The Etiology of Auditory Hallucinations in Schizophrenia: From Multidimensional Levels

Abstract

Enormous efforts have been made to unveil the etiology of auditory hallucinations (AHs), and multiple genetic and neural factors have already been shown to have their own roles. Previous studies have shown that AHs in schizophrenia vary from those in other disorders, suggesting that they have unique features and possibly distinguishable mechanisms worthy of further investigation. In this review, we intend to offer a comprehensive summary of current findings related to AHs in schizophrenia from aspects of genetics and transcriptome, neurophysiology (neurometabolic and electroencephalogram studies), and neuroimaging (structural and functional magnetic resonance imaging studies and transcriptome–neuroimaging association study). Main findings include gene polymorphisms, glutamate level change, electroencephalographic alterations, and abnormalities of white matter fasciculi, cortical structure, and cerebral activities, especially in multiple regions, including auditory and language networks. More solid and comparable research is needed to replicate and integrate ongoing findings from multidimensional levels.

Third-generation genome sequencing implicates medium-sized structural variants in chronic schizophrenia

“…Therefore genetic factors related to hearing impairment may also contribute to risk of schizophrenia. Some previous studies have identified genes associated with auditory hallucinations, but none overlap with the proband-specific SV-containing genes identified in this study (Hugdahl et al, 2008;Shao et al, 2021). Furthermore, GWAS of common variants have found no evidence for enrichment of auditory-related pathways in schizophrenia (Trubetskoy et al, 2022).…”

Language abnormalities in schizophrenia: binding core symptoms through contemporary empirical evidence

“…In conducting our review, we looked for studies examining schizophrenia-risk genetic variants that are parallelly implicated in both the development and dysfunction of language, and we also retrieved genetic studies specifically focused on FTD and AVHs in schizophrenia [154][155][156][157] . To systematically obtain the genetic variants that overlap between schizophrenia and language disorders, we first retrieved language-related genes from two recent reviews 158,159 .…”

Circadian rhythms in auditory hallucinations and psychosis

“…Auditory hallucinations are a cardinal symptom of psychotic disorders, affecting more than two thirds of patients with a diagnosis of schizophrenia 1,2 . Hallucinations thus constitute one of the main diagnostic positive symptoms of schizophrenia spectrum disorders in the two major classification systems, in distinction of the usually longer-lasting and potentially more debilitating negative symptoms, such as cognitive decline, anhedonia, or flat affect 3 .…”

“…Auditory hallucinations are a cardinal symptom of psychotic disorders, affecting more than two-thirds of patients with a diagnosis of schizophrenia. 1,2 Hallucinations thus constitute one of the main diagnostic positive symptoms of schizophrenia spectrum disorders in the two major classification systems, in distinction of the usually longerlasting and potentially more debilitating negative symptoms, such as cognitive decline, anhedonia, or flat affect. 3 However, auditory hallucinations are not pathognomonic for psychotic disorders, as they present with significant frequency (recent estimates ranging from 45% to 60%) in the context of a number of other mental disorders such as mood, dissociative, personality, and post-traumatic stress disorders, and may also affect approximately a third of patients with neurodegenerative disorders such as Parkinson's disease.…”