Gene expression in blood is associated with risperidone response in children with autism spectrum disorders.

Children with autism spectrum disorders (ASDs) often have severe behavioral problems. Not all children with these problems respond to atypical antipsychotic medications; therefore, we investigated whether peripheral blood gene expression before treatment with risperidone, an atypical antipsychotic, was associated with improvements in severe behavioral disturbances 8 weeks following risperidone treatment in 42 ASD subjects (age 112.7±51.2 months). Exon expression levels in blood before risperidone treatment were compared with pre-post risperidone change in Aberrant Behavior Checklist-Irritability (ABC-I) scores. Expression of exons within five genes was correlated with change in ABC-I scores across all risperidone-treated subjects: GBP6, RABL5, RNF213, NFKBID and RNF40 (α<0.001). RNF40 is located at 16p11.2, a region implicated in autism and schizophrenia. Thus, these genes expressed before treatment were associated with subsequent clinical response. Future studies will be needed to confirm these results and determine whether this expression profile is associated with risperidone response in other disorders, or alternative antipsychotic response within ASD.

Review of neuroimaging studies of child and adolescent psychiatric disorders from the past 10 years.

OBJECTIVES: To review recent neuroimaging studies of serious emotional disorders in youth and identify problems and promise of neuroimaging in clinical practice. METHOD: Published reports from refereed journals are briefly described, critiqued, and synthesized into a summary of the findings to date. RESULTS: Childhood-onset schizophrenia shows progressive ventricular enlargement, reduction in total brain and thalamus volume, changes in temporal lobe structures, and reductions in frontal metabolism. Autistic disorder is associated with cerebellar changes, greater total brain and lateral ventricle volume, and asymmetry. The prefrontal cortex and the basal ganglia are consistently reported as abnormal in attention-deficit/hyperactivity disorder. Patients with anorexia nervosa show enlarged CSF spaces and reductions in gray and white matter that are only partially reversible with weight recovery. CONCLUSIONS: Results from neuroimaging studies of childhood-onset psychiatric disorders suggest consistency in the structures found to be abnormal, but inconsistencies in the nature of these abnormalities. Although neuroimaging technology holds great promise for neurodevelopmental research, it is not yet a diagnostic instrument.

Frontal lobe of children with schizophrenia spectrum disorders: a proton magnetic resonance spectroscopic study.

BACKGROUND: Schizophrenia is commonly considered a neurodevelopmental disorder. Our aim was to determine whether the proton magnetic resonance spectroscopic (1H-MRS) changes seen in adults with schizophrenia are displayed in children at risk for developing schizophrenia. METHODS: Children with symptoms of schizophrenia-spectrum disorders (n = 16; mean age = 132 months) and a comparison group (n = 12; mean age 130 months) took part in a 1H-MRS study of the left frontal lobe. Areas of peaks from N-acetylaspartate (NAA), choline (Cho), and creatine (Cre) were determined and ratios of NAA/Cre and Cho/Cre calculated and compared between groups. RESULTS: The mean ratio of NAA/Cre was significantly lower in schizophrenia-spectrum subjects than the comparison group (1.67 vs. 1.92; p < .05). Medication status did not affect results in schizophrenia-spectrum subjects. CONCLUSIONS: Our findings suggest that the metabolic changes associated with adult schizophrenia are observed in children with some or all of the symptoms of schizophrenia, supporting a neurodevelopmental theory for schizophrenia.

Brain abnormalities in schizophrenia-spectrum children: implications for a neurodevelopmental perspective.

Children with symptoms of schizophrenia-spectrum disorder (N = 20) were compared to controls (N = 20) matched for age and socioeconomic status. Structural brain abnormalities were assessed with magnetic resonance imaging and functional brain abnormalities with neuropsychological tests. Children with schizophrenia-spectrum disorder had smaller amygdala and temporal cortex volumes, along with reduced callosal areas and an unusual pattern of neuroanatomic asymmetries. No differences were noted in overall brain volume, ventricular volume, hippocampal volume, or frontal area. Schizophrenia-spectrum children were also characterized by deficits in all neuropsychological functions examined. Some types of verbal memory and frontal lobe skills were especially deficient. These results support the hypothesis that children with schizophrenia-spectrum disorder have significant brain abnormalities, similar in some ways to those seen in adult schizophrenics. In conjunction with recent primate studies, the current results draw attention to the role of the amygdala as one relevant factor in the pathogenesis of schizophrenia.

Neuropsychophysiological study of children at risk for schizophrenia: a preliminary report.

OBJECTIVE: This initial report, from an ongoing study, examines whether children who have symptoms of schizophrenia spectrum disorder display neuropsychological or neuroanatomic abnormalities similar to those seen in adults with schizophrenia. METHOD: Experimental subjects were 12 children between 8 and 12 years of age who displayed symptoms of early-onset schizophrenia or schizotypal personality disorder, as assessed through the Schedule for Affective Disorders and Schizophrenia for School-Age Children. The experimental subjects were compared with 13 controls on neuropsychological test performance, magnetic resonance imaging measurements, and proton magnetic resonance spectroscopy results. RESULTS: Findings from the first phase of this project reveal significant overall group differences for several morphometric magnetic resonance imaging measurements and all neuropsychological measures. Differences between the groups were found for amygdala volume, mesial temporal volume, callosal area, and anatomic asymmetry. Magnetic resonance spectroscopy data showed a trend toward group differences. CONCLUSIONS: These findings support a neurodevelopmental model of schizophrenia which postulates that environmentally or genetically programmed events in utero disrupt the establishment of fundamental aspects of brain structure and function.

Adolescent psychotherapy research: a practical review.

Most of the review studies, including meta-analyses that pay special attention to internal and external validity, support the efficacy of individual psychotherapy for children and adolescent. However, methodological flaws in existing research on outcome of this form of therapy prevents us from getting incontrovertible proof. This paper reviews these studies, emphasizes factors thought to be important to the outcome--variables such as the development process, family and environment, the young person's motivation for therapy, etc.--that have to be taken into consideration by researchers. Special recommendations for the design of future research are offered.

Ethical perspectives on managed care as it relates to child and adolescent psychiatry.

Managed health care is providing an increasing influence in the way child and adolescent psychiatry is practiced. The goals of managed care have been to manage price, service, and quality. As external forces are brought to bear on child and adolescent psychiatry, ethical and legal dilemmas are faced. Underlying principles and the impact of society force physicians to reexamine their values and reeducate themselves about legal developments.

Magnetic resonance imaging of severely disturbed children--a preliminary study.

This study investigates the relationship between brain pathology and psychiatric disturbance in 37 psychiatric inpatients between 5 and 14 years of age referred for magnetic resonance imaging (MRI). Of 37 images, 13 were categorized as abnormal by neuroradiologists who were blind to the diagnoses of subjects. Three of six children with schizophrenia-related diagnoses had abnormal scans. In contrast, only one of 15 children with a primary disruptive behavior disorder diagnosis had an abnormal magnetic resonance image. A greater proportion of children with schizophrenia spectrum diagnoses had greater left than right frontal horns of the lateral ventricles than children with other diagnoses.

An autistic boy copes with a terminal illness.

David, a 12-year-old boy with autism, developed Ewing's Sarcoma and died 3 months later. This report describes the effects of both illnesses on David, his parents, and his care givers. The difficulties encountered in finding appropriate help in the care of both illnesses and in making difficult decisions are described. The presence of autism can affect medical management and the presence of terminal illness can affect the management of autism. Suggestions are offered for effective medical and psychiatric interventions that include a sensitivity to both illnesses in physicians and other care givers; a case manager to help find appropriate medical and psychiatric services; and the availability of combined medical and psychiatric units.

Predicting success and failure of medical students at risk for dismissal.

An analysis of the records of 41 students at risk for dismissal while studying at the George Washington University School of Medicine and Health Sciences was undertaken to identify characteristics that correlated with future success or failure. Four distinct groups were identified and their outcomes followed. The group with academic problems lacked the academic capabilities to compete successfully; 57 percent graduated. Those in the group with intrapersonal problems were hindered by personal conflicts and excessive anxiety; 71 percent graduated. The group with interpersonal problems consisted of students who did not relate effectively to professors, clinicians, physicians, or patients; 8 percent graduated. The fourth group encompassed those students who suffered both from excessive anxiety and limited academic ability; 71 percent graduated. Accepting psychotherapeutic help when recommended was related to graduation and was greatest in the group with intrapersonal problems. Seven of the eight students who threatened litigation after dismissal were from the group with interpersonal problems.

Childhood depression.

This paper reviews the development of the current understanding of childhood depression. Psychoanalytic thought is briefly reviewed and recent studies regarding diagnosis, incidence, etiology, treatment, and prognosis are covered. The Diagnostic and Statistical Manual III is thought to adequately diagnose both adult and childhood depression. Depressive disorder in children is more frequently recognized and important studies are enhancing our knowledge of biologic, genetic, and psychological factors in depression. Treatment of depression is being refined and developed. The authors suggest that the understanding of childhood depression continues to be best conceptualized within a biopsychosocial model.