Rearing complexity affects branching of dendrites in the visual cortex of the rat.

Higher-order dendritic branching is considerably greater in Golgistained neurons from the occipital cortex of rats reared in groups in a complex environment than in similar neurons of littermates reared individually in laboratory cages have intermediate amounts of branching, while lower-order branching did not appear to be affected by any rearing environment.

A double-blind, placebo-controlled study of fluvoxamine in adults with autistic disorder.

BACKGROUND: Autistic disorder is characterized by a fundamental disturbance in social interaction, impairments in communication, and a markedly restricted repertoire of activities and interests. Abnormalities in the serotonin neurotransmitter system have been identified in some persons with autism. No consistently effective and safe drugs have been developed for treating the symptoms of autism. METHODS: Thirty adults with autistic disorder completed a 12-week double-blind, placebo-controlled trial of the potent and selective serotonin uptake inhibitor fluvoxamine maleate. Behavioral ratings were obtained at baseline and after 4, 8, and 12 weeks of treatment. RESULTS: Eight (53%) of 15 patients in the fluvoxamine-treated group were categorized as responders compared with none of 15 in the placebo group (P = .001). Fluvoxamine was superior to placebo in reducing repetitive thoughts and behavior (P < .001), maladaptive behavior (P < .001), and aggression (P < .03), and in improving some aspects of social relatedness (P < .04), especially language usage (P < .008). Treatment response was not correlated with age level of autistic behavior, or full-scale IQ. Other than mild sedation and nausea in a few patients, fluvoxamine was well tolerated. No dyskinesias, adverse cardiovascular events, or seizures occurred. CONCLUSIONS: Fluvoxamine is more effective than placebo in the short-term treatment of the symptoms of autistic disorder in adults. Controlled studies of fluvoxamine and other potent and selective serotonin uptake inhibitors seem warranted in children and adolescents with autism.

High attrition rates in commercial weight reduction programs.

The management of obesity is increasingly dominated by nonprofessional self-helping groups. Little information about the efficacy of these groups is available from independent sources. In a study of 108 women enrolled in a commercial weight reduction program, we found very high attrition rates; 50% of the members dropped out in six weeks and 70% in 12 weeks. Similar attrition rates have been reported in five other programs in three different countries. Very high attrition rates diminish the effectiveness of commercial weight reduction programs, and they suggest caution in the interpretation of data based on weight losses of persons who remain in these programs.

Noradrenergic and adrenergic functioning in autism.

A neurochemical assessment of noradrenergic and adrenergic functioning was carried out with autistic patients and normal control individuals. Norepinephrine and related compounds were measured in autistic (n = 17 unmedicated, 23 medicated; age range 9-29 years old) and normal controls (n = 27; age range 9-36 years old). Plasma levels and urinary excretion of 3-methoxy-4-hydroxy-phenylglycol (MHPG) were measured, as were urinary excretion rates of norepinephrine (NE), epinephrine (EPI), and vanillylmandelic acid (VMA). No significant group mean differences were seen between the autistic and control groups. In both the autistic and control groups urinary excretion rates of norepinephrine and epinephrine were substantially higher in the afternoon-evening (5-11 PM) compared to the overnight (11 PM-7 AM) collection period. Based on our neurochemical assessment, marked abnormalities in basal noradrenergic functioning do not appear to be present in autism.

Urinary 5-hydroxyindoleacetic acid and whole blood serotonin and tryptophan in autistic and normal subjects.

Urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion in two consecutive collection periods (5:00 PM-11:00 PM and 11:00 PM-8:00 AM) and whole blood serotonin (5-HT) and tryptophan (TRP) were measured in groups of unmedicated autistics (n = 16), medicated autistics (n = 20), and normal controls (n = 27). Whole blood 5-HT values were significantly higher in unmedicated autistics compared to normal controls. No significant differences were found in 5-HIAA excretion (microgram/mg creatinine, mean +/- SD) between unmedicated autistics (4.07 +/- 1.52) and normal controls (3.50 +/- 1.07), or between medicated (5.35 +/- 2.93) and drug-free autistic individuals. No correlations were found between 5-HT values and urinary 5-HIAA excretion. Urinary 5-HIAA (microgram/mg creatinine, mean +/- SD) was significantly greater in hyperserotonemic autistic subjects (4.88 +/- 0.87) compared to normal controls (3.50 +/- 1.07, total collection period; p = 0.002). The relevance of these findings to the possibility that increased gut production of 5-HT might cause the elevated whole blood 5-HT levels seen in autism is discussed.

Comorbid association of autism and schizophrenia.

OBJECTIVE: In the last several decades, considerable evidence has suggested that autism and schizophrenia are unrelated. However, recent reports have suggested that individuals with autism may be at greater risk for schizophrenia and that the conditions may be more closely related than generally believed. METHOD: The authors examined detailed case records of 163 adolescents and adults with well-documented histories of autism. These cases included 139 males and 24 females. RESULTS: Only one individual had an unequivocal history of schizophrenia. CONCLUSIONS: If the present study group is taken to be representative, it appears that the frequency of schizophrenia among autistic patients (0.6%) is roughly comparable to the frequency of schizophrenia in the general population. It does not appear that the two conditions are more commonly observed together than would be expected on a chance basis; therefore, the current (DSM-III-R) approach to dual diagnosis of these conditions appears reasonable.

Age of recognition of pervasive developmental disorder.

In DSM-III, pervasive developmental disorder is divided into two major categories: infantile autism and childhood onset pervasive developmental disorder. The criteria differ, primarily, in the age of onset. The authors studied 129 patients who had received diagnoses of pervasive developmental disorder or a related disorder and found only five cases of apparent childhood onset pervasive developmental disorder. These five patients were behaviorally indistinguishable from those with other diagnoses. Practically, age of onset may be more appropriately termed "age of recognition," and its use as a major diagnostic criterion for such disorders may not be justified.

DSM-III and DSM-III-R diagnoses of autism.

The authors examined the reliability, sensitivity, and specificity of DSM-III and DSM-III-R criteria for autism in relation to each other and to clinical diagnoses in 114 children and adults (52 diagnosed by clinicians' best judgment as autistic and 62 as nonautistic but developmentally disordered). They used a standard, structured coding scheme to evaluate each patient. The reliability of specific criteria was generally high. Although DSM-III criteria were highly specific, they were less sensitive; the reverse was true for DSM-III-R. The authors conclude that the diagnostic concept of autism in DSM-III-R appears to have been substantially broadened.

Field trial for autistic disorder in DSM-IV.

OBJECTIVE: This project focused on the development of the definition of autism for DSM-IV. METHOD: Multiple sites were involved in obtaining information regarding 977 patients with the following clinician-assigned diagnoses: autism (N = 454), other pervasive developmental disorders (N = 240), and other disorders (N = 283). A standard coding system was used, and the raters (N = 125) had a range of experience in the diagnosis of autism. Patterns of agreement among existing diagnostic systems were examined, as was the rationale for inclusion of other disorders within the class of pervasive developmental disorders. RESULTS: The DSM-III-R definition of autism was found to be overly broad. The proposed ICD-10 definition most closely approximated the clinicians' diagnoses. Inclusion of other disorders within pervasive developmental disorders appeared justified. Partly on the basis of these data, modifications in the ICD-10 definition were made; this and the DSM-IV definition are conceptually identical. CONCLUSIONS: The resulting convergence of the DSM-IV and ICD-10 systems should facilitate both research and clinical service.

A case-controlled study of repetitive thoughts and behavior in adults with autistic disorder and obsessive-compulsive disorder.

OBJECTIVE: The purpose of this study was to investigate the types of repetitive thoughts and behavior demonstrated by adults with autistic disorder and compare them with those of age- and sex-matched adults with obsessive-compulsive disorder. METHOD: Fifty consecutive patients admitted to the Yale Adult Pervasive Developmental Disorders (Autism) Clinic with a primary diagnosis of autistic disorder (DSM-III-R and DSM-IV) completed the symptom checklist of the Yale-Brown Obsessive Compulsive Scale. Types of current obsessions and compulsions were evaluated. The comparison group consisted of 50 age- and sex-matched adults with obsessive-compulsive disorder (without tics) (DSM-III-R and DSM-IV). RESULTS: Direct discriminant function analysis showed that the patients with autistic disorder could be distinguished from those with obsessive-compulsive disorder on the basis of the types of current repetitive thoughts and behavior that they demonstrated. Compared to the obsessive-compulsive group, the autistic patients were significantly less likely to experience thoughts with aggressive, contamination, sexual, religious, symmetry, and somatic content. Repetitive ordering; hoarding; telling or asking (trend); touching, tapping, or rubbing; and self-damaging or self-mutilating behavior occurred significantly more frequently in the autistic patients, whereas cleaning, checking, and counting behavior was less common in the autistic group than in the patients with obsessive-compulsive disorder. In addition, a specific subset of seven obsessive-compulsive variables from the Yale-Brown Obsessive Compulsive Scale symptom checklist was identified that reliably predicted membership in the autistic group. CONCLUSIONS: These results suggest that the repetitive thoughts and behavior characteristics of autism differ significantly from the obsessive-compulsive symptoms displayed by patients with obsessive-compulsive disorder. Future studies are warranted to assess the treatment response and neurobiological underpinnings of repetitive thoughts and behavior in patients with autism and obsessive-compulsive disorder.

Computed tomographic brain scanning in four neuropsychiatric disorders of childhood.

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.

Practice parameter: screening and diagnosis of autism: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Child Neurology Society.

Autism is a common disorder of childhood, affecting 1 in 500 children. Yet, it often remains unrecognized and undiagnosed until or after late preschool age because appropriate tools for routine developmental screening and screening specifically for autism have not been available. Early identification of children with autism and intensive, early intervention during the toddler and preschool years improves outcome for most young children with autism. This practice parameter reviews the available empirical evidence and gives specific recommendations for the identification of children with autism. This approach requires a dual process: 1) routine developmental surveillance and screening specifically for autism to be performed on all children to first identify those at risk for any type of atypical development, and to identify those specifically at risk for autism; and 2) to diagnose and evaluate autism, to differentiate autism from other developmental disorders.

Childhood and adolescent psychosis: a review of the past 10 years.

OBJECTIVE: Developmental aspects of psychosis are reviewed and related to the more frequent psychotic conditions in children and adolescents. METHOD: The review of the recent literature focuses on developmental aspects of psychotic phenomena, i.e., hallucinations, delusions, and thought disorder. RESULTS: While the applicability of much early work on this topic is limited, more recent work suggests that psychotic conditions are observed in childhood and increase in frequency during adolescence. CONCLUSIONS: Developmental factors in the expression of psychosis are relevant to the diagnosis and treatment of such conditions.

Elective mutism and mental retardation.

The association of elective mutism and mental retardation is noted. Two cases of elective mutism associated with mental retardation are presented. Both individuals had long-standing patterns of inhibition, shyness, and anxiety manifested by general refusal to talk outside the home, particularly at school. The importance of assessment of intellectual functioning and linguistic skills for the establishment of intervention priorities and clinical management is discussed. The possibility of the presence of mental retardation in individuals with elective mutism should be considered.

Childhood disintegrative disorder: results of the DSM-IV autism field trial.

OBJECTIVE: This report is concerned with the classification of children in whom an "autistic-like" syndrome develops after some years of normal development. In DSM-IV the term "childhood disintegrative disorder" (CDD) is used to describe such cases. METHOD: Data collected as part of the international, multisite DSM-IV field trial for autism and related conditions were examined and cases that met DSM-IV criteria for CDD were identified. RESULTS: In 16 cases the clinician had given a CDD diagnosis; in an additional 10 cases criteria for the condition were met even though this diagnosis was not given by the clinician rating the case. CONCLUSIONS: The available data suggest that CDD cases can be differentiated from those with autism; these two groups appear to differ in important ways. The identification of cases of CDD may be of particular importance for research.

Reactive attachment disorder of infancy or early childhood.

Since its introduction into DSM-III, reactive attachment disorder has stood curiously apart from other diagnoses for two reasons; it remains the only diagnosis designed for infants, and it requires the presence of a specific etiology. This paper describes the pattern of disturbances demonstrated by some children who meet DSM-III-R criteria for reactive attachment disorder. Three suggestions are made: (1) the sensitivity and specificity of the diagnostic concept may be enhanced by including criteria detailing the developmental problems exhibited by these children; (2) the etiological requirement should be discarded given the difficulties inherent in obtaining complete histories for these children, as well as its inconsistency with ICD-10; and (3) the diagnosis arguably is not a disorder of attachment but rather a syndrome of atypical development.

Seizure disorders in autism.

Several reports have suggested that autistic individuals are at greater risk for developing seizure disorders, particularly in adolescence. In this study the frequency of seizures in a series of 192 autistic individuals was examined; 21% of cases had exhibited a seizure disorder. Seizure disorders were more common among individuals with lower IQ. Age specific incidence revealed a 3- to 22-fold increase in risk for seizure relative to the normal population. In contrast to previous studies, risk for developing seizures was highest during early childhood although it was also elevated during early adolescence.

Higher-functioning pervasive developmental disorders: rates and patterns of psychotropic drug use.

OBJECTIVE: To explore the frequency, characteristics, and associated target symptoms of psychotropic drug use among subjects with higher-functioning pervasive developmental disorders (HFPDDs). METHOD: A total of 109 children, adolescents, and adults (mean age = 13.9 years, SD = 6.9) consecutively seeking enrollment into the Yale Child Study Center's Project on Social Learning Disabilities were included in the study. Individuals in whom Asperger's disorder, autism, or pervasive developmental disorder-not otherwise specified had been previously diagnosed and who had a documented Full Scale IQ > or = 70 completed surveys on demographic, clinical, and medication history information. To naturalistically evaluate medication use patterns in this population, each drug class was analyzed with respect to demographic and clinical variables. RESULTS: In all, 55% of subjects were taking psychotropics, with 29.3% taking 2 or more medications simultaneously. Antidepressants were the most commonly used agents (32.1%), followed by stimulants (20.2%) and neuroleptics (16.5%). The clinical presentation of subjects taking psychotropic agents was heterogeneous, and most consistently included anxiety-related target symptoms (in 65% of medicated individuals). CONCLUSIONS: Psychotropic medication use appears to be common among subjects with HFPDDs, yet not generally based on the results of empirical research. Clinical heterogeneity among treated subjects suggests that psychiatric comorbidity may be overlooked in this population.

Quantifying social development in autism.

OBJECTIVE: This study was concerned with the development of quantitative measures of social development in autism. METHOD: Multiple regression equations predicting social, communicative, and daily living skills on the Vineland Adaptive Behavior Scales were derived from a large, normative sample and applied to groups of autistic and nonautistic, developmentally disordered children. Predictive models included either mental or chronological age and other relevant variables. RESULTS: Social skills in the autistic group were more than two standard deviations below those predicted by their mental age; an index derived from the ratio of actual to predicted social skills correctly classified 94% of the autistic and 92% of the nonautistic, developmentally disordered cases. CONCLUSIONS: The findings are consistent with the idea that social disturbance is central in the definition of autism. The approach used in this study has potential advantages for providing more precise measures of social development in autism.

A custody and placement evaluation of an infant with a psychotic, mentally retarded mother.

An emergency evaluation was requested on a 16-week-old infant and her parents. The child's mother had a long history of schizophrenia and mental retardation and was noted to decompensate following the child's birth; the mother was hospitalized and the child placed in foster care. Although the mother was severely impaired, the family had a reasonable and appropriate plan for the infant's care and reunification of the family was recommended. Aspects of custody and placement recommendations, the risk of the child for subsequent disorder, and legal issues involved in the evaluation are discussed.