Acta Neuropsychiatrica最新文献

{"title":"Polymorphisms in ERBB4 and TACR1 associated with dry mouth in clozapine-treated patients","authors":"Hanna Puolakka, Anssi Solismaa, Leo-Pekka Lyytikäinen, Merja Viikki, Niko Seppälä, Nina Mononen, Terho Lehtimäki, Olli Kampman","doi":"10.1017/neu.2024.9","DOIUrl":"https://doi.org/10.1017/neu.2024.9","url":null,"abstract":"Objective: Sialorrhea is a common and uncomfortable adverse effect of clozapine, and its severity varies between patients. The aim of the study was to select broadly genes related to the regulation of salivation and study associations between sialorrhea and dry mouth and polymorphisms in the selected genes. Methods: The study population consists of 237 clozapine-treated patients, of which 172 were genotyped. Associations between sialorrhea and dry mouth with age, sex, BMI, smoking, clozapine dose, clozapine and norclozapine serum levels, and other comedication were studied. Genetic associations were analyzed with linear and logistic regression models explaining sialorrhea and dry mouth with each SNP added separately to the model as coefficients. Results: Clozapine dose, clozapine or norclozapine concentration and their ratio were not associated with sialorrhea or dryness of mouth. Valproate use (p=0.013) and use of other antipsychotics (p=0.015) combined with clozapine were associated with excessive salivation. No associations were found between studied polymorphisms and sialorrhea. In analyses explaining dry mouth with logistic regression with age and sex as coefficients, two proxy-SNPs were associated with dry mouth: <jats:italic>epidermal growth factor receptor 4</jats:italic> (<jats:italic>ERBB4</jats:italic>) rs3942465 (adjusted p=0.025) <jats:italic>and tachykinin receptor 1 (TACR1)</jats:italic> rs58933792 (adjusted p=0.029). Conclusion: Use of valproate or antipsychotic polypharmacy may increase the risk of sialorrhea. Genetic variations in <jats:italic>ERBB4</jats:italic> and <jats:italic>TACR1</jats:italic> might contribute to experienced dryness of mouth among patients treated with clozapine.","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":"6 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140626144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Cortical Thickness or Surface Area and Divergent Thinking in Patients with Bipolar Disorder","authors":"Pei-Chi Tu, Wan-Chen Chang, Yi-Hsuan Kuan, Mu-Hong Chen, Tung-Ping Su","doi":"10.1017/neu.2024.17","DOIUrl":"https://doi.org/10.1017/neu.2024.17","url":null,"abstract":"Objective: Divergent thinking is a critical creative cognitive process. Its neural mechanisms have been well-studied through structural and functional imaging in healthy individuals but are less explored in patients with bipolar disorder (BD). Because of the traditional link between creativity and BD, this study investigated the structural correlates of divergent thinking in patients with BD through surface-based morphometry. Methods: Fifty-nine patients diagnosed with BD I or BD II (35.3 ± 8.5 years) and 56 age- and sex-matched controls (33.9 ± 7.4 years) were recruited. The participants underwent structural magnetic resonance imaging and an evaluation of divergent thinking by using the Chinese version of the Abbreviated Torrance Test for Adults (ATTA). FreeSurfer 7.0 was used to generate thickness and surface area maps for each participant. Brainwise regression of the association between cortical thickness or surface area and ATTA performance was conducted using general linear models. Results: Divergent thinking performance did not differ significantly between the patients with BD and the healthy controls. In these patients, total ATTA score was negatively correlated with cortical thickness in the right middle frontal gyrus, right occipital, and left precuneus but positively correlated with the surface area of the right superior frontal gyrus. By contrast, total ATTA scores and cortical thickness or surface area were not significantly correlated among the controls. Conclusion: The findings indicate that divergent thinking involves cerebral structures for executive control, mental imagery, and visual processing in patients with BD, and the right prefrontal cortex might be the most crucial of these structures.","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":"56 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140614457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Elevated Body Mass Index (BMI) on Cognitive Functioning and Inflammation in Persons with Post-COVID-19 Condition: A Secondary Analysis","authors":"Gia Han Le, Angela T.H. Kwan, Ziji Guo, Sabrina Wong, Sebastian Badulescu, Hartej Gill, Kayla M. Teopiz, Shakila Meshkat, Felicia Ceban, Lee Phan, Mehala Subramaniapillai, Joshua D. Di Vincenzo, Joshua D. Rosenblat, Rodrigo B. Mansur, Giacomo d’Andrea, Roger Ho, Taeho Greg Rhee, Roger S. McIntyre","doi":"10.1017/neu.2024.16","DOIUrl":"https://doi.org/10.1017/neu.2024.16","url":null,"abstract":"<jats:underline>ABSTRACT</jats:underline> Background: Individuals who have recovered from the acute stage of SARS-CoV-2 infection may be at risk of developing post-COVID-19 condition (PCC), characterized by a spectrum of persisting, non-specific, and functionally impairing symptoms across multiple organ systems. Obesity has been implicated as a risk factor for PCC, mediated by chronic systemic inflammation. The foregoing has also been separately reported to mediate cognitive dysfunction in PCC. Methods: This is a post-hoc analysis of a randomized, double-blinded, placebo-controlled clinical trial evaluating vortioxetine treatment for cognitive impairments in persons with PCC who received vortioxetine or placebo for eight weeks. This analysis comprises baseline data, examining the impacts of BMI on cognitive functioning measured by the Digit Symbol Substitution Test (DSST) and Trails Making Tests (TMT)-A/B, as well as inflammation, via serum c-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Results: Complete data from 70 participants were statistically analyzed and adjusted for age and sex. BMI is negatively correlated with performance on the DSST (β=-0.003, <jats:italic>p</jats:italic>=0.047), TMT-A (β=-0.006, <jats:italic>p</jats:italic>=0.025), and TMT-B (β=-0.006, <jats:italic>p</jats:italic>=0.002). BMI is positively correlated with serum CRP (unstandardized β=0.193, standardized β=0.612, <jats:italic>p</jats:italic>&lt;0.001) and ESR (β=0.039, <jats:italic>p</jats:italic>&lt;0.001) levels. Conclusion: We observed a significant negative correlation between BMI and cognitive functioning, and a significant positive correlation between BMI and inflammation in persons with PCC, suggesting a bidirectional interplay between BMI, PCC, and cognitive function; individuals with an elevated BMI may be at a greater risk of developing PCC and/or presenting with greater cognitive deficits mediated by chronic systemic inflammation.","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":"19 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140568903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reactivation of herpesvirus type 6 and IgA/IgM-mediated responses to activin-A underpin long COVID, including affective symptoms and chronic fatigue syndrome","authors":"Aristo Vojdani, Abbas F. Almulla, Bo Zhou, Hussein K. Al-Hakeim, Michael Maes","doi":"10.1017/neu.2024.10","DOIUrl":"https://doi.org/10.1017/neu.2024.10","url":null,"abstract":"Background: Persistent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), reactivation of dormant viruses, and immune-oxidative responses are involved in long COVID. Objectives: To investigate whether long COVID and depressive, anxiety, and chronic fatigue syndrome (CFS) symptoms are associated with IgA/IgM/IgG to SARS-CoV-2, human herpesvirus type 6 (HHV-6), Epstein-Barr Virus (EBV), and immune-oxidative biomarkers. Methods: We examined 90 long COVID patients and ninety healthy controls. We measured serum IgA/IgM/IgG against HHV-6 and EBV and their deoxyuridine 5′-triphosphate nucleotidohydrolase (duTPase), SARS-CoV-2, and activin-A, C-reactive protein (CRP), advanced oxidation protein products (AOPP), and insulin resistance (HOMA2-IR). Results: Long COVID patients showed significant elevations in IgG/IgM-SARS-CoV-2, IgG/IgM-HHV-6, and HHV-6-duTPase, IgA/IgM-activin-A, CRP, AOPP, and HOMA2-IR. Neural network analysis yielded a highly significant predictive accuracy of 80.6% for the long COVID diagnosis (sensitivity: 78.9%, specificity: 81.8%, area under the ROC curve = 0.876); the topmost predictors were as follows: IGA-activin-A, IgG-HHV-6, IgM-HHV-6-duTPase, IgG-SARS-CoV-2, and IgM-HHV-6 (all positively) and a factor extracted from all IgA levels to all viral antigens (inversely). The top 5 predictors of affective symptoms due to long COVID were IgM-HHV-6-duTPase, IgG-HHV-6, CRP, education, IgA-activin-A (predictive accuracy of <jats:italic>r</jats:italic> = 0.636). The top 5 predictors of CFS due to long COVID were in descending order: CRP, IgG-HHV-6-duTPase, IgM-activin-A, IgM-SARS-CoV-2, and IgA-activin-A (predictive accuracy: <jats:italic>r</jats:italic> = 0.709). Conclusion: Reactivation of HHV-6, SARS-CoV-2 persistence, and autoimmune reactions to activin-A combined with activated immune-oxidative pathways play a major role in the pathophysiology of long COVID as well as the severity of its affective symptoms and CFS.","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":"50 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140568901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles of cannabinoid CB1 and CB2 receptors in the modulation of psychostimulant responses.","authors":"P H Gobira, S R Joca, F A Moreira","doi":"10.1017/neu.2022.23","DOIUrl":"10.1017/neu.2022.23","url":null,"abstract":"<p><p>Addiction to psychostimulant drugs, such as cocaine, D-amphetamine, and methamphetamine, is a public health issue that substantially contributes to the global burden of disease. Psychostimulant drugs promote an increase in dopamine levels within the mesocorticolimbic system, which is central to the rewarding properties of such drugs. Cannabinoid receptors (CB₁R and CB₂R) are expressed in the main areas of this system and implicated in the neuronal mechanisms underlying the rewarding effect of psychostimulant drugs. Here, we reviewed studies focusing on pharmacological intervention targeting cannabinoid CB₁R and CB₂R and their interaction in the modulation of psychostimulant responses.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":" ","pages":"67-77"},"PeriodicalIF":3.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40716172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between community-level patterns of prenatal alcohol and tobacco exposure on brain structure in a non-clinical sample of 6-year-old children: a South African pilot study.","authors":"Kristina A Uban, Deborah Jonker, Kirsten A Donald, Stefanie C Bodison, Samantha J Brooks, Eric Kan, Babette Steigelmann, Annerine Roos, Andrew Marshall, Shana Adise, Letitia Butler-Kruger, Brigitte Melly, Katherine L Narr, Shantanu H Joshi, Hein J Odendaal, Elizabeth R Sowell, Dan J Stein","doi":"10.1017/neu.2022.34","DOIUrl":"10.1017/neu.2022.34","url":null,"abstract":"<p><p>The current small study utilised prospective data collection of patterns of prenatal alcohol and tobacco exposure (PAE and PTE) to examine associations with structural brain outcomes in 6-year-olds and served as a pilot to determine the value of prospective data describing community-level patterns of PAE and PTE in a non-clinical sample of children. Participants from the Safe Passage Study in pregnancy were approached when their child was ∼6 years old and completed structural brain magnetic resonance imaging to examine with archived PAE and PTE data (<i>n</i> = 51 children-mother dyads). Linear regression was used to conduct whole-brain structural analyses, with false-discovery rate (FDR) correction, to examine: (a) main effects of PAE, PTE and their interaction; and (b) predictive potential of data that reflect <i>patterns</i> of PAE and PTE (e.g. quantity, frequency and timing (QFT)). Associations between PAE, PTE and their interaction with brain structural measures demonstrated unique profiles of cortical and subcortical alterations that were distinct between PAE only, PTE only and their interactive effects. Analyses examining associations between patterns of PAE and PTE (e.g. QFT) were able to significantly detect brain alterations (that survived FDR correction) in this small non-clinical sample of children. These findings support the hypothesis that considering QFT and co-exposures is important for identifying brain alterations following PAE and/or PTE in a small group of young children. Current results demonstrate that teratogenic outcomes on brain structure differ as a function PAE, PTE or their co-exposures, as well as the pattern (QFT) or exposure.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":" ","pages":"87-96"},"PeriodicalIF":3.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10368794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9869721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A single dose of cocaine raises SV2A density in hippocampus of adolescent rats.","authors":"Rachele Rossi, Simone Larsen Bærentzen, Majken B Thomsen, Caroline C Real, Gregers Wegener, Rodrigo Grassi-Oliveira, Albert Gjedde, Anne M Landau","doi":"10.1017/neu.2023.14","DOIUrl":"10.1017/neu.2023.14","url":null,"abstract":"<p><strong>Objective: </strong>Cocaine is a highly addictive psychostimulant that affects synaptic activity with structural and functional adaptations of neurons. The transmembrane synaptic vesicle glycoprotein 2A (SV2A) of pre-synaptic vesicles is commonly used to measure synaptic density, as a novel approach to the detection of synaptic changes. We do not know if a single dose of cocaine suffices to affect pre-synaptic SV2A density, especially during adolescence when synapses undergo intense maturation. Here, we explored potential changes of pre-synaptic SV2A density in target brain areas associated with the cocaine-induced boost of dopaminergic neurotransmission, specifically testing if the effects would last after the return of dopamine levels to baseline.</p><p><strong>Methods: </strong>We administered cocaine (20 mg/kg i.p.) or saline to rats in early adolescence, tested their activity levels and removed the brains 1 hour and 7 days after injection. To evaluate immediate and lasting effects, we did autoradiography with [³H]UCB-J, a specific tracer for SV2A, in medial prefrontal cortex, striatum, nucleus accumbens, amygdala, and dorsal and ventral areas of hippocampus. We also measured the striatal binding of [³H]GBR-12935 to test cocaine's occupancy of the dopamine transporter at both times of study.</p><p><strong>Results: </strong>We found a significant increase of [³H]UCB-J binding in the dorsal and ventral sections of hippocampus 7 days after the cocaine administration compared to saline-injected rats, but no differences 1 hour after the injection. The [³H]GBR-12935 binding remained unchanged at both times.</p><p><strong>Conclusion: </strong>Cocaine provoked lasting changes of hippocampal synaptic SV2A density after a single exposure during adolescence.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":" ","pages":"109-117"},"PeriodicalIF":3.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9159281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cingulate cortical thickness in cocaine use disorder: mediation effect between early life stress and cocaine consumption.","authors":"Augusto Martins Lucas Bittencourt, Bárbara Luiza Belmonte da Silveira, Lucca Pizzato Tondo, Leonardo Melo Rothmann, Alexandre Rosa Franco, Pedro Eugenio Mazzucchi Santana Ferreira, Thiago Wendt Viola, Rodrigo Grassi-Oliveira","doi":"10.1017/neu.2022.33","DOIUrl":"10.1017/neu.2022.33","url":null,"abstract":"<p><strong>Objective: </strong>The cingulate gyrus is implicated in the neurobiology of addiction, such as chronic cocaine consumption. Early life stress (ELS) is an important moderator of cocaine use disorder (CUD). Therefore, we investigated the effect of CUD on cingulate cortical thickness and tested whether a history of ELS could influence the effects of CUD.</p><p><strong>Methods: </strong>Participants aged 18-50 years (78 with CUD due to crack cocaine consumption and 53 healthy controls) underwent magnetic resonance imaging and the cingulate thickness (rostral anterior, caudal anterior, posterior, and isthmus regions) was analysed. The clinical assessment comprised the Childhood Trauma Questionnaire (CTQ) and the Addiction Severity Index. Group comparisons adjusting by sex, age, and education were performed. Mediation models were generated where lifetime cocaine use, CTQ score, and cortical thickness corresponded to the independent variable, intermediary variable, and outcome, respectively.</p><p><strong>Results: </strong>Group comparisons revealed significant differences in six out of eight cingulate cortices, showing lower thickness in the CUD group. Furthermore, years of regular cocaine use was the variable most associated with cingulate thickness. Negative correlations were found between CTQ scores and the isthmus cingulate (right hemisphere), as well as with the rostral anterior cingulate (left hemisphere). In the mediation analysis, we observed a significant negative direct effect of lifetime cocaine use on the isthmus cingulate and an indirect effect of cocaine use mediated by CTQ score.</p><p><strong>Conclusion: </strong>Our findings suggest that a history of ELS could aggravate the negative effects of chronic cocaine use on the cingulate gyrus, particularly in the right isthmus cingulate cortex.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":" ","pages":"78-86"},"PeriodicalIF":3.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10203054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9505949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased markers of inflammation after cannabis cessation and their association with psychotic symptoms.","authors":"Bruno Romeo, Valentine Lestra, Catherine Martelli, Ammar Amirouche, Amine Benyamina, Nora Hamdani","doi":"10.1017/neu.2023.24","DOIUrl":"10.1017/neu.2023.24","url":null,"abstract":"<p><strong>Introduction: </strong>A dysbalance of the immune system in psychotic disorders has been well investigated. However, despite a higher prevalence of cannabis (THC) consumption in patients with psychosis, few studies have investigated the impact of this use on inflammatory markers.</p><p><strong>Methods: </strong>One hundred and two inpatients were included in this retrospective study. Leukocytic formula, hsCRP, fibrinogen levels and urinary THC were measured, and comparisons were performed at baseline and after 4 weeks of cannabis cessation between cannabis users (THC+) and non-users (THC-).</p><p><strong>Results: </strong>After cannabis cessation, we found a greater increase in leucocyte level (<i>p</i> < 0.01), monocyte level (<i>p</i> = 0.05) and a statistical trend to a highest increase of lymphocyte level (<i>p</i> = 0.06) between baseline and 4 weeks in the THC+ group as compared to the THC- group. At 4 weeks, highest leucocyte (<i>p</i> = 0.03), lymphocyte (<i>p</i> = 0.04) and monocyte (<i>p</i> < 0.01) counts were found in the THC+ group, whereas at baseline no difference was found. A positive correlation was found between monocyte count at 4 weeks and baseline Positive and Negative Syndrome Scale (PANSS) negative subscore (<i>p</i> = 0.045) and between the variation of monocyte count between baseline and 4 weeks and the PANSS total score at 4 weeks (<i>p</i> = 0.05).</p><p><strong>Conclusion: </strong>THC cessation is associated with an increase in inflammatory markers, including white blood cell, lymphocyte and monocyte levels, which correlates with symptomatology of patients with psychosis.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":" ","pages":"118-127"},"PeriodicalIF":3.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9478837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cocaine-use disorder and childhood maltreatment are associated with the activation of neutrophils and increased inflammation.","authors":"Giselle A Funchal, Jaqueline B Schuch, Aline Zaparte, Breno Sanvicente-Vieira, Thiago W Viola, Rodrigo Grassi-Oliveira, Moisés E Bauer","doi":"10.1017/neu.2023.11","DOIUrl":"10.1017/neu.2023.11","url":null,"abstract":"<p><strong>Background: </strong>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 signalling. We also investigated the role of early life stress in inflammatory profiles.</p><p><strong>Methods: </strong>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 (HCs). Plasma cytokines, neutrophil phagocytosis, NETs, intracellular reactive oxygen species (ROS) generation, and phosphorylated protein kinase B (Akt) and mitogen-activated protein kinases (MAPK)s were assessed by flow cytometry.</p><p><strong>Results: </strong>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 to HC. Neutrophils of CUD subjects also produced high levels of intracellular ROS and had more activated Akt and MAPKs (p38/ERK), which are essential signalling pathways involved in cell survival and NETs production. Childhood trauma scores were significantly associated with neutrophil activation and peripheral inflammation.</p><p><strong>Conclusion: </strong>Our study reinforces that smoked cocaine and early life stress activate neutrophils in an inflammatory environment.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":" ","pages":"97-108"},"PeriodicalIF":3.8,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9109529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}