Pharmaco-Magnetic Resonance as a Tool for Monitoring the Medication-Related Effects in the Brain May Provide Potential Biomarkers for Psychotic Disorders

Abstract

The neurodegenerative and neurodevelopmental hypotheses represent the basic etiological framework for the origin of schizophrenia. Additionally, the dopamine hypothesis, adopted more than two decades ago, has repeatedly asserted the position of dopamine as a pathobiochemical substrate through the action of psychostimulants and neuroleptics on the mesolimbic and mesocortical systems, giving insight into the origin of positive and negative schizophrenic symptoms. Meanwhile, cognitive impairments in schizophrenia remain incompletely understood but are thought to be present during all stages of the disease, as well as in the prodromal, interictal and residual phases. On the other hand, observations on the effects of NMDA antagonists, such as ketamine and phencyclidine, reveal that hypoglutamatergic neurotransmission causes not only positive and negative but also cognitive schizophrenic symptoms. This review aims to summarize the different hypotheses about the origin of psychoses and to identify the optimal neuroimaging method that can serve to unite them in an integral etiological framework. We systematically searched Google scholar (with no concern to the date published) to identify studies investigating the etiology of schizophrenia, with a focus on impaired central neurotransmission. The complex interaction between the dopamine and glutamate neurotransmitter systems provides the long-needed etiological concept, which combines the neurodegenerative hypothesis with the hypothesis of impaired neurodevelopment in schizophrenia. Pharmaco-magnetic resonance imaging is a neuroimaging method that can provide a translation of scientific knowledge about the neural networks and the disruptions in and between different brain regions, into clinically applicable and effective therapeutic results in the management of severe psychotic disorders.

Keywords: brain connectivity; cognitive symptoms; dopamine; glutamate; neurotransmission; pharmacological magnetic resonance imaging; psychosis; schizophrenia.

Figure 1

The dopamine hypothesis for schizophrenia.

Figure 2

Dopamine pathways’ regulation by the glutamate pathways (green—dopaminergic; yellow—glutamatergic; blue—GABA-ergic): (a) Descending glutamatergic pathway connect to the dopaminergic mesolimbic system via a GABA interneuron between them. In the case of disruption, psychotic symptoms emerge; (b) The descending glutamatergic pathway exhibits excitatory influence on the mesocortical dopamine pathway, and, in the case of disruption, cognitive deficits emerge.

Figure 3

“Triple network”: (a) Default mode network; (b) Salience network; (c) Central executive network. AG—Angular gyrus; mPFC—medial prefrontal cortex; PCC—Posterior cingulate cortex; AI—Anterior insula; ACC—Anterior cingulate cortex; DLPFC—Dorsolateral prefrontal cortex; PPC—Posterior parietal cortex.

Figure 4

Integral etiological model of schizophrenia.

Figure 5

Resting-state aberrant connectivity and task-related abnormal activations that are observed in schizophrenic patients. AG—Angular gyrus; mPFC—Medial prefrontal cortex; PCC—Posterior cingulate cortex; AI—Anterior insula; ACC—Anterior cingulate cortex; DLPFC—Dorsolateral prefrontal cortex; PPC—Posterior parietal cortex.