Testing the expanded continuum hypothesis of schizophrenia and bipolar disorder. Neural and psychological evidence for shared and distinct mechanisms

Abstract

Despite the traditional view of Schizophrenia (SZ) and Bipolar disorder (BD) as separate diagnostic categories, the validity of such a categorical approach is challenging. In recent years, the hypothesis of a continuum between Schizophrenia (SZ) and Bipolar disorder (BD), postulating a common pathophysiologic mechanism, has been proposed. Although appealing, this unifying hypothesis may be too simplistic when looking at cognitive and affective differences these patients display. In this paper, we aim to test an expanded version of the continuum hypothesis according to which the continuum extends over three clusters: the psychotic, the cognitive, and the affective. We applied an innovative approach known as Source-based Morphometry (SBM) to the structural images of 46 individuals diagnosed with SZ, 46 with BD and 66 healthy controls (HC). We also analyzed the psychological profiles of the three groups using cognitive, affective, and clinical tests. At a neural level, we found evidence for a shared psychotic core in a distributed network involving portions of the medial parietal and temporo-occipital areas, as well as parts of the cerebellum and the middle frontal gyrus. We also found evidence of a cognitive core more compromised in SZ, including alterations in a fronto-parietal circuit, and mild evidence of an affective core more compromised in BD, including portions of the temporal and occipital lobes, cerebellum, and frontal gyrus. Such differences were confirmed by the psychological profiles, with SZ patients more impaired in cognitive tests, while BD in affective ones. On the bases of these results we put forward an expanded view of the continuum hypothesis, according to which a common psychotic core exists between SZ and BD patients complemented by two separate cognitive and affective cores that are both impaired in the two patients' groups, although to different degrees.

Altered Temporal Variability of Local and Large-Scale Resting-State Brain Functional Connectivity Patterns in Schizophrenia and Bipolar Disorder

“…As for the bipolar disorder patients in the present study, FC variabilities in these regions and networks did not differ significantly from either of the other groups, which fell in the intermediate range between those of healthy controls and schizophrenia patients (Figures 2 and 3). Thus, we propose that our findings may offer support for the hypothesis of a psychosis continuum between schizophrenia and bipolar disorder, with more severe brain deficits and disabling symptoms in schizophrenia compared to bipolar disorder (63,64); moreover, changes in dynamic FC may serve as objective biomarkers for such differences in neuropathology between these two disorders. However, future investigation with a larger sample size and a higher statistical power is required to confirm if these changes would be significant in patients with bipolar disorder, as compared to healthy controls and schizophrenia patients.…”

Effective Connectivity between Major Nodes of the Limbic System, Salience and Frontoparietal Networks Differentiates Schizophrenia and Mood Disorders from Healthy Controls

“…Noto et al (2019) reported that first episode psychosis, which later evolves into schizophrenia and bipolar disorder, is characterized by a cytokine storm which is somewhat more pronounced is subjects who will develop schizophrenia. The expanded continuum hypothesis was recently supported by the study of Sorella et al [3]. They found clear evidence in SCZ and BD of a shared altered network of brain areas (including ventrotemporal, medial parieto-occipital areas, as well as portions of the cerebellum and the middle frontal gyrus), which could represent the neural underpinnings of an altered interpretation of reality connected with psychosis.…”

“…The BOLD timeseries were then extracted for eight predefined right sided regions of interest (ROI) using 6 mm radius spheres. These ROIs were the following (MNI coordinates given in brackets): ROI_1 -anterior insula (AI) [38,22,3], ROI_2 -inferior frontal gyrus (IFG) [50,26,16], ROI_3 -middle frontal gyrus (MFG) [36,42,28] corresponding to dorsolateral prefrontal cortex (DLPFC), ROI_4 -frontal eye field (FEF) [31, -5, 58], ROI_5 -anterior cingulate cortex (ACC) [5,45,12], ROI_6 -superior parietal lobe (SPL) [24, -54, 68], ROI_7 -amygdala (AMY) [24, 3, -16] and ROI_8 -hippocampus (HPC) [30, -11, -17].…”

Tune in to the right frequency: Theta changes when distancing from emotions elicited by unpleasant images and words

“…Strategies proved to be efficacious in regulating emotions inside the lab have increasingly been incorporated in various models of therapy to help clients suffering from dysregulated emotions (e.g. Barlow et al, 2017; Dadomo et al., 2016; Grecucci et al, 2015, 2017; Pappaianni et al., 2019; Sorella et al., 2019). Unfortunately, some relevant aspects of what is regulated when we regulate emotional responses are still not clear, and the application of principles and methods of the science of emotion regulation inside the consulting room are still based on communi sensu and not on scientific based prescriptions.…”