Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"The GABAB receptor agonist baclofen inhibits the reconsolidation of methamphetamine reward memory in adolescent and adult REM sleep-deprived rats","authors":"Christian P. Müller ,&nbsp;Mehdi Khodamoradi","doi":"10.1016/j.pnpbp.2025.111472","DOIUrl":"10.1016/j.pnpbp.2025.111472","url":null,"abstract":"<div><div>Methamphetamine (METH) is a highly addictive psychostimulant drug. A key behavior of addiction is the relapse to drug-seeking and self-administration after abstinence. Like small amounts of a drug, does sleep deprivation increase the risk of relapse. Thus, identifying the mechanisms of relapse, and inhibiting them, is one strategy to develop a better treatment of addiction. In this study, adolescent and adult male rats underwent a 7-day episode of REM sleep deprivation (RSD). Following this, they were trained to establish a METH (2 mg/kg, i.p.)-induced conditioned place preference (CPP). After CPP extinction, rats received a memory reactivation session to trigger METH-CPP reinstatement. Immediately after this session, they received the GABA_B receptor (GABA_B-R) agonist baclofen (0, 2.5, or 5 mg/kg, i.p.). The results showed that baclofen, administered during the reconsolidation phase of METH CPP, significantly reduced METH reinstatement in both adolescent and adult rats in a dose-dependent manner. In adolescent rats, RSD enhanced METH reward memory, while it had no effect on adult rats. Although baclofen consistently reduced METH reinstatement in RSD adolescent rats, this effect was not observed in RSD adult rats. Furthermore, RSD increased GABA_B-R₁ subunit expression in the prefrontal cortex of both age groups. However, baclofen did not affect GABA_B-R₁ subunit expression in either group. These findings provide evidence for a role of the GABA_B-R in METH memory reconsolidation across different ages, its vulnerability to RSD. They further support the potential of baclofen as a treatment for mitigating behaviors associated with METH abuse.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"141 ","pages":"Article 111472"},"PeriodicalIF":3.9,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144864256","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":"Whole blood BDNF is lower in patients with depression and unchanged by escitalopram in patients and healthy controls","authors":"Miriam L. Navarro ,&nbsp;Alberte Wollesen Breum ,&nbsp;Brice Ozenne ,&nbsp;Arafat Nasser ,&nbsp;Sagar Sanjay Aripaka ,&nbsp;Sophia Armand ,&nbsp;Martin Balslev Jorgensen ,&nbsp;Vibe G. Frokjaer ,&nbsp;Gitte M. Knudsen","doi":"10.1016/j.pnpbp.2025.111470","DOIUrl":"10.1016/j.pnpbp.2025.111470","url":null,"abstract":"<div><h3>Background</h3><div>Brain-derived neurotrophic factor (BDNF) plays a key role in neuroplasticity and has been implicated in both the pathophysiology of Major Depressive Disorder (MDD) and treatment effects. Unlike serum BDNF (s-BDNF), which largely reflects platelet-derived BDNF released during coagulation, whole blood BDNF (wb-BDNF) measures the total blood BDNF pool, minimizing confounds related to platelet aggregation. This study aims to assess whether wb-BDNF levels can serve as a biomarker for MDD and/or as a predictor of antidepressant treatment response.</div></div><div><h3>Methods</h3><div>We measured wb-BDNF before and after 4–12 weeks of escitalopram intervention in two studies: a non-randomized, single-arm clinical trial of 97 unmedicated patients with MDD and a randomized, double-blind, placebo-controlled trial with 66 healthy controls (HC). The BDNF Val65Met polymorphism was also determined.</div></div><div><h3>Results</h3><div>Unmedicated patients with MDD had 14 % lower wb-BDNF than HC, but wb-BDNF prior to intervention was not associated with symptom severity, nor did it predict drug treatment outcome in the patients. Further, improvements in depression scores after 8 and 12 weeks of escitalopram was not associated with changes in wb-BDNF. In HC, wb-BDNF was similar in the placebo and escitalopram groups after 4 weeks of intervention. BDNF polymorphism was similar between HC and MDD, and responders and non-responders, and was not associated with wb-BDNF levels.</div></div><div><h3>Conclusion</h3><div>wb-BDNF reflects the total blood BDNF pool and avoids platelet aggregation-related confounds seen in s-BDNF measures. wb-BDNF could be used as diagnosis but not as a prognosis biomarker, in MDD. Further research is needed to investigate changes in BDNF reservoirs and their implications.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"141 ","pages":"Article 111470"},"PeriodicalIF":3.9,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859936","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":"Tph2 deficiency leads to alterations in social adjustment and socio-affective communication in neonatal rats: No rescue effect of communal nesting","authors":"Tianhua Wang ,&nbsp;Aaron L. Gnade ,&nbsp;Judith R. Homberg ,&nbsp;Marta C.F. Samina ,&nbsp;Rogério C.R. Castro ,&nbsp;Sharon M. Kolk ,&nbsp;Natalia Alenina ,&nbsp;Michael Bader ,&nbsp;Jinye Dai ,&nbsp;Markus Wöhr","doi":"10.1016/j.pnpbp.2025.111469","DOIUrl":"10.1016/j.pnpbp.2025.111469","url":null,"abstract":"<div><div>Deficiency of tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme for serotonin (5-hydroxytryptamine, 5-HT) synthesis in the brain, was repeatedly reported to cause impairments in socio-affective communication and maternal affiliation across species, including mice, rats, and monkeys. We recently applied a rescue protocol in the <em>Tph2</em> knockout rat model and demonstrated that communal nesting ameliorates maternal affiliation impairments. Interestingly, however, this rescue strategy did not lead to improvements in socio-affective communication and was associated with an aggravated growth retardation phenotype in <em>Tph2</em>-deficient offspring. In the present study, we aimed to gain deeper insight into the interplay between socio-affective communication, nesting condition, and test context. To this aim, we studied <em>Tph2</em>^{<em>−/−</em>} knockout, <em>Tph2</em>^{<em>+/−</em>} heterozygous, and <em>Tph2</em>^<em>+/+</em> wildtype rat pups of both sexes, randomly assigned to standard versus communal nesting. We performed detailed spectrographic analyses and compared the emission of isolation-induced ultrasonic vocalizations under social test conditions, i.e., the maternal preference test and the homing test, to non-social test conditions, i.e., the isolation box test. Our results show that <em>Tph2</em> deficiency causes prominent alterations in isolation-induced ultrasonic calling linked to reduced maternal responsiveness, including changes in acoustic features, e.g., increased call duration but reduced frequency modulation. Remarkably, irrespective of communal nesting, <em>Tph2</em>^{<em>−/−</em>} pups typically displayed either no evidence for social adjustment or even changes opposite to <em>Tph2</em>^<em>+/+</em> littermates, suggesting a reduction and/or delay in the capability and/or motivation to appropriately adjust to changes in the social environment. Such alterations in social adjustment likely contribute to growth retardation through reduced quality of mother-pup interactions.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"141 ","pages":"Article 111469"},"PeriodicalIF":3.9,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857056","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":"Genetic and clinical factors associated with the metabolism of valproic acid in post-neurosurgery patients","authors":"Xinfeng Cai ,&nbsp;Hongping Wen ,&nbsp;Jiuhong Ma ,&nbsp;Xingang Li ,&nbsp;Gang Cheng ,&nbsp;Shuangshuang Tian ,&nbsp;Xinjing Wu ,&nbsp;Zhiying Hao ,&nbsp;Jinlin Guo","doi":"10.1016/j.pnpbp.2025.111468","DOIUrl":"10.1016/j.pnpbp.2025.111468","url":null,"abstract":"<div><div>Valproic acid (VPA) is commonly used to treat epilepsy and bipolar disorder, requiring therapeutic concentrations of 50–100 mg/L to balance efficacy and safety. Despite known clinical and genetic factors influencing VPA metabolism, integrated predictive models are limited. This study analyzed VPA concentrations in 497 samples from 275 Chinese participants, examining 23 clinical variables and 24 genetic SNPs. Participants were grouped by SNP profiles, with one cluster showing significantly elevated VPA levels. Key factors influencing VPA concentrations included genetic variants (e.g., rs12233719, rs12769205, CYP2C19 SNPs), dosage interval, solvent volume, BMI, and propacetamol co-administration. Network analysis highlighted the independence of genetic and clinical variables in influencing VPA concentrations. A regression model with the random forest algorithm demonstrated superior performance, with dosage interval, BMI, and genetic factors among the top predictors. A classification model using a parallel random forest algorithm achieved a median accuracy of 73 % in distinguishing VPA concentrations below the therapeutic threshold. Functional analyses linked associated SNPs to CYP-mediated omega-oxidation. This study highlights the interplay of genetic and clinical factors in VPA metabolism, advancing personalized dosing strategies to improve outcomes and minimize side effects.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"141 ","pages":"Article 111468"},"PeriodicalIF":3.9,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144857055","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":"Enhancing addiction care: Benefits of urinary screening with LC-HRMS (liquid chromatography-high resolution mass spectrometry) for psychoactive substances and drugs","authors":"Edouard Le Carpentier ,&nbsp;Morgane Helesbeux ,&nbsp;Vanessa Biering ,&nbsp;Aurélie Aquizerate ,&nbsp;Morgane Rousselet ,&nbsp;Malcolm Barrangou-Poueys-Darlas ,&nbsp;Audrey Verholleman ,&nbsp;Eric Dailly ,&nbsp;Matthieu Grégoire ,&nbsp;Caroline Victorri-Vigneau ,&nbsp;Mélanie Duval","doi":"10.1016/j.pnpbp.2025.111465","DOIUrl":"10.1016/j.pnpbp.2025.111465","url":null,"abstract":"<div><h3>Introduction</h3><div>Immunoassay (IA) is currently used at Nantes University Hospital to perform urine drug screening in the inpatient addiction unit. Given its numerous limitations, we aimed to assess the overall benefit of the Liquid-Chromatography-High-Resolution-Mass Spectrometry (LC-HRMS), and to identify the profiles of patients for whom its use provided a clinical benefit.</div></div><div><h3>Methods</h3><div>All adult patients admitted to this unit between January and September 2023 were systematically included. A part of the urine sample routinely collected on admission was retained for subsequent analysis by LC-HRMS. For each active molecule, the analytical performance of LC-HRMS compared with IA was evaluated by biologists. Then unit's physicians assessed for each patient whether the new data provided by LC-HRMS would have had an impact on their management. A multivariate analysis was carried out to identify the profiles of these patients.</div></div><div><h3>Results</h3><div>154 patients were included with 293 non-prescribed molecules and 434 prescribed drugs. For 2/3 of all molecules, LC-HRMS performed better than IA. Most of these molecules were not detectable by IA but some were not detected even though they belonged to the panel of detectable substances. Physicians considered that the new results provided by LC-HRMS would have had an impact on the management of 1/4 of patients. A history of opiate abuse/dependence was associated with a clinical benefit of LC-HRMS in the multivariate analysis.</div></div><div><h3>Conclusion</h3><div>These results confirm the benefit of LC-HRMS for urine drug screening in inpatient addiction units for patients with multiple substance use, especially those with a history of opioid use.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"141 ","pages":"Article 111465"},"PeriodicalIF":3.9,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144831171","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":"EEG microstates, acute phase negative symptoms of schizophrenia and antipsychotic treatment response","authors":"Marco De Pieri ,&nbsp;Vincent Rochas ,&nbsp;Dafni Apostolopoulou ,&nbsp;Matthias Kirschner ,&nbsp;Michel Sabe ,&nbsp;Javier Bartolomei ,&nbsp;Indrit Bègue ,&nbsp;Thomas Koenig ,&nbsp;Stefan Kaiser","doi":"10.1016/j.pnpbp.2025.111466","DOIUrl":"10.1016/j.pnpbp.2025.111466","url":null,"abstract":"<div><div>EEG microstates are transient scalp topographies reflecting whole-brain electric potential that remain quasi-stable for 60–120 ms. Microstates exhibitalterations across all phases of schizophrenia; especially an increased microstate C and a decreased microstate D were linked to aberrant salience.</div><div>We aimed to investigate the relationship of microstates with illness severity in the positive, negative, disorganized, excited and depressed symptoms domains, and with response to antipsychotics.</div><div>Forty-five inpatients were clinically evaluated at admission and 40 patients were also assessed after 6 weeks, to determine response to treatment; patients and 31 healthy controls underwent a 5-min resting-state EEG with 128-electrodes, to assess microstates A-E.</div><div>The severity of negative symptoms was negatively associated with microstate C time coverage (trend = − 0.5249; <em>P</em> = 0.0078) and duration (trend = −0.737; <em>P</em> = 0.0001).</div><div>In responders vs non-responders to treatment, microstate C had increased time coverage (<em>p</em> = 0.0052; d = −0.979), duration (<em>P</em> = 0.0168; <em>d</em> = −0.836) and global explained variance (GEV; <em>P</em> = 0.0046; <em>d</em> = −0.995), microstate D occurrence was reduced (<em>P</em> = 0.0044; d = −1.010), microstate E time coverage (<em>p</em> = 0.0148; d = 0.853), occurrence (<em>P</em> = 0.0037; <em>d</em> = 1.030) and GEV were reduced (<em>P</em> = 0.0115; <em>d</em> = 0.885). All the above reported findings remained significant when controlling for multiple comparisons.In conclusion, findings corroborate the hypothesis that the microstate C<img>D imbalance is a key pathophysiology mechanism of schizophrenia, herein not only related to negative symptoms, but also predicting the response to antipsychotics, together with microstate E dynamics.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"141 ","pages":"Article 111466"},"PeriodicalIF":3.9,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144805301","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":"Adolescent nicotine abstinence increases anxiety and depressive-like behaviors, alcohol consumption, oxidative stress and inflammatory response accompanied by attenuated serotonergic/dopaminergic and cholinergic function in rats","authors":"S. Mohammad Ahmadi-Soleimani ,&nbsp;Samaneh Kakhki ,&nbsp;Atefeh Shirinzadeh Feizabadi ,&nbsp;Mobina Mahdizadeh ,&nbsp;Kiarash Sabet ,&nbsp;Farimah Beheshti","doi":"10.1016/j.pnpbp.2025.111464","DOIUrl":"10.1016/j.pnpbp.2025.111464","url":null,"abstract":"<div><div>During the last decade adolescent nicotine exposure has become a growing concern worldwide and the significance of this issue has even been further highlighted by recent evidence indicating long-term behavioral complications associated with nicotine abstinence. In addition, nicotine has been suggested to serve as a gate for inclination and susceptibility to other drugs of abuse such as alcohol. The present study was designed to investigate how nicotine abstinence during adolescence may affect the expression of anxiety- and depressive-like signs, as well as the alcohol consumption in adult rats. In order to quantify the behavioral manifestations, open filed test, elevated plus maze, marble burying test and forced swimming test were applied. In addition to these behavioral tests, biochemical markers of oxidative stress, inflammatory cytokines, brain monoaminergic status and cholinergic transmission were assessed in cortical tissues. Moreover, involvement of serotonergic and dopaminergic functions were further investigated by administration of MAO-B inhibitor and SSRI drugs (selegiline and sertraline). Results indicated that nicotine abstinence increases the physical signs of anxiety and depression in parallel with exacerbation of oxidative and inflammatory profile and attenuation of monoaminergic and cholinergic tone in cortex. Another interesting finding was enhancement of ethanol drinking in nicotine-abstained group, compared to saline-treated rats. Treatment by higher doses of selegiline/sertraline could markedly prevent the mentioned behavioral and biochemical consequences induced by nicotine abstinence.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"141 ","pages":"Article 111464"},"PeriodicalIF":3.9,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144762274","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":"Potential causal link between antiseizure medication targets and cognitive function: A mendelian randomization study","authors":"Kun Zhu ,&nbsp;Jian Yu ,&nbsp;Junyan Liu ,&nbsp;Yingzi Liu ,&nbsp;Danfeng Cao ,&nbsp;Honghao Zhou ,&nbsp;Feiyue Zeng ,&nbsp;Zhaoqian Liu ,&nbsp;Xiaoyuan Mao","doi":"10.1016/j.pnpbp.2025.111463","DOIUrl":"10.1016/j.pnpbp.2025.111463","url":null,"abstract":"<div><div>A common strategy for treating epilepsy is the use of antiseizure medications (ASMs). However, ASMs usually raise concerns about accompanying side effects on the cognitive function of patients. Understanding the causal relationship between ASMs targets and cognitive function is crucial for developing therapeutic strategies that mitigate cognitive side effects while effectively managing seizures. This study aimed to explore the relationship between expression of ASMs targets and cognitive function through Mendelian randomization (MR). ASMs targets were collected from the Drugbank database, and genetic instruments for these targets were identified from publicly available expression quantitative trait loci (eQTL) data of blood samples. They underwent two-sample MR and summary data-based MR analyses with two genome-wide association study (GWAS) datasets on cognitive outcomes. Further sensitivity analyses such as assessment of horizontal pleiotropy, colocalization, and multiple tissue sensitivity were performed to confirm the discovered MR associations. A total of 160 targets for 38 approved ASMs were collected. Among these target genes, 3789 SNPs with <em>p</em>-value &lt;5.0e-8 in whole blood were extracted from the eQTL dataset. Results from the MR analysis indicated that carbonic anhydrase 13 (CA13) has a potential causal link with both cognitive performance and fluid intelligence score, independent of epilepsy. The expression of CA13, an ASM target, is significantly associated with cognitive function, highlighting the potential for this target to influence cognitive outcomes during epilepsy treatment. While the findings suggest CA13 could be a potential modulator of cognitive function, MR cannot definitively confirm causality, and further functional studies are required to validate this association and elucidate the underlying mechanisms.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"141 ","pages":"Article 111463"},"PeriodicalIF":3.9,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144739270","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":"Uric acid metabolism and brain dysfunction linking childhood maltreatment to self-harm in adolescents with mood disorders","authors":"Yufei Wu ,&nbsp;Jiaxin Li ,&nbsp;Junjie Zheng ,&nbsp;Ran Zhang ,&nbsp;Juan Liu ,&nbsp;Yao Xiao ,&nbsp;Jingyu Yang ,&nbsp;Jingshuai Zhou ,&nbsp;Pengfei Zhao ,&nbsp;Lifei Wang ,&nbsp;Yuenan Yu ,&nbsp;Rongxin Zhu ,&nbsp;Fei Wang","doi":"10.1016/j.pnpbp.2025.111460","DOIUrl":"10.1016/j.pnpbp.2025.111460","url":null,"abstract":"<div><h3>Background</h3><div>Childhood maltreatment (CM) elevates self-harm behavior (SHB) risk, potentially through uric acid (UA) dysregulation and UA-mediated neural dysfunction. Targeting these mechanisms may offer valuable insights into preventive strategies.</div></div><div><h3>Methods</h3><div>This study analyzed 540 adolescent inpatients (12–18 years, 74.6 % female) with mood disorders and major depressive episodes, stratified into SHB (<em>N</em> = 397) and NSHB (<em>N</em> = 143) groups. Multimodal assessments incorporated clinical evaluations, serum UA quantification, and resting-state functional magnetic resonance imaging (rs-fMRI) with mean amplitude of low-frequency fluctuations (mALFF) analysis. Analyses encompassed between-group comparisons, logistic regression, and structural equation modeling (SEM) to identify SHB pathways.</div></div><div><h3>Results</h3><div>Stepwise regression identified elevated serum UA as a protective factor against SHB (<em>β</em> = −0.011, <em>P</em> &lt; 0.001; OR = 0.989, 95 %CI: 0.984–0.994). Significant risk factors included: elevated HAMA (<em>β</em> = 0.089, <em>P</em> &lt; 0.01; OR = 1.094, 95 %CI: 1.025–1.166), higher CTQ emotional abuse (<em>β</em> = 0.142, <em>P</em> &lt; 0.001; OR = 1.153, 95 %CI: 1.059–1.255), and reduced ALFF in bilateral middle temporal gyri (left: <em>β</em> = −3.226, <em>P</em> &lt; 0.01; OR = 0.040, <em>P</em> &lt; 0.01, 95 %CI: 0.004–0.399; right: <em>β</em> = −3.008, <em>P</em> &lt; 0.01; OR = 0.049, <em>P</em> &lt; 0.01, 95 %CI: 0.007–0.352). Critically, SEM revealed that CM indirectly increased SHB risk through a sequential pathway: CM led to UA dysregulation, impairing spontaneous activity within the middle temporal gyri, thereby elevating SHB risk (<em>β</em> = 0.020, <em>P</em>_corrected &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>Our findings reveal that childhood maltreatment elevates SHB risk via UA-linked metabolic dysregulation and middle temporal gyri hypoactivity, highlighting purine metabolism and temporal circuits as promising targets for precision interventions.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"141 ","pages":"Article 111460"},"PeriodicalIF":3.9,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144735483","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":"The role of BDNF on food intake and overweight: Linking neuroplasticity and obesity","authors":"Andrey Sequeira-Cordero ,&nbsp;Juan C. Brenes ,&nbsp;Rebeca Vindas-Smith","doi":"10.1016/j.pnpbp.2025.111457","DOIUrl":"10.1016/j.pnpbp.2025.111457","url":null,"abstract":"<div><div>Overweight and obesity are escalating global health issues significantly driven by poor diet quality and energy balance alterations. The typical Western diet, rich in saturated fats, refined sugars, and salt, not only increases calorie intake but also modifies eating behaviors. Among many neurobiological factors, brain-derived neurotrophic factor (BDNF) has emerged as a crucial modulator of these behaviors. BDNF controls neural development, neurogenesis, synaptogenesis, neuroprotection, survival, and neural signaling. Its role in eating behaviors is complex as it exerts different and sometimes opposing effects depending on the form (i.e., mature BDNF, pro-BDNF, and its pro-domain part) and the brain region involved. This review provides an integrated view of how BDNF relates to food intake and obesity along three main lines. Firstly, exposure to rewarding food triggers BDNF expression/release in the hypothalamus, reducing appetite and achieving satiety. Secondly, BDNF's expression/release within the reward system —e.g., the ventral tegmental area, nucleus accumbens, and dorsal striatum— modulates food-induced motivational/hedonic responses. Thirdly, BDNF in the prefrontal cortex and the hippocampus influences executive functions, learning, and memory processes, modifying decision-making about and behavioral responses to food and its related cues. However, repeated exposure to highly palatable foods induces long-term changes in BDNF expression/release, which along with alterations in other neurobiological factors, may change appetite patterns and hedonic responses. These changes could result in an increase of hunger and food craving leading to overeating and weight gain. This panorama positions BDNF at the forefront in the field of nutrition and related disciplines in the study of obesity.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"141 ","pages":"Article 111457"},"PeriodicalIF":5.3,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687035","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}