Multiple memory systems are involved in parallel processing of spatial information during navigation. A series of studies have distinguished between hippocampus-dependent ‘spatial’ navigation, which relies on knowledge of the relationship between landmarks in one’s environment to build a cognitive map, and habit-based ‘response’ learning, which requires the memorization of a series of actions and is mediated by the caudate nucleus. Studies have demonstrated that people spontaneously use one of these two alternative navigational strategies with almost equal frequency to solve a given navigation task, and that strategy correlates with functional magnetic resonance imaging (fMRI) activity and grey matter density. Although there is evidence for experience modulating grey matter in the hippocampus, genetic contributions may also play an important role in the hippocampus and caudate nucleus. Recently, the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene has emerged as a possible inhibitor of hippocampal function. We have investigated the role of the BDNF Val66Met polymorphism on virtual navigation behaviour and brain activation during an fMRI navigation task. Our results demonstrate a genetic contribution to spontaneous strategies, where ‘Met’ carriers use a response strategy more frequently than individuals homozygous for the ‘Val’ allele. Additionally, we found increased hippocampal activation in the Val group relative to the Met group during performance of a virtual navigation task. Our results support the idea that the BDNF gene with the Val66Met polymorphism is a novel candidate gene involved in determining spontaneous strategies during navigation behaviour.

BackgroundThe desired (therapeutic) and undesired (side) effects of methylphenidate might have underlying correlations. The aim of this study was to explore the strength and the possible sources of these correlations.MethodsOne hundred and fifty-seven children with ADHD (6-12 years) were administered placebo and methylphenidate (0.5 mg/kg in a divided b.i.d. dose), each for a one-week period, in a double-blind, crossover trial. Therapeutic response was assessed using the Conners' Global Index for parents (CGI-Parents) and teachers (CGI-Teachers), while side effects were assessed using the Barkley Side Effects Rating Scale (SERS).ResultsThe side effect profile as assessed by the SERS was similar to that of previous studies with insomnia, decreased appetite, and headaches showing significant treatment effects (p < 0.005). These "somatic/physical" side effects did not correlate with CGI-Parents or CGI-Teachers. However, the side effects of "irritability", "proneness to crying", and "anxiousness" showed significant relationships with CGI-Parents. These "mood/anxiety" side effects showed no significant correlations with the CGI-Teachers.ConclusionThe greater "mood/anxiety" side effects on methylphenidate and placebo, the less the parents observe improvement of their children while treated with methylphenidate. This suggests that the correlations between "mood/anxiety" side effects and poor response to treatment may be driven by observer effects rather than biological commonalities between therapeutic and side effects of methylphenidate.

Objective: The aim of this study was to examine the relation between therapeutic response to methylphenidate (MPH) and its associated short term cardiovascular side effects (Systolic Blood Pressure-SBP, Diastolic Blood Pressure-DBP and Heart Rate-HR changes) in children with ADHD, based on the hypothesis that these parameters share common underlying mechanisms.Method: A double-blind placebo-controlled crossover clinical trial of children 6 to 12 years old diagnosed with ADHD was done. The children were given one week of 0.5 mg/kg MPH and one week of placebo (divided into two equal doses, given twice every day). On the morning of the third day of each week, Blood Pressure (BP) and HR were recorded immediately before (at time 0) and after (at time 10 and 45 minutes ) administration of MPH. Children were grouped into 4 categories according to their therapeutic response (large, moderate, mild or no response) to MPH. A mixed model analysis of variance was performed to determine whether response groups were different with regard to cardiovascular side effects.Results: All variables were comparable among the four groups 10 min after treatment with MPH and with placebo. Small but signifi cant (p Ͻ 0.001) increases were seen in SBP (3.65 mm of Hg) and DBP (3.99 mm of Hg) 45 minutes after administration of MPH. A small but signifi cant decrease in HR (3.3 beats per minute) was observed 45 min after administration of placebo. No signifi cant differences in SBP, DBP and HR were found between response groups.Conclusions: MPH causes a small but signifi cant change in BP at 45 minutes after administration. No changes in HR were observed with MPH at 45 minutes. Responders to MPH treatment do not differ from non-responders in occurrence of BP and HR changes, at least within 45 minutes after administration and with the MPH dosage used in the study.