Famotidine treatment of children with autistic spectrum disorders: pilot research using single subject research design.

Using single subject research design, we performed pilot research to evaluate the safety and efficacy of famotidine for the treatment of children with autistic spectrum disorders. We studied 9 Caucasian boys, 3.8-8.1 years old, with a DSM-IV diagnosis of a pervasive developmental disorder, living with their families, receiving no chronic medications, and without significant gastrointestinal symptoms. The dose of oral famotidine was 2 mg/kg/day (given in two divided doses); the maximum total daily dose was 100 mg. Using single-subject research analysis and medication given in a randomized, double-blind, placebo-controlled, cross-over design, 4 of 9 children randomized (44%) had evidence of behavioral improvement. Primary efficacy was based on data kept by primary caregivers, including a daily diary; daily visual analogue scales of affection, reciting, or aspects of social interaction; Aberrant Behavior Checklists (ABC, Aman); and Clinical Global Improvement scales. Children with marked stereotypy (meaningless, repetitive behaviors) did not respond. Our subjects did not have prominent gastrointestinal symptoms and endoscopy was not part of our protocol; thus, we cannot exclude the possibility that our subjects improved due to the effective treatment of asymptomatic esophagitis. The use of famotidine for the treatment of children with autistic spectrum disorders warrants further investigation.

The timing of psychiatric consultation requests. Utilization, liaison, and diagnostic considerations.

Psychiatric consultation timing results from the interaction of multiple systems. This study examines the key clinical and systems variables and the effect of consultation timing on subsequent length of hospital stay. One hundred and forty-five consecutive psychiatric consultations at a New York City teaching hospital were assessed by demographic criteria, medical and psychiatric diagnoses, reasons for consultation, and the timing of the consultation with respect to the academic year. Twenty-five percent of the consultations occurred within the first 48 hours after admission and 32% occurred between Days 2 and 5. Consultations for schizophrenia patients were called earlier (P < 0.02) than those for patients with other diagnoses, and those for patients with the acquired immunodeficiency syndrome were called later (P < 0.04). Earlier consultations were associated with a shorter time to discharge (P < 0.002).

Homovanillic acid and dopamine-beta-hydroxylase in male youth: relationships with paternal substance abuse and antisocial behavior.

Recent research suggests that dopaminergic/noradrenergic system dysfunction may be associated with substance abuse and/or antisocial behavior. In order to determine whether male youth of fathers with these disorders would manifest differences in these systems when compared with youth of nonsubstance-abusing or nonantisocial fathers, levels of homovanillic acid (HVA), the metabolite of dopamine (DA) and dopamine-beta-hydroxylase (DBH), the enzyme facilitating the conversion of dopamine to norepineprhine, were studied in offspring blood samples. The subjects were 65 male youth aged 6-15 years admitted to a residential center because of behavioral disorders. Parental substance abuse and antisocial behavior were assessed through interviews, rating scales, and/or chart review. HVA and DBH were determined from blood samples obtained after admission. The findings indicated that youth of substance-abusing fathers had significantly greater levels of HVA than yough of nonsubstance-abusing fathers. Younger (< 12.0 years) boys of antisocial fathers had significantly lower DBH activity than comparably aged youth of nonantisocial fathers. The results suggest that common generational links in substance abuse and antisocial behavior in males may be associated with detectable biological parameters in susceptible youth.

Postprandial sleep in healthy men.

Twenty-one healthy men between 18 and 30 years of age were studied to determine the effects of midday food intake on sleep. Twelve subjects were administered liquid carbohydrate meals at lunchtime on 2 consecutive days. Subjects slept on 22 of the 24 study days for an average of 93 minutes during 3 hours of postprandial polysomnographic recording. Nine subjects were used as controls and were deprived of a lunch meal. Six of the nine subjects slept for an average of 30 minutes during the postprandial period. This time was significantly shorter than that of subjects in the meal condition (p < 0.005). There was no difference in latency to sleep onset following food intake between the two study groups. The results of this study suggest that lunchtime food intake does not promote the initiation of sleep, but that it does increase the duration of sleep episodes occurring during the postprandial period.

Monoamine oxidase and homovanillic acid in boys with predispositions to substance abuse.

Both dopaminergic dysregulation and abnormalities in monoamine oxidase (MAO) have been postulated as etiological factors in substance abuse. This study assessed whether MAO activity differed in sons of substance-abusing fathers compared with sons of nonsubstance-abusing fathers. It also assessed the levels of homovanillic acid (HVA), the metabolite of dopamine, and MAO in a group of substance-using/-abusing boys compared with peers without this history in the same setting. Sixty-five boys admitted to a residential center were evaluated on blood tests for HVA and MAO, and on a series of diagnostic instruments and questionnaires designed to elicit information about parental substance abuse and about the subject's own substance use/abuse. The results indicated tentatively that younger (< 12.0 years) sons of substance-abusing fathers had higher levels of MAO than younger sons of nonsubstance-abusing fathers. Levels of MAO in older (> or = 12.0 years) sons of substance-abusing and nonsubstance-abusing fathers did not differ. Boys with histories of significant use/abuse of substances themselves had significantly higher MAO levels and significantly lower HVA levels than peers of the same age without substance use/abuse histories.

Sensation seeking in psychiatrically disturbed youth: relationship to biochemical parameters and behavior problems.

OBJECTIVE: Relatively little research has been conducted on the relationship of personality traits or behavioral tendencies with biological parameters in youth. This study was intended to determine whether relationships exist between self-reported sensation-seeking tendencies and biochemical parameters in boys. METHOD: Twenty-five male youth aged 8 to 15 years admitted to a residential diagnostic center because of noncompliant, disruptive, and/or antisocial behavior were studied. Biochemical parameters associated with sensation seeking in adults or antisocial behavior were measured along with diagnoses, behavior ratings, and self-reported sensation seeking. RESULTS: High sensation seeking, as assessed on a newly developed sensation-seeking scale for children, was inversely correlated with 3-methoxy-4-hydroxyphenylglycol (MHPG) levels in the older youth (> or = 12.0 years) but not in the younger boys (< 12.0 years) in the group. Elevations on the sensation seeking scale also correlated marginally in these older youth with parent-reported problems on a behavior rating scale, reflecting "delinquent" behavioral tendencies. CONCLUSIONS: The findings support hypothesized noradrenergic dysregulation in some sensation-seeking persons (including youth > or = 12.0 years) and the relationship between high sensation-seeking tendencies and antisocial or disruptive behavioral disorder.

Dopamine-beta-hydroxylase in behaviorally disturbed youth. Relationship between teacher and parent ratings.

A series of neurotransmitters, metabolites, and enzymes considered relevant to emotional and behavioral disorders was studied in blood samples obtained from boys admitted to a residential setting because of disruptive or unmanageable behavior in their home environments. The youth were categorized into mainly prepubertal (under 12.0 years) and pubertal/post pubertal (12.0 years and over) groups. Behavior ratings of the younger group completed by parents revealed significant inverse correlations between several behavioral factors and dopamine-beta-hydroxylase (DBH) activity levels, notably in the aggressive behavior and antisocial domains. Teacher ratings completed after about 1 month of living in the residential setting also showed numerous significant, but positive, correlations between several behavior factors and DBH activity levels. Furthermore, teacher and parent ratings themselves often were significantly and inversely correlated. The findings related to DBH activity levels were strongest in the younger group of boys. The results are discussed in terms of the possibility that low DBH activity in boys reflects a vulnerability towards behavioral disorder, which in certain environments becomes manifested by conduct problems and antisocial behavior.

Characteristics of children whose parents have been incarcerated.

OBJECTIVE: The study sought to determine the relationship between parental incarceration and behavioral and family characteristics among children in a day hospital. METHODS: Chi square analysis and t tests were used to compare preadmission characteristics and teachers' behavioral ratings of a group of 16 children in a day hospital setting who had experienced the incarceration of one or both parents and a group of 21 children in that setting who had no history of parental incarceration. RESULTS: Children in the parental incarceration group were significantly more likely to have experienced parental substance abuse than those whose parents had not been incarcerated. A history of child abuse or maltreatment appeared to be more likely among the parental incarceration group. Boys whose fathers had been incarcerated received higher teacher ratings of delinquent and aggressive behavior. Paternal incarceration among girls was associated with a significant increase in attention problems. CONCLUSIONS: A history of parental incarceration may be quite common in some mental health samples of children. It appears to be associated with severe family dysfunction and behavioral disorders.

Biodevelopmental aspects of conduct disorder in boys.

The association between biochemical parameters and conduct disorder (CD) was studied in 22 boys admitted to a residential center. Three-methoxy-4-hydroxyphenylglycol (MHPG) levels were significantly higher in prepubertal CD youth than in pubertal/post pubertal CD youth. Homovanillic acid (HVA) levels were significantly lower in CD youth under age 12.0 years than in non CD youth under age 12.0 years. The implications of these biodevelopmental findings in the study of CD are discussed.

Pain perception in self-injurious patients with borderline personality disorder.

Pain ratings during the cold pressor test were significantly lower in female inpatients with borderline personality disorder who report that they do not experience pain during self-injury (BPD-NP group, n = 11), compared with similar patients who report that they do experience pain during self-injury (BPD-P group, n = 11), and normal female subjects (n = 6). Pain ratings were not significantly different in the BPD-P and normal control groups. Self-report ratings of depression, anger, anxiety, and confusion were significantly lower, and ratings of vigor significantly higher following the cold pressor test in the BPD-NP group, but not in the BPD-P group. Only anxiety was significantly lower in the normal control group following the cold pressor test. The implications and limitations of these preliminary findings are discussed.

Postprandial sleep and thermogenesis in normal men.

Twelve normal male subjects were given low- (16.77 kj/kg) and high- (54.49 kj/kg) calorie liquid carbohydrate lunch meals on 4 days, during which measures of sleep EEG, thermogenesis (heat production), core body temperature, and skin surface temperature were obtained. On 2 days subjects were required to remain awake, and on 2 days sleep was allowed. Both meals were administered in each condition. On the days that subjects were instructed to remain awake, thermogenesis was significantly greater following high-calorie meals than low-calorie meals, and both meal conditions produced levels of thermogenesis that were greater than those observed when sleep was allowed. When given the opportunity, 11 of 12 subjects slept following both low- and high-calorie meals. There was no difference between meal conditions in the total minutes or percent of stages 1, 2, 3/4, or rapid eye movement (REM) sleep following meals. However, the onset of postprandial sleep episodes was associated with the peak of the postprandial rise in thermogenesis, and the occurrence of sleep was followed by precipitous and statistically significant declines in thermogenesis and core body temperature, as well as increases in skin surface temperature. These data suggest that postprandial sleep is associated with rises in thermogenesis, and that its occurrence decreases postprandial heat production and body temperature.

Incarceration in parents of day hospital youth: relationship to parental substance abuse and suspected child abuse/maltreatment.

The number of individuals incarcerated in penal institutions in the United States has increased dramatically in recent years. Children of incarcerated parents have been studied infrequently. They appear to be at high risk for present and future behavioral disorders, although their rate of utilization of mental health services is not known. This study compares a group of behaviorally disturbed children in day hospital treatment who have had incarcerated parents with a group of children without this history who were treated in the same facility at the same time. Children with histories of incarcerated parents account for almost 40% of those treated. They are more likely than their peers without histories of having had an incarcerated parent to have had substance abusing parents and to have been involved in at least one report of suspected child abuse/maltreatment. These variables together are taken as signs of severe family disorganization or dysfunction. In previous studies they have also been associated with poor outcome in mental health treatment. Clinical and social implications of these findings are discussed.

Intake of different concentrations of sucrose and corn oil in preweanling rats.

To investigate the orosensory control of ingestion in preweanling rats, we infused one of the following liquids continuously through anterior sublingual intraoral catheters for 20 min: sucrose solutions (5, 10, 20, and 40%) and corn oil emulsions (6.25, 12.5, 25, 50, and 100%). Pups were tested at 7, 14, 21, and 28 days of age. Each pup was tested only once. Intake of sucrose and of corn oil became increasingly correlated with concentration from 7 to 21 days. Sucrose elicited more intake than water by day 7, whereas corn oil did not until day 14. Low concentrations of sucrose had differential effects on intake by day 14, but low concentrations of corn oil emulsions did not have differential effects on intake until day 21. At all ages, the peak intake of sucrose was significantly larger than the peak intake of corn oil. These differences are probably not based on prior experience because each test of ingestion represented a first exposure to the stimulus. Thus we suggest that the differences are due to the maturation of the orosensory control of ingestion by sucrose and corn oil.

Brain computed tomography findings in geriatric depression and primary degenerative dementia.

Brain computed tomography (CT) scans were performed in hospitalized geriatric patients with major depression (n = 45) or primary degenerative dementia (n = 21). Depressed patients with onset of illness at age 60 years or older (n = 32) had greater ventricular size than geriatric depressives with earlier age of illness onset (n = 13). CT parameters of late-onset depressives were comparable to those of patients with primary degenerative dementia. However, early-onset geriatric depressives had significantly smaller ventricles and less sulcal widening than demented patients. The findings suggest that late-onset depression may have a stronger association with neurological dementing disorders than early-onset depression.

Behavior problems in sons and daughters of substance abusing parents.

Information to address the question of whether sex specific features exist in behavioral characteristics of children of substance abusing parents was gathered from the records of a large number of hospital treated youth. There was a trend for sons of substance abusing parents to have more conduct disorder diagnoses in association with severe aggressive/destructive behavior than sons of non substance abusing parents. Girls of substance abusing parents generally were more likely to have attention deficit/hyperactive, aggressive and conduct disorder problems than girls of non substance abusing parents.

Adolescent psychiatric inpatients: Characteristics, outcome, and comparison between discharged patients from a specialized adolescent unit and nonspecialized units.

We have recently studied the outcome of school-aged children treated in day hospital and inpatient psychiatric units using four operationally defined preadmission child and parent/family variables as predictors of outcome. Our studies have provided considerable support for these preadmission variables singly and/or in combination in predicting poor outcome in school-aged children in these hospital settings. The present study describes the prevalence of these variables and their ability to predict outcome in two groups of adolescent psychiatric inpatients in the same hospital: one group placed on a specialized adolescent unit and one group placed on other inpatient psychiatric units. The findings indicate that overall there is a lower prevalence of the preadmission variables in the adolescent group compared to the school-aged inpatient group. In the adolescent group, only the preadmission variable of severe aggressive/destructive behavior predicted poor outcome. There appears to be a greater prevalence of severe behavioral disturbance in the group of adolescents discharged from the specialized adolescent unit compared to adolescents discharged from other psychiatric units, and an associated poorer outcome in the former group. Possible reasons for these findings and their implications for the hospital-based evaluation and treatment of aggressive and severely disturbed adolescents are discussed.

Aggressive behavior in youth: characteristics, outcome, and psychiatric diagnoses.

This study evaluated the characteristics and outcome of a group of children and adolescents treated in day hospital and inpatient settings. Severe aggressive/destructive behavior was present in about one-third of the sample and was more common in boys, in children and adolescents with history of parental substance abuse, and in those with a concurrent diagnosis of conduct disorder. Although both an admission diagnosis of conduct disorder and aggressive/destructive behavior as a preadmission variable predicted poor outcome, aggressive/destructive behavior was the more important of the two. Aggressive/destructive behavior in association with conduct disorder seems to confer an especially poor prognosis in hospital-treated youth.

Suicidal behavior and hypothalamic-pituitary-adrenocortical axis indices in child psychiatric inpatients.

Studies of adults have reported associations between suicidal behavior and hypothalamic-pituitary-adrenocortical (HPA) axis functioning, but these associations were inconsistent. Very few studies of prepubertal children evaluating these relations exist. This study of 49 prepubertal psychiatric inpatients evaluates associations between suicidal behavior and predexamethasone and postdexamethasone plasma cortisol levels shortly after hospital admission and 7 weeks later. Results suggest that associations between suicidal behavior and plasma cortisol levels are independent of diagnosis. Covariation of predexamethasone and postdexamethasone plasma cortisol levels with major depression was associated with severity of suicidal behavior. Implications of these results for childhood suicidal risk are discussed.

Verbal memory and plasma drug concentrations in elderly depressives treated with nortriptyline.

Performance on a verbal memory task and affective state were assessed in geriatric major depressives before and during 6 weeks of treatment with nortriptyline (NT) in a fixed-dose design study. Higher plasma NT concentration was associated with poorer free recall but better affective outcome. In contrast, higher plasma Z-10-hydroxynortriptyline (Z-10-OH-NT) concentration was associated with more efficient free recall. Concentration-effect relationships were noted in patients later classified as cognitively unimpaired using the Dementia Rating Scale after optimal treatment, rather than in those with residual cognitive impairment.

Outcome in children's day treatment: relationship to preadmission variables.

Outcome in children's day treatment has been studied infrequently. There is little information available to suggest which types of children may or may not benefit from day treatment services. In an earlier study, Gabel et al. (1988) found that preadmission factors related to parental/family dysfunction (i.e., suspected child abuse/maltreatment and parental substance abuse) and preadmission factors related to child dysfunction (i.e., suicidality and severe aggressive/destructive behavior) correlated with poor outcome in day treatment by the criterion of a recommended out-of-home placement on discharge. Of these factors, severe aggressive/destructive behavior was most important in predicting outcome. In this study, discharges from two additional centers were reviewed to determine if these findings could be generalized. There is support for the earlier results when the three centers' discharges are considered as a whole but not when the two new centers' discharges are considered separately. Reasons for these findings are discussed. Further study of these preadmission variables, especially severe aggressive/destructive behavior, as possible predictors of poor outcome in children's day treatment, seems warranted.