or fetal factors, and was about half the value of the maternal blood. High levels of 5-HIAA and evidence of an active decomposition of 5-HT were found in the amniotic fluid. These findings suggest that 5-HT in utero is subjected to a very active metabolic turnover. The origin of the fetal blood 5-HT and the significance of the placenta in the control of intrauterine 5-HT metabolism is discussed. There was no clear evidence of abnormal 5-HT metabolism in toxemic pregnancies, premature babies, and an infant with Down's syndrome in the perinatal period.

Iron deficiency in two adolescents with conduct, dysthymic and movement disorders.

Enquiry into a marginally subnormal hemogram in two adolescents with complex conduct, dysthymic and movement disorders uncovered a striking iron deficiency and prompted a trial of replacing psychotropic medication with iron therapy. The rationale of iron therapy for behavioural disturbance was examined from the clinical, neurochemical and psychopharmacological points of view. Although further study is required to confirm the therapeutic efficacy and to define the precise nature of iron deficiency in conduct disorder, the weight of the evidence suggests that correcting the nutrient deficit may be an essential step toward a refinement of therapeutic strategies. The presence of a borderline hemogram, hypermenorrhea and malnutrition should alert clinicians to the possibility of iron deficiency, and laboratory screening for hypoferremia should be considered when assessing conduct disorder.