{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T06:42:03Z","timestamp":1776062523226,"version":"3.50.1"},"reference-count":77,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Anxiety is a prevalent non-motor symptom in Parkinson\u2019s disease (PD) with observed sex differences. This study aimed to investigate sex-specific gray matter volume (GMV) associations with anxiety and preliminarily explore the potential mediating role of these regional GMV alterations in the relationship between depressive and anxiety symptoms in\n                      <jats:italic>de novo<\/jats:italic>\n                      PD patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A total of 108\n                      <jats:italic>de novo<\/jats:italic>\n                      PD patients were enrolled. Anxiety and depressive symptoms were assessed using the Hamilton Anxiety Rating Scale (HAMA) and the 24-item Hamilton Depression Rating Scale (HAMD-24), respectively. Whole-brain GMV was analyzed using voxel-based morphometry (VBM) on T1-weighted MRI data. A 2\u202f\u00d7\u202f2 analysis of variance (sex \u00d7 anxiety status) was conducted to examine main and interaction effects, controlling for age, education, HAMD-24 total score, and total intracranial volume. Sex-stratified, cross-sectional mediation analyses were subsequently performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Whole-brain analysis revealed a significant sex-by-anxiety interaction in the right precuneus (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.015). Post-hoc correlation analyses indicated that anxiety severity was negatively associated with GMV in the right precuneus in male patients (\n                      <jats:italic>r<\/jats:italic>\n                      \u202f=\u202f\u22120.387,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.010) and with GMV in the left insula in female patients (\n                      <jats:italic>r<\/jats:italic>\n                      \u202f=\u202f\u22120.437,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.004). Mediation analyses suggested that right precuneus GMV partially mediated the association between HAMD-24 and HAMA scores in males (mediation proportion: 17.1%). Similarly, left insular GMV partially mediated this association in females (mediation proportion: 15.4%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study identified sex-specific GMV correlates of anxiety in\n                      <jats:italic>de novo<\/jats:italic>\n                      PD, primarily involving the precuneus in males and the insula in females. These structural differences may partially underlie the co-occurrence of depressive and anxiety symptoms, highlighting sexually dimorphic neuroanatomical substrates for affective disturbances in PD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1769488","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T05:43:25Z","timestamp":1776059005000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Sex-specific gray matter underpinnings of anxiety and their mediating mechanisms in de novo Parkinson\u2019s disease"],"prefix":"10.3389","volume":"18","author":[{"given":"Guixiang","family":"He","sequence":"first","affiliation":[{"name":"Department of Neurology, Affiliated Hospital 6 of Nantong University, Yancheng Third People's Hospital","place":["Yancheng, China"]},{"name":"Department of Neurology, Affiliated Nanjing Brain Hospital, Nanjing Medical University","place":["Nanjing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofang","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Affiliated Nanjing Brain Hospital, Nanjing Medical University","place":["Nanjing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Neurology, Affiliated Nanjing Brain Hospital, Nanjing Medical University","place":["Nanjing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingling","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Affiliated Hospital 6 of Nantong University, Yancheng Third People's Hospital","place":["Yancheng, China"]},{"name":"Department of Neurology, Affiliated Nanjing Brain Hospital, Nanjing Medical University","place":["Nanjing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haicun","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Affiliated Hospital 6 of Nantong University, Yancheng Third People's Hospital","place":["Yancheng, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haihua","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurology, Affiliated Hospital 6 of Nantong University, Yancheng Third People's Hospital","place":["Yancheng, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiguo","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Affiliated Nanjing Brain Hospital, Nanjing Medical University","place":["Nanjing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanzhang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Immunology, School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine","place":["Nanjing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pinglei","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Affiliated Hospital 6 of Nantong University, Yancheng Third People's Hospital","place":["Yancheng, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.neuroimage.2007.07.007","article-title":"A fast diffeomorphic image registration algorithm","volume":"38","author":"Ashburner","year":"2007","journal-title":"NeuroImage"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1006\/nimg.2000.0582","article-title":"Voxel-based morphometry\u2014the methods","volume":"11","author":"Ashburner","year":"2000","journal-title":"NeuroImage"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1038\/s41583-021-00513-0","article-title":"Sex differences in anxiety and depression: circuits and mechanisms","volume":"22","author":"Bangasser","year":"2021","journal-title":"Nat. Rev. Neurosci."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e775","DOI":"10.1212\/wnl.0000000000200667","article-title":"Novelty-related fMRI responses of precuneus and medial temporal regions in individuals at risk for Alzheimer disease","volume":"99","author":"Billette","year":"2022","journal-title":"Neurology"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1002\/mds.26643","article-title":"Prevalence of anxiety in Parkinson's disease: a systematic review and meta-analysis","volume":"31","author":"Broen","year":"2016","journal-title":"Mov. Disord."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1101\/lm.70504","article-title":"Sex-related hemispheric lateralization of amygdala function in emotionally influenced memory: an FMRI investigation","volume":"11","author":"Cahill","year":"2004","journal-title":"Learn. Mem."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1016\/j.biopsych.2020.08.016","article-title":"Dopamine release in the midbrain promotes anxiety","volume":"88","author":"Calipari","year":"2020","journal-title":"Biol. Psychiatry"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1002\/mds.28404","article-title":"Neuroimaging of anxiety in Parkinson's disease: a systematic review","volume":"36","author":"Carey","year":"2021","journal-title":"Mov. Disord."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/s40120-024-00687-6","article-title":"Sex differences in Parkinson's disease: a narrative review","volume":"14","author":"Cattaneo","year":"2025","journal-title":"Neurol. Ther."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1136\/jnnp.73.6.629","article-title":"The Parkinson's disease sleep scale: a new instrument for assessing sleep and nocturnal disability in Parkinson's disease","volume":"73","author":"Chaudhuri","year":"2002","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1718","DOI":"10.3390\/cells13201718","article-title":"The role of the insular cortex and serotonergic system in the modulation of long-lasting nociception","volume":"13","author":"Coffeen","year":"2024","journal-title":"Cells"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"3598","DOI":"10.1093\/brain\/awad181","article-title":"The functional role of the precuneus","volume":"146","author":"Dadario","year":"2023","journal-title":"Brain"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.neubiorev.2019.10.015","article-title":"Stress-induced plasticity and functioning of ventral tegmental dopamine neurons","volume":"108","author":"Douma","year":"2020","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1016\/j.parkreldis.2012.05.022","article-title":"Anxiety is associated with striatal dopamine transporter availability in newly diagnosed untreated Parkinson's disease patients","volume":"18","author":"Erro","year":"2012","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1186\/s12906-023-04240-0","article-title":"Effectiveness of an amygdala and insula retraining program combined with mindfulness training to improve the quality of life in patients with long COVID: a randomized controlled trial protocol","volume":"23","author":"Gasi\u00f3n","year":"2023","journal-title":"BMC Complement. Med. Ther."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1002\/mds.20213","article-title":"Movement disorder society task force report on the Hoehn and Yahr staging scale: status and recommendations","volume":"19","author":"Goetz","year":"2004","journal-title":"Mov. Disord."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"S147","DOI":"10.3233\/jpd-230211","article-title":"Alleviating stress in Parkinson's disease: symptomatic treatment, disease modification, or both?","volume":"14","author":"Goltz","year":"2024","journal-title":"J. Parkinsons Dis."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1111\/j.2044-8341.1959.tb00467.x","article-title":"The assessment of anxiety states by rating","volume":"32","author":"Hamilton","year":"1959","journal-title":"Br. J. Med. Psychol."},{"key":"ref19","first-page":"21","article-title":"Rating depressive patients","volume":"41","author":"Hamilton","year":"1980","journal-title":"J. Clin. Psychiatry"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"10240","DOI":"10.1073\/pnas.0701519104","article-title":"Network structure of cerebral cortex shapes functional connectivity on multiple time scales","volume":"104","author":"Honey","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1212\/wnl.40.10.1529","article-title":"Variable expression of Parkinson's disease: a base-line analysis of the DATATOP cohort. The Parkinson Study Group","volume":"40","author":"Jankovic","year":"1990","journal-title":"Neurology"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1136\/jnnp-2017-316193","article-title":"Serotonin transporter binding and anxiety symptoms in Parkinson's disease","volume":"89","author":"Joling","year":"2018","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.yfrne.2017.09.002","article-title":"Sex differences in Parkinson's disease: features on clinical symptoms, treatment outcome, sexual hormones and genetics","volume":"50","author":"Jurado-Coronel","year":"2018","journal-title":"Front. Neuroendocrinol."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/s13195-025-01709-7","article-title":"Effects of 52 weeks of precuneus rTMS in Alzheimer's disease patients: a randomized trial","volume":"17","author":"Koch","year":"2025","journal-title":"Alzheimer's Res. Ther."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.jad.2017.12.086","article-title":"The regional homogeneity of cingulate-precuneus regions: the putative biomarker for depression and anxiety","volume":"229","author":"Lai","year":"2018","journal-title":"J. Affect. Disord."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"2433","DOI":"10.1038\/s41467-025-56660-w","article-title":"Dopaminergic modulation and dosage effects on brain state dynamics and working memory component processes in Parkinson's disease","volume":"16","author":"Lee","year":"2025","journal-title":"Nat. Commun."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1002\/mds.23184","article-title":"Anxiety rating scales in Parkinson's disease: a validation study of the Hamilton anxiety rating scale, the Beck anxiety inventory, and the hospital anxiety and depression scale","volume":"26","author":"Leentjens","year":"2011","journal-title":"Mov. Disord."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"487","DOI":"10.3233\/jad-160119","article-title":"Mini-mental state examination in elderly Chinese: a population-based normative study","volume":"53","author":"Li","year":"2016","journal-title":"J. Alzheimer's Dis"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"2221","DOI":"10.1038\/s41467-020-15920-7","article-title":"Identification of a prefrontal cortex-to-amygdala pathway for chronic stress-induced anxiety","volume":"11","author":"Liu","year":"2020","journal-title":"Nat. Commun."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"e70123","DOI":"10.1111\/bcpt.70123","article-title":"The incidence of benzodiazepine and benzodiazepine-related drug use in people with and without Parkinson's disease-a nationwide cohort study","volume":"137","author":"Lonka","year":"2025","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.dcn.2010.10.001","article-title":"Local brain connectivity and associations with gender and age","volume":"1","author":"Lopez-Larson","year":"2011","journal-title":"Dev. Cogn. Neurosci."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"2486","DOI":"10.1093\/brain\/aww162","article-title":"The prominent role of serotonergic degeneration in apathy, anxiety and depression in de novo Parkinson's disease","volume":"139","author":"Maillet","year":"2016","journal-title":"Brain"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/s41531-025-00907-2","article-title":"Systematic review and consensus conceptual model of meaningful symptoms and functional impacts in early Parkinson's disease","volume":"11","author":"Mammen","year":"2025","journal-title":"NPJ Parkinsons Dis."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"106120","DOI":"10.1016\/j.neubiorev.2025.106120","article-title":"Predicting responses of neuromodulation and psychotherapies for major depressive disorder: a coordinate-based meta-analysis of functional magnetic resonance imaging studies","volume":"172","author":"Mao","year":"2025","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/npp.2015.171","article-title":"Stress effects on neuronal structure: Hippocampus, amygdala, and prefrontal cortex","volume":"41","author":"McEwen","year":"2016","journal-title":"Neuropsychopharmacology"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1016\/j.neuron.2019.03.004","article-title":"Circuit mechanisms of Parkinson's disease","volume":"101","author":"McGregor","year":"2019","journal-title":"Neuron"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1038\/s41582-019-0294-x","article-title":"Sex differences in movement disorders","volume":"16","author":"Meoni","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"5604","DOI":"10.1038\/s41467-025-60512-y","article-title":"Acute stress causes sex-specific changes to ventral subiculum synapses, circuitry, and anxiety-like behavior","volume":"16","author":"Miller","year":"2025","journal-title":"Nat. Commun."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/s41586-019-1235-y","article-title":"Dissociable dopamine dynamics for learning and motivation","volume":"570","author":"Mohebi","year":"2019","journal-title":"Nature"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"104736","DOI":"10.1016\/j.neubiorev.2022.104736","article-title":"Anterior insula as a gatekeeper of executive control","volume":"139","author":"Molnar-Szakacs","year":"2022","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.jns.2011.06.056","article-title":"Increased dopamine transporter density in Parkinson's disease patients with social anxiety disorder","volume":"310","author":"Moriyama","year":"2011","journal-title":"J. Neurol. Sci."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/j.eurpsy.2007.02.006","article-title":"Insular cortex and neuropsychiatric disorders: a review of recent literature","volume":"22","author":"Nagai","year":"2007","journal-title":"Eur. Psychiatry"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.cell.2014.09.020","article-title":"Oxytocin modulates female sociosexual behavior through a specific class of prefrontal cortical interneurons","volume":"159","author":"Nakajima","year":"2014","journal-title":"Cell"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.tins.2017.02.002","article-title":"The insula: an underestimated brain area in clinical neuroscience, psychiatry, and neurology","volume":"40","author":"Namkung","year":"2017","journal-title":"Trends Neurosci."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"2604","DOI":"10.1016\/j.neuron.2021.06.013","article-title":"Nicotine inhibits the VTA-to-amygdala dopamine pathway to promote anxiety","volume":"109","author":"Nguyen","year":"2021","journal-title":"Neuron"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"110641","DOI":"10.1016\/j.neuropharm.2025.110641","article-title":"Estrogenic regulation of perineuronal nets in the mouse insular cortex and hippocampus","volume":"279","author":"Nguyen","year":"2025","journal-title":"Neuropharmacology"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"111821","DOI":"10.1016\/j.mad.2023.111821","article-title":"Sex and gender differences in Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis: a narrative review","volume":"212","author":"Nicoletti","year":"2023","journal-title":"Mech. Ageing Dev."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"102353","DOI":"10.1016\/j.pneurobio.2022.102353","article-title":"Chromosomal and environmental contributions to sex differences in the vulnerability to neurological and neuropsychiatric disorders: implications for therapeutic interventions","volume":"219","author":"Pallier","year":"2022","journal-title":"Prog. Neurobiol."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"1642","DOI":"10.1007\/s00259-019-04324-5","article-title":"Extrastriatal dopaminergic and serotonergic pathways in Parkinson's disease and in dementia with Lewy bodies: a (123)I-FP-CIT SPECT study","volume":"46","author":"Pilotto","year":"2019","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/s41531-019-0102-8","article-title":"Report from a multidisciplinary meeting on anxiety as a non-motor manifestation of Parkinson's disease","volume":"5","author":"Pontone","year":"2019","journal-title":"NPJ Parkinsons Dis."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1016\/j.jagp.2021.02.037","article-title":"Optimal treatment of depression and anxiety in Parkinson's disease","volume":"29","author":"Pontone","year":"2021","journal-title":"Am. J. Geriatr. Psychiatry"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1002\/mds.26424","article-title":"MDS clinical diagnostic criteria for Parkinson's disease","volume":"30","author":"Postuma","year":"2015","journal-title":"Mov. Disord."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1159\/000509421","article-title":"Sex differences in the control of social investigation and anxiety by vasopressin cells of the paraventricular nucleus of the hypothalamus","volume":"111","author":"Rigney","year":"2021","journal-title":"Neuroendocrinology"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.parkreldis.2017.01.015","article-title":"The bidirectional longitudinal relationship between insomnia, depression and anxiety in patients with early-stage, medication-na\u00efve Parkinson's disease","volume":"39","author":"Rutten","year":"2017","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"1490","DOI":"10.1038\/s41386-020-0702-3","article-title":"The role of dopaminergic and serotonergic transmission in the processing of primary and monetary reward","volume":"45","author":"Schmidt","year":"2020","journal-title":"Neuropsychopharmacology"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"9878","DOI":"10.1523\/jneurosci.1138-17.2019","article-title":"The salience network: a neural system for perceiving and responding to homeostatic demands","volume":"39","author":"Seeley","year":"2019","journal-title":"J. Neurosci."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"104583","DOI":"10.1016\/j.neubiorev.2022.104583","article-title":"Resting-state fMRI functional connectivity and mindfulness in clinical and non-clinical contexts: a review and synthesis","volume":"135","author":"Sezer","year":"2022","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"1094808","DOI":"10.3389\/fncel.2023.1094808","article-title":"Stress-altering anterior insular cortex activity affects risk decision-making behavior in mice of different sexes","volume":"17","author":"Shi","year":"2023","journal-title":"Front. Cell. Neurosci."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"117087","DOI":"10.1016\/j.neuroimage.2020.117087","article-title":"The influence of microsatellite polymorphisms in sex steroid receptor genes ESR1, ESR2 and AR on sex differences in brain structure","volume":"221","author":"Tan","year":"2020","journal-title":"NeuroImage"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1007\/s11910-017-0788-0","article-title":"Imaging the etiology of apathy, anxiety, and depression in Parkinson's disease: implication for treatment","volume":"17","author":"Thobois","year":"2017","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/s41531-024-00690-6","article-title":"Genetic and phenotypic characterization of Parkinson's disease at the clinic-wide level","volume":"10","author":"Tropea","year":"2024","journal-title":"NPJ Parkinsons Dis."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/nrn3857","article-title":"Salience processing and insular cortical function and dysfunction","volume":"16","author":"Uddin","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1016\/j.bbi.2024.03.035","article-title":"Microglial sex differences in innate high anxiety and modulatory effects of minocycline","volume":"119","author":"Ugursu","year":"2024","journal-title":"Brain Behav. Immun."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1055\/s-0041-1722840","article-title":"Anxiety in Parkinson's disease: correlation with depression and quality of life","volume":"12","author":"Upneja","year":"2021","journal-title":"J. Neurosci. Rural Pract."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1002\/mds.27465","article-title":"Frequency of mood and anxiety fluctuations in Parkinson's disease patients with motor fluctuations: a systematic review","volume":"33","author":"van der Velden","year":"2018","journal-title":"Mov. Disord."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"S135","DOI":"10.3233\/jpd-230228","article-title":"Non-pharmacological interventions for depression and anxiety in Parkinson's disease","volume":"14","author":"van Wegen","year":"2024","journal-title":"J. Parkinsons Dis."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"3308","DOI":"10.1002\/hbm.24078","article-title":"BrainMap VBM: an environment for structural meta-analysis","volume":"39","author":"Vanasse","year":"2018","journal-title":"Hum. Brain Mapp."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1038\/nrneurol.2010.111","article-title":"Neuropsychiatric effects of subthalamic neurostimulation in Parkinson disease","volume":"6","author":"Volkmann","year":"2010","journal-title":"Nat. Rev. Neurol."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1136\/jnnp-2015-310383","article-title":"A smaller amygdala is associated with anxiety in Parkinson's disease: a combined FreeSurfer-VBM study","volume":"87","author":"Vriend","year":"2016","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1038\/s41531-023-00469-1","article-title":"Common and distinct roles of amygdala subregional functional connectivity in non-motor symptoms of Parkinson's disease","volume":"9","author":"Wang","year":"2023","journal-title":"NPJ Parkinsons Dis."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1007\/s00415-025-12934-3","article-title":"Gray matter structural and functional brain abnormalities in Parkinson's disease: a meta-analysis of VBM and ALFF data","volume":"272","author":"Wang","year":"2025","journal-title":"J. Neurol."},{"key":"ref72","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.neulet.2017.05.062","article-title":"Cerebral metabolic change in Parkinson's disease patients with anxiety: a FDG-PET study","volume":"653","author":"Wang","year":"2017","journal-title":"Neurosci. Lett."},{"key":"ref73","first-page":"227","article-title":"Striatal dopamine transporter imaging correlates with anxiety and depression symptoms in Parkinson's disease","volume":"46","author":"Weintraub","year":"2005","journal-title":"J. Nucl. Med."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1111\/ene.14132","article-title":"Grey matter abnormalities in Parkinson's disease: a voxel-wise meta-analysis","volume":"27","author":"Xu","year":"2020","journal-title":"Eur. J. Neurol."},{"key":"ref75","doi-asserted-by":"publisher","first-page":"1055160","DOI":"10.3389\/fnagi.2022.1055160","article-title":"Regional activity alterations in Parkinson's disease patients with anxiety disorders: a resting-state functional magnetic resonance imaging study","volume":"14","author":"Zhang","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"ref76","doi-asserted-by":"publisher","first-page":"107717","DOI":"10.1016\/j.phrs.2025.107717","article-title":"Multidimensional mechanisms of anxiety and depression in Parkinson's disease: integrating neuroimaging, neurocircuits, and molecular pathways","volume":"215","author":"Zhao","year":"","journal-title":"Pharmacol. Res."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"110424","DOI":"10.1016\/j.neuropharm.2025.110424","article-title":"T-type calcium channels attenuate anxiety in MPTP-treated mice through modulating burst firing of dopaminergic neuron","volume":"272","author":"Zhao","year":"","journal-title":"Neuropharmacology"}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2026.1769488\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T05:43:26Z","timestamp":1776059006000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2026.1769488\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,13]]},"references-count":77,"alternative-id":["10.3389\/fnagi.2026.1769488"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2026.1769488","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,13]]},"article-number":"1769488"}}