Following graduation from the University of Melbourne in Medicine, Prof Velakoulis completed a Diploma of Criminology before successfully completing his Fellowship for the RANZCP and a Masters of Medicine in Psychiatry in neuroimaging. Following this he was appointed an NH&MRC Fellow at the Mental Health Research Institute of Victoria, where he worked in Cognitive Neuropsychiatry and began world-leading research into the volumetric measurement of the hippocampus and other brain regions in schizophrenia, which comprised his Doctorate of Medical Science at the University of Melbourne, and which was published in journals such as The Lancet and high-impact psychiatric journals including Archives of General Psychiatry. He has published over 180 Medline-indexed scientific papers. He continues to be involved in research into first-episode and established schizophrenia, epilepsy, multiple sclerosis, Huntington's disease and early-onset dementia.

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Prof Velakoulis has been the Clinical Director of the Neuropsychiatry Unit, Royal Melbourne Hospital since 2001 and has expertise in the assessment and management of patients with neuropsychiatric disorders. In his private practice, Dr Velakoulis sees patients with neuropsychiatric disorders (either as one off assessments, for ongoing management or for medicolegal assessments).