Acute dopamine depletion with branched chain amino acids decreases auditory top-down event-related potentials in healthy subjects.

Cerebral dopamine homeostasis has been implicated in a wide range of cognitive processes and is of great pathophysiological importance in schizophrenia. A novel approach to study cognitive effects of dopamine is to deplete its cerebral levels with branched chain amino acids (BCAAs) that acutely lower dopamine precursor amino acid availability. Here, we studied the effects of acute dopamine depletion on early and late attentive cortical processing. Auditory event-related potential (ERP) components N2 and P3 were investigated using high-density electroencephalography in 22 healthy male subjects after receiving BCAAs or placebo in a randomized, double-blind, placebo-controlled crossover design. Total free serum prolactin was also determined as a surrogate marker of cerebral dopamine depletion. Acute dopamine depletion increased free plasma prolactin and significantly reduced prefrontal ERP components N2 and P3. Subcomponent analysis of N2 revealed a significant attenuation of early attentive N2b over prefrontal scalp sites. As a proof of concept, these results strongly suggest that BCAAs are acting on basic information processing. Dopaminergic neurotransmission seems to be involved in auditory top-down processing as indexed by prefrontal N2 and P3 reductions during dopamine depletion. In healthy subjects, intact early cortical top-down processing can be acutely dysregulated by ingestion of BCAAs. We discuss the potential impact of these findings on schizophrenia research.

Dissociation of perceptual and motor inhibition processes through the use of novel computerized conflict tasks.

Efficient behavioral functioning requires early perceptual inhibition of irrelevant stimuli and later motor inhibition of inappropriate responses. The Perceptual and Motor Conflict Tasks were developed to differentially assess perceptual and motor inhibition, and to determine whether these processes utilize separate or shared cognitive resources. The computerized tasks include six subtests involving a box or an arrow appearing in various locations. Subjects respond by pressing a key on the left or right side of a keyboard. In different subtests, arrow direction or stimulus location determines correct responses. Perceptual inhibition assessment requires the subject to respond to a conflicting arrow direction while ignoring stimulus location. Motor inhibition assessment involves the subject responding in the direction opposite to that indicated by a centrally located arrow. In a neurologically normal sample (N = 44), reaction time analyses yielded significant Perceptual and Motor Conflict main effects, with slower performance under conflict conditions, but no significant Perceptual x Motor interaction. The lack of a significant Perceptual x Motor interaction, according to the additive factor model, indicates that these two processes utilize distinct cognitive resources. Nevertheless, performance on the two conflict tasks was significantly correlated with each other, and Perceptual Conflict performance was significantly correlated with Stroop interference.

No evidence for phenotypic variation between probands in case-control versus family-based association studies of schizophrenia.

Traditional case-control genetic association studies utilizing unrelated probands are often used interchangeably with family-based designs to detect genes for complex psychiatric disorders. This strategy may be limited, however, if significant phenotypic variation exists between probands enrolled in these two types of studies. The present study compared 37 probands enrolled in a case-control study of schizophrenia with 37 age-, sex-, and ethnically matched probands enrolled in a family-based study of schizophrenia. Age of onset of illness was compared as well as performance on a battery of cognitive tests assessing attention, working memory, executive function, and verbal memory. Results revealed no significant differences in age of onset between the two groups or on any measure of cognitive performance. These data do not support reports of significant phenotypic variation between probands in case-control and family-based studies, and suggest that studies utilizing family-based approaches may be used to replicate reports of association made with case-control designs in schizophrenia.