The development of conditioned blocking and monoamine metabolism in children with attention-deficit-hyperactivity disorder or complex tics and healthy controls: an exploratory analysis

Abstract

Introduction: Conditioned blocking (CB) measures the transient suppression of learning that a new stimulus, added during learning, has the same consequences as the conditioned stimulus already present. Normal CB increases from puberty across adolescence, between the age of 8 and 20 years (Oades et al., 1996). Is there a delay in the development of selective attention abilities in children with a primary diagnosis of attention-deficit/hyperactivity disorder (ADHD) and does this differ from children with Tourette syndrome who also express some symptoms of attention deficit? Methods: CB development was compared between 13 healthy children (CN: mean age 11.0 years), 13 with attention-deficit/hyperactivity disorder (ADHD: mean 10.5y) and 11 with complex tic or Tourette syndrome who also showed some attention-deficit symptoms (TS: mean 11.8y). The ADHD group were medication naive, but 3 TS were receiving tiapride, and two pimozide. The 'mouse-in-house' task form was used. Results: 1. All children required fewer trials to learn the task with increasing age: (the ADHD group was slightly slower). 2. However, only healthy controls improved CB with increasing age (figure 1, left). 3. TS patients under 11y tended to show impaired CB, and over 11y they were significantly worse than controls. 4. While ADHD children over 11y showed less CB than controls, under 11y they tended to show more CB. 5. A correlational analysis of the status of monoamine metabolism in 24h urine samples showed a positive relationship for CB with dopamine (DA) metabolism in normal and TS children, but a negative relationship in ADHD patients (figure 1, right). 6. In contrast, increases of serotonin (5-HT) metabolism were negatively related to CB in TS, but positively related to CB in ADHD children (figure 1, right). 7. Both ADHD and TS groups showed a depressed NA turnover compared to normal children: but the ADHD showed a marked suppression of the ratio of DA and 5HT metabolites (i.e. HVA/5HIAA) that reflected their higher 5-HIAA levels. [The TS group showed increased DA turnover possibly reflecting medication.] see figure 2. Conclusions: When selective information processing abilities reflected by CB start to develop at the onset of puberty, there is a relative worsening in ADHD patients. In contrast TS patients show an impairment independent of age. Changes in the balance between dopamine and serotonin systems may contribute to normal and to abnormal cognitive development.