Exploring cellular markers of metabolic syndrome in peripheral blood mononuclear cells across the neuropsychiatric spectrum

Lago, Santiago G.; Tomasik, Jakub; Rees, Geertje F. van; Rubey, Marina; Ramsey, Jordan M.; Haenisch, F.; Broek, Jantine A.C.; Vázquez-Bourgon, Javier; Papiol, Sergi; Suárez-Pinilla, Paula; Ruland, Tillmann; Auyeug, Bonnie; Mikova, Olya; Kabacs, Nikolett; Arolt, Volker; Baron‐Cohen, Simon; Crespo‐Facorro, Benedicto; Bahn, Sabine

doi:10.1016/j.bbi.2020.07.043

Cited by 17 publications

(14 citation statements)

References 108 publications

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“…However, previous studies have suggested that individuals with psychosis may be at greater risk of presenting abnormal glucose metabolism even before the onset of psychosis [ 31 , 32 ]. This probable inherent risk could be due to genetic differences; thus, it has been described an association between insulin resistance and polygenic risk score in antipsychotic naive patients [ 33 ] and other biomarkers [ 34 ], and insulin resistance in unaffected siblings of psychosis patients [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Pattern of long-term weight and metabolic changes after a first episode of psychosis: Results from a 10-year prospective follow-up of the PAFIP program for early intervention in psychosis cohort

et al. 2022

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Section: Discussionmentioning

confidence: 99%

Pattern of long-term weight and metabolic changes after a first episode of psychosis: Results from a 10-year prospective follow-up of the PAFIP program for early intervention in psychosis cohort

et al. 2022

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“…An interesting connection between possible immune system dysregulation and the metabolic dysregulation that is frequently observed in schizophrenia patients was discovered by researchers when they observed that schizophrenia patient peripheral monocytes have alterations in insulin receptor expression. This could potentially indicate that in some patients, insulin signaling may be involved in peripheral immune dysregulation (Lago et al, 2021).…”

Section: Peripheral Immune Activation In Schizophrenia Patientsmentioning

confidence: 99%

Schizophrenia Hypothesis: Autonomic Nervous System Dysregulation of Fetal and Adult Immune Tolerance

Carnac¹

2022

Front. Syst. Neurosci.

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The autonomic nervous system can control immune cell activation via both sympathetic adrenergic and parasympathetic cholinergic nerve release of norepinephrine and acetylcholine. The hypothesis put forward in this paper suggests that autonomic nervous system dysfunction leads to dysregulation of immune tolerance mechanisms in brain-resident and peripheral immune cells leading to excessive production of pro-inflammatory cytokines such as Tumor Necrosis Factor alpha (TNF-α). Inactivation of Glycogen Synthase Kinase-3β (GSK3β) is a process that takes place in macrophages and microglia when a toll-like receptor 4 (TLR4) ligand binds to the TLR4 receptor. When Damage-Associated Molecular Patterns (DAMPS) and Pathogen-Associated Molecular Patterns (PAMPS) bind to TLR4s, the phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt) pathway should be activated, leading to inactivation of GSK3β. This switches the macrophage from producing pro-inflammatory cytokines to anti-inflammatory cytokines. Acetylcholine activation of the α7 subunit of the nicotinic acetylcholine receptor (α7 nAChR) on the cell surface of immune cells leads to PI3K/Akt pathway activation and can control immune cell polarization. Dysregulation of this pathway due to dysfunction of the prenatal autonomic nervous system could lead to impaired fetal immune tolerance mechanisms and a greater vulnerability to Maternal Immune Activation (MIA) resulting in neurodevelopmental abnormalities. It could also lead to the adult schizophrenia patient’s immune system being more vulnerable to chronic stress-induced DAMP release. If a schizophrenia patient experiences chronic stress, an increased production of pro-inflammatory cytokines such as TNF-α could cause significant damage. TNF-α could increase the permeability of the intestinal and blood brain barrier, resulting in lipopolysaccharide (LPS) and TNF-α translocation to the brain and consequent increases in glutamate release. MIA has been found to reduce Glutamic Acid Decarboxylase mRNA expression, resulting in reduced Gamma-aminobutyric acid (GABA) synthesis, which combined with an increase of glutamate release could result in an imbalance of glutamate and GABA neurotransmitters. Schizophrenia could be a “two-hit” illness comprised of a genetic “hit” of autonomic nervous system dysfunction and an environmental hit of MIA. This combination of factors could lead to neurotransmitter imbalance and the development of psychotic symptoms.

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“…A high prevalence of obesity and obesity-related disorders (type 2 diabetes mellitus, hypertension, hyperlipidemia, and non- alcoholic fatty liver disease/nonalcoholic steatohepatitis) have been reported in children [ 202 ], which might in many instances be iatrogenic, although the use of psychotropic drugs is probably not the only explanation for these abnormalities. In fact, recent evidence suggests that metabolic syndrome may precede and even exacerbate long-term side-effects of psychiatric medications [ 203 ]. Other prevailing comorbidities are allergies and gastrointestinal (GI) diseases, which are predictable, given the wide array of immune imbalances and the intestinal dysbiosis described in ASD [ 13 , 204 ].…”

Section: Much More Than Behavioral Abnormalities In People With Asdmentioning

confidence: 99%

Dynamic and Systemic Perspective in Autism Spectrum Disorders: A Change of Gaze in Research Opens to A New Landscape of Needs and Solutions

Panisi¹,

Marini

2022

Brain Sciences

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The first step for a harmonious bio-psycho-social framework in approaching autism spectrum disorders (ASD) is overcoming the conflict between the biological and the psychosocial perspective. Biological research can provide clues for a correct approach to clinical practice, assuming that it would lead to the conceptualization of a pathogenetic paradigm able to account for epidemiologic and clinical findings. The upward trajectory in ASD prevalence and the systemic involvement of other organs besides the brain suggest that the epigenetic paradigm is the most plausible one. The embryo-fetal period is the crucial window of opportunity for keeping neurodevelopment on the right tracks, suggesting that women’s health in pregnancy should be a priority. Maladaptive molecular pathways beginning in utero, in particular, a vicious circle between the immune response, oxidative stress/mitochondrial dysfunction, and dysbiosis-impact neurodevelopment and brain functioning across the lifespan and are the basis for progressive multisystemic disorders that account for the substantial health loss and the increased mortality in ASD. Therefore, the biological complexity of ASD and its implications for health requires the enhancement of clinical skills on these topics, to achieve an effective multi-disciplinary healthcare model. Well-balanced training courses could be a promising starting point to make a change.

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Exploring cellular markers of metabolic syndrome in peripheral blood mononuclear cells across the neuropsychiatric spectrum

Cited by 17 publications

References 108 publications

Pattern of long-term weight and metabolic changes after a first episode of psychosis: Results from a 10-year prospective follow-up of the PAFIP program for early intervention in psychosis cohort

Pattern of long-term weight and metabolic changes after a first episode of psychosis: Results from a 10-year prospective follow-up of the PAFIP program for early intervention in psychosis cohort

Schizophrenia Hypothesis: Autonomic Nervous System Dysregulation of Fetal and Adult Immune Tolerance

Dynamic and Systemic Perspective in Autism Spectrum Disorders: A Change of Gaze in Research Opens to A New Landscape of Needs and Solutions

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