Negative symptoms are commonly found in patients with schizophrenia (SCZ) spectrum disorders. Recent findings suggest negative symptoms are not unitary construct but a 2一facet construct comprising the Motivation and Pleasure (MAP) deficit, and the Expressivity (EXP) deficit. These two factors may have distinct behavioural and neural manifestations. Social functioning, on the other hand, is an important long-term prognostic goal in the treatment of mental illness, and the severity of negative symptoms have been consistently found to strongly determine SCZ patients' levels of social functioning. However, most of the previous studies investigating the relationship between negative symptoms and social functioning were limited to a unitary construct of negative symptoms. It is still unclear how the MAP and EXP factors may affect social functioning in SCZ patients and individuals with high level of social anhedonia. Similarly, limited empirical findings based on a unitary construct of negative symptoms suggest that negative symptoms are correlated with cortico-striatal resting-state functional connectivity (rs-FC). It remains unclear whether the MAP and EXP factors of negative symptoms may correlate distinctively with the altered cortico-striatal rs-FC as well as the whole-brain rs-FC in patients with SCZ and individuals with high level of social anhedonia.
To bridge such a gap of knowledge, this dissertation adopted a two-factor structure of negative symptoms to examine the relationship between MAP and EXP factors with social functioning and rs-FC in both patients with SCZ and individuals with high level social anhedonia.
Study 1 examined the overall interaction pattern of MAP and EXP deficits and social functioning in 269 SCZ patients using network analysis and relative importance contribution analyses. The Clinical Assessment Interview for Negative Symptoms (CAWS) was adopted to capture the MAP and EXP factors of negative symptoms. Results showed that the MAP deficit, rather than the EXP deficit, was closely related to social functioning in SCZ patients. Network centrality estimates and relative importance analysis showed that MAP deficit played the central role in the network and accounted for the largest proportion of variance of social functioning. These findings suggested that the pivotal role of the MAP deficit to determine SCZ patients' social functioning.
Study 2 examined the overall interactions between MAP and EXP factors and social functioning in 2889 college students using network analysis. Results showed that the reduction in motivation factor showed close and negative connection with social functioning. Network centrality estimates showed that motivation factor played a relatively central role in the network. The relative importance analysis further showed motivation factor explaining larger proportion of variance of social functioning.
Study 3 examined the relationships between the MAP and EXP deficits and the altered rs-FC in 73 patients with SCZ based on CAWS, we also recruited 28 controls for rs-FC comparison. Results showed that, compared to healthy controls, SCZ patients exhibited altered rs-FC of the bilaterally dorsal striatum and cortical areas (mainly involving the left anterior cingulate gyros, superior frontal gyros, cuneus, superior temporal gyros and middle temporal gyros). Hyper-connectivity of the right dorsal striatum and left anterior cingulate gyros (ACC) was positively correlated with MAP deficits in SCZ patients. We did not find significant correlation between rs-FC and EXP deficits. The whole-brain graphical analysis showed that the MAP deficits were positively correlated with the rs-FC of the right thalamus and left precentral gyros, the rs-FC of right caudate and left superior temporal gyros, whereas the MAP deficits were positively correlated with the rs-FC of the right putamen and temporal pole. The findings of MAP deficits correlating with the rs-FC of the right dorsal striatum and left ACC were replicated in an independent sample of 51 SCZ patients and 49 controls.
Study 4 further examined the relationships between the MAP and EXP deficits and the altered rs-FC in 42 participants with high level of social anhedonia and 53 participants with low level of anhedonia. Results showed that, compared to participants with low level of anhedonia, participants with high level of social anhedonia exhibited altered rs-FC of the right dorsal striatum and cortical areas (mainly involving the inferior parietal gyros, superior temporal gyros and middle temporal gyros). We did not find significant correlation between MAP and EXP deficits and the altered cortico-striatal rs-FC in both pariticpants with high and low levels of social anhedonia.
Taken together, the present findings suggest the important role of the MAP factor to determine social functioning in both SCZ patients and individuals with high level of social anhedonia. Our findings also suggest that MAP deficits shown in SCZ patients are specifically correlated with the rs-FC of the right dorsal striatum and left ACC. These all highlight MAP deficit and its associated rs-FC may be potential biomarkers for SCZ, and provide important implications for the intervention development.
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