Magnetic resonance imaging of the dopamine system in schizophrenia – A scoping review

Abstract

For decades, aberrant dopamine transmission has been proposed to play a central role in schizophrenia pathophysiology. These theories are supported by human in vivo molecular imaging studies of dopamine transmission, particularly positron emission tomography. However, there are several downsides to such approaches, for example limited spatial resolution or restriction of the measurement to synaptic processes of dopaminergic neurons. To overcome these limitations and to measure complementary aspects of dopamine transmission, magnetic resonance imaging (MRI)-based approaches investigating the macrostructure, metabolism, and connectivity of dopaminergic nuclei, i.e., substantia nigra pars compacta and ventral tegmental area, can be employed. In this scoping review, we focus on four dopamine MRI methods that have been employed in patients with schizophrenia so far: neuromelanin MRI, which is thought to measure long-term dopamine function in dopaminergic nuclei; morphometric MRI, which is assumed to measure the volume of dopaminergic nuclei; diffusion MRI, which is assumed to measure fiber-based structural connectivity of dopaminergic nuclei; and resting-state blood-oxygenation-level-dependent functional MRI, which is thought to measure functional connectivity of dopaminergic nuclei based on correlated blood oxygenation fluctuations. For each method, we describe the underlying signal, outcome measures, and downsides. We present the current state of research in schizophrenia and compare it to other disorders with either similar (psychotic) symptoms, i.e., bipolar disorder and major depressive disorder, or dopaminergic abnormalities, i.e., substance use disorder and Parkinson’s disease. Finally, we discuss overarching issues and outline future research questions.

Synergistic, long-term effects of glutamate dehydrogenase 1 deficiency and mild stress on cognitive function and mPFC gene and miRNA expression

“…Our previous studies in mice with a homozygotic deletion of Glud1 in CNS (C-Glud1 -/mice) revealed elevated hippocampal cerebral blood volume (CBV) and glutamate levels in medial PFC (mPFC) and hippocampus, along with baseline and amphetamine-induced hyperlocomotion. These ndings resonate with human schizophrenia data showing decreased Glud1 expression 14 , elevated hippocampal CBV and glutamate/glutamine (Glx) levels 17,18 and a hyperdopaminergic response to amphetamine 19 . C-Glud1 -/mice also show prominent abnormalities in tasks relevant to cognitive impairment in schizophrenia, including working, spatial and social memory tasks and reversal and extra-dimensional set shifting (EDSS) in the Water T-maze 14,20 .…”

Working memory-related activity in catecholaminergic nuclei in schizophrenia

“…Currently, there is a general recognition that catecholaminergic systems play a role in schizophrenia symptomatology (Howes et al, 2023;Os & Kapur, 2009;Abi-Dargham et al, 2000;Perez-Costas et al, 2010;Tost et al, 2010;Chen et al, 2021). This view is supported by post-mortem studies on brainstem nuclei, structural studies using magnetic resonance imaging (MRI), and pharmacological studies (Rice et al, 2016;Howes et al, 2023;Schulz et al, 2022;Weinstein et al, 2017;van Kammen & Kelley, 1991). However, few studies aimed to directly measure activity in catecholaminergic structures in patients in vivo.…”