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. 2023 Apr 6;12(7):2749.
doi: 10.3390/jcm12072749.

Cognitive Stress Regulation in Schizophrenia Patients and Healthy Individuals: Brain and Behavior

Lydia Kogler  1 , Christina Regenbogen  2 , Veronika I Müller  3   4 , Nils Kohn  2   5 , Frank Schneider  2   6 , Ruben C Gur  7 , Birgit Derntl  1   2   8   9
Affiliations

Cognitive Stress Regulation in Schizophrenia Patients and Healthy Individuals: Brain and Behavior

Lydia Kogler et al. J Clin Med. .

Abstract

Stress is an important factor in the development, triggering, and maintenance of psychotic symptoms. Still, little is known about the neural correlates of cognitively regulating stressful events in schizophrenia. The current study aimed at investigating the cognitive down-regulation of negative, stressful reactions during a neuroimaging psychosocial stress paradigm (non-regulated stress versus cognitively regulated stress). In a randomized, repeated-measures within-subject design, we assessed subjective reactions and neural activation in schizophrenia patients (SZP) and matched healthy controls in a neuroimaging psychosocial stress paradigm. In general, SZP exhibited an increased anticipation of stress compared to controls (p = 0.020). During non-regulated stress, SZP showed increased negative affect (p = 0.033) and stronger activation of the left parietal operculum/posterior insula (p < 0.001) and right inferior frontal gyrus/anterior insula (p = 0.005) than controls. Contrarily, stress regulation compared to non-regulated stress led to increased subjective reactions in controls (p = 0.003) but less deactivation in SZP in the ventral anterior cingulate cortex (p = 0.027). Our data demonstrate stronger reactions to and anticipation of stress in patients and difficulties with cognitive stress regulation in both groups. Considering the strong association between mental health and stress, the investigation of cognitive regulation in individuals vulnerable to stress, including SZP, has crucial implications for improving stress intervention trainings.

Keywords: IFG/VLPF; amygdala; emotion regulation; hippocampus; insula; parietal cortex; schizophrenia; stress; ventral ACC.

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Conflict of interest statement

The authors declare no conflict of interest related to the manuscript. The funders had no role in the design of the study; in the collection, analysis, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Timeline of the paradigm within the fMRI scanner and timeline for one run. Block A and Block B were either the non-regulation or the regulation block. The non-regulation and regulation blocks were presented in a randomized order across participants. A resting-state scan (RS) and an anatomical scan (anat) were assessed before Block A and Block B to adapt subjective arousal levels before each block.
Figure 2
Figure 2
Illustration of significant interactions as revealed by the ANOVAs for subjective ratings. (A) Subjective stress, interaction “time-by-group”: SZP compared to HC had higher subjective stress before the stress paradigm. Subjective stress increased in both groups from before to after the stress paradigm. (B,C) are disentangling the 3-way interaction “regulation-by-time-by-group” for negative affect. (B) Pre-stress, group main effect: SZP compared to HC had higher negative affect before the stress paradigm. (C) Post-stress, interaction “regulation-by-group”: SZP had higher negative affect than HC after the non-regulation block. HC reported higher negative affect after the regulation compared to the non-regulation block. No significant group difference appeared after the regulation block. non-reg = non-regulation block; reg = regulation block. Significant differences are marked with *.
Figure 3
Figure 3
The cluster in the pOP/pI (red) showed a significant interaction “regulation-by-condition-by-group” on whole-brain level: HC showed stronger activation than SZP during the control condition in the regulation block (left). SZP showed higher activation than HC during the stress condition in the non-regulation block (right). HC showed higher activation during stress in the regulation block compared to the non-regulation block (right). non-reg = non-regulation block; reg = regulation block; L = left. Significant differences are marked with *.
Figure 4
Figure 4
Region-of-interest analysis of the ventral ACC (red) showed a “regulation-by-condition-by-group” interaction. While no group differences emerged for the stress condition, SZP showed less deactivation compared to HC in the control condition in the regulation block. Additionally, in SZP, the ventral ACC was less deactivated in the control condition in the regulation block compared to the control condition in the non-regulation block. non-reg = non-regulation block; reg = regulation block. Significant differences are marked with *.
Figure 5
Figure 5
Region-of-interest-analysis of the right IFG/aI (red) showed a “regulation-by-group” interaction. SZP showed higher activation than HC within the non-regulation block. For HC, higher activation was seen in the regulation block compared to the non-regulation block. non-reg = non-regulation block; reg = regulation block; R = right. Significant differences are marked with *.
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