Journal of Neuroendocrinology最新文献

{"title":"Bonding before birth: Maternal–fetal attachment and maternal cortical connectivity in late pregnancy","authors":"Kathy Ayala,&nbsp;Kezhu Niu,&nbsp;Clíona L. Murray,&nbsp;Kristin Voegtline,&nbsp;Helena J. V. Rutherford","doi":"10.1111/jne.70251","DOIUrl":"10.1111/jne.70251","url":null,"abstract":"<p>Emerging research suggests that pregnancy and motherhood are associated with neural adaptations that support caregiving. Maternal–fetal attachment (MFA), representing the emotional bond between a pregnant woman and their fetus, is thought to be an early precursor to maternal–infant bonding and sensitive caregiving, yet its neural underpinnings remain largely unexplored. Resting-state electroencephalogram (EEG) coherence is a well-established measure of regional cortical connectivity and has been implicated in cognitive, attentional, and emotional processes related to parenting and might be implicated in MFA. Thirty-five pregnant women in their third trimester (mean 36.8 gestational weeks) participated. Resting-state EEG was collected, and alpha band coherence was computed for intra-frontal, intra-parietal, and frontoparietal regions. MFA was assessed using the Prenatal Attachment Inventory-Revised (PAI-R). Increased left frontoparietal and intra-frontal alpha coherence was associated with higher scores on the anticipation and interaction subscales of the PAI-R. These associations remained after controlling for parity and gestational age. No significant associations were observed between alpha coherence and the differentiation PAI-R subscale. These findings suggest that individual differences in cortical connectivity are associated with MFA, particularly anticipatory and interactional aspects of psychological engagement with the fetus. Identifying neural correlates of MFA suggests that maternal attachment-related processes toward the fetus are reflected in brain connectivity during pregnancy and offers insight into the neurobiological basis of early bonding.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906332","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":"When CO2 sensing fails: Protective effects of sex hormones and potential mechanisms","authors":"Tara A. Janes,&nbsp;Silvia Cardani,&nbsp;Silvia Pagliardini","doi":"10.1111/jne.70256","DOIUrl":"10.1111/jne.70256","url":null,"abstract":"<p>Breathing movements driven by the brainstem rhythmogenic neural networks rely on chemosensory inputs to produce a motor output that is homeostatically adjusted to the prevailing metabolic demand. The central CO₂ chemoreflex is a critical component of respiratory neural circuitry, as defects in these sensors cause hypoventilation syndromes, which are typically difficult to manage pharmacologically. Progesterone has long been known to stimulate breathing in both sexes, and remarkably, a potent progestin drug, etonogestrel (ETO), has been shown to enhance CO₂-chemosensitivity in animal models and in a subset of female patients affected by congenital central hypoventilation syndrome. Our recent work shows that systemic chronic ETO treatment recovered the CO₂ chemoreflex in female rats in which &lt;80% of neurons of the key CO₂ chemosensory structure of the retrotrapezoid nucleus (RTN) were eliminated, whereas male rats with similar lesions and ETO serum levels did not show recovery of the CO₂ chemoreflex. Interestingly, female respiratory recovery was associated with increased expression of the pH sensors <i>Task2</i> and <i>Gpr4</i> mRNA in the surviving RTN neurons, suggesting that progestin drugs may recover the CO₂ chemoreflex responses in a sex-specific fashion.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13551639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906503","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":"Marine flatworms as windows into the evolution of bilaterian neuropeptide signalling","authors":"Ryo Nakamura,&nbsp;Mayuko Hamada,&nbsp;Xavier Bailly,&nbsp;Hirotaka Sakamoto,&nbsp;Tatsuya Sakamoto","doi":"10.1111/jne.70259","DOIUrl":"10.1111/jne.70259","url":null,"abstract":"<p>The evolutionary origin(s) of neuropeptide signalling is still largely unknown. It has been hypothesised that signal transmission via neuropeptides played a crucial role in the regulation of nervous systems in the bilaterian ancestor. Identification, expression and functional analyses of neuropeptides and their receptors across different taxonomic groups are important for better understanding the origin(s) of bilaterian neuropeptide signalling. An example is flatworms belonging to the Platyhelminthes (spiralian protostomes) and Xenacoelomorpha (sister to all Bilateria or sister to Ambulacraria). Despite their simple morphology (i.e., a body plan lacking a coelom and circulatory system), they often possess brain-like central nervous systems and a number of bilaterian-conserved neuropeptides. This feature makes them useful models for analyses of neuropeptides and their links to nervous systems. Although previous studies have revealed orthologous relationships between vertebrate neuropeptides and those found in both marine Platyhelminthes and Xenacoelomorpha, our work suggests possible ancestral functions of vasopressin/oxytocin (VP/OT) peptides (platytocin) in these groups.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13551398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906370","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":"Molecular characterization of circannual interval timing in the preoptic area and anteroventral periventricular nucleus in the Djungarian hamster (Phodopus sungorus)","authors":"Calum Stewart,&nbsp;Christopher Marshall,&nbsp;Tyler J. Stevenson","doi":"10.1111/jne.70258","DOIUrl":"10.1111/jne.70258","url":null,"abstract":"<p>Most temperate animals exhibit seasonal rhythms in reproductive physiology and behaviour. Gonadotropin-releasing hormone (<i>GnRH</i>) cells in the preoptic area (POA) and kisspeptin (<i>Kiss</i>) cells in the anteroventral periventricular (AvPv) nucleus are critical for timing photoperiod-induced changes in seasonal reproduction. In response to prolonged exposure to photoperiod cues, many rodents exhibit endogenously generated programmed changes in physiology that reflect a circannual timing mechanism. Here we used transcriptome sequencing coupled with measurements of surface body temperature and testes mass across a simulated circannual interval timer to characterize the molecular changes involved in the seasonal control of reproduction and surface body temperature. Adult male Djungarian hamsters were collected after exposure to short photoperiod on 4-week intervals from 4 to 32 weeks. The POA and AvPv transcriptomes from short-photoperiod hamsters were compared to a long photoperiod reference group. Our analyses confirmed robust photoperiodic regulation of <i>Kiss1</i> mRNA expression in the AvPv. Weighted gene co-expression network analyses (WGCNAs) identified hundreds (POA: 211, AvPv: 415) of transcripts that were associated with testes mass. Gene set enrichment analysis (GSEA) identified ‘gonadotropin secretion’ and ‘glial cell proliferation’ as the primary pathways associated with circannual interval timing. Vimentin had a strong negative association with testes mass, indicating AvPv glial morphology may increase during gonadal involution. In the POA, pathways associated with ‘regulation at synapse’ and ‘regulation of synaptic plasticity’ were highly enriched and transcripts positively associated with gonadal involution indicated that ribosomal plasticity and intracellular calcium signalling are key mechanisms involved in seasonal reproduction. WGCNAs identified 567 transcripts in the POA that were significantly associated with surface body temperature. GSEA discovered thyrotrophin-releasing hormone was significantly negatively associated with surface body temperature. Overall, the POA and AvPv transcriptome datasets provide the foundation to expand our understanding of the molecular representation of seasonal time in the mammalian hypothalamus.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900702","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":"A symmetric systemic challenge elicits a right-biased response mediated by vasopressin signaling","authors":"Hiroyuki Watanabe,&nbsp;Yaromir Kobikov,&nbsp;Sara Yusuf Mohamed,&nbsp;Karen Rich,&nbsp;Daniil Sarkisyan,&nbsp;Olga Nosova,&nbsp;Alfhild Grönbladh,&nbsp;Mathias Hallberg,&nbsp;Jens Schouenborg,&nbsp;Georgy Bakalkin,&nbsp;Mengliang Zhang","doi":"10.1111/jne.70257","DOIUrl":"10.1111/jne.70257","url":null,"abstract":"<p>Bilaterian animals exhibit functional asymmetry—population-level, directional left–right differences in physiology and behavior, including responses to spatially symmetric environmental challenges. Whether such symmetry-to-asymmetry conversion can be driven at the systems level by neurohormonal regulators remains unclear. Here we tested whether a spatially symmetric neuroendocrine challenge—water deprivation (WD)—can elicit a directional left–right physiological response in rats using hindlimb postural asymmetry (HL-PA), a binary readout that quantifies left- versus right-sided hindlimb flexion. Twenty-four hours of WD induced robust HL-PA with right hindlimb flexion, revealed under anesthesia. The asymmetry persisted after complete thoracic spinal cord transection, suggesting that humoral signaling, rather than descending neural commands, maintains the postural bias. Dehydration activated the hypothalamic arginine vasopressin (AVP) system. Furthermore, a V1B antagonist (SSR-149415) and a V1A/V2 antagonist (conivaptan) abolished and partially attenuated WD-induced HL-PA, respectively, supporting an AVP-dependent mechanism that likely operates at least two anatomical sites. AVP signaling may involve pituitary V1B-dependent endocrine output and spinal V1A actions; consistent with the latter, expression of AVP V1A receptors is right-biased in lumbar spinal cord. Together, these findings identify WD as a symmetric systemic challenge capable of unmasking a directional peripheral bias and implicate vasopressin signaling in left–right physiological regulation. More broadly, they suggest that symmetric homeostatic challenges engage neuroendocrine mechanisms that shift the balance between left- and right-sided physiological functions.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13547646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900727","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":"Evaluation of metabolic, reproductive, and gut microbiota alterations in a comparative study of different preclinical models of polycystic ovary syndrome","authors":"Nisha H. Khobragade,&nbsp;Devang B. Sheth,&nbsp;Chirag A. Patel,&nbsp;Jayesh V. Beladiya,&nbsp;Sandip Patel,&nbsp;Mittal Dalal,&nbsp;Sandip Dholakia","doi":"10.1111/jne.70247","DOIUrl":"10.1111/jne.70247","url":null,"abstract":"<p>Polycystic ovary syndrome (PCOS) is a multifaceted, complex metabolic and endocrine disease where gut flora is considered an important factor in causing PCOS. This study aimed to identify a suitable PCOS model that contributes to gut microbial dysbiosis and metabolic and hormonal disturbances. Prepubertal SD rats were administered with normal control (NC), dihydrotestosterone (DHT), DHT with fructose (F), DHT+ high fat diet (HFD) for 91 days, dehydroepiandrosterone (DHEA), DHEA with fructose, DHEA with HFD for 30 days, sodium valproate (SV), sodium valproate with fructose, and sodium valproate with HFD for 21 days. The estrous cycles were assessed over this timeframe. At the end of the experiment, superoxide dismutase and uterine and ovarian morphology were evaluated, along with hormone levels, lipid profiles, and 16S rRNA genomic sequencing. All models exhibited PCOS characteristics, including hormonal imbalances, insulin resistance (<i>p</i> ≤ .001), multiple follicular cysts on ultrasonography, and histological alterations. Gut microbial dysbiosis was observed across all PCOS-induced groups; however, the DHT alone group showed more pronounced alterations in microbial composition than the other experimental groups. Specifically, the DHT alone group exhibited reduced abundance of Firmicutes and increased abundance of Proteobacteria. Among the evaluated models, the DHT-only model showed more pronounced metabolic, hormonal, reproductive, and gut microbial alterations and may serve as a suitable model for PCOS research.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891968","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":"Examining dynamic changes in prefrontal connectivity and internalizing symptoms during the first and third trimesters of pregnancy","authors":"Emily B. K. Thomas,&nbsp;Micah A. Williams,&nbsp;Patrick Breheny,&nbsp;Abigél Miskolczi,&nbsp;Ö. Ece Demir-Lira","doi":"10.1111/jne.70252","DOIUrl":"10.1111/jne.70252","url":null,"abstract":"<p>Pregnancy is characterized by pronounced neuroplasticity and heightened risk for psychopathology. While previous research has primarily examined postpartum depression, less work has investigated changes in internalizing symptoms measured dimensionally across the peripartum period. Furthermore, limited research has identified functional changes in the prefrontal cortex (PFC) across pregnancy, a brain area implicated in psychopathology. Understanding the dynamic changes in internalizing symptoms and PFC neuroconnectivity throughout pregnancy and their interrelations is crucial for early identification of perinatal psychopathology. This pre-registered longitudinal study examined changes in and associations between internalizing symptoms and PFC functional connectivity throughout the first and third trimesters of pregnancy. Pregnant individuals recruited from a community sample of females engaged in prenatal care (<i>N</i> = 60, <i>M</i>_age = 32.31, SD = 5.34, 90% White, 91.7% non-Hispanic/Latine) completed structured clinical interviews assessing mood and anxiety symptoms and resting-state functional near-infrared spectroscopy measuring PFC connectivity during the first and third trimesters of pregnancy. From the first to third trimester, longitudinal results revealed a significant decrease in symptoms of distress and fear and significant increases in neuroconnectivity anchored in left medial frontal areas of the PFC. Cross-sectionally, higher first trimester fear was associated with lower within-region right medial PFC and higher within-region left medial PFC connectivity. Longitudinal decreases in distress from first to third trimester were associated with increased connectivity between left medial and right lateral PFC, alongside weakened connectivity between bilateral medial frontal regions. These findings demonstrate that internalizing symptoms relate to prefrontal connectivity from first to third trimester in a community sample of pregnant women. Examining internalizing symptoms dimensionally across pregnancy allows for characterization of the full range of symptoms that impact pregnant individuals. Future research should explore prevention and intervention implications of the relations between neural profiles and internalizing symptoms during pregnancy to improve long-term outcomes for the mother and child.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891955","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":"Periestropause enhances hypoxia-induced panic and microglial remodelling without altering respiratory control","authors":"Angela Cristina Nicola,&nbsp;Luana Tenório-Lopes,&nbsp;Luis Gustavo A. Patrone,&nbsp;Mariana Bernardes-Ribeiro,&nbsp;Heloisa H. Vilela-Costa,&nbsp;Daniele Gandra,&nbsp;Ana Clara Campideli-Santana,&nbsp;Raphael E. Szawka,&nbsp;Kênia C. Bícego,&nbsp;Rita Cássia M. Dornelles,&nbsp;Luciane H. Gargaglioni","doi":"10.1111/jne.70254","DOIUrl":"10.1111/jne.70254","url":null,"abstract":"<p>Perimenopause is characterised by irregular reproductive cycles and hormonal fluctuations, notably decreased estradiol (E₂), which are linked to increased susceptibility to panic disorder and neuroinflammation. We examined whether panic-related respiratory and behavioural responses to respiratory challenges vary across reproductive stages. Female rats with regular estrous cycles (RC), representing reproductive cyclicity, and rats in periestropause (PE), a stage similar to perimenopause, were exposed to normoxia, hypoxia, and hypercapnia. Ventilation (V̇_E) and metabolism (V̇O₂) were measured during diestrus in RC and PE rats. Additionally, to measure levels of neuroinflammation, microglial reactivity in the Locus coeruleus (LC) in response to hypoxia-induced panic-like attacks was assessed. Under normoxia, there were no differences in V̇_E or V̇O₂ between groups. Hypercapnia increased V̇_E in both groups by elevating respiratory frequency (f_R) and tidal volume (V_T), without changing body temperature (Tb). Hypoxia also raised V̇_E in both groups, primarily driven by increased f_R, and hypoxia-induced hypothermia occurred in RC and PE females. Both hypercapnia and hypoxia elevated the V̇_E/V̇O₂ ratio. Exposure to 7% O₂ heightened panic-like behaviours in PE rats. Hypoxia increased LC microglial number, density, and mean soma size, while decreasing arborization area. PE rats also showed a higher microglial morphological index and a shorter nearest neighbour distance (NND). Jump frequency and freezing duration positively correlated with the morphological index and negatively with arborization area. These findings suggest that respiratory regulation remains intact, but behavioural and neuroimmune responses are amplified during the transition to estropause, heightening vulnerability to panic and anxiety-related disorders in ageing females.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880965","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":"Multidimensional maturation of oxytocin neurons: A principal component analysis of postnatal development","authors":"Yuko Maejima,&nbsp;Manabu Suzuki,&nbsp;Wataru Matsuoka,&nbsp;Yoichi Ueta,&nbsp;Kenju Shimomura","doi":"10.1111/jne.70260","DOIUrl":"10.1111/jne.70260","url":null,"abstract":"<p>Oxytocin (Oxt) is a neuropeptide critical for higher brain functions, with its physiological functions dependent on the activity of Oxt-producing neurons in the paraventricular nucleus (PVN). However, the postnatal maturation process of these neurons remains poorly understood, particularly whether it involves a uniform trajectory or a dynamic functional reorganization. Here, we investigated the electrophysiological maturation of PVN Oxt neurons in rats using a multifaceted approach including electrophysiology, principal component analysis (PCA), and f–I curve fitting. Our analysis revealed a highly heterogeneous maturation timeline for individual electrophysiological parameters. While action potential amplitude and half-width matured relatively early, the resting membrane potential (RMP) and firing threshold showed a much more protracted maturation. To comprehensively capture this, we applied PCA and found that the first principal component (PC1) exhibited a striking inverted U-shaped pattern over time. This pattern suggests a dynamic transition through three distinct functional states: an initial immature state, an intermediate transitional state, and a later mature state. Furthermore, <i>f</i>–<i>I</i> curve fitting provided mechanistic insights, identifying a “high-gain” state around postnatal Day 7, characterized by high firing threshold (<i>I</i>_th) and gain (<i>k</i>). This period temporally overlaps with peak Oxt receptor expression, hinting at a critical window for experience-dependent circuit refinement. Our findings provide a new perspective on neuronal maturation as a complex process of dynamic functional reorganization. The identified “high-gain” state may represent a critical period for Oxt system development, offering a crucial foundation for understanding neurodevelopmental disorders and developing targeted early interventions.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887980","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":"The neurosteroid paradigm in perinatal depression: From pathophysiology to precision therapeutics","authors":"Nevena V. Radonjić,&nbsp;Khatiya C. Moon,&nbsp;Kristina M. Deligiannidis","doi":"10.1111/jne.70253","DOIUrl":"10.1111/jne.70253","url":null,"abstract":"<p>Neurosteroids and their role in the pathophysiology of perinatal depression have been in the focus of scientific investigation for several decades. Recently, two synthetic analogs of the neurosteroid allopregnanolone—brexanolone and zuranolone—received approval in the United States for the treatment of postpartum depression (PPD) exhibiting a rapid, long-lasting antidepressant effect through a novel mechanism of action. These developments mark a milestone in psychiatric research and advancement in available treatment options. In this review, we examine the role of neurosteroids in perinatal depression, with particular emphasis on their impact on network states and functional connectivity. We synthesize current clinical experience with brexanolone and zuranolone in the treatment of PPD, highlighting efficacy and practical considerations. Finally, we explore emerging precision medicine approaches that leverage the heterogeneity of clinical presentations and treatment responses in PPD to guide the development of targeted therapeutic strategies for this widely prevalent and debilitating condition.</p>","PeriodicalId":16535,"journal":{"name":"Journal of Neuroendocrinology","volume":"38 9","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880949","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}