AbstractsPsychology

Attention-deficit/hyperactivity disorder (ADHD) is an early-onset and highly heritable human psychiatric disorder with negative adult outcomes. ADHD affects about 2 to 5 % of all children, mainly boys. The clinical symptoms are heterogenous with problems of sustained attention, overactivity and impulsiveness, yielding three subtypes of ADHD; the predominantly inattentive (ADHD-PI), the hyperactive-impulsive (ADHD-HI) and the combined (ADHD-C) subtype, the most common subtype and the target of investigations in this study. ADHD is diagnosed by only behavioural criteria, and no biological marker is found although a hypofunctioning catecholamine system is seen. The energy deficiency hypothesis of ADHD proposes an explanation of the ADHD-C symptoms as caused by slowed neuronal firing resulting from a deficiency in the astrocytes producing and releasing the lactate to fuel the neurons. The result is an energy deficiency in the neurons in the brain of the patients. However, the reason for this energy deficiency is not yet known, and this hypothesis is therefore the target of investigation of this study, performed on the animal ADHD-model; SHR/NCrl. Lactate is transported through membranes with a proton-coupled mechanism through monocarboxylate transporters, MCTs. We hypothesized that in ADHD-C, the overactivity of the patients is a compensatory mechanism to be able to introduce more blood lactate to the brain through MCT1, situated in the blood brain barrier, to elevate lactate levels so lactate could be transported into neurons by the neuronal monocarboxylate transporter MCT2. Before birth and under lactation our neurons are fuelled with monocarboxylates such as lactate, and post weaning our brain shifts the preference for monocarboxylates to glucose as the main energy substrate fuelling the brain. In this study we investigated this hypothesis in different brain areas. We found that the lactate transporter MCT1 was upregulated in hilus of DG in the hippocampus, the transporter GLUT1 was upregulated in the prefrontal cortex (although decreased in the other areas), and that the transporter MCT2 was upregulated in stratum lucidum of hippocampus, and downregulated in the striatum, prefrontal cortex and cerebellum. Generally, this is interpreted as that the SHR are having an energy deficiency caused by a prolonged neuronal preference for direct blood lactate fuelling, and not indirect astrocytic lactate import through MCT2. Future studies will reveal if MCT4 is also downregulated, as predicted by this interpretation.