Metabolomics in Psychiatric Disorders: What We Learn from Animal Models

Abstract

Biomarkers are a recent research target within biological factors of psychiatric disorders. There is growing evidence for deriving biomarkers within psychiatric disorders in serum or urine samples in humans, however, few studies have investigated this differentiation in brain or cerebral fluid samples in psychiatric disorders. As brain samples from humans are only available at autopsy, animal models are commonly applied to determine the pathogenesis of psychiatric diseases and to test treatment strategies. The aim of this review is to summarize studies on biomarkers in animal models for psychiatric disorders. For depression, anxiety and addiction disorders studies, biomarkers in animal brains are available. Furthermore, several studies have investigated psychiatric medication, e.g., antipsychotics, antidepressants, or mood stabilizers, in animals. The most notable changes in biomarkers in depressed animal models were related to the glutamate-γ-aminobutyric acid-glutamine-cycle. In anxiety models, alterations in amino acid and energy metabolism (i.e., mitochondrial regulation) were observed. Addicted animals showed several biomarkers according to the induced drugs. In summary, animal models provide some direct insights into the cellular metabolites that are produced during psychiatric processes. In addition, the influence on biomarkers due to short- or long-term medication is a noticeable finding. Further studies should combine representative animal models and human studies on cerebral fluid to improve insight into mental disorders and advance the development of novel treatment strategies.

Metabolomics in Sleep, Insomnia and Sleep Apnea

“…Furthermore, studies conducted on the most relevant sampling substrates for identifying biomarkers of mental disorders, brain tissues, have solely been conducted using animal models as brain-derived samples from humans are commonly only available at autopsy [ 101 ]. Although these animal models are helpful to study causal links between mental disorders and the affected molecular pathways, they face several limitations, as reviewed recently [ 102 ]. A further important limitation is that studies investigating prognostic utility are missing so far.…”

Behavioral and Metabolome Differences between C57BL/6 and DBA/2 Mouse Strains: Implications for Their Use as Models for Depression- and Anxiety-Like Phenotypes

“…Identified metabolite level differences in both specimens were predominantly involved in amino acid and nucleotide metabolism. Amino acid metabolism is a pathway that has been previously reported to be affected in rodent anxiety models [ 12 , 13 ]. Both amino acid and nucleotide metabolism were also affected in the prefrontal cortex of animal models of depression [ 14 ], whereas changes in purine and pyrimidine metabolism were observed in response to antidepressants in mice and patients [ 15 ].…”

Searching for the Needles in a Haystack; Is It Needless? The Search for Peripheral Biomarkers in Psychiatry

“…In addition, the influence on biomarkers due to short-or long-term medication can be observed under controlled conditions. Thus, a combination of representative animal models and human studies are a promising pathway to improve the potential use of biomarkers in psychiatry (5).…”