Comparison of clinical and neurological mechanisms of bipolar disorder with and without psychotic symptoms
Year: 2026
Type: article
Abstract: Objective : This review aims to narratively synthesize and compare clinical characteristics, neuroimaging signatures, and neurobiological mechanisms in bipolar disorder with psychotic symptoms (PBD) versus non-psychotic bipolar disorder (NPBD), and to outline implications for diagnosis, prognosis, and treatment. Methods : Relevant studies published over the past three decades were identified through searches of PubMed, Web of Science. Literature was selected based on its focus on bipolar disorder with and without psychotic symptoms, emphasizing clinical, neuroimaging, and neurobiological comparisons. As this is a narrative review, findings were synthesized qualitatively. Results : Psychotic symptoms are highly prevalent in bipolar disorder, especially in type I. PBD typically presents earlier than NPBD, often in late adolescence, with comparable gender distribution between the two groups. Neuroimaging studies reveal consistent prefrontal cortical alterations and disrupted dorsolateral prefrontal connectivity, alongside more extensive white-matter abnormalities in PBD, whereas NPBD changes are more restricted. In adolescents, diminished supplementary motor area activity appears specific to PBD. At the biological level, PBD shares several vulnerabilities with schizophrenia, including striatal dopaminergic dysregulation, glial pathology, susceptibility genes such as CACNA1C and ANK3, and distinct epigenetic patterns, notably elevated DTNBP1 methylation. Conclusion : We emphasize the complexity of BD and highlight the importance of psychotic symptoms as a potential basis for subtyping, PBD constitutes a clinically important subgroup of bipolar disorder, marked by earlier onset, greater severity, and distinct neural alterations that overlap with schizophrenia. Current evidence remains heterogeneous, partly due to small samples and methodological variability, suggesting that further large-scale, longitudinal, and multimodal studies are needed.
Authors: Jiao Li, Yan Zhang, Qiangli Dong
Institution: Lanzhou University
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,630
Awards: G2237382273, G4872344380
OpenAlex ID: W7135377186
