A Longitudinal and Reproducible Anti-coactivation Pattern Between the Cerebellum and the Ventral Tegmental Area Relates to Apathy in Schizophrenia

Article Article scientifique Article A Longitudinal and Reproducible Anti-coactivation Pattern Between the Cerebellum and the Ventral Tegmental Area Relates to Apathy in Schizophrenia eng 2025-06-18 author Awada Jade Neuroimaging and translational psychiatry lab, Department of psychiatry, University of Geneva, Switzerland. 907265 Département de psychiatrie (PSYAT) author Delavari Farnaz Developmental Imaging and Psychopathology Laboratory, University of Geneva School of Medicine, Geneva, Switzerland; Neuro-X Institute, École Polytechnique Fédérale de Lausanne, Switzerland. 930325 author Bolton Thomas Neuroimaging and translational psychiatry lab, Department of psychiatry, University of Geneva, Switzerland. 421651 Département de psychiatrie (PSYAT) author Alouf Fares Neuroimaging and translational psychiatry lab, Department of psychiatry, University of Geneva, Switzerland. 858517 author Carruzzo Fabien 0000-0003-2386-3389 Laboratory for experimental psychopathology, Department of psychiatry, University of Geneva, Switzerland. 834756 SYNAPSY Centre de recherche translationnelle en neurosciences psychiatriques (CTNP) (SYNAPM) author Kuenzi Noémie 0000-0003-1368-167X Laboratory for experimental psychopathology, Department of psychiatry, University of Geneva, Switzerland. 752759 author Kaliuzhna Mariia Laboratory for experimental psychopathology, Department of psychiatry, University of Geneva, Switzerland. 904560 Département de psychiatrie (PSYAT) author Geffen Tal Department of Psychiatry and Neurosciences, Campus Charité Mitte, Berlin, Germany. author Katthagen Teresa Department of Psychiatry and Neurosciences, Campus Charité Mitte, Berlin, Germany. author Schlagenhauf Florian Department of Psychiatry and Neurosciences, Campus Charité Mitte, Berlin, Germany. author Van De Ville Dimitri 0000-0002-2879-3861 Neuro-X Institute, École Polytechnique Fédérale de Lausanne, Switzerland; Department of radiology and medical informatics, University of Geneva, Switzerland. 638484 Département de radiologie et informatique médicale (RADIO) author Eliez Stéphan 0000-0002-8269-3028 Developmental Imaging and Psychopathology Laboratory, University of Geneva School of Medicine, Geneva, Switzerland. 39336 Département de psychiatrie (PSYAT) author Kaiser Stefan 0000-0002-3013-2034 Laboratory for experimental psychopathology, Department of psychiatry, University of Geneva, Switzerland; Adult psychiatry division, Department of psychiatry, University Hospitals of Geneva, Switzerland. 868946 Département de psychiatrie (PSYAT) author Bègue Indrit 0000-0001-5350-4454 Neuroimaging and translational psychiatry lab, Department of psychiatry, University of Geneva, Switzerland; Adult psychiatry division, Department of psychiatry, University Hospitals of Geneva, Switzerland. Electronic address: indrit.begue@unige.ch. 715639 Département de psychiatrie (PSYAT) 10.1016/j.biopsych.2025.06.009 40541592 0006-3223 https://www.sciencedirect.com/science/article/pii/S0006322325012521 Background: Negative symptoms of schizophrenia lack effective treatments. Anomalies in the reward system and cerebellum have been linked to these symptoms. The cerebellum modulates reward circuitry via the ventral tegmental area (VTA). The "cognitive dysmetria theory" posits that reduced cerebellar inhibition in schizophrenia may underlie striatal hyperdopaminergia. However, the role of cerebellum-VTA connectivity in negative symptoms remains unclear. Methods: From 427 individuals screened, 146 were recruited: 90 with schizophrenia (SZ) and 56 healthy controls (HC). At 3 months (T2), 65 individuals (36 SZ, 29 HC) completed follow-up. SZ participants were invited for clinical interviews at 9 months (T3; 33 SZ). After quality check, 105 participants were retained at T1, 41 at T2, and 21 at T3. A validation cohort included 53 individuals (28 SZ, 25 HC). The Brief Negative Symptom Scale quantified negative symptoms. Dynamic functional connectivity of the cerebellum and VTA was analyzed using coactivation patterns analysis. Results: A reproducible cerebellum-VTA anti-coactivation pattern was found across T1 and T2 (r = 0.98) in bilateral paravermal Crus I/II. Anti-coactivation emergence at T1 correlated negatively with apathy, particularly asociality and avolition. At T2, anti-coactivation persistence related negatively to apathy, especially anhedonia, and to anhedonia at T3. Similarly, reduced emergence at T2 was linked to worse asociality at T3. In the validation cohort, we replicated the pattern (r = 0.93), and its emergence negatively correlated with apathy, particularly asociality. Conclusion: Reduced cerebellum-VTA anti-coactivation is a reproducible neural marker of apathy in schizophrenia, highlighting its potential as a therapeutic target. Dewey 616.89 Dewey 616.0757 Hôpitaux Universitaires Genève Fondation Leenaards Swiss National Science Foundation Neural and behavioral markers for the motivational negative symptoms of schizophrenia - a longitudinal approach 169783 CH Projects 60 Département de psychiatrie 225 62 Département de radiologie et informatique médicale 227 false 1431 Neuroimagerie et psychiatrie translationnelle 1058 150 L'imagerie cérébrale 184 1236 Psychopathologie clinique et expérimentale 987 495 Neuroimagerie du Sommeil et de la Cognition 832 552 Traitement d'images médicales 893 421 Laboratoire d'imagerie et de psychopathologie développementale 693 Biological psychiatry 87496092-47bb-4b3f-9161-b80ff9d5b715 Article (Accepted version) Public PIIS00063223250125211.pdf 6153097 application/pdf 2c42939e371a9463fb2e0c0a0054dd04b1538fc1fb11bf7a42a281917cc2d1ae openAccess Faculté de médecine / Section de médecine clinique / Département de psychiatrie Faculté de médecine / Section de médecine clinique / Département de radiologie et informatique médicale

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A Longitudinal and Reproducible Anti-coactivation Pattern Between the Cerebellum and the Ventral Tegmental Area Relates to Apathy in Schizophrenia	Biological psychiatry	2025	78	409
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