Magnetic resonance (MR) imaging studies have identified hippocampal structural alterations in the pathogenesis of schizophrenia. Brain-derived neurotrophic factor (BDNF) is one of the neurotrophins that is widely expressed in the hippocampal formation and has been implicated in the neurobiology of schizophrenia. Polymorphisms in the BDNF gene may therefore confer risk for schizophrenia through hippocampal pathogenesis and/or making the hippocampus more susceptible to environmental insults. In this study, we investigated whether val66met, a functional and abundant missense polymorphism in the coding region of the BDNF gene, was associated with the volume of the hippocampal formation in 19 patients with first-episode schizophrenia and 25 healthy volunteers. A total of 124 contiguous T1-weighted coronal MR images (slice thickness ¼ 1.5 mm) were acquired through the whole head using a 3D Fast SPGR IR Prep sequence on a 1.5 T GE imaging system. Volumes of the right and left hippocampal formation were measured manually by an operator blind to group status and genotype. All participants were genotyped for the BDNF val66met locus. Mixed model analyses revealed a main effect of BDNF val66met genotype such that in the combined sample of patients and healthy volunteers, val/val homozygotes (N ¼ 27) had larger volumes of the hippocampal formation compared to val/met heterozygotes (N ¼ 17). In separate analyses by group, however, val66met genotype accounted for a greater proportion of the variance in the volume of the hippocampal formation in patients compared to healthy volunteers. These findings implicate genetic involvement of BDNF in variation of human hippocampal volume and suggest that this effect may be greater among patients compared to healthy volunteers. Molecular Psychiatry (2005) 10, 631-636.

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The effect of focal 5 Hz repetitive transcranial magnetic stimulation (rTMS) of the motor hand area (M1) on bradykinesia was studied in 12 unmedicated patients with Parkinson's disease (PD). On 2 separate days, a real-rTMS was applied to M1 contralaterally to the more severely affected limb or a frontal sham-rTMS was applied 3 cm anteriorly to Fz in a random order. Stimulus intensity was 10% below resting motor threshold. Before and 20 min after rTMS, patients performed 15 consecutive pointing movements with the index finger contralaterally to the stimulated M1. Compared with sham-rTMS, real-rTMS over the contralateral M1 caused a significant decrease in total movement time without affecting end-point accuracy. Our data provide evidence that 5 Hz rTMS over M1 can improve bradykinesia in PD patients beyond the time of magnetic stimulation.

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