Psychopharmacology最新文献

{"title":"Working memory processes and the histamine-3 receptor in schizophrenia: a [¹¹C]MK-8278 PET-fMRI study.","authors":"Atheeshaan Arumuham, Ekaterina Shatalina, Matthew M Nour, Mattia Veronese, Ellis Chika Onwordi, Stephen J Kaar, Sameer Jauhar, Eugenii A Rabiner, Oliver D Howes","doi":"10.1007/s00213-024-06730-6","DOIUrl":"https://doi.org/10.1007/s00213-024-06730-6","url":null,"abstract":"<p><strong>Rationale: </strong>Working memory impairment is a prominent feature of schizophrenia which predicts clinical and functional outcomes. Preclinical data suggest histamine-3 receptor (H3R) expression in cortical pyramidal neurons may have a role in working memory, and post-mortem data has found disruptions of H3R expression in schizophrenia.</p><p><strong>Objectives: </strong>We examined the role of H3R in vivo to elucidate its role on working memory impairment in schizophrenia.</p><p><strong>Methods: </strong>We used positron emission tomography (PET) with the selective H3R radioligand [¹¹C]MK-8278 to measure H3R availability, and employed a task during functional magnetic resonance imaging (fMRI) to assess working memory-evoked brain activation and cognitive task performance, in patients with schizophrenia (n = 12) and matched healthy volunteers (n = 12). We assessed the relationship between H3R availability and both task performance and working memory-evoked brain activation in regions of interest (ROIs), including the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (DLPFC).</p><p><strong>Results: </strong>Patients with schizophrenia showed a strong positive correlation, after corrections for multiple comparisons, between ACC H3R availability and task performance (rho = 0.73, p = 0.007), which was absent in the control group (rho = 0.03, p = 0.94). Further ROI analysis did not find a significant relationship between H3R availability and working memory-evoked brain activation.</p><p><strong>Conclusions: </strong>These results provide support for the role of H3R on working memory processes in patients with schizophrenia.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repeated toluene inhalation in male and female adolescent rats induces persistent drug preference and impairs cognitive and social behavior.","authors":"Joannes Luke B Asis, Ajina C Carampel, Jariel Naomi B Bacar, Johanna C Munar, Cynthia Grace C Gregorio, Paul Mark B Medina, Leslie Michelle M Dalmacio, Jesus Emmanuel A D Sevilleja, Gregory J Quirk, Rohani Cena-Navarro","doi":"10.1007/s00213-024-06731-5","DOIUrl":"https://doi.org/10.1007/s00213-024-06731-5","url":null,"abstract":"<p><strong>Rationale: </strong>Adolescent inhalant use is an understudied and undertreated disorder, particularly in females. Chronic exposure to inhalants, like toluene, can have long-lasting effects on behavior. However, most animal studies lack the incorporation of both sexes and do not focus on the abstinence period.</p><p><strong>Objective: </strong>We assessed the behavioral effects during prolonged abstinence following repeated toluene inhalation in adolescent male and female rats.</p><p><strong>Methods: </strong>We repeatedly exposed adolescent male and female Sprague Dawley rats to toluene vapor (1500 or 3000 ppm) for 6 days using the conditioned place preference (CPP) procedure. We tested drug-associated context preference, locomotion, anxiety-like behavior, object memory, social preference, and cognitive flexibility across 22 days of abstinence.</p><p><strong>Results: </strong>In females, 3000 ppm toluene increased CPP on days 8 and 22 of abstinence but this effect did not reach significance in males. Instead, males showed a significant increase in locomotion on days 7 and 21. Toluene also impaired social novelty preference and reversal learning during long-term abstinence, but not anxiety-like behavior or object recognition memory.</p><p><strong>Conclusions: </strong>Our rodent findings suggest that female inhalant users may show persistent drug preference during abstinence following chronic use. Furthermore, prolonged cognitive and social deficits should be addressed in treatment programs for adolescents.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Substance use disorder severity is associated with sensitivity to effort-related decision-making constraints.","authors":"Samuel F Acuff, Louisa Kane, Zachary J Stewart, Justin Riddle, Stacey B Daughters","doi":"10.1007/s00213-024-06732-4","DOIUrl":"https://doi.org/10.1007/s00213-024-06732-4","url":null,"abstract":"<p><strong>Rationale: </strong>Several studies have reported associations between substance use and effort-related decision making, or the degree to which effort expenditure impacts the choice between lower and higher value rewards. However, previous research has not explored effort-related decision making in populations with severe substance use disorder.</p><p><strong>Objectives: </strong>Investigate the association between effort-related decision-making and substance use disorder severity.</p><p><strong>Methods: </strong>Adults with substance use disorders (n = 106) enrolled in intensive outpatient treatment completed clinician administered diagnostic interviews and the effort expenditure for rewards task (EEfRT). General linear mixed methods tested the interactive effect of substance use disorder severity and trial-level probability and value on the likelihood of selecting a high-effort choice.</p><p><strong>Results: </strong>There was a significant interaction between SUD severity and both reward value and reward probability on high-effort choice. The strength of the association between both reward value and probability on high-effort choice significantly increased with SUD severity.</p><p><strong>Conclusions: </strong>These results support theories of reward sensitivity and behavioral economics and highlight an emerging risk factor that may serve as a useful target for treatment.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genotype-dependent functional role of the anterior and posterior paraventricular thalamus in pavlovian conditioned approach.","authors":"Valeria Tarmati, Andrea Sepe, Alessandra Accoto, David Conversi, Daniela Laricchiuta, Anna Panuccio, Sonia Canterini, Maria Teresa Fiorenza, Simona Cabib, Cristina Orsini","doi":"10.1007/s00213-024-06726-2","DOIUrl":"https://doi.org/10.1007/s00213-024-06726-2","url":null,"abstract":"<p><strong>Rationale: </strong>The specific location of deviations from normative models of brain function varies considerably across individuals with the same diagnoses. However, as pathological processes are distributed across interconnected systems, this heterogeneity of individual brain deviations may also reveal similarities and differences between disorders. The paraventricular nucleus of the thalamus (PVT) is a potential switcher to various behavioral responses where functionally distinct cell types exist across its antero-posterior axis.</p><p><strong>Objectives: </strong>This study aimed to test the hypothesis that genotype-dependent differences in the anterior and posterior PVT subregions (aPVT and pPVT) are involved in the Sign-tracking (ST) behavior expressed by C57BL/6J (C57) and DBA/2J (DBA) inbred mice.</p><p><strong>Methods: </strong>Based on previous findings, male mice of the two strains were tested at ten weeks of age. The density of c-Fos immunoreactivity along the antero-posterior axis of PVT was assessed following the expression of ST behavior. Selective excitotoxic lesions of the aPVT or the pPVT by the NMDA infusion were performed prior to development of ST behavior. Finally, the distribution of neuronal populations expressing the Drd2 and Gal genes (D2R + and Gal +) was measured by in situ hybridization (ISH).</p><p><strong>Results: </strong>The involvement of PVT subregions in ST behavior is strain-specific, as aPVT is crucial for ST acquisition in DBA mice while pPVT is crucial for C57 mice. Despite similar antero-posterior distribution of D2R + and Gal + neurons, density of D2R + neurons differentiate aPVT in C57 and DBA mice.</p><p><strong>Conclusions: </strong>These genotype-dependent results offer valuable insights into the nuanced organization of brain networks and individual variability in behavioral responses.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SK609, a novel dopamine D3 receptor agonist and norepinephrine transporter blocker with putative pro-cognitive actions, does not induce psychostimulant-like increases in risky choice during probabilistic discounting.","authors":"Christopher P Knapp, Brooke Fallon, Sandhya Kortagere, Barry D Waterhouse, Stan B Floresco, Rachel L Navarra","doi":"10.1007/s00213-024-06727-1","DOIUrl":"https://doi.org/10.1007/s00213-024-06727-1","url":null,"abstract":"<p><strong>Rationale: </strong>Psychostimulants, such as amphetamine (AMPH) and methylphenidate (MPH), non-selectively elevate extracellular concentrations of the catecholamine neurotransmitters, dopamine (DA) and norepinephrine (NE), and are common pharmacological strategies used to improve prefrontal cortex (PFC)-dependent cognitive dysfunction. However, this approach can be problematic given AMPH has been shown to increase preference for risky choices in a rodent assay of risk/reward decision making. SK609 is a novel NE reuptake blocker that selectively activates DA D3 receptors without affinity for the DA transporter. SK609 has been shown to improve cognitive performance without increasing psychostimulant-like spontaneous locomotor activity, suggesting SK609 may benefit neurocognitive function without psychostimulant-like side effect liability.</p><p><strong>Objectives: </strong>We compared AMPH, MPH, and SK609 within dose ranges that display their cognitive enhancing properties in a probabilistic discounting task (PDT) of risk/reward decision making behavior to assess their potential to increase risky choice preference.</p><p><strong>Methods: </strong>Rats chose between small/certain rewards delivered with 100% certainty and large/risky rewards delivered with descending probabilities across a session (100 - 6.25%) following administration of AMPH (0.25-1 mg/kg), MPH (2-8 mg/kg), and SK609 (4 mg/kg).</p><p><strong>Results: </strong>AMPH and MPH increased risky choice behavior at doses previously reported to enhance cognition, whereas SK609 did not. AMPH and MPH also reduced sensitivity to non-rewarded risky choices.</p><p><strong>Conclusions: </strong>These data highlight the combination of NE transporter blockade and selective D3 activation in pro-cognitive action without psychostimulant-like side effect liability. The absence of DA transporter blockade and non-selective dopaminergic activation are beneficial properties of SK609 that differentiates it from the traditional pro-cognitive psychostimulants.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TSPO activation ameliorates maternal immune activation induced PV interneuron deficits via BDNF/TrkB signaling.","authors":"Ming-Jie Mao, Hui-Ling Yu, Qing-Zhen Liu, Ya-Zhou Wen, Ming Jiang, Hong-Mei Yuan, Hua-Bei Zeng, Li-Dong Zhang, Shan-Wu Feng","doi":"10.1007/s00213-024-06728-0","DOIUrl":"https://doi.org/10.1007/s00213-024-06728-0","url":null,"abstract":"<p><strong>Rationale: </strong>Prenatal maternal immune activation (MIA) is an etiological risk factor for schizophrenia in offspring. Recently, parvalbumin (PV) positive interneuron deficits has been considered a critical pathology of many psych-cognitive disorders. Nevertheless, whether and how prenatal MIA affected PV interneuron in offspring remains largely unknown.</p><p><strong>Objectives: </strong>Here, we aimed to assess the relationship between MIA with PV interneuron deficits in offspring, and explored the underling mechanisms.</p><p><strong>Methods and results: </strong>Mouse model of MIA was induced using lipopolysaccharide (120 µg/kg) on gestational day 15-17. Open field, elevated plus maze, Y-Maze and novel object recognition tests were performed and local field potential was recorded on adult male offspring. PV interneuron, Translocator protein 18 kDa (TSPO), and BDNF/TrkB signaling were then evaluated. Using TPSO agonist and TrkB antagonist, the function of TSPO on PV interneuron deficits was elucidated. Our results showed that MIA induced cognitive symptoms in the adult male offspring, accompanied by down-regulated PV and TSPO expression as well as decreased theta oscillation. Notably, activating TSPO reversed MIA-induced PV interneuron defects and behavioral abnormalities. Furthermore, specific inhibition of BDNF/TrkB signaling intercepted the protective effect of TSPO activation on PV interneuron deficits.</p><p><strong>Conclusions: </strong>Our results highlight TSPO activation might prevented PV interneuron deficits and behavioral abnormalities after MIA via BDNF/TrkB signaling.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corticotropin releasing hormone receptor 1 in the medial prefrontal cortex mediates aversion resistant alcohol intake.","authors":"Miranda E Arnold, Cecelia E Harber, Lauren A Beugelsdyk, Ellie B Decker Ramirez, Grace B Phillips, Jesse R Schank","doi":"10.1007/s00213-024-06707-5","DOIUrl":"10.1007/s00213-024-06707-5","url":null,"abstract":"<p><strong>Rationale: </strong>Alcohol consumption despite negative consequences is a core symptom of Alcohol Use Disorder. In animal models, this is studied by pairing aversive stimuli with alcohol access, and continuation of drinking under these conditions is known as aversion resistance. Previously, we found that female mice are more aversion resistant than males. Corticotropin releasing hormone (Crh) and the Crh receptor 1 (Crhr1) regulate stress-induced reinstatement, alcohol dependence, and binge-like drinking. However, the role of the Crh system in aversion resistance has not been assessed.</p><p><strong>Objectives: </strong>We aimed to identify sex differences in the Crh system during quinine-adulterated alcohol intake.</p><p><strong>Methods: </strong>We used two-bottle choice and adulterated the alcohol solution with quinine. Next, we measured Crh and Crhr1 levels in brain tissue using real-time polymerase chain reaction (RT-qPCR) and RNAscope in situ hybridization. We then infused a Crhr1 antagonist into the medial prefrontal cortex (mPFC) prior to quinine-alcohol intake.</p><p><strong>Results: </strong>After quinine-alcohol consumption, females exhibited increased mPFC Crhr1 mRNA levels as measured by RT-qPCR. This was confirmed with greater anatomical specificity using RNAscope, with females exhibiting an increased number of Crhr1 + cells in the dorsomedial PFC and the ventromedial PFC. mPFC Crhr1 antagonist treatment reduced quinine-alcohol consumption in females but did not impact consumption in males. Quinine-free alcohol intake was unaffected by Crhr1 antagonist treatment.</p><p><strong>Conclusions: </strong>Our findings suggest that Crhr1 in mPFC plays a role in aversion resistant alcohol intake in females. Future experiments will examine the sources of Crh innervation to the mPFC and their distinct roles in alcohol seeking.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2539-2550"},"PeriodicalIF":4.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fear generalization modulated by shock intensity and protein synthesis inhibitor.","authors":"Xinwen Dong, Yunyun Wang, Yudan Liu, Yonghui Li","doi":"10.1007/s00213-024-06662-1","DOIUrl":"10.1007/s00213-024-06662-1","url":null,"abstract":"<p><strong>Rationale: </strong>Maladaptive fear responses, including sensitized threat reactions and overgeneralization, contribute to anxiety disorders such as generalized anxiety disorder and post-traumatic stress disorder. Although stress intensity influences the generation and extent of these maladaptive fears, the underlying mechanisms remain unclear.</p><p><strong>Objectives: </strong>The present study examined whether varying footshock stress intensity and inhibition of protein synthesis have differential effect on fear sensitization and generalization in mice.</p><p><strong>Methods: </strong>Mice were subjected to a classic fear conditioning protocol involving five different levels of footshock intensities. Prior to fear acquisition, the protein synthesis inhibitor cycloheximide (CHX) was administered intraperitoneally. Fear sensitization to white noise and fear generalization to tones with frequencies differing from the conditioned tone were assessed at either 2 or 4 days after fear acquisition.</p><p><strong>Results: </strong>The results showed that, although varying shock intensities (except the lowest) led to a similar pattern of increased freezing during auditory cues in fear acquisition, the extent of both fear sensitization and generalization increased with the intensity of the footshock in the following days. As shock intensities increased, there was a proportional rise in sensitized fear to white noise and generalized freezing to tones with frequencies progressively closer to the conditioned stimulus. Mildest shocks did not induce discriminative conditioned fear memory, whereas the most intense shocks led to pronounced fear generalization. Administration of CHX before fear acquisition did not affect sensitized fear but reduced generalization of freezing to tones dissimilar from the conditioned stimulus in the group exposed to the most intense shock.</p><p><strong>Conclusions: </strong>Our results suggest that maladaptive fear responses elicited by varying stress intensities exhibit distinct characteristics. The effect of CHX to prevent overgeneralization without affecting discriminative fear memory points to potential therapeutic approaches for fear-related disorders, suggesting the possibility of mitigating overgeneralization while preserving necessary fear discrimination.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2627-2637"},"PeriodicalIF":4.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A potential role of gut microbiota in stroke: mechanisms, therapeutic strategies and future prospective.","authors":"Manpreet Kaur, Khadga Raj Aran, Raju Paswan","doi":"10.1007/s00213-024-06708-4","DOIUrl":"10.1007/s00213-024-06708-4","url":null,"abstract":"<p><strong>Rationale: </strong>Neurological conditions like Stroke and Alzheimer's disease (AD) often include inflammatory responses in the nervous system. Stroke, linked to high disability and mortality rates, poses challenges related to organ-related complications. Recent focus on understanding the pathophysiology of ischemic stroke includes aspects like cellular excitotoxicity, oxidative stress, cell death mechanisms, and neuroinflammation.</p><p><strong>Objective: </strong>The objective of this paper is to summarize and explore the pathophysiology of ischemic stroke, elucidates the gut-brain axis mechanism, and discusses recent clinical trials, shedding light on novel treatments and future possibilities.</p><p><strong>Results: </strong>Changes in gut architecture and microbiota contribute to dementia by enhancing intestinal permeability, activating the immune system, elevating proinflammatory mediators, altering blood-brain barrier (BBB) permeability, and ultimately leading to neurodegenerative diseases (NDDs). The gut-brain axis's potential role in disease pathophysiology offers new avenues for cell-based regenerative medicine in treating neurological conditions.</p><p><strong>Conclusion: </strong>In conclusion, the gut microbiome significantly impacts stroke prognosis by highlighting the role of the gut-brain axis in ischemic stroke mechanisms. This insight suggests potential therapeutic strategies for improving outcomes.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2409-2430"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between angiotensin-converting enzyme gene insertion/deletion polymorphism and cognition impairment in patients with schizophrenia.","authors":"Li Mu, Dongmei Wang, Meihong Xiu, Xiang-Yang Zhang","doi":"10.1007/s00213-024-06657-y","DOIUrl":"10.1007/s00213-024-06657-y","url":null,"abstract":"<p><strong>Rationale: </strong>Several lines of evidence indicate that an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene (ACE) gene may be involved in the pathogenesis of schizophrenia and cognitive impairment. However, the relationship between ACE I/D polymorphism and cognitive impairment in patients with schizophrenia remains unclear.</p><p><strong>Objectives: </strong>The aim of this study was to examine whether ACE gene I/D polymorphism contributed to cognitive impairment in Chinese patients with schizophrenia, and whether the association between clinical symptoms and cognitive impairment depended on different ACE genotypes.</p><p><strong>Methods: </strong>The ACE I/D polymorphism was genotyped in 928 schizophrenia patients and 325 healthy controls using a case-control design. The severity of psychopathological symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). Cognitive functioning was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).</p><p><strong>Results: </strong>There were significant differences in genotype and allele frequencies of the ACE I/D polymorphism between patients and healthy controls (both P < 0.01). After controlling for demographic characteristics, patients who are homozygous carriers of D and I performed worse on the RBANS attention index than heterozygous carriers (P = 0.009). In addition, attention index score was negatively correlated with PANSS negative symptom score in patients of all genotypes (all P < 0.05), and positively correlated with positive symptom score only in the I/I genotype (P = 0.005).</p><p><strong>Conclusions: </strong>These findings suggest that ACE I/D gene variants play a role in susceptibility to schizophrenia, specific cognitive impairment and the association between clinical symptoms and cognitive impairment in schizophrenia patients.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"2551-2563"},"PeriodicalIF":3.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}