Recent discoveries in the field of molecular biology and increased attention to genetic epidemiology have stimulated renewed interest in the genetics of psychiatric disorders. Tourette's syndrome, a neuropsychiatric disorder characterized by motor and phonic tics, is used as a model to describe the research strategies employed in the genetic epidemiology of child psychiatric disorders. The relevance of genetic research findings to child psychiatric nursing is also discussed.

The trajectory of cognitive development in males with fragile X syndrome was identified in a cross-sectional study of 56 males and in a smaller, longitudinal study of 10 fragile X males. Results from both studies indicated steady cognitive growth until late childhood and early adolescence (10 to 15 years of age), at which point mental age plateaued and IQ declined. Males with higher initial IQ scores manifested more IQ decline than those with initial lower levels of intelligence. The trajectories of IQ differ from those in other etiological groups and mixed groups of retarded individuals. Results have direct implications for intervention strategies with fragile X males. Parents and teachers should be informed about the possibility of an early plateau in mental age, the impact this may have on the child's academic performance, and that the plateau and IQ decline may not be apparent in the child's adaptive behaviors.

Abstract Fragile-X syndrome is a recently described X-linked disorder that ranks second to Down syndrome as the most prevalent chromosomal form of mental retardation. Affected male individuals manifest a variable clinical phenotype that includes distinctive facial features, macroorchidism, cognitive and language impairments, and an impressive prevalence of attention deficit disorder and infantile autism. A sizable proportion of female carriers are similarly affected. The molecular basis for these phenotypic features has not been established, nor have the factors mediating the variable expression of the syndrome in vulnerable individuals. However, improved behavioral functioning in prepubertal children may result from early identification and folate supplementation.

To the Editor.— Interest in a possible hereditary component in the transmission and expression of Gilles de la Tourette's syndrome (TS) is longstanding. Although no specific genetic mechanism has been identified, several studies have reported a pattern of transmission that is consistent with an incompletely penetrant autosomal gene (D.L.P., J.F.L., unpublished data, 1985).1-4The importance of nongenetic factors has also recently been emphasized by a twin study of TS reported by Price et al5in which seven (23%) of the 30 monozygotic pairs were fully discordant for TS. In preparing for a more extensive evaluation of these discordant twin pairs, we recently examined unpublished data from the original study and found that in each case the unaffected co-twin had a higher birth weight than the affected twin (Table). These data must be considered as preliminary, since detailed case histories of the twin pregnancies were not obtained as part

Following an open trial of clonidine hydrochloride (3 to 8 micrograms/kg/day for 12 weeks), we studied the behavioral, cardiovascular, and neurochemical effects of abrupt clonidine withdrawal in seven patients with Tourette's syndrome aged 9 to 13 years. Five patients showed marked worsening of tics. After reinitiation of clonidine therapy, the time required for patients to return to prewithdrawal levels of tic symptoms ranged from two weeks to four months. Increases in motor restlessness, blood pressure, and pulse rate were also observed over the 72-hour period following abrupt withdrawal of clonidine. Plasma levels of free 3-methoxy-4-hydroxyphenylglycol, homovanillic acid, and urinary excretion of norepinephrine and epinephrine increased during the withdrawal period. Clonidine's effectiveness in Tourette's syndrome may be dependent on changes in dopaminergic as well as adrenergic mechanisms.

CAT scans were performed in 66 patients with neuropsychiatric disorders of childhood (infantile autism, attention deficit disorder, Tourette's disorder, and language disorder) and a control group of 20 medical patients. Ventricular volume and brain density were determined by quantitative, computer-based methods by researchers blind to the patients' diagnoses. There were no significant differences among diagnostic groups or between neuropsychiatric patients and medical control patients in total ventricular volume, right-left ventricular volume ratio, ventricular asymmetries, ventricle-brain ratios, or brain density.

The relationship between various sociodemographic, reproductive, and other factors to the occurrence of fibrocystic breast disease was evaluated in a case-control study undertaken at five Connecticut hospitals from 1979 to 1981. The study groups comprised 590 women with biopsy-proven fibrocystic breast disease and 1,018 women with other surgical conditions. Among the premenopausal women, multivariate analysis suggested that high socioeconomic status, Jewish religion, low parity, a history of benign breast disease, a history of breast cancer in the mother or a sister, and low Quetelet index were associated with increased odds ratios (OR) for fibrocystic breast disease. Similar analysis for the postmenopausal women revealed increased OR for women with high socioeconomic status, a late age at menopause, and a history of benign breast disease. Current smokers as well as those who had had a tubal sterilization had significantly reduced odds of fibrocystic disease. There was no convincing evidence of linear trends according to degree of epithelial atypia for any of the variables considered. Although some variation in the OR emerged in the analysis according to selected histologic components, the results provided little evidence that women with biopsy specimens exhibiting gross cysts, sclerosing adenosis, papillary hyperplasia, or papillomatosis showed epidemiologic similarities with breast cancer patients.

Thirteen patients with Gilles de la Tourette's syndrome were treated with clonidine (0.125 to 0.3 mg/d) for at least 60 weeks. In a single-blind, placebo-controlled trial, 6 of the 13 patients were judged to be unequivocal responders to clonidine, and 6 other patients had an equivocal response. There was significant improvement in motor and phonic tics, as well as in associated behavior problems, and there were no serious side effects. Tolerance to clonidine did not develop. Further placebo-controlled, randomized, double-blind studies of clonidine in Tourette's syndrome are needed to establish the drug's efficacy.

The association between estrogen replacement therapy and fibrocystic breast disease was assessed in a hospital-based case-control study undertaken in Connecticut from 1979 to 1981. The cases were 143 postmenopausal women with biopsy-confirmed fibrocystic breast disease, and the controls were 355 postmenopausal women with other surgical conditions. Use of estrogen replacement therapy was positively associated with fibrocystic breast disease; the odds of disease increased with duration of use, reaching an approximately fivefold excess odds for those who had taken menopausal estrogens for 10 or more years. There was no evidence that the positive association between estrogen replacement therapy and the occurrence of fibrocystic breast disease could be explained by differential medical care utilization or other possible risk factors of biopsied fibrocystic breast disease.

In a hospital‐based case‐control study of 590 women with biopsy‐proven fibrocystic breast disease and 1,018 control women with other surgical conditions, no linear relationship was evident between the use of oral contraceptives or of estrogen replacement therapy and the degree of epithelial atypia of the fibrocystic lesions. Case‐control and intracase comparisons suggested that oral contraceptive use might be associated with an increased occurrence of sclerosing adenosis among the premenopausal women and of gross cysts among the postmenopausal women. Estrogen replacement therapy, which was positively associated with fibrocystic breast disease as a whole among the postmenopausal women, was most frequently used among the cases whose biopsy specimens exhibited gross cysts, papillomatosis or papillary hyperplasia.

In a hospital-based case-control study that included 634 women with fibrocystic breast disease and 1,066 comparison women in Connecticut, the occurrence of fibrocystic breast disease was positively associated with average daily consumption of caffeine. Women who consumed 31-250 mg of caffeine/day had a 1.5-fold increase in the odds of disease, whereas women who drank over 500 mg/day had a 2.3-fold increase in the odds. The association with caffeine consumption was especially high among women with atypical lobular hyperplasia and with sclerosing adenosis with concomitant papillomatosis or papillary hyperplasia, both of which have been associated with an increased breast cancer risk. The association was specific to fibrocystic breast disease in that there was no association of caffeine consumption with fibroadenoma or other forms of benign breast disease.

The association between use of oral contraceptives and fibrocystic breast disease was assessed among women aged 20-74 years in a hospital-based case-control study conducted between November 1979 and November 1981 in Connecticut. The study groups comprised 633 women with biopsy-proven fibrocystic breast disease and 1,062 controls who had been admitted, as inpatients or outpatients, to general surgical services. For the premenopausal women, there was no evidence that long-term use of oral contraceptives was associated with a decreased frequency of fibrocystic breast disease among either current or past users. For the postmenopausal women, previous oral contraceptive exposure was associated with an increased occurrence of cystic disease. These findings contradict previous investigations reporting a negative association between oral contraceptive use and the development of fibrocystic breast disease.

The cell membranes of the acinar cells in the parotid gland contain both α-adrenergic receptors (which regulate the volume of saliva and the release of potassium ions) and β-adrenergic receptors (which regulate the secretion of amylase). We used parotid salivary volume and amylase secretion as indicators of adrenergic functioning in 11 young male patients with Tourette's syndrome (TS). Parotid saliva was collected for 1 hour before and 4 hours following placebo or a single dose of clonidine (0.05–0.15 mg) in five drug-free TS patients and in six TS patients who had shown good therapeutic responses to long-term clonidine treatment. Following placebo, drug-free patients showed increased salivary volume and total amylase secretion over a 4-hour collection period. Clonidine produced decreased salivary volume for both the drug-free (-63% decrease) and chronically treated patients (-56%). Also, following a single dose of clonidine, 5/6 of the chronically treated patients and 1/3 of the drug-free patients showed decreased salivary amylase concentration; all showed decreased total secretion of amylase. Untreated TS patients may experience nor-adrenergic hyper-reactivity to stressful situations. Clonidine inhibits noradrenergic functioning in TS patients even after treatment for up to 4 years.

Growth hormone response to α-adrenergic receptor agonists such as clonidine has been reported to be useful in assessing changes in the responsiveness of central α-adrenergic receptors. In the present study, growth hormone response to 2.5–5.3 μg/kg, PO of clonidine was studied in 18 children with Tourette's syndrome (TS) and in 26 children with short stature. Subjects ranged in age from 4 to 17 years, with a mean age of 12 years. TS children were studied prior to and following a minimum of 3 weeks of oral clonidine. After controlling for the effects of age, weight, and dose, children with short stature were found to have a significantly higher growth hormone peak (p < 0.05) and earlier peak time (p < 0.01) compared to TS children in pretreatment conditions. These effects were most notable at 60 and 90 min following oral clonidine. With chronic treatment with this agent, the growth hormone response in the TS children increased toward that observed in children of short stature although the peak time remained delayed. The pretreatment growth hormone response was not useful in predicting therapeutic response to clonidine in TS.