Pharmacotherapy of schizophrenia: toward a metabolomic-based approach

Abstract

Approximately 20%-30% of schizophrenia patients are resistant to current standard pharmacotherapies. Recent schizophrenia research aims to identify specific pathophysiological abnormalities and novel targets in the disease, with the goals of identifying at-risk individuals, facilitating diagnosis, prompting early and personalized interventions, and helping predict response to treatment. Metabolomics involves the systematic study of the profile of biochemical alterations early in the course of a given disorder. Major aspects of the schizophrenia metabolome have been characterized, uncovering potential selective biomarkers for the disease that may change how the disorder is diagnosed, and how patients are stratified and treated. This review focuses on the most common metabolomic fingerprints of the different pathways involved in the pathophysiology of schizophrenia, and the potential development of novel metabolomic-related pharmacotherapies for improved treatment of schizophrenia and other related idiopathic psychotic disorders.

Metabolomics approach revealed robust changes in amino acid and biogenic amine signatures in patients with schizophrenia in the early course of the disease

“…Endogenous metabolites, including AAs and BAs, are important in biological systems and are attractive candidates for understanding the disease entity 12 . Furthermore, the metabolomic profile of SCH has been shown to dynamically change with AP treatment 13 . Thus, longitudinal metabolomics profiling techniques are important to understand the disease or effect of the drugs across time and can provide an enhanced understanding of the underlying biology of the disease.…”

Alterations of Astrocytes in the Context of Schizophrenic Dementia

“…The basis of the modified glutamate transmission is increased glutamate excretion in the hippocampus, in which the dysfunction of inhibitory interneurons in the hippocampus and prefrontal cortex also plays a role (Millan et al, 2016). Reduced activation of NMDA on inhibitory interneurons leads to increased release of glutamate by pyramidal hippocampal neurons (Tayeb et al, 2019).…”

“…Tryptophan is elevated in the cerebrospinal fluid of patients with schizophrenia, along with one of its metabolites-kynurenic acid (KYNA) (Linderholm et al, 2012;Kegel et al, 2017;Tayeb et al, 2019). Ninety percent of tryptophan is metabolized in KYNA.…”

Amino acids and acylcarnitines as potential metabolomic markers of schizophrenia: new approaches to diagnostics and therapy

“…Âûÿâëÿåìûå èçìåíåíèÿ â àìèíîêèñëîòíîì ñïåêòðå ñîçäàþò ïðåäïîñûëêè äëÿ ðàçâèòèÿ íîâûõ ïåðñïåêòèâíûõ òåðàïåâòè÷åñêèõ ñòðàòåãèé â ïëàíå ïðèìåíåíèÿ â òåðàïèè ïñèõè÷åñêèõ ðàññòðîéñòâ àìèíîêèñëîò èëè ïðåïàðàòîâ, âîçäåéñòâóþùèõ íà èõ ìåòàáîëèçì [54][55][56][57][58][59][60].…”