Dysfunction of orbitofrontal and dorsolateral prefrontal cortices in children and adolescents with high-functioning pervasive developmental disorders

Study participants included 19 Japanese patients with autistic disorder or Asperger's disorder (aged 10–15 years) who were admitted as either inpatients or outpatients at Kohnodai Hospital, National Center for Global Health and Medicine. In order to include only patients with overt clinical features of PDD, those diagnosed as PDD-NOS were not included in the study. Two trained child and adolescent psychiatrists diagnosed their condition according to the DSM-IV-TR criteria [12]. Patients with a current or past diagnosis of mood disorders, schizophrenia, substance-related disorders, attention-deficit and disruptive behavior disorders, or mental retardation were excluded from this study. Eleven patients (ten males and one female) were diagnosed with autistic disorder, and eight patients (seven males and one female) were diagnosed with Asperger's syndrome. Normal healthy controls were recruited from two local public schools by word of mouth, and a total of 47 students volunteered to participate. A child psychiatrist conducted a 30-min clinical interview with each potential control subject to rule out any prevalent or past history of psychiatric disorders. Subjects with prevalent or past history of psychiatric diagnosis, those who underwent treatment for psychiatric or psychological disorders, or those who had a history of absenteeism from school were excluded from the control group. Two of the 47 volunteers were excluded because they exhibited obsessive symptoms: one because of tic disorder, and three because of PDD. After matching these subjects with the patients for gender, age, handedness, and intelligence, 19 volunteers were enrolled as control subjects.

Handedness was determined for each subject using the hand usage questionnaire [13]. The IGT [14] was assigned by a trained child and adolescent psychiatrist following the previously described procedures of the original IGT version. The only difference from the original task was that play money was converted from US dollars to Japanese yen [15]. The IGT requires subjects to repeatedly select 100 cards from four decks and maximize their profit. The goal is to win as much money as possible, or, as far as possible, avoid losing money. To achieve this, subjects must discover the most advantageous decks and preferentially select cards from them. Each time they turn over a card, subjects win money; however, when turning over a card, subjects sometimes have to pay a penalty according to a preprogrammed reward/punishment schedule. Gains and losses are different for each card selected from the four decks. Although they yield 10,000 yen rewards, decks A and B are 'disadvantageous’ because their penalties are higher than those of decks C and D. Therefore, they cost more in the long run. These decks are also termed high-paying decks. Decks C and D are 'advantageous’ because while they yield only 5,000 yen, their penalties are lower in amount to gains in the long term. These decks are also termed low-paying decks. Thus, successful task performance requires frequent sampling from decks C and D than from decks A and B. In the present study, subjects were informed that they would get a special gift if they earned at least 300,000 yen at the end of the task [16]. The 100 selections were divided into five blocks of 20 selections each, which allowed us to verify changes in selection patterns throughout the experiment. We recorded the number of disadvantageous cards selected in the overall task and in each block of 20 selections. Four clinical psychologists individually administered the Wechsler Intelligence Scale for Children-Third Edition and the Keio version of the WCST [17]. The WCST was used to determine executive function or abstract reasoning that involves working memory [1] and to examine DLPFC function [18]. In the WCST, we evaluated the number of categories achieved (CA), total errors (TE), and perseverative errors (PE) as reported by Nelson [19]. Categories achieved indicated the ability to change abstract categories, and PEs represent perseveration of preceding errors or the inability to inhibit preceding incorrect responses.

Data were analyzed using the Statistical Package for the Social Sciences (SPSS; IBM, Armonk, NY, USA) version 16 for Windows (Microsoft, Redmond, WA, USA). We compared continuous variables (i.e., age and IQ) using t tests and ordinal variables using the Mann-Whitney test. The results were considered statistically significant at p < 0.05.

This study was designed in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the National Center for Global Health and Medicine. Written informed consent was obtained from all participants and their parents after they had received a description of the study.