Psychiatric diagnostic dilemmas among people with intellectual and developmental disabilities.

BACKGROUND: Research regarding the accuracy of co-morbid psychiatric diagnoses in individuals with intellectual and developmental disabilities (IDD) is sparse. Yet correct diagnostic assignment is vital so that effective and appropriate treatment can be implemented, especially for the large numbers of individuals requiring expensive and restrictive behavioural health crisis services. METHOD: A retrospective review of de-identified data from multidisciplinary specialty team assessments completed for 50 individuals with ID (IntellectualDisability) with and without ASD and unresolved behavioural health challenges was conducted. The accuracy and reliability of the psychiatric diagnoses upon referral were compared with the diagnoses after the comprehensive team evaluation, and within-individual diagnostic agreement was calculated. The agreement between the Mood and Anxiety Semi-Structured interview tool (MASS) and the full team evaluation was also calculated. The influence of demographic and clinical characteristics on diagnostic agreement was explored. RESULTS: The most common chief complaints upon referral were aggression to others and self-injurious behaviour. Individuals were taking a median of six medications (interquartile range: 5 to 7); 80% were taking an antipsychotic medication. The most common medical conditions were constipation (70%) and gastroesophageal reflux disease (52%). Measures of interrater reliability of the referral diagnoses with the team assessment were below 0.5 (kappa range: -0.04 to 0.39), with the exception of ruling out dementia (kappa = 0.85). The interrater reliability estimates for the MASS evaluations for depression and anxiety were higher (kappa = 0.69 and 0.64) and reflected higher sensitivity and PPV. The odds of any referral diagnosis being confirmed by team evaluation were low: 0.25 (range: 0 to 0.67). The level of diagnostic agreement for each patient was not significantly attributable to demographic or clinical characteristics, although effect sizes indicate a possible positive relationship to age and the number of prescribed psychotropic medications at referral. CONCLUSION: Individuals in the current study had serious psychiatric and behavioural problems despite psychiatric care in their communities. The majority of psychiatric diagnoses provided upon referral were not supported by the multidisciplinary specialty team's assessment. In addition to possible diagnostic inaccuracy, the group in the study suffered from multiple medical co-morbidities and were exposed to polypharmacy. Results emphasise the importance of multidisciplinary evaluation by clinicians with expertise in neurodevelopmental disabilities when people with ID with and without ASD have complex behavioural health needs that are unresponsive to usual care. In addition, based on agreement with the full team evaluation, the MASS shows promise as an assessment tool, especially with regards to identifying anxiety and depression.

Prenatal tobacco smoke exposure and neurological impairment at 10 years of age among children born extremely preterm: a prospective cohort.

OBJECTIVE: To determine the association between prenatal tobacco smoke exposure and neurological impairment at 10 years of age among children born extremely preterm (<28 weeks of gestation). DESIGN: The Extremely Low Gestational Age Newborn (ELGAN) Study, a prospective cohort. SETTING: Ten-year follow-up of extremely preterm infants born at 14 US hospitals between 2002 and 2004. METHODS: Prenatal tobacco smoke exposure was defined as a mother's report at enrolment of active (i.e. maternal) and passive smoking during pregnancy. Poisson regression with generalized estimating equations was used. Models adjusted for mother's age, race/ethnicity, education, insurance, pre-pregnancy body mass index, US region, multiple gestation and infant's sex; and in sensitivity analysis, gestational age at delivery and clinical subtype of preterm birth, given their classification as intermediate and non-confounding variables. MAIN OUTCOMES: Neurological impairment at 10 years, epilepsy, cerebral palsy and cognitive impairment. RESULTS: Of 1200 ELGAN study survivors, 856 were assessed at 10 years of age with neurological outcomes, of whom 14% (118/856) had active tobacco exposure during pregnancy and 24% (207/852) had passive tobacco exposure. Compared with children who were not exposed prenatally to tobacco, children exposed to active tobacco use during pregnancy had a higher risk of epilepsy (14% versus 5%; adjusted relative risk: 1.68, 95% CI 1.45-1.92). This risk remained after adjustment for gestational age at delivery and clinical subtype of preterm birth. Prenatal tobacco smoke exposure was not associated with other assessed neurological outcomes, including cerebral palsy and multiple measures of cognitive impairment. CONCLUSIONS: Among children born extremely preterm, prenatal active tobacco smoke exposure was associated with an increased risk of epilepsy at 10 years of life. TWEETABLE ABSTRACT: Among infants born before 28 weeks of gestation, prenatal active tobacco smoke exposure was associated with an increased risk of epilepsy at 10 years of life.

Polymerization of purified yeast septins: evidence that organized filament arrays may not be required for septin function.

The septins are a family of proteins required for cytokinesis in a number of eukaryotic cell types. In budding yeast, these proteins are thought to be the structural components of a filament system present at the mother-bud neck, called the neck filaments. In this study, we report the isolation of a protein complex containing the yeast septins Cdc3p, Cdc10p, Cdc11p, and Cdc12p that is capable of forming long filaments in vitro. To investigate the relationship between these filaments and the neck filaments, we purified septin complexes from cells deleted for CDC10 or CDC11. These complexes were not capable of the polymerization exhibited by wild-type preparations, and analysis of the neck region by electron microscopy revealed that the cdc10Delta and cdc11Delta cells did not contain detectable neck filaments. These results strengthen the hypothesis that the septins are the major structural components of the neck filaments. Surprisingly, we found that septin dependent processes like cytokinesis and the localization of Bud4p to the neck still occurred in cdc10Delta cells. This suggests that the septins may be able to function in the absence of normal polymerization and the formation of a higher order filament structure.

Actin cytoskeleton: are FH proteins local organizers?

The FH proteins, defined by the presence of 'formin homology' regions, are important for a number of actin-dependent processes, including polarized cell growth and cytokinesis. They are large, probably multi-domain, proteins and their function may be in part mediated by an interaction with profilin.

Left ventricular performance in patients with coexistent mitral stenosis and aortic insufficiency.

Isolated mitral stenosis and isolated aortic insufficiency impose unique and opposite loading conditions on the left ventricle. To assess these combined effects, hemodynamic and angiographic factors were compared among normal subjects and patients with isolated mitral stenosis, isolated aortic insufficiency or combined mitral stenosis and aortic insufficiency. Left ventricular end-diastolic volume index was lower in patients with combined lesions and severe or moderate aortic insufficiency than in patients with isolated severe or moderate aortic insufficiency (138 +/- 19 versus 206 +/- 20 cc/m2 and 87 +/- 5 versus 145 +/- 22 cc/m2, respectively) (p less than 0.05 for both). Left ventricular end-diastolic and end-systolic volume indexes were normal in two-thirds of patients with combined lesions and moderate or severe aortic insufficiency, whereas these indexes were high in all but one patient with isolated moderate or severe aortic insufficiency. Among patients with moderate or severe aortic insufficiency, 8 of 14 with isolated insufficiency had a reduced ejection fraction or circumferential fiber shortening rate compared with 5 of the 9 patients with combined lesions. Among patients with isolated aortic insufficiency, left ventricular end-systolic wall stress and end-diastolic and end-systolic volume indexes were higher (p less than 0.05) in those with reduced ejection performance than in those with normal ejection performance. These variables did not differ between patients with reduced or normal ejection performance in the group with combined lesions. The contractile index (ratio of end-systolic wall stress to end-systolic volume index) was significantly depressed in patients with severe aortic insufficiency in the groups with isolated aortic insufficiency or combined lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Autonomic nervous system markers of psychopathology in childhood-onset schizophrenia.

BACKGROUND: Consistent abnormalities in peripheral indicators of autonomic activity, ie, skin conductance (SC) and heart rate (HR), have been reported in adult-onset schizophrenia. Herein, we use these markers to test the hypothesis of continuity between childhood-onset schizophrenia and adult-onset schizophrenia. METHODS: Skin conductance and HR were recorded from 21 severely ill children and adolescents (mean age, 14.1 years) with childhood-onset (< or = 12 years) schizophrenia (patient group) and from 54 age-matched controls (control group) during a rest period, a series of innocuous tones, reaction time instructions, and a simple warned reaction time task. RESULTS: During rest, patients had higher rates of spontaneous SC responses (SCRs) and HRs than controls, but their SC level was marginally lower and declined more slowly over time. Half of the patients, compared with 4% of the controls, failed to give SC-orienting responses to the first 2 tones. Patients who responded had impaired SCR magnitudes, and their habituation was more erratic than that of controls. The increase in SC level and SCR frequency at the onset of the task period was greatly attenuated in the patients, so that both variables were higher in controls. Patients had smaller SCRs and anticipatory HR responses to the reaction time stimuli. Skin conductance nonresponding was associated with negative and total symptoms, and spontaneous SCR frequency was associated with positive symptoms. CONCLUSIONS: The findings show similar abnormalities in autonomic nervous system activity in childhood-onset schizophrenia to those found in adult chronic schizophrenia, thus supporting the hypothesis of continuity of the childhood and adult forms of the illness. Comparisons with data from other childhood disorders suggest that the combination of low-elicited SC activity with high levels of spontaneous SC activity may be specific to schizophrenia.

Childhood-onset schizophrenia. A double-blind clozapine-haloperidol comparison.

BACKGROUND: Childhood-onset schizophrenia is a rare but severe form of the disorder that is often treatment-refractory. In this study, the efficacy and adverse effects of clozapine and haloperidol were compared for children and adolescents with early-onset schizophrenia. METHODS: Twenty-one patients (mean [+/-SD] age, 14.0 +/- 2.3 years) with onset of Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition-defined schizophrenia that began by age 12 years and who had been nonresponsive to typical neuroleptics participated in the study. Patients were randomized to a 6-week double-blind parallel comparison of clozapine (mean [+/-SD] final dose, 176 +/- 149 mg/d), or haloperidol, (16 +/- 8 mg/d). RESULTS: Clozapine was superior to haloperidol on all measures of psychosis (P = .04-.002). Positive and negative symptoms of schizophrenia improved. However, neutropenia and seizures were major concerns. To date, one third of the group has discontinued using clozapine. CONCLUSIONS: Clozapine has striking superiority for positive and negative symptoms in treatment-refractory childhood-onset schizophrenia. However, due to possibly increased toxic effects in this pediatric population, close monitoring for adverse events is essential.

Brain anatomic magnetic resonance imaging in childhood-onset schizophrenia.

BACKGROUND: Early-onset schizophrenia (first psychotic symptoms by age 12 years) has been the subject of a small number of studies, and its biological continuity with later-onset disorder has not been established. In this study quantitative anatomic brain magnetic resonance images of children and adolescents with early-onset schizophrenia were compared with those of matched controls. Brain abnormalities in childhood-onset schizophrenia were examined in relation to those reported for later-onset schizophrenics. METHODS: Anatomic brain magnetic resonance imaging scans were obtained for 21 patients (mean +/- SD age, 14.6 +/- 2.1 years; range, 10 to 18 years) with childhood-onset schizophrenia (13 males, eight females) and 33 age-, sex-, height-, and weight-matched normal controls. Quantitative measurements were obtained for the cerebrum, anterior frontal region, lateral ventricles, thalamus, caudate, putamen, and globus pallidus. RESULTS: Total cerebral volume and midsagittal thalamic area were smaller in the patients (analysis of variance, P = .002, and analysis of covariance, P = .03, respectively); the caudate, putamen, and globus pallidus were larger in the patients (analysis of covariance, P = .05, P = .007, and P < .001, respectively); and the lateral ventricles tended to be larger in the patients (analysis of covariance, P = .06). Globus pallidus enlargement correlated with neuroleptic exposure and with age of onset of psychosis. The magnitude of abnormalities compared with controls was similar to that reported in adult studies, although there was a trend toward relatively smaller cerebral volumes for the childhood-onset group compared with controls. CONCLUSION: Brain anatomic abnormalities in childhood-onset schizophrenia are similar to those reported for adult populations, indicating overall continuity between these rare childhood cases and the adult schizophrenia populations.

Blink rate in childhood-onset schizophrenia: comparison with normal and attention-deficit hyperactivity disorder controls.

Several lines of evidence have implicated central dopaminergic pathways in the modulation of blink rate. In the present study, blink rate during smooth pursuit was examined in 17 children with childhood-onset schizophrenia, on and off of clozapine, and compared to that of age-matched normal children and unmedicated children with attention-deficit hyperactivity disorder (ADHD). As has been observed in adolescent and adult schizophrenics, blink rate was significantly higher in schizophrenic children relative to normal and ADHD controls. Within the schizophrenic group, blink rate did not significantly change with the introduction of clozapine and was not related to clinical variables. Blink rate was positively correlated with deterioration in smooth pursuit in normal subjects.

Anterior cingulate cortex dysfunction in attention-deficit/hyperactivity disorder revealed by fMRI and the Counting Stroop.

BACKGROUND: The anterior cingulate cognitive division (ACcd) plays a central role in attentional processing by: 1) modulating stimulus selection (i.e., focusing attention) and/or 2) mediating response selection. We hypothesized that ACcd dysfunction might therefore contribute to producing core features of attention-deficit/hyperactivity disorder (ADHD), namely inattention and impulsivity. ADHD subjects have indeed shown performance deficits on the Color Stroop, an attentional/cognitive interference task known to recruit the ACcd. Recently, the Counting Stroop, a Stroop-variant specialized for functional magnetic resonance imaging (fMRI), produced ACcd activation in healthy adults. In the present fMRI study, the Counting Stroop was used to examine the functional integrity of the ACcd in ADHD. METHODS: Sixteen unmedicated adults from two groups (8 with ADHD and 8 matched control subjects) performed the Counting Stroop during fMRI. RESULTS: While both groups showed an interference effect, the ADHD group, in contrast to control subjects, failed to activate the ACcd during the Counting Stroop. Direct comparisons showed ACcd activity was significantly higher in the control group. ADHD subjects did activate a frontostriatal-insular network, indicating ACcd hypoactivity was not caused by globally poor neuronal responsiveness. CONCLUSIONS: The data support a hypothesized dysfunction of the ACcd in ADHD.

Smooth pursuit eye movements in childhood-onset schizophrenia: comparison with attention-deficit hyperactivity disorder and normal controls.

Abnormalities of the smooth pursuit eye movements of adults with schizophrenia have been well described. We examined smooth pursuit eye movements in schizophrenic children, contrasting them with normal and attention-deficit hyperactivity disorder (ADHD) subjects, to determine whether there is continuity of eye movement dysfunction between childhood- and adult-onset forms of schizophrenia. Seventeen schizophrenic children with onset of illness by age 12, 18 ADHD children, and 22 normal children were studied while engaged in a smooth pursuit eye tracking task. Eye tracking variables were compared across the three groups. Schizophrenic children exhibited significantly greater smooth pursuit impairments than either normal or ADHD subjects. Within the schizophrenic group, there were no significant relationships between eye tracking variables and clinical variables, or ventricular/brain ratio. Childhood-onset schizophrenia is associated with a similar pattern of smooth pursuit abnormalities to that seen in later-onset schizophrenia.

Childhood-onset schizophrenia: biological markers in relation to clinical characteristics.

OBJECTIVE: The purpose of this study was to examine the relationships between clinical and neurobiological measures of childhood-onset schizophrenia. It was hypothesized that there would be a more striking pattern in the rare cases with very early onset than is seen in subjects with later onset. METHOD: Premorbid, clinical, prenatal, perinatal, and magnetic resonance imaging brain measures were examined in 29 children and adolescents who met the DSM-III-R criteria for schizophrenia with onset before age 12. Specifically, gender, premorbid adjustment, and clinical symptoms were examined in relation to cerebral volume, ventricular volume, and maternal obstetrical complications. RESULTS: Males were more likely to have had an insidious onset than females. There was a significant negative correlation between score on the Scale for the Assessment of Negative Symptoms and total cerebral volume. CONCLUSIONS: These neurobiological associations support the continuity of early-onset schizophrenia with the later-onset disorder; the striking association between smaller cerebral volume and negative symptoms suggests a more homogeneous or more potent neurobiological basis for very early-onset schizophrenia.

Abnormal neurologic maturation in adolescents with early-onset schizophrenia.

OBJECTIVE: This study evaluated neurologic functioning in adolescents with schizophrenia with onset of psychosis before age 13. METHOD: The authors administered a structured neurologic examination to 21 adolescents with early-onset schizophrenia and 27 healthy age- and sex-matched comparison subjects. RESULTS: The adolescents with schizophrenia had a high frequency of neurologic abnormalities. Neurologic signs decreased with age in the healthy comparison subjects but not in the subjects with schizophrenia. CONCLUSIONS: The adolescents with schizophrenia had a high burden of neurologic impairment and a pattern of abnormalities similar to that of adults with schizophrenia. The persistence of neurologic signs in the adolescents with schizophrenia, which faded with age in the healthy comparison adolescents, supports earlier evidence of a delay in or failure of normal brain development during adolescence.

Childhood-onset schizophrenia: brain MRI rescan after 2 years of clozapine maintenance treatment.

OBJECTIVE: The effect of clozapine on striatal morphology was examined in adolescents with childhood-onset schizophrenia. METHOD: Eight adolescent patients with onset of psychosis before age 12 and eight matched comparison subjects had initial and 2-year follow-up brain magnetic resonance imaging scans. Basal ganglia and lateral ventricle volumes were measured. The patients were on a clozapine regimen during the 2-year interim. RESULTS: Caudate volume was larger in the patients at the initial scanning, decreased in the patients between scans, and did not differ significantly between the patients and the comparison subjects at the second scanning. CONCLUSIONS: Caudate enlargement in patients with childhood-onset schizophrenia who are taking typical neuroleptics appears to be secondary to medication exposure. Rescanning to examine basal ganglia morphology is indicated for these patients when they are taking an atypical neuroleptic.

Cerebrospinal fluid monoamine metabolites in childhood-onset schizophrenia.

OBJECTIVE: Pediatric studies of cerebrospinal fluid (CSF) monoamine metabolites in childhood-onset schizophrenia may help to elucidate both pathophysiology and treatment response in early-onset psychosis. METHOD: CSF homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) and serum prolactin were measured during drug-free and antipsychotic medication conditions in 18 patients (mean age = 14.2 years, SD = 1.7) who had onset of schizophrenia by age 12 (mean age at onset = 9.9 years, SD = 1.8). Relationships between changes in CSF monoamines and serum prolactin and clinical outcome were examined, and the degree of change in CSF monoamines in response to clozapine treatment was compared with that for 16 patients with later-onset schizophrenia. RESULTS: Despite patients' significant clinical improvement with treatment, CSF monoamine concentrations and ratios of HVA/5-HIAA and HVA/MHPG did not significantly change with 6 weeks of either haloperidol or clozapine treatment. Serum prolactin levels increased during haloperidol treatment. Clozapine had similar effects on CSF monoamines in patients with childhood- and later-onset schizophrenia. CONCLUSIONS: While these data are compatible with continuity between childhood- and later-onset schizophrenia, they also highlight the complexity of the biochemical events mediating clinical changes in schizophrenia.

Temporal lobe morphology in childhood-onset schizophrenia.

OBJECTIVE: Neurodevelopmental models of schizophrenia imply that a more severe early brain lesion may produce earlier onset of psychotic symptoms. The medial temporal lobes have been proposed as possible locations for such a lesion. The authors tested this hypothesis in a group of children and adolescents with childhood-onset schizophrenia who had severe, chronic symptoms and who were refractory to treatment with typical neuroleptics. METHOD: Anatomic brain magnetic resonance imaging scans were acquired with a 1.5-T scanner for 21 patients (mean age=14.6 years, SD=2.1) who had onset of schizophrenia by age 12 (mean age at onset=10.2, SD=1.5) and 41 normal children. Volumes of the temporal lobe, superior temporal gyrus, amygdala, and hippocampus were measured by manually outlining these structures on contiguous 2-mm thick coronal slices. RESULTS: Patients with childhood-onset schizophrenia had significantly smaller cerebral volumes. With no adjustment for brain volume, no diagnostic differences were observed for any temporal lobe structure. Unexpectedly, with adjustment for total cerebral volume, larger volumes of the superior temporal gyrus and its posterior segment and a trend toward larger temporal lobe volume emerged for the patients with schizophrenia. These patients lacked the normal (right-greater-than-left) hippocampal asymmetry. CONCLUSIONS: These findings do not indicate a more severe medial temporal lobe lesion as the basis of very early onset schizophrenia.

Plasma clozapine and haloperidol concentrations in adolescents with childhood-onset schizophrenia: association with response.

BACKGROUND: Plasma clozapine and haloperidol concentrations were studied in adolescents being treated for childhood-onset schizophrenia. METHOD: Eleven patients (9 boys, 2 girls; mean age = 14.1 +/- 2.1 years) received a 6-week blinded or open trial of clozapine. Five patients also received 6 weeks of blinded or open haloperidol. Doses were increased on an individual basis to a mean 6-week dose of 5.99 +/- 2.6 mg/kg/day for clozapine and 0.24 +/- 0.20 mg/kg/day for haloperidol. The Brief Psychiatric Rating Scale and Bunney Hamburg Rating Scale were completed weekly for each subject. Weekly blood samples were obtained during therapy and assayed by high performance liquid chromatography. RESULTS: The mean clozapine level at Week 6 was 378.3 ng/mL and ranged from 77.5 to 1050 ng/mL. The mean Week 6 haloperidol level was 23.0 ng/mL (range, 6.2-44.3 ng/mL). The clozapine desmethyl and N-oxide metabolites achieved mean concentrations of 77% and 18%, respectively, of those of the parent compound. The mean ratio of haloperidol/reduced haloperidol was 4.48 (range, 0.76-8.76). Clozapine concentrations versus clinical benefit exhibited a consistent linear relationship among patients (correlation range, 0.26-0.96). Conversely, poor and inconsistent correlations between haloperidol concentrations and clinical effects were observed. No relationships were noted between clozapine or haloperidol dose and clinical effects. CONCLUSION: Adolescents with schizophrenia produce a greater amount of desmethylclozapine than previously seen in adults. Plasma clozapine concentrations appear to be related in a linear fashion to clinical improvement.

An open trial of clozapine in 11 adolescents with childhood-onset schizophrenia.

OBJECTIVE: To review the response of 11 adolescents with childhood-onset schizophrenia to a 6-week open clozapine trial. METHOD: Eleven children meeting DSM-III-R criteria for schizophrenia had a 6-week open trial of clozapine (mean sixth week daily dose 370 mg). Behavioral ratings included the Brief Psychiatric Rating Scale and Children's Global Assessment Scale. RESULTS: More than half showed marked improvement in Brief Psychiatric Rating Scale ratings by 6 weeks of clozapine therapy compared to admission drug rating and compared to a systematic 6-week trial of haloperidol. CONCLUSIONS: This open trial indicates that clozapine may be a promising treatment for children and adolescents with schizophrenia who do not respond well to typical neuroleptics. A double-blind placebo-controlled study is ongoing.

Distinguishing illness severity from tic severity in children and adolescents with Tourette's disorder.

OBJECTIVE: To examine whether tic severity, comorbid disorders, or both are associated with illness morbidity in youths with Tourette's disorder (TD). METHOD: Subjects were 156 consecutively referred youths (aged 5-20 years) who met DSM-III-R criteria for Tourette's disorder at a major academic medical center. All subjects were evaluated with a clinical interview by a child and adolescent psychiatrist and an assessment battery that included the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic version. Statistical analysis used chi 2 and multivariate logistic regression. RESULTS: Nineteen (12%) of the 156 youths with TD required psychiatric hospitalization. Current age, TD severity, TD duration, obsessive-compulsive disorder, psychosis, major depression, bipolar disorder, panic disorder, and overanxious disorder were significant univariate predictors of psychiatric hospitalization (p < .01). While tic severity was marginally significant as a predictor of psychiatric hospitalization (p < .05), major depression (p < .016) and bipolar disorder (p < .001) were robust predictors of psychiatric hospitalization, even after statistical adjustment for collinearity and correction for all other variables assessed. CONCLUSION: The findings indicate that comorbid mood disorders are strongly associated with illness morbidity in youths with TD, highlighting the importance of attention to comorbidity in patients with TD.

Risperidone treatment for juvenile bipolar disorder: a retrospective chart review.

OBJECTIVE: To investigate the effectiveness and tolerability of the atypical neuroleptic risperidone in the treatment of juvenile mania. METHOD: This is a retrospective chart review of outpatients with the diagnosis of bipolar disorder (DSM-IV) treated with risperidone at a university center. Response to treatment was evaluated using the Clinical Global Impression Scale (CGI) with separate assessments of mania, psychosis, aggression, and attention-deficit/hyperactivity disorder (ADHD). RESULTS: Twenty-eight youths (mean +/- SD age, 10.4 +/- 3.8 years) with bipolar disorder (25 mixed and 3 hypomanic) who had been treated with risperidone were identified. These children received a mean dose of 1.7 +/- 1.3 mg over an average period of 6.1 +/- 8.5 months. Using a CGI Improvement score of < or = 2 (very much/much improved) to define robust improvement, 82% showed improvement in both their manic and aggressive symptoms, 69% in psychotic symptoms, but only 8% in ADHD symptoms. CONCLUSIONS: Although limited by its retrospective nature, this study suggests that risperidone may be effective in the treatment of manic young people and indicates the need for controlled clinical trials of risperidone and other atypical neuroleptics in juvenile mania.