Revealing differential psychotic symptoms in schizophrenia and bipolar I disorder by manifold learning and network analyses

Abstract

The field of psychiatry has encountered ongoing challenges in understanding the intricate nature of psychotic symptoms, particularly when they manifest in individuals diagnosed with bipolar disorder or schizophrenia. In this study, we employed manifold and network analyses to investigate whether the pattern of symptom occurrence differs between schizophrenia and bipolar I disorder. We analyzed data collected from 555 individuals, 282 of whom were diagnosed with schizophrenia-related disorders and 273 with bipolar I disorder. In the context of schizophrenia, negative symptoms, particularly avolition, were prominent with manifold and network analyses, identifying avolition as a high central symptom associated with clozapine use, patterns of deterioration, tendency toward remission, and illness severity. Conversely, bipolar I disorder exhibits discernible patterns where positive symptoms play a central role in network analysis. Unexpectedly, manifold analysis revealed two distinct clusters of patients, suggesting variability in psychotic symptom profiles within bipolar I disorder. In conclusion, schizophrenia and bipolar I disorder, while sharing psychotic symptoms, exhibit distinct co-occurrence patterns. Schizophrenia demonstrates negative symptoms, whereas bipolar I disorder exhibits a stronger interconnectivity of psychotic symptoms, highlighting the complexity of psychotic symptom patterns and their relevance for understanding psychiatric disorders. These findings highlight the complexity of psychotic symptom patterns and their relevance for understanding psychiatric disorders.

Fig. 1. Low-dimensional symptom manifolds reveal heterogeneity in schizophrenia.

a Symptom manifolds projected into 2D space in schizophrenia patients. The color shows the normalized number of symptoms that the patient has ever experienced. b Scatter plot of people with schizophrenia, with each color representing the number of negative symptoms (avolition, mutism, and anhedonia). The number of negative symptoms is comparable between the total number of psychotic and anxiety symptoms. c Using the coordinates in the 2D U-MAP space, a support vector machine was trained to predict the presence of negative symptoms. Each of the three symptoms had a well-defined vector support border. Therefore, the presence or absence of these symptoms indicated the diversity of schizophrenia patients.

Fig. 2. Symptom manifolds reveal distinct clustering patterns in bipolar I disorder.

a Symptom manifolds projected into two-dimensional space for bipolar I disorder patients. The color indicates the patient’s normalized lifetime symptom count. In the reduced feature space, unlike schizophrenia, patients are clustered into two distinct groups. b A manifold reduction was performed on cluster 1, which is the group of patients located at the top left. Greater numbers of psychotic and anxiety-related symptoms were experienced by the majority of patients. c For cluster 2, the group of patients located in the lower right-hand corner, a manifold reduction was performed. Unlike cluster 1, patients in this cluster exhibited fewer psychotic and anxiety-related symptoms.

Fig. 3. Network structure of psychotic and anxiety-related symptoms in schizophrenia and bipolar I disorder.

a, b Network analysis of psychotic and anxiety-related symptoms in schizophrenia (left) and bipolar I disorder (right) par; paranoid delusion, rfr; delusion of reference, doc; delusion of being controlled, ah; auditory hallucination, vh; visual hallucination, dsr; disorganized behavior, frm; thought form disorder, grn; grandiose delusion, rlg; religious delusion, ero; erotic delusion, glt; delusion of guilt, avl; avolition, anh; anhedonia, mut; mutism, brd; thought broadcasting, ins; thought insertion, oc; obsession/compulsion, pho; phobia.

Fig. 4. Centrality profiles of psychotic and anxiety-related symptoms in schizophrenia and bipolar I disorder networks.

a, b Centrality measures of psychotic and anxiety-related symptoms for the schizophrenia network (upper panel) and bipolar I disorder network (lower panel). Four different centralities were measured: Katz, betweenness, closeness, and strength. par; paranoid delusion, rfr; delusion of reference, doc; delusion of being controlled, ah; auditory hallucination, vh; visual hallucination, dsr; disorganized behavior, frm; thought form disorder, grn; grandiose delusion, rlg; religious delusion, ero; erotic delusion, glt; delusion of guilt, avl; avolition, anh; anhedonia, mut; mutism, brd; thought broadcasting, ins; thought insertion, oc; obsession/compulsion, pho; phobia.