Inflammatory Markers in Substance Use and Mood Disorders: A Neuroimaging Perspective

Agarwal, Khushbu; Manza, Peter; Chapman, Marquis; Nawal, Nafisa; Biesecker, Erin; McPherson, Katherine; Dennis, Evan; Johnson, Allison M.; Volkow, Nora D.; Joseph, Paule V.

doi:10.3389/fpsyt.2022.863734

Cited by 19 publications

(23 citation statements)

References 181 publications

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“…It is involved in the regulation of inflammatory responses via its interaction with L-selectin (Ivetic et al, 2019). These observations support the notion that METH use disorder might involve the activation of neuroinflammatory cascades in the brain (Sekine et al, 2008;Agarwal et al, 2022), with METH-induced neuroinflammation being responsible, in part, for the learning and memory deficits reported in patients with MUD (Moszczynska and Callan, 2017;Paulus and Stewart, 2020). Neuroinflammation-induced changes in the basic processes that regulate synaptic plasticity (Cornell et al, 2022;Mancini et al, 2022) might also promote the perpetuation of substance use disorders.…”

Section: Discussionsupporting

confidence: 72%

Compulsive methamphetamine self-administration in the presence of adverse consequences is associated with increased hippocampal mRNA expression of cellular adhesion molecules

Munoz

Jayanthi²,

Ladenheim³

et al. 2023

Front. Mol. Neurosci.

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Methamphetamine (METH) is a popular but harmful psychostimulant. METH use disorder (MUD) is characterized by compulsive and continued use despite adverse life consequences. METH users experience impairments in learning and memory functions that are thought to be secondary to METH-induced abnormalities in the hippocampus. Recent studies have reported that about 50% of METH users develop MUD, suggesting that there may be differential molecular effects of METH between the brains of individuals who met criteria for addiction and those who did not after being exposed to the drug. The present study aimed at identifying potential transcriptional differences between compulsive and non-compulsive METH self-administering male rats by measuring global gene expression changes in the hippocampus using RNA sequencing. Herein, we used a model of METH self-administration (SA) accompanied by contingent foot-shock punishment. This approach led to the separation of animals into shock-resistant rats (compulsive) that continued to take METH and shock-sensitive rats (non-compulsive) that suppressed their METH intake in the presence of punished METH taking. Rats were euthanized 2 h after the last METH SA plus foot-shock session. Their hippocampi were immediately removed, frozen, and used later for RNA sequencing and qRT-PCR analyses. RNA sequencing analyses revealed differential expression of mRNAs encoding cell adhesion molecules (CAMs) between the two rat phenotypes. qRT-PCR analyses showed significant higher levels of Cdh1, Glycam1, and Mpzl2 mRNAs in the compulsive rats in comparison to non-compulsive rats. The present results implicate altered CAM expression in the hippocampus in the behavioral manifestations of continuous compulsive METH taking in the presence of adverse consequences. Our results raise the novel possibility that altered CAM expression might play a role in compulsive METH taking and the cognitive impairments observed in MUD patients.

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Section: Discussionsupporting

confidence: 72%

Compulsive methamphetamine self-administration in the presence of adverse consequences is associated with increased hippocampal mRNA expression of cellular adhesion molecules

Munoz

Jayanthi²,

Ladenheim³

et al. 2023

Front. Mol. Neurosci.

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“…During early abstinence, many subjects present a prodrome of cognitive and behavioural changes that are strikingly similar to those of sickness behaviour syndrome due to increased levels of pro-inflammatory cytokines (Dantzer et al ., 2008). Therefore, considering drug abuse from a chronic stress perspective, cytokine-related damage observed in chronic stress, neuroinflammation, and drug abuse may lead to sickness behaviour syndrome-like symptoms and open the door for relapse (Agarwal et al ., 2022). The elevated inflammatory profile may thus influence peripheral leukocytes as well as brain cells involved with changes in behaviour and related symptomatology in CUD.…”

Section: Discussionmentioning

confidence: 99%

Cocaine-use disorder and childhood maltreatment are associated with the activation of neutrophils and increased inflammation

Funchal

Schuch

Zaparte

et al. 2023

Acta Neuropsychiatr.

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Background: Cocaine use disorder (CUD) has been associated with early life adversity and activated cellular immune responses. Women are most vulnerable to complications from chronic substance disorders, generally presenting an intense feeling of abstinence and consuming significant drug amounts. Here, we investigated neutrophil functional activities in CUD, including the formation of Neutrophil Extracellular Traps (NETs) and related intracellular signaling. We also investigated the role of early-life stress in inflammatory profiles. Methods: Blood samples, clinical, data, and history of childhood abuse or neglect were collected at the onset of detoxification treatment of 41 female individuals with CUD and 31 healthy controls (HC). Plasma cytokines, neutrophil phagocytosis, NETs, intracellular ROS generation, and phosphorylated protein kinase B (Akt) and mitogen-activated protein kinases (MAPK)s were assessed by flow cytometry. Results: CUD subjects had higher scores of childhood trauma than controls. Increased plasma cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-12, and IL-10), neutrophil phagocytosis, and production of NETs were reported in CUD subjects as compared with HC. Neutrophils of CUD subjects also produced high levels of intracellular ROS and had more activated Akt and MAPKs (p38/ERK), which are essential signaling pathways involved in cell survival and NETs production. Childhood trauma scores were significantly associated with neutrophil activation and peripheral inflammation. Conclusion: Our study reinforces that smoked cocaine and early life stress activate neutrophils in an inflammatory environment.

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“…Brain atrophy, commonly seen with chronic alcohol consumption, likely results from hyperglutamatergic activity and neuroinflammation 110111. It is important to recognize and inform your patient that functional and structural recovery occurs with abstinence, particularly in the frontal cortex 112113…”

Section: Neurobiology In Alcohol Use Disordersmentioning

confidence: 99%

Advances in the understanding and management of alcohol-related liver disease

Thursz,

Lingford-Hughes

2023

BMJ

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Alcohol-related liver disease (ALD) is a major cause of liver-related morbidity and mortality. Epidemiological trends indicate recent and predicted increases in the burden of disease. Disease progression is driven by continued alcohol exposure on a background of genetic predisposition together with environmental cofactors. Most individuals present with advanced disease despite a long history of excessive alcohol consumption and multiple missed opportunities to intervene. Increasing evidence supports the use of non-invasive tests to screen for and identify disease at earlier stages. There is a definite role for public health measures to reduce the overall burden of disease. At an individual level, however, the ability to influence subsequent disease course by modifying alcohol consumption or the underlying pathogenic mechanisms remains limited due to a comparative lack of effective, disease-modifying medical interventions. Abstinence from alcohol is the key determinant of outcome in established ALD and the cornerstone of clinical management. In those with decompensated ALD, liver transplant has a clear role. There is consensus that abstinence from alcohol for an arbitrary period should not be the sole determinant in a decision to transplant. An increasing understanding of the mechanisms by which alcohol causes liver disease in susceptible individuals offers the prospect of new therapeutic targets for disease-modifying drugs. Successful translation will require significant public and private investment in a disease area which has traditionally been underfunded when compared to its overall prevalence.

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Inflammatory Markers in Substance Use and Mood Disorders: A Neuroimaging Perspective

Cited by 19 publications

References 181 publications

Compulsive methamphetamine self-administration in the presence of adverse consequences is associated with increased hippocampal mRNA expression of cellular adhesion molecules

Compulsive methamphetamine self-administration in the presence of adverse consequences is associated with increased hippocampal mRNA expression of cellular adhesion molecules

Cocaine-use disorder and childhood maltreatment are associated with the activation of neutrophils and increased inflammation

Advances in the understanding and management of alcohol-related liver disease

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