Altered Monoamine and Acylcarnitine Metabolites in HIV-Positive and HIV-Negative Subjects With Depression.

TitleAltered Monoamine and Acylcarnitine Metabolites in HIV-Positive and HIV-Negative Subjects With Depression.
Publication TypeJournal Article
Year of Publication2015
AuthorsCassol, E, Misra, V, Morgello, S, Kirk, GD, Mehta, SH, Gabuzda, D
JournalJ Acquir Immune Defic Syndr
Volume69
Issue1
Pagination18-28
Date Published2015 May 1
ISSN1944-7884
KeywordsAdult, Biogenic Monoamines, Carnitine, Cohort Studies, Depression, Female, HIV Infections, Humans, Male, Metabolome, Middle Aged, Plasma
Abstract

BACKGROUND: Depression is a frequent comorbidity in HIV infection that has been associated with worse treatment outcomes and increased mortality. Recent studies suggest that increased innate immune activation and tryptophan catabolism are associated with higher risk of depression in HIV infection and other chronic inflammatory diseases, but the mechanisms leading to depression remain poorly understood.METHODS: The severity of depressive symptoms was assessed by Beck Depression Inventory or Center for Epidemiological Studies Depression Scale. Untargeted metabolomic profiling of plasma from 104 subjects (68 HIV-positive and 36 HIV-negative) across 3 independent cohorts was performed using liquid or gas chromatography followed by mass spectrometry. Cytokine profiling was by Bioplex array. Bioinformatic analysis was performed in Metaboanalyst and R.RESULTS: Decreased monoamine metabolites (phenylacetate, 4-hydroxyphenylacetate) and acylcarnitines (propionylcarnitine, isobutyrylcarnitine, isovalerylcarnitine, 2-methylbutyrylcarnitine) in plasma distinguished depressed subjects from controls in HIV-positive and HIV-negative cohorts, and these alterations correlated with the severity of depressive symptoms. In HIV-positive subjects, acylcarnitines and other markers of mitochondrial function correlated inversely with tryptophan catabolism, a marker of interferon responses, suggesting interrelationships between inflammatory pathways, tryptophan catabolism, and metabolic alterations associated with depression. Altered metabolites mapped to pathways involved in monoamine metabolism, mitochondrial function, and inflammation, suggesting a model in which complex relationships between monoamine metabolism and mitochondrial bioenergetics contribute to biological mechanisms involved in depression that may be augmented by inflammation during HIV infection.CONCLUSIONS: Integrated approaches targeting inflammation, monoamine metabolism, and mitochondrial pathways may be important for prevention and treatment of depression in people with and without HIV.

DOI10.1097/QAI.0000000000000551
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID25942456
PubMed Central IDPMC4562456
Grant ListDP1 DA028994 / DA / NIDA NIH HHS / United States
K24 AI118591 / AI / NIAID NIH HHS / United States
N01 MH022005 / MH / NIMH NIH HHS / United States
N01 MH032002 / MH / NIMH NIH HHS / United States
N01-MH-22005 / MH / NIMH NIH HHS / United States
N01-MH-32002 / MH / NIMH NIH HHS / United States
P30 AI060354 / AI / NIAID NIH HHS / United States
P30 CA06516 / CA / NCI NIH HHS / United States
R01 DA004334 / DA / NIDA NIH HHS / United States
R01 DA012568 / DA / NIDA NIH HHS / United States
R01 DA030985 / DA / NIDA NIH HHS / United States
R01 MH097659 / MH / NIMH NIH HHS / United States
R01-DA-04334 / DA / NIDA NIH HHS / United States
R01-DA-12568 / DA / NIDA NIH HHS / United States
R01-DA-30985 / DA / NIDA NIH HHS / United States
R01-MH-097659 / MH / NIMH NIH HHS / United States
R24 MH059656 / MH / NIMH NIH HHS / United States
R24 MH059724 / MH / NIMH NIH HHS / United States
R24 MH059745 / MH / NIMH NIH HHS / United States
R24 NS038841 / NS / NINDS NIH HHS / United States
R24 NS045491 / NS / NINDS NIH HHS / United States
R24-MH-59724 / MH / NIMH NIH HHS / United States
R24-MH-59745 / MH / NIMH NIH HHS / United States
R24-NS-38841 / NS / NINDS NIH HHS / United States
R24-NS-45491 / NS / NINDS NIH HHS / United States
U01 DA023832 / DA / NIDA NIH HHS / United States
U01 DA036297 / DA / NIDA NIH HHS / United States
U01 MH083500 / MH / NIMH NIH HHS / United States
U01 MH083501 / MH / NIMH NIH HHS / United States
U01 MH083506 / MH / NIMH NIH HHS / United States
U01 MH083507 / MH / NIMH NIH HHS / United States
U01 MH083545 / MH / NIMH NIH HHS / United States
U01-DA-023832 / DA / NIDA NIH HHS / United States
U01-MH-083500 / MH / NIMH NIH HHS / United States
U01-MH-083501 / MH / NIMH NIH HHS / United States
U01-MH-083506 / MH / NIMH NIH HHS / United States
U01-MH-083507 / MH / NIMH NIH HHS / United States
U01-MH-083545 / MH / NIMH NIH HHS / United States
U24 MH100928 / MH / NIMH NIH HHS / United States
U24 MH100931 / MH / NIMH NIH HHS / United States