Age, Rapid-Cycling, and Pharmacotherapy Effects on Ventral Prefrontal Cortex in Bipolar Disorder: A Cross-Sectional Study
Abstract
Background Neuroimaging data suggest that deficits in ventral prefrontal cortex (VPFC) function in bipolar disorder (BD) progress during adolescence and young adulthood. However, the developmental trajectory of VPFC morphological abnormalities in BD is unknown. This study investigated potential age-dependent volume abnormalities in VPFC in BD. Methods Thirty-seven individuals diagnosed with BD I (14 adolescents, 10 young adults and 13 older adults) and 56 healthy comparison subjects (HC) participated in imaging. Gray and white matter volumes of VPFC were measured using high-resolution structural magnetic resonance imaging (MRI). We used a mixed model, repeated measures analysis to examine VPFC volumes across age groups while co-varying for total brain volume. Potential effects of illness features including rapid-cycling and medication were explored. Results VPFC volumes declined with age (p Conclusions These preliminary findings suggest the presence of a more rapid initial decline in VPFC volumes with age in adolescents and young adults with BD than HC. These findings also suggest that the rapid-cycling subtype of BD is associated with larger VPFC volume deficits than the non-rapid-cycling subtype, and that pharmacotherapy may have trophic or protective effects on VPFC volumes in BD patients.
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Lithium can restore PFC activity and grey matter levels in patients with bipolar disorder.
“There is recent evidence that lithium can restore PFC activity and grey matter levels in patients with bipolar disorder141–143.”
From Stress signalling pathways that impair prefrontal cortex structure and function (2009) · cites this paper as [141]
There is loss of dlPFC gray matter in schizophrenia and Alzheimer's disease, while changes in more ventral and medial PFC regions are evident in mood disorders and in post-traumatic-stress disorder (PTSD).
“For example, there is loss of dlPFC gray matter in schizophrenia4,5 and Alzheimer’s disease6, while changes in more ventral and medial PFC regions are evident in mood disorders7 and in post-traumatic-stress disorder (PTSD)8.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [7]
In bipolar disorder, the disinhibitory symptoms of mania are associated with dysfunction of the right hemisphere.
“In bipolar disorder, the disinhibitory symptoms of mania are associated with dysfunction of the right hemisphere7, consistent with the specialized inhibitory role of this hemisphere.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [7]
There is evidence of vmPFC gray matter loss in mood disorders.
“There is evidence of vmPFC gray matter loss in mood disorders7,115,116, which implies dendritic atrophy.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [7]
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- Authors
- Blumberg, H. P., Krystal, J. H., Bansal, R., Martin, A., Dziura, J., Durkin, K., Martin, L., Gerard, E., Charney, D. S., & Peterson, B. S.
- Affiliations
- United States Department of Veterans Affairs (US)
- Columbia University (US)
- Yale University (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Blumberg, Hilary P.
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2006-04
- Volume
- 59
- Issue
- 7
- Pages
- 611-618
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2025591694
- Cited by
- 171
- References
- 7
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 25 · 2020: 6 · 2019: 3 · 2018: 6 · 2017: 7 · 2016: 5 · 2015: 4 · 2014: 9 · 2013: 10 · 2012: 18
- FWCI
- 10.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k02mh074677-05, 5k01mh001792-05, 5k05aa014906-03)
- National Institute on Alcohol Abuse and Alcoholism (KO5AA14906-01)
- National Institute of Mental Health (MH01792, K02 MH-74677, MH59139, R01MH059139, MH-01232, R01 MH69747, R01MH068318, MH 068318, K08MH001232, R01MH069747, R01MH070902, R25MH077823)
- National Institute on Drug Abuse (R01DA017820)
- National Center for Research Resources (M01RR000125, M01 RR-00125)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Social Sciences › Psychology › Clinical Psychology › Personality Disorders and Psychopathology
- Keywords
- bipolar disorder, ventral prefrontal cortex, gray matter volume, white matter volume, rapid cycling bipolar disorder, brain development, adolescents, young adults
- MeSH terms
- Adult, Bipolar Disorder, Cross-Sectional Studies, Drug Therapy, Female, Humans, Magnetic Resonance Imaging, Male, Periodicity, Prefrontal Cortex, Diagnostic and Statistical Manual of Mental Disorders
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