Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"Predicting drug craving among ketamine-dependent users through machine learning based on brain structural measures","authors":"Yunkai Sun ,&nbsp;Qiuxia Wu ,&nbsp;Jinsong Tang ,&nbsp;Yanhui Liao","doi":"10.1016/j.pnpbp.2024.111216","DOIUrl":"10.1016/j.pnpbp.2024.111216","url":null,"abstract":"<div><h3>Background</h3><div>Craving is a core factor driving drug-seeking and -taking, representing a significant risk factor for relapse. This study aims to identify neuroanatomical biomarkers for quantifying and predicting craving.</div></div><div><h3>Methods</h3><div>The study enrolled 94 ketamine-dependent users and 103 healthy controls (HC). Utilizing support vector regression (SVR) with 10-fold cross-validated framework, we developed a neuroanatomical craving model based on measures of regional cortical thickness (CT), surface area (SA), and subcortical volume (SV) derived from T1 images. The generalizability of neuroanatomical craving model was examined in an independent set. Spatial correlation analysis was employed to assess the relationship between the regional contribution to craving and density maps of receptors/transporters from previous molecular imaging studies.</div></div><div><h3>Results</h3><div>The neuroanatomical craving model identified neuroanatomical biomarkers that predicted self-report craving (<em>r</em> = 0.635). The most importance of predictors of craving included the SA of the left medial orbitofrontal cortex and the left supramarginal gyrus, CT in the left caudal anterior cingulate, the left cuneus, the right lateral occipital cortex and the right lingual gyrus, as well as the left amygdala GMV. Importantly, these predictors were generalized to an independent sample. Moreover, nodal contribution to predicted craving scores were associated with DA2, 5-HTa, 5-HTb receptor and serotonin reuptake transporter densities.</div></div><div><h3>Conclusion</h3><div>The results offer a key perspective on craving prediction among ketamine-dependent users, and identify neuroanatomical areas associated with craving in the frontal and parietal regions. Additionally, the underlying neuroanatomical structures involved in the craving process may be linked to the dopaminergic and serotonergic systems.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111216"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurotyping depression using multiple event-related potentials (ERPs): Leveraging task-based variation to predict remission in depression","authors":"Greg Hajcak ,&nbsp;Nicholas Santopetro ,&nbsp;Kazutaka Okuda","doi":"10.1016/j.pnpbp.2024.111233","DOIUrl":"10.1016/j.pnpbp.2024.111233","url":null,"abstract":"<div><h3>Aims</h3><div>Depression is a prevalent, burdensome, and difficult mental health disorder to treat. Significant heterogeneity in clinical characteristics and course of depression hinders treatment success. Efforts to identify more homogeneous subgroups of depression could reduce heterogeneity of depression and therefore improve treatment development and randomized clinical trial outcomes. Event-related potentials (ERPs) derived from continuous electroencephalogram (EEG) can be used to identify depression and predict course (i.e., advance precision psychiatry).</div></div><div><h3>Methods</h3><div>In the current study, we demonstrate how multiple ERPs collected from the same individual across different experimental paradigms can provide insight into brain function and individual differences in depression using factor analysis. This approach for neurotyping depression exploits the high within-task and low between-task associations between ERPs to better understand brain function and depression.</div></div><div><h3>Results</h3><div>We observed three neurotypes, two of which differentiated depressed from non-depressed individuals. Only one neurotype – related to affective processing – prospectively predicted full remission. This neurotype predicted remission even when accounting for other clinical and demographic variables related to subsequent remission. The AUC of this neurotype was acceptable (i.e., 0.72) in predicting remission, exceeding previous study's measures within a single task.</div></div><div><h3>Conclusion</h3><div>Leveraging multiple ERPs derived from many tasks is an important yet underutilized approach in precision psychiatry.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111233"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A computational and multi-brain signature for aberrant social coordination in schizophrenia","authors":"Ya-Jie Wang ,&nbsp;Yalan Wen ,&nbsp;Leilei Zheng ,&nbsp;Ji Chen ,&nbsp;Zheng Lin ,&nbsp;Yafeng Pan","doi":"10.1016/j.pnpbp.2024.111225","DOIUrl":"10.1016/j.pnpbp.2024.111225","url":null,"abstract":"<div><div>Social functioning impairment is a core symptom of schizophrenia (SCZ). Yet, the computational and neural mechanisms of social coordination in SCZ under real-time and naturalistic settings are poorly understood. Here, we instructed patients with SCZ to coordinate with a healthy control (HC) in a joint finger-tapping task, during which their brain activity was measured by functional near-infrared spectroscopy simultaneously. The results showed that patients with SCZ exhibited poor rhythm control ability and unstable tapping behaviour, which weakened their interpersonal synchronization when coordinating with HCs. Moreover, the dynamical systems modeling revealed disrupted between-participant coupling when SCZ patients coordinated with HCs. Importantly, increased inter-brain synchronization was identified within SCZ-HC dyads, which positively correlated with behavioural synchronization and successfully predicted dimensions of psychopathology. Our study suggests that SCZ individuals may require stronger interpersonal neural alignment to support their deficient coordination performance. This hyperalignment may be relevant for developing inter-personalized treatment strategies.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111225"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early auditory impairments as a candidate marker of attenuated sensory symptoms of psychosis","authors":"Clément Dondé ,&nbsp;Emma Palmer-Cooper ,&nbsp;Christophe Gauld ,&nbsp;Mircea Polosan ,&nbsp;Ben Alderson-Day","doi":"10.1016/j.pnpbp.2024.111214","DOIUrl":"10.1016/j.pnpbp.2024.111214","url":null,"abstract":"<div><h3>Background and hypothesis</h3><div>Deficits in early auditory processing (EAP), as indexed by tone-matching performance, have been consistently demonstrated in individuals with schizophrenia spectrum disorders. However, the ontogeny of tone-matching deficits in schizophrenia remains relatively unknown. The current study aims to determine the relationship between clinical high risk for psychosis and EAP.</div></div><div><h3>Study design</h3><div>We employed a web-based screening approach to identify CHR individuals. A sample of 892 community dwelling participants completed the 16-tem version of the prodromal questionnaire (PQ16) for the assessment of attenuated psychotic symptoms, a 9-item questionnaire of perceptual and cognitive aberrations (PCA) for the assessment of basic symptoms and a tone-matching task.</div></div><div><h3>Study results</h3><div>505 (43.4 %) participants met cut-off criteria for attenuated psychotic symptoms (PQ16 ≥ 6 endorsed items), 614 (68.3 %) for basic symptoms (PCA ≥ 3 endorsed items), 647 (72.0 %) for either and 358 (40.1 %) for both of them. No significant differences in tone-matching performance were observed between CHR and non-CHR subjects, using either attenuated psychotic symptoms, basic symptoms, either or both cutoffs. In the CHR group screened with attenuated psychotic symptoms, auditory and tactile sensory symptoms were significantly associated with tone-matching deficits.</div></div><div><h3>Conclusion</h3><div>Tone-matching may not serve as a reliable biomarker for CHR status but rather a risk marker for the emergence of early sensory manifestations.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111214"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of factors associated with antipsychotic-induced weight gain: A nationwide cohort study","authors":"Shuhei Ishikawa ,&nbsp;Naoki Hashimoto ,&nbsp;Ryo Okubo ,&nbsp;Ryo Sawagashira ,&nbsp;Ryodai Yamamura ,&nbsp;Yoichi M. Ito ,&nbsp;Norihiro Sato ,&nbsp;Ichiro Kusumi","doi":"10.1016/j.pnpbp.2024.111231","DOIUrl":"10.1016/j.pnpbp.2024.111231","url":null,"abstract":"<div><h3>Background</h3><div>The incidence of antipsychotic-induced weight gain (AIWG) is difficult to predict in real-world practice because various factors influence it. This study aimed to explore background and medication-related factors associated with weight gain in patients newly prescribed with antipsychotic medication.</div></div><div><h3>Methods</h3><div>This nationwide, multicenter, prospective cohort study was conducted in Japan. The primary endpoint was the incidence of AIWG (≥7 % weight gain) over 12 months after initiation of antipsychotic treatment. Factors influencing AIWG incidence were assessed using Cox proportional hazards regression analysis stratified by facility characteristics.</div></div><div><h3>Results</h3><div>Of the 865 enrolled participants, 262 developed AIWG. Compared with aripiprazole, clozapine and olanzapine were related to a higher AIWG incidence (hazard ratio [HR] = 2.17, 95 % confidence interval [CI] = 1.05–4.51; HR = 2.01, 95 % CI = 1.36–2.96, respectively), whereas blonanserin was related to a lower AIWG incidence (HR = 0.49, 95 % CI = 0.24–0.98). Furthermore, co-administration of antidepressants and mood stabilizers increased the AIWG incidence (HR = 1.94, 95 % CI = 1.35–2.77; HR = 1.47, 95 % CI = 1.07–2.01, respectively). The impact of concomitant medications on AIWG incidence varied by the pharmacological characteristics of the newly initiated antipsychotic, in addition to the type and duration of concomitant medications.</div></div><div><h3>Conclusions</h3><div>The findings of this study suggest that the risk of AIWG incidence may be estimated by assessing the type of concomitant medication and its duration of use, type of newly initiated antipsychotic, and background factors prior to initiation of antipsychotic treatment.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111231"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in transcranial focused ultrasound neuromodulation for mental disorders","authors":"Yu Shi,&nbsp;Wen Wu","doi":"10.1016/j.pnpbp.2024.111244","DOIUrl":"10.1016/j.pnpbp.2024.111244","url":null,"abstract":"<div><div>Mental disorders are a major public health concern, affecting millions worldwide. Current treatments have limitations, highlighting the need for novel, effective, and safe interventions. Transcranial focused ultrasound (tFUS), a non-invasive neuromodulation technology, has emerged as a promising tool for treating mental disorders due to its high controllability, precision, and safety. This review summarizes the research progress of tFUS in several major mental disorders, including depression, anxiety, schizophrenia, and substance use disorders (SUDs). Animal studies have demonstrated the efficacy of tFUS in improving psychiatric symptoms and modulating neural circuits through various mechanisms, such as enhancing neuronal activity, synaptic plasticity, and neurotransmitter release. Preliminary clinical trials have also shown the potential of tFUS in alleviating symptoms in patients with treatment-resistant mental disorders. Safety evaluation studies across in vitro, animal, and human levels have supported the overall safety of tFUS under commonly used parameters. tFUS has shown broad application prospects in treating mental disorders, supported by its efficacy in animal models and preliminary clinical trials. By modulating neuronal activity, synaptic plasticity, neurotransmitters, and brain networks, tFUS could improve psychiatric symptoms and regulate neural circuits. However, current research on tFUS in mental disorders is still in its early stages, and further studies are needed to elucidate its mechanisms of action, expand its applications, and conduct large-sample, long-term clinical trials to systematically evaluate its efficacy, protocol optimization, and safety. As an innovative neuromodulation technology, tFUS has the potential to complement conventional therapies and provide new hope for addressing the global challenge of mental disorders.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111244"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of depression, suicide attempt history and childhood trauma in neutrophil-to-lymphocyte ratio dynamics: A 30-week prospective study","authors":"M. Lion ,&nbsp;M. Muller ,&nbsp;E.C. Ibrahim ,&nbsp;W. El-Hage ,&nbsp;A. Lengvenyte ,&nbsp;P. Courtet ,&nbsp;A. Lefrere ,&nbsp;R. Belzeaux","doi":"10.1016/j.pnpbp.2024.111227","DOIUrl":"10.1016/j.pnpbp.2024.111227","url":null,"abstract":"<div><div>Studying the biology of suicidal behaviour and developing blood-based biomarkers may help stratify individuals with suicidal behaviors into clinically relevant categories. Literature suggests that people diagnosed with mood disorders and suicidal behaviour show an increased neutrophil to lymphocyte ratio (NLR). For the first time, we investigated NLR variability in mood disorders, a critical aspect of biomarker development. Our study provides a result on the influence of our variables on the NLR and also on the intrinsic properties of the ratio. Consequently, our objective was to analyse the differences in NLR between healthy subjects and patients diagnosed with mood disorder with suicidal behaviour or mood disorder without suicidal attempt. A prospective study was conducted on 97 healthy subjects, 63 patients with mood disorder without suicidal behaviour and 61 patients with mood disorder with suicidal behaviour (mean age [SD] = 44.2 [14.31]; 66.1 % female). Participants were assessed four times over 30 weeks, where blood samples and clinical data were collected. After controlling for confounding factors such as smoking and medical history, we found that NLR stability was low but NLR was significantly associated with a history of suicide attempt (mixed linear model, F = 4.044; <em>p</em> = 0.018). We also observed a significant interaction between NLR values and childhood trauma (<em>p</em> = 0.002). Furthermore, our results demonstrate that NLR is influenced by childhood trauma, including in controls (<em>p</em> = 0.014). Finally, NLR expression differs between patients with and without suicidal behaviour, but only in those without a history of childhood trauma (<em>p</em> = 0.026). Despite its variability over time, our data suggest that NLR may be a promising biomarker for identifying individuals at high risk of suicidal behaviour among patients with mood disorders.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111227"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Putative epicenters identified by transcriptome-neuromorphic interactions in attention-deficit/hyperactivity disorder biotypes","authors":"Qin Tang ,&nbsp;Jinzhong Peng ,&nbsp;Yilu Li ,&nbsp;Lin Liu ,&nbsp;Pan Wang ,&nbsp;Huafu Chen ,&nbsp;Bharat B. Biswal","doi":"10.1016/j.pnpbp.2025.111247","DOIUrl":"10.1016/j.pnpbp.2025.111247","url":null,"abstract":"<div><div>Attention-deficit hyperactivity disorder (ADHD) is a heterogenous behavioral disorder with inattention, hyperactivity and impulsivity symptoms, indicating the important implication of identifying biotypes and its epicenters in understanding disease's pathogenesis. The study investigated the neuromorphic heterogeneity relating to transcriptional similarity architecture in ADHD, and further analyzed the epicenters of network-spreading in each ADHD biotype and their correlations with clinical characteristics. Individuals with ADHD could be identified into two discriminative biotypes that exhibited distinct neuromorphic aberrances. As increased regional cortical thickness deviation in ADHD, the first component of partial least squares (PLS1) positively weighted genes were over-expressed, whereas PLS1 negatively weighted genes were under-expressed as its reduction. Both ADHD biotypes exhibited distinct disease epicenters that distributed in cognitive control and attention networks with significantly heterogeneous characteristics, holding promise for advancing our understanding, and ultimately the treatment, of ADHD. Overall, our findings identified two discriminative biotypes and its epicenters in ADHD, promoting the understanding of underlying transcriptome-neuroimaging relationships.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111247"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142962558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential effects of gestational Cannabis smoke and phytocannabinoid injections on male and female rat offspring behavior","authors":"Tallan Black ,&nbsp;Ilne L. Barnard ,&nbsp;Sarah L. Baccetto ,&nbsp;Quentin Greba ,&nbsp;Spencer N. Orvold ,&nbsp;Faith V.L. Austin-Scott ,&nbsp;Genre B. Sanfuego ,&nbsp;Timothy J. Onofrychuk ,&nbsp;Aiden E. Glass ,&nbsp;Rachel M. Andres ,&nbsp;Leah M. Macfarlane ,&nbsp;Jesse C. Adrian ,&nbsp;Ashton L. Heidt ,&nbsp;Dan L. McElroy ,&nbsp;Robert B. Laprairie ,&nbsp;John G. Howland","doi":"10.1016/j.pnpbp.2024.111241","DOIUrl":"10.1016/j.pnpbp.2024.111241","url":null,"abstract":"<div><div>Our understanding of the implications of gestational <em>Cannabis</em> exposure (GCE) remains unclear as <em>Cannabis</em> use increases worldwide. Much of the existing knowledge of the effects of GCE has been gained from preclinical experiments using injections of isolated Δ⁹-tetrahydrocannabinol (THC) at relatively high doses. Few investigations of the effects of GCE to smoke from the whole <em>Cannabis</em> flower have been conducted, despite this being the most common mode of human consumption. Here, we compared the effects of repeated gestational exposure to high-THC or high-cannabidiol (CBD) <em>Cannabis</em> smoke to <em>i.p.</em> THC or <em>i.p.</em> CBD to those of GCE to high-THC or high-CBD <em>Cannabis</em> smoke on litter health and the offspring. We found that injecting phytocannabinoids generally had a more severe impact on measures of maternal and litter health and produced distinct behavioral phenotypes when compared to offspring from dams treated with high-THC and high-CBD smoke during gestation. GCE to high-THC smoke decreased prepulse inhibition (PPI) and MK-801-induced locomotor activity in female adolescent offspring, which normalized in adulthood. GCE to <em>i.p.</em> THC increased exploratory behavior in the open field test in adolescent offspring of both sexes. GCE had a negative impact on offspring performance in the Identical Stimuli Test and Different Stimuli Test with odors regardless of gestational treatment, sex, or age. CBD (<em>i.p</em>) impaired PPI in both male and female offspring in adulthood and increased time spent in proximity during social interaction for male offspring. There were no effects of GCE in the 5 Choice Serial Reaction Time Task. These data establish distinct behavioral phenotypes in the offspring between smoked and injected GCE, further demonstrating that route and specific phytocannabinoid dose produce differential outcomes across offspring lifespan. Smoked <em>Cannabis</em> is still the most common means of consumption, and more preclinical investigation is needed to determine the effects of smoked <em>Cannabis</em> on developmental trajectories.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111241"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implications of prenatal exposure to hyperandrogen for hippocampal neurodevelopment and autism-like behavior in offspring","authors":"Dan Qiao ,&nbsp;Chenyu Mu ,&nbsp;Huan Chen ,&nbsp;Di Wen ,&nbsp;Zhao Wang ,&nbsp;Bohan Zhang ,&nbsp;Fangzhen Guo ,&nbsp;Chang Wang ,&nbsp;Rong Zhang ,&nbsp;Chongying Wang ,&nbsp;Huixian Cui ,&nbsp;Sha Li","doi":"10.1016/j.pnpbp.2024.111219","DOIUrl":"10.1016/j.pnpbp.2024.111219","url":null,"abstract":"<div><div>Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder that significantly jeopardizes the physical and mental well-being of children. Autism spectrum disorder results from a combination of environmental and genetic factors. Hyperandrogenic exposure during pregnancy increases their risk of developing autism. Nevertheless, the prenatal exposure to androgens affects offspring neurodevelopment and the underlying mechanisms have not been fully elucidated. In the present study, administration of excessive dihydrotestosterone (DHT) to pregnant mice was found to impair neuronal development and dendritic spine formation in offspring, inducing autism-like behaviors. Furthermore, through mRNA transcriptome sequencing technology, the key molecule Nr4a2 was identified during this process of change. Overexpression of Nr4a2 and treatment with amodiaquine (AQ) significantly improved the abnormal phenotypes in offspring caused by prenatal exposure to androgens. Overall, Nr4a2 emerges as a crucial molecule involved in the impairment of offspring neurodevelopment due to prenatal androgen exposure, which provides a new perspective for the in-depth study of the influencing factors and underlying mechanisms.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111219"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}