State-of-the-Art: Inflammatory and Metabolic Markers in Mood Disorders

Mucci, Federico; Marazziti, Donatella; Vecchia, Alessandra Della; Baroni, Stefano; Morana, Paolo; Carpita, Barbara; Mangiapane, Paola; Morana, Florinda; Morana, Benedetto; Dell’Osso, Liliana

doi:10.3390/life10060082

Cited by 13 publications

(20 citation statements)

References 219 publications

(341 reference statements)

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“…According to the most comprehensive hypotheses, MDD results from the interaction between an individual vulnerability and a variety of stressors/triggers entailing anatomic, physiologic and neurochemical modifications [ 91 , 92 , 93 , 94 , 95 , 96 , 97 ]. Besides the classical biomarkers that have been widely described in the past few decades, it is now evident that they are part of a more complex picture involving inflammatory/immune systems dysfunctions [ 98 , 99 , 100 , 101 , 102 ], up to the point that MDD is considered a systemic disease [ 103 , 104 ]. Basically, different intestinal bacteria influence the metabolism of neurotransmitters, by modifying the availability of tryptophan and tyrosine and, consequently, 5-HT and dopamine, respectively [ 105 ].…”

Section: Microbiota and Psychiatric Disordersmentioning

confidence: 99%

The Microbiota/Microbiome and the Gut–Brain Axis: How Much Do They Matter in Psychiatry?

Marazziti

Palermo

Parra

et al. 2021

Life

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The functioning of the central nervous system (CNS) is the result of the constant integration of bidirectional messages between the brain and peripheral organs, together with their connections with the environment. Despite the anatomical separation, gut microbiota, i.e., the microorganisms colonising the gastrointestinal tract, is highly related to the CNS through the so-called “gut–brain axis”. The aim of this paper was to review and comment on the current literature on the role of the intestinal microbiota and the gut–brain axis in some common neuropsychiatric conditions. The recent literature indicates that the gut microbiota may affect brain functions through endocrine and metabolic pathways, antibody production and the enteric network while supporting its possible role in the onset and maintenance of several neuropsychiatric disorders, neurodevelopment and neurodegenerative disorders. Alterations in the gut microbiota composition were observed in mood disorders and autism spectrum disorders and, apparently to a lesser extent, even in obsessive-compulsive disorder (OCD) and related conditions, as well as in schizophrenia. Therefore, gut microbiota might represent an interesting field of research for a better understanding of the pathophysiology of common neuropsychiatric disorders and possibly as a target for the development of innovative treatments that some authors have already labelled “psychobiotics”.

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Section: Microbiota and Psychiatric Disordersmentioning

confidence: 99%

The Microbiota/Microbiome and the Gut–Brain Axis: How Much Do They Matter in Psychiatry?

Marazziti

Palermo

Parra

et al. 2021

Life

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“…IDO induction, a switch toward the TRP-KYN metabolic pathway and the disruption of the equilibrium between neurotoxic and neuroprotective actions all confirm the significance of KYN system activation in depression [92]. Psychological stress elevates brain KYN levels and switches TRP metabolism to the TRP-KYN metabolic pathway [14,93].…”

Section: Kynurenine Aminotransferasesmentioning

confidence: 85%

Immune Influencers in Action: Metabolites and Enzymes of the Tryptophan-Kynurenine Metabolic Pathway

et al. 2021

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The tryptophan (TRP)-kynurenine (KYN) metabolic pathway is a main player of TRP metabolism through which more than 95% of TRP is catabolized. The pathway is activated by acute and chronic immune responses leading to a wide range of illnesses including cancer, immune diseases, neurodegenerative diseases and psychiatric disorders. The presence of positive feedback loops facilitates amplifying the immune responses vice versa. The TRP-KYN pathway synthesizes multifarious metabolites including oxidants, antioxidants, neurotoxins, neuroprotectants and immunomodulators. The immunomodulators are known to facilitate the immune system towards a tolerogenic state, resulting in chronic low-grade inflammation (LGI) that is commonly present in obesity, poor nutrition, exposer to chemicals or allergens, prodromal stage of various illnesses and chronic diseases. KYN, kynurenic acid, xanthurenic acid and cinnabarinic acid are aryl hydrocarbon receptor ligands that serve as immunomodulators. Furthermore, TRP-KYN pathway enzymes are known to be activated by the stress hormone cortisol and inflammatory cytokines, and genotypic variants were observed to contribute to inflammation and thus various diseases. The tryptophan 2,3-dioxygenase, the indoleamine 2,3-dioxygenases and the kynurenine-3-monooxygenase are main enzymes in the pathway. This review article discusses the TRP-KYN pathway with special emphasis on its interaction with the immune system and the tolerogenic shift towards chronic LGI and overviews the major symptoms, pro- and anti-inflammatory cytokines and toxic and protective KYNs to explore the linkage between chronic LGI, KYNs, and major psychiatric disorders, including depressive disorder, bipolar disorder, substance use disorder, post-traumatic stress disorder, schizophrenia and autism spectrum disorder.

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“…The most prominent cytokines associated with mood disorders include: interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and C-reactive protein (CRP) ( 51 ) (see Figure 1C ). Interleukin-6 was shown to be increased in BD patients when unwell.…”

Section: Systemic Inflammation In Bd and Irmentioning

confidence: 99%

“…Interestingly, levels of IL-6 were decreased following 6 weeks of mood stabilizing treatment ( 52 ). Indeed, increased activity of pro-inflammatory cytokines and an imbalance with anti-inflammatory cytokines have been implicated in the development of BD and neuroprogression ( 51 – 53 ) and (see Figure 1C ). Of particular interest, varying cytokine profiles have been identified in distinct mood states of BD, including in mania, depression, euthymia and in healthy controls ( 54 , 55 ).…”

Section: Systemic Inflammation In Bd and Irmentioning

confidence: 99%

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Insulin Resistance and Blood-Brain Barrier Dysfunction Underlie Neuroprogression in Bipolar Disorder

et al. 2021

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Bipolar disorder (BD) often progresses to a more chronic and treatment resistant (neuroprogressive) course. Identifying which patients are at risk could allow for early intervention and prevention. Bipolar disorder is highly comorbid with metabolic disorders including type II diabetes mellitus (T2DM), hypertension, obesity, and dyslipidemia. Our studies have shown that insulin resistance (IR) is present in over 50% of patients with BD and that IR might underlie the progression of BD. While no confirmed predictors exist for identifying which patients with BD are likely to develop a more chronic course, emerging evidence including our own studies suggest that IR and related inflammatory pathways lead to impairments in blood-brain barrier (BBB) functioning. For the first time in living psychiatric patients, we have shown that the severity of BBB leakage is proportional to BD severity and is associated with IR. In this hypothesis paper we (i) highlight the evidence for a key role of IR in BD, (ii) show how IR in BD relates to shared inflammatory pathways, and (iii) hypothesize that these modulations result in BBB leakage and worse outcomes in BD. We further hypothesize that (iv) reversing IR through lifestyle changes or the actions of insulin sensitizing medications such as metformin, or optimizing BBB function using vascular protective drugs, such as losartan, could provide novel strategies for the prevention or treatment of neuroprogressive BD.

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State-of-the-Art: Inflammatory and Metabolic Markers in Mood Disorders

Cited by 13 publications

References 219 publications

The Microbiota/Microbiome and the Gut–Brain Axis: How Much Do They Matter in Psychiatry?

The Microbiota/Microbiome and the Gut–Brain Axis: How Much Do They Matter in Psychiatry?

Immune Influencers in Action: Metabolites and Enzymes of the Tryptophan-Kynurenine Metabolic Pathway

Insulin Resistance and Blood-Brain Barrier Dysfunction Underlie Neuroprogression in Bipolar Disorder

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