Predictive validity of DSM‐IV oppositional defiant and conduct disorders in clinically referred preschoolers

Background: Diagnostic validity of oppositional defiant and conduct disorders (ODD and CD) for preschoolers has been questioned based on concerns regarding the ability to differentiate normative, transient disruptive behavior from clinical symptoms. Data on concurrent validity have accumulated, but predictive validity is limited. Predictive validity is critical to refuting the hypothesis that diagnosing ODD and CD in young children leads to pathologizing normal behavior. ODD and CD have emerged as gateway disorders to many forms of adult psychopathology. Establishing how early we can identify symptoms and disorders that herald poor prognosis is one of the most important goals for research on etiology and prevention. Methods: Subjects were 3–5‐year‐old consecutive referrals to a child psychiatry clinic (n = 123) and demographically matched children from a pediatric clinic (n = 100). A diagnostic interview was used to assess DSM‐IV ODD and CD in a prospective follow‐up design from preschool to school age. Stability of ODD and CD diagnoses and level of impairment were tested as a function of preschool diagnosis. Results: Over 80% of preschoolers diagnosed with ODD and approximately 60% of preschoolers diagnosed with CD met criteria for the same disorder during follow‐up. Impairment over time varied significantly as a function of stability of diagnosis across three years. Conclusions: These results provide the first evidence of the predictive validity of DSM‐IV ODD and CD in clinically referred preschool children. The findings challenge the assumption that symptoms of disruptive behavior disorders that occur during the preschool period tend to be transient.     

Two‐year diagnostic stability in early‐onset first‐episode psychosis

Background: Only one study has used a prospective method to analyze the diagnostic stability of first psychotic episodes in children and adolescents. The Child and Adolescent First‐Episode Psychosis Study (CAFEPS) is a 2‐year, prospective longitudinal study of early‐onset first episodes of psychosis (EO‐FEP). Aim: To describe diagnostic stability and the variables related to diagnostic changes. Methods: Participants were 83 patients (aged 9–17 years) with an EO‐FEP consecutively attended. They were assessed with a structured interview (Kiddie‐Schedule for Affective Disorders and Schizophrenia, Present and Lifetime version) and clinical scales at baseline and after 2 years. Results: The global consistency for all diagnoses was 63.9%. The small group of bipolar disorder had high stability (92.31%) as did the group with schizophrenia spectrum disorders (90.00%). Depressive disorder had lower stability (37.50%) and the lowest values were for psychotic disorder not otherwise specified (11.76%) and brief psychotic disorder (0%).The most frequent diagnostic shift was to schizophrenia spectrum and bipolar disorders. One group of patients did not meet the criteria for any diagnosis at follow‐up. Independent predictors of change to schizophrenia spectrum disorders were lower scores on the Children’s Global Assessment Scale (CGAS) and the Hamilton Depression Rating Scale. Predictors of not having a diagnosis at follow‐up were the CGAS and the Strauss–Carpenter Outcome Scale. Conclusions: Global diagnostic stability was 63.9%. Bipolar and schizophrenia spectrum disorders were the most stable diagnoses, while depressive disorder and other psychosis the least stable. Psychosocial functioning at baseline was a good predictor of diagnosis at follow‐up. These data show the need for longitudinal follow‐up in EO‐FEP before a stable diagnosis is reached.     

Ifosfamide‐induced encephalopathy and movement disorder

Ifosfamide is a widely used chemotherapeutic agent for the treatment of a broad spectrum of solid tumors. CNS toxicity is a well‐described side effect of ifosfamide, but the mechanism of ifosfamide‐induced neurotoxicity remains poorly defined. We present two pediatric cases of hemiballismic limb movements in the setting of ifosfamide‐associated encephalopathy. To our knowledge, there have been no prior reports of ifosfamide‐induced hemiballism in pediatric patients. One of our patient's encephalopathy and abnormal movements may have improved after the administration of methylene blue and thiamine. Pediatr Blood Cancer 2010;54:624–626. © 2009 Wiley‐Liss, Inc.     

Living‐donor liver transplantation for mild Zellweger spectrum disorder: Up to 17 years follow‐up

Mild Zellweger spectrum disorder, also described as Infantile Refsum disease, is attributable to mutations in PEX genes. Its clinical course is characterized by progressive hearing and vision loss, and neurodevelopmental regression. Supportive management is currently considered the standard of care, as no treatment has shown clinical benefits. LT was shown to correct levels of circulating toxic metabolites, partly responsible for chronic neurological impairment. Of three patients having undergone LT for mild ZSD, one died after LT, while the other two displayed significant neurodevelopmental improvement on both the long‐term (17 years post‐LT) and short‐term (9 months post‐LT) follow‐up. We documented a sustained improvement of biochemical functions, with a complete normalization of plasma phytanic, pristanic, and pipecolic acid levels. This was associated with stabilization of hearing and visual functions, and improved neurodevelopmental status, which has enabled the older patient to lead a relatively autonomous lifestyle on the long term. The psychomotor acquisitions have been markedly improved as compared to their affected siblings, who did not undergo LT and exhibited a poor neurological outcome with severe disabilities. We speculate that LT performed before the onset of severe sensorineural defects in mild ZSD enables partial metabolic remission and improved long‐term clinical outcomes.     

Incentive‐elicited mesolimbic activation and externalizing symptomatology in adolescents

Background: Opponent‐process theories of externalizing disorders (ExD) attribute them to some combination of overactive reward processing systems and/or underactive behavior inhibition systems. Reward processing has been indexed by recruitment of incentive‐motivational neurocircuitry of the ventral striatum (VS), including nucleus accumbens (NAcc). Methods: We used functional magnetic resonance imaging (fMRI) with an incentive task to determine whether externalizing symptomatology in adolescence is correlated with an enhanced VS recruitment by cues for rewards, or by deliveries of rewards. Twelve community‐recruited adolescents with externalizing disorders (AED) and 12 age/gender‐matched controls responded to targets to win or avoid losing $0, $0.20, $1, $5, or an unknown amount (ranging from $0.20 to $5). Results: Cues to respond for rewards activated the NAcc (relative to cues for no incentive), in both subject groups similarly, with greatest NAcc recruitment by cues for the largest reward. Loss‐anticipatory NAcc signal increase was detected in a volume‐of‐interest analysis – but this increase occurred only in trials when subjects hit the target. Relative to controls, AED showed significantly elevated NAcc activation by a linear contrast between reward notification versus notification of failure to win reward. In a post hoc reanalysis, VS and pregenual anterior cingulate activation by the reward versus non‐reward outcome contrast also directly correlated with Child Behavior Checklist (CBCL) Externalizing total scores (across all subjects) in lieu of a binary diagnosis. Finally, both groups showed right insula activation by loss notifications (contrasted with avoided losses). Conclusions: Externalizing behavior, whether assessed dimensionally with a questionnaire, or in the form of a diagnostic categorization, is associated with an exaggerated limbic response to outcomes of reward‐directed behavior. This could be a neurobiological signature of the behavioral sensitivity to laboratory reward delivery that is characteristic of children with externalizing symptomatology. Of interest is future research on incentive‐motivational processing in more severe, clinically referred AED.     

Atomoxetine improves communication in a girl with semantic‐pragmatic disorder

This report describes the case of an ADHD girl (hereafter referred to as K) with semantic‐pragmatic disorder, she was treated with atomoxetine. K was a 9‐year‐old girl. She had difficulty understanding words or sentences, finding words, and producing sentences. K also displayed symptoms of severe inattentiveness. K was diagnosed with DSM‐IV‐defined¹ ADHD, predominantly the inattentive type. Her communication impairment was considered symptomatic of semantic‐pragmatic disorder. K was started on atomoxetine, the dose was increased to 50 mg/day (dosage based on weight: 1.8 mg/kg). Her communication activities were improved a few weeks after atomoxetine 50 mg/day was administered. She was unable to organize information pertaining to words, and so could not use words in expressive language. These problems were mitigated through the administration of atomoxetine. Further prospective studies are needed to better understand the therapeutic effects of atomoxetine in patients with semantic‐pragmatic disorder.