The neurochemical pathology of schizophrenia: post-mortem studies from dopamine to parvalbumin

Research in Peter Riederer’s lab in Vienna in the late 1970’s came from a strong tradition in post-mortem neurochemical studies, at that time a relatively niche approach in neuroscience research. He was also early to recognise the value of post-mortem brain tissue in elucidating pharmacological mechanisms of neuropsychiatric treatments. I was fortunate to have Peter Riederer as a mentor in my early post-doctoral career; his generous support and the opportunities to use post-mortem brain tissue provided an invaluable grounding on which much of my future research was based. In this paper, I shall provide a brief overview of one trajectory of my research into the neurobiology of schizophrenia that started in the Riederer lab in Vienna investigating dopamine and the D2 receptor. Subsequent research to understand findings of increased dopamine resulted in the identification of reduced GABAergic innervation, culminating in the finding of a deficit in the parvalbumin-containing subtype of GABAergic neurons. Most recent work has been studying how changes in DNA methylation of the parvalbumin gene may relate to these findings in psychotic illness and its animal models.

Neurochemical pathology of dementia

This chapter considers the neurodegenerative disorders Alzheimer’s disease (AD), Lewy body dementias (dementia with Lewy bodies (DLB) and Parkinson’s disease dementia(PDD)), frontotemporal dementia (FTD); and also vascular dementia (VaD) which results from cerebrovascular disease. These different conditions, which give rise to dementia syndromes, each have distinct neurochemical pathologies, with important implications for treatment. As increased age is the common risk factor generally associated with dementing illnesses, neurochemical changes are set in the context of the changes which occur during ageing. A detailed understanding of the neurotransmitter function in each condition can lead to rational drug design and treatment strategies appropriate for each group of patients. Neurochemical pathology in transmitter systems underlying clinical features of these disorders are reviewed.