Altered static and dynamic functional connectivity of habenula in first-episode, drug-naïve schizophrenia patients, and their association with symptoms including hallucination and anxiety.

Background and objective: The pathogenesis of schizophrenia (SCH) is related to the dysfunction of monoamine neurotransmitters, and the habenula participates in regulating the synthesis and release of dopamine. We examined the static functional connectivity (sFC) and dynamic functional connectivity (dFC) of habenula in first-episode schizophrenia patients using resting state functional magnetic resonance imaging (rs-fMRI) in this study. Methods: A total of 198 first-Episode, drug-Naïve schizophrenia patients and 199 healthy controls (HC) underwent rs-fMRI examinations. The sFC and dFC analysis with habenula as seed was performed to produce a whole-brain diagram initially, which subsequently were compared between SCH and HC groups. Finally, the correlation analysis of sFC and dFC values with the Positive and Negative Symptom Scale (PANSS) were performed. Results: Compared with the HC groups, the left habenula showed increased sFC with the bilateral middle temporal gyrus, bilateral superior temporal gyrus, and right temporal pole in the SCH group, and the right habenula exhibited increased sFC with the left middle temporal gyrus, left superior temporal gyrus, and left angular gyrus. Additionally, compared with the HC group, the left habenula showed decreased dFC with the bilateral cuneus gyrus and bilateral calcarine gyrus in the SCH group. The PANSS negative sub-scores were positively correlated with the sFC values of the bilateral habenula with the bilateral middle temporal gyrus, superior temporal gyrus and angular gyrus. The PANSS general sub-scores were positively correlated with the sFC values of the right habenula with the left middle temporal gyrus and left superior temporal gyrus. The hallucination scores of PANSS were negatively correlated with the sFC values of the left habenula with the bilateral cuneus gyrus and bilateral calcarine gyrus; The anxiety scores of PANSS were positively correlated with the dFC values of the left habenula with the right temporal pole. Conclusion: This study provides evidence that the habenula of the first-episode schizophrenia patients presented abnormal static functional connectivity with temporal lobe and angular gyrus, and additionally showed weakened stability of functional connectivity in occipital lobe. This abnormality is closely related to the symptoms of hallucination and anxiety in schizophrenia, which may indicate that the habenula involved in the pathophysiology of schizophrenia by affecting the dopamine pathway.