Brain Dysfunction In Early-Onset Schizophrenia Based On Magnetic Resonance Imaging

Schizophrenia is one of the most common mental illnesses in modern society,which is characterized by high prevalence,high recurrence rate,and high morbidity.Patients with schizophrenia often represent the positive symptoms of unknown etiology such as delusion,hallucination,and thought disorders,as well as the negative symptoms such as avolition/apathy asociality,anhedonia,and social avoidance,along with cognitive impairment and emotional disorders.Multi-dimensional clinical characterization,complex etiology,and other issues still impede the exploration of robust biological markers and targeted therapies for schizophrenia.Nevertheless,studies from genetics,physiology,and neuroscience all suggest that brain dysfunction is the neurobiological basis for the clinical representation of schizophrenia.In recent years,magnetic resonance imaging technology,as a safe and non-invasive neuroimaging technology,has provided important technical support to explore the imaging markers and the pathophysiological process in schizophrenia.Adolescents with early-onset schizophrenia provide a unique perspective to investigate the brian dysfunction during the adolescent period in schizophrenia,as they are less affected by chronic antipsychotic medication and interaction with age-related neurodegeneration.Therefore,in this study,based on the magnetic resonance imaging technology,we focused on exploring the dysfunction of the brain in adolescents with early-onset schizophrenia,to find the robust imaging markers and the underlying neuropathological mechanism of the clinical symptoms in schizophrenia.The current work contents include the following parts:1.By using the functional connection density(FCD)approach,we investigated the frequency-specific functional connection characteristics in the adolescents with early-onset schizophrenia.The results revealed that,in the slow-4(0.027-0.08 Hz)frequency band,the functional connection of default mode network(DMN)is prominent,while in slow-5(0.01-0.027 Hz)frequency band,the connection of subcortical regions is prominent.Importantly,a significant frequency-by-group interaction was observed in the left precuneus with significantly lower FCD in the slow-4 frequency band,but no significant effect in the slow-5 frequency band.Furthermore,the change in FCD in the precuneus was inversely proportional to the clinical symptom in the slow-4 band.In this study,we figure out the functional connection patterns at different frequency bands and demonstrated the abnormal regulation mechanism of the precuneus in the slow-4 band.These findings provided a new perspective to investigate the pathophysiological mechanism of schizophrenia.2.By utilizing the dynamic functional connectivity,we detected the global and local dynamic information exchange patterns in adolescents with early-onset schizophrenia.The results demonstrated that the topography of the global signal(GS)can be divided into five different states.In the state1,the GS mainly affected the sensory regions.In the state2,the GS mainly affected the default mode network.In the state3,the GS mainly affected the frontoparietal network and the cingulate-opercular network.In the state4,the GS mainly affected the sensory and subcortical regions.In the state5,the GS mainly affected the sensory regions and DMN.In particular,the changes in the cerebellum,putamen,and supramarginal gyrus were inversely proportional to the clinical symptoms.Our findings demonstrated that the influence of the GS on brain networks was dynamic.In patients with schizophrenia,this pattern is altered and related to the clinical symptoms.The current findings provided a new way to explore the spatiotemporal mechanism of schizophrenia.3.By using the functional connectivity density method,we assessed the white matter functional connection in adolescents with early-onset schizophrenia in the local and long scales.The results showed that the white matter existed functional connectivity hubs similar to the gray matter.Specifically,in the local scale,the white matter functional hubs are mainly in the corona radiata and cerebellum.In the long scale,the white matter functional hubs are mainly in the external capsule and pons.Compared with the healthy controls,the adolescents with early-onset schizophrenia showed decreased FCD in the superior corona radiata in the local scale.In the long scale,the adolescents with early-onset schizophrenia showed increased FCD in the cingulum but decreased FCD in the dorsal raphe nuclei(DR).Moreover,the changes of the white matter functional connection in the DR implying the potential contribution of abnormal DR-related circuits to the clinical symptoms in schizophrenia.These findings indicated that the pathophysiology of schizophrenia may also lie in white matter functional dysconnectivity.4.The support vector model was used to explore the reliability of the integrated characteristics and the predictive effect of them on clinical symptoms in schizophrenia.The results showed that the integrated features were better at classifying the schizophrenia patients and healthy controls than the divided features.However,in the prediction model,there was no significant advantage in the predicted effect for the integrated features.Our findings suggested that integrated multiple imaging features may provide a reference for the early diagnosis of schizophrenia,and the physiopathological mechanisms of each dimension of clinical symptoms may be different.5.Based on multimodal magnetic resonance imaging data,brain imaging analysis was used to explore the underlying pathological mechanisms of negative symptoms in adolescents with early-onset schizophrenia.Results revealed that the functional and structural connections of the left frontal white matter(FWM)were associated with individual negative symptoms.Moreover,the serotonin network and FWM-cingulum networks were identified as associated with the negative symptom severity in adolescents with early-onset schizophrenia.Furthermore,the abnormal functional and structural connectivity between the interhemispheric FWM was associated with the negative symptoms in adolescents with early-onset schizophrenia.Our findings revealed the imaging basis of individual negative symptoms and offered initial evidence to uncover white matter functional information by using white matter connectome in schizophrenia.