Brain Network Degeneration In Schizophrenia: A Structural And Functional Connectivity Study

BackgroundSchizophrenia is a complex genetic heterogeneous mental disorder. Its clinical manifestations are various, including hallucinations, delusions, thought disorders and affective disorders, often accompanied by abnormal perception and cognitive dysfunction. It’s lifelong since the onset of the illness, brought a heavy burden on family and society.Schizophrenia is a multifactorial disease. Generally, genetic factors, neurobiochemical abnormalities, environmental factors and neurodevelopmental factors have been involved in the pathogenesis of schizophrenia. Some researchers believed schizophrenia may originate from developmental abnormalities. However, other studies showed that schizophrenia is progressive. Whether schizophrenia is attributable to degenerative or developmental abnormalities has been debated for many years.The development of brain imaging techniques provides an opportunity to study the neural mechanisms of neuropsychiatric disorders. In recent years, network degenerative hypothesis is applied to the study of neurodegenerative diseases. This hypothesis proposed that neurodegenerative processes originate from key nodes that are more vulnerable in specific networks and spread within the network, gradually extending into adjacent networks.The present study aimed to examine whether there was a network degenerationcomponent along the course of schizophrenia in the view of the relationship between structural and functional connectivity and illness duration of schizophrenia via magnetic resonance imaging technology. However, it’s worthwhile to note that different illness duration, antipsychotic type, dosage and medication duration act on the result. The following studies were carried out.Experiment 1:The structural and functional connectivity were examined via diffusion tensor imaging(DTI) and functional connectivity magnetic resonance imaging in early schizophrenia patients who were first-admission,drug-na?ve and healthy controls. The intergroup differences and correlation with illness duration in patients group were surveyed in order to uncover whether a neurodegenerative process was involved in the decline of structural and functional networks in early schizophrenia patients.Experiment 2:The structural and functional connectivity were examined via DTI and f MRI in chronic schizophrenia patients treated with atypical antipsychotic. The intergroup differences and correlation with illness duration and cumulative medication duration were surveyed respectively in order to uncover whether a neurodegenerative process was involved in the course of chronic schizophrenia. If degeneration is present, what is the role of illness duration and atypical antipsychotic treatment in the degenerative process.MethodsExperiment 1:Twenty-eight first-admission patients with schizophrenia(SZ) with illness-duration within 3 years(13 females and 15 males) and twenty-six age-, and sex-matched healthy controls(HC)(13 females and 13 males) participated in this study, ranging in age from17 to 42 years. Of the 28 schizophrenia patients, 16 were drug-na?ve and 12 had received minimal antipsychotic treatment for no more than 10 days.Experiment 2:The healthy controls were the same as the Experiment 1. Twenty-five atypical antipsychotics treated chronic schizophrenic patients(15 females and 10 males) with mean illness duration 35.50 ± 34.21 months were recruited. The two groups were well matched with age and sex.The structural and functional connectivity of all participants were measured via DTI and f MRI separately. TBSS and ROI were used to study: 1) the differences of structure and function connectivity between control and patient groups; 2) the changing trends of structure and function connectivity associated with the illness duration in the patient group.ResultsExperiment 1:The results from Experiment 1 showed that 1) The FA values were significantly lower for early schizophrenia patients across a wide range in the corpus callosum and corona radiate. 2) The functional connectivity between bilateral temporo-parietal junction and posterior cingulate cortex, dorsolateral prefrontal cortex reduced. 3) There is a negative correlation between illness duration and the FA value in corpus callosum, corona radiata in schizophrenia. 4) There is a negative correlation between illness duration and functional connectivity between temporo-parietal junction and posterior cingulate cortex, dorsolateral prefrontal cortex.Experiment 2:The results from Experiment 2 showed that 1) The FA values were significantly lower for chronic schizophrenia patients across a wide range in the corpus callosum and corona radiata. 2) The functional connectivity between bilateral temporo-parietal junction and posterior cingulate cortex, dorsolateral prefrontal cortex reduced in early schizophrenia patients 3) The FA value in corpus callosum, internal capsule, corona radiata, posterior thalamic radiation, superior longitudinal fasciculus, fornix, superior fronto-occipital fasciculus of chronic schizophrenia showed negative correlations with illness duration. 4) The functional connectivity of temporo-parietal junction-posterior cingulate cortex, temporo-parietal junction- dorsolateral prefrontal cortex negatively correlated with illness duration in patient group. 5) No relationship had been found in cumulative medication time and the changes of functional connectivity or structural connectivity.Based on the results from the first and second experiments, this thesis suggested that 1) the degenerative process affected both brain function and structure in schizophrenia. 2) The degenerative process in schizophrenia affected both functional and structural networks. 3) Corpus callosum and corona radiata, which play an important role in intelligence, excutive control, working memory et al., were severely damaged in schizophrenia patients. 4) Temporo-parietal junction was the key brain region in functional network degeneration of schizophrenia. Temporo-parietal junction receives the projections from thalamus, limbic system, visual cortex et al., takes part in the self-information process. The injury of temporo-parietal junction might lead to the self-related cognitive function deficits. 5) Though it had been reported that atypical antipsychotics may change the structure and function of the brain, this thesis showed there was no correlation between cumulative medication duration and structural and functional changes in schizophrenia. That illustrated the degenerative process wasn’t caused by atypical antipsychotic mediation but the schizophrenia course itself.