Clinical and Structural Differences in Delusions Across Diagnoses: A Systematic Review

Abstract

Delusions are marked, fixed beliefs that are incongruent with reality. Delusions, with comorbid hallucinations, are a hallmark of certain psychotic disorders (e.g., schizophrenia). Delusions can present transdiagnostically, in neurodegenerative (e.g., Alzheimer's disease and fronto-temporal dementia), nervous system disorders (e.g., Parkinson's disease) and across other psychiatric disorders (e.g., bipolar disorder). The burden of delusions is severe and understanding the heterogeneity of delusions may delineate a more valid nosology of not only psychiatric disorders but also neurodegenerative and nervous system disorders. We systematically reviewed structural neuroimaging studies reporting on delusions in four disorder types [schizophrenia (SZ), bipolar disorder (BP), Alzheimer's disease (AD), and Parkinson's disease (PD)] to provide a comprehensive overview of neural changes and clinical presentations associated with delusions. Twenty-eight eligible studies were identified. This review found delusions were most associated with gray matter reductions in the dorsolateral prefrontal cortex (SZ, BP, and AD), left claustrum (SZ and AD), hippocampus (SZ and AD), insula (SZ, BP, and AD), amygdala (SZ and BP), thalamus (SZ and AD), superior temporal gyrus (SZ, BP, and AD), and middle frontal gyrus (SZ, BP, AD, and PD). However, there was a great deal of variability in the findings of each disorder. There is some support for the current dopaminergic hypothesis of psychosis, but we also propose new hypotheses related to the belief formation network and cognitive biases. We also propose a standardization of assessments to aid future transdiagnostic study approaches. Future studies should explore the neural and biological underpinnings of delusions to hopefully, inform future treatment.

Self-Entropic Broadening Theory: Toward a New Understanding of Self and Behavior Change Informed by Psychedelics and Psychosis

“…Bilateral reductions in volume of the claustrum have been found in patients with both schizophrenia and depression, but are largely confounded by chronic medication use (Bernstein et al, 2016). Decreases in gray matter volume of the left claustrum have been correlated with delusions in both Alzheimer's Disease and schizophrenia (Rootes-Murdy et al, 2022). Lesions to the claustrum have been implicated in a number of case studies where patients develop delusions and/or seizures (Milardi et al, 2015;Patru and Reser, 2015), but these case studies often include adjacent structures making it difficult to infer the claustrum-specific function.…”

Psychiatric manifestations in moyamoya disease: more than a puff of smoke? a systematic review and a case-reports meta-analysis

“…Thalamus involvement in psychosis is, indeed, well-established and supported by fMRI studies (63). Finally, a systematic review on neural underpinnings of delusional symptoms in schizophrenia and Alzheimer's disease patients reported lateralized findings of gray matter reductions in the left claustrum (64), reinforcing the notion of left hemisphere involvement in the genesis of psychotic symptoms. While these observations align with the hypothesis of left hemisphere involvement in psychotic symptoms in some populations, a systematic review in patients with post-stroke psychosis found that right hemisphere lesions were more common (in around 40% of the cases, against 11% with a different pattern of lesions).…”

Clinical and Cortical Similarities Identified Between Bipolar Disorder I and Schizophrenia: A Multivariate Approach

“…However, given the symptom variation within each disorder, we hypothesized that there may be subclusters within and across each disorder, that may help distinguish the underlying neural networks involved in each disorder. For example, delusions in bipolar disorder, were associated with gray matter reductions largely in the frontal cortex and amygdala and SZ showed similar patterns with additional contributions from subcortical regions (Rootes-Murdy et al, 2022). Within individuals with SZ, a symptom phenotype consisting of higher delusional symptoms, suspiciousness, hallucinations, and anxiety [measured from the Positive and Negative Syndrome Scale (PANSS); (Kay et al, 1987)] was associated with a covarying pattern of lower GM concentration in inferior temporal gyri and fusiform gyri and higher GM concentration in the sensorimotor cortex (Mennigen et al, 2019).…”