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Regional brain changes in bipolar I depression: a functional magnetic resonance imaging study
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Objective: To investigate neural activity in prefrontal cortex and amygdala during bipolar depression. Methods: Eleven bipolar I depressed and 17 normal subjects underwent functional magnetic resonance imaging (fMRI) while performing a task known to activate prefrontal cortex and amygdala. Whole brain activation patterns were determined using statistical parametric mapping (SPM) when subjects matched faces displaying neutral or negative affect (match condition) or matched a geometric form (control condition). Contrasts for each group for the match versus control conditions were used in a second‐level random effects analysis. Results: Random effects between‐group analysis revealed significant attenuation in right and left orbitofrontal cortex (BA47) and right dorsolateral prefrontal cortex (DLPFC) (BA9) in bipolar depressed subjects. Additionally, random effects analysis showed a significantly increased activation in left lateral orbitofrontal cortex (BA10) in the bipolar depressed versus control subjects. Within‐group contrasts demonstrated significant amygdala activation in the controls and no significant amygdala activation in the bipolar depressed subjects. The amygdala between‐group difference, however, was not significant. Conclusions: Bipolar depression is associated with attenuated bilateral orbitofrontal (BA47) activation, attenuated right DLPFC (BA9) activation and heightened left orbitofrontal (BA10) activation. BA47 attenuation has also been reported in mania and may thus represent a trait feature of the disorder. Increased left prefrontal (BA10) activation may be a state marker to bipolar depression. Our findings suggest dissociation between mood‐dependent and disease‐dependent functional brain abnormalities in bipolar disorder.
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“Because the pathophysiology of bipolar disorder is strongly associated with prefrontal cortex neurocircuitry, 28 it is important to determine if there are advantages to stimulating over this area compared with the vertex.”
From Magnetic seizure therapy is efficacious and well tolerated for treatment-resistant bipolar depression: An open-label clinical trial (2020) · cites this paper as [28]
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“On balance, patients with mood disorders experience substantial disruptions in interpersonal function, [30][31][32][33][34]”
From Systematic review of the neural basis of social cognition in patients with mood disorders (2012) · cites this paper as [30]
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“Depressed patients with bipolar disorder have also shown elevated activity in the amygdala 102 and attenuated responses in the OFC and DLPFC to neutral and negative (e.g., angry, fearful, sad) faces.”
From Systematic review of the neural basis of social cognition in patients with mood disorders (2012) · cites this paper as [30]
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“On average, neural activityis most commonly decreased in the DLPFC 30,59,68,76 and increased in the left amygdala, 55,74,76,79,98,99 the fusiform gyrus 82,93,98 and the inferior frontal gyrus 82,90,98 in patients with mood disorders.”
From Systematic review of the neural basis of social cognition in patients with mood disorders (2012) · cites this paper as [30]
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Phillips, M. L., & Swartz, H. A. (2014) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2014.13081008 · Cited by 636
“The finding of decreased ventrolateral prefrontal cortex activity parallels that shown during similar tasks by euthymic and depressed adults with bipolar disorder type I(13-16,19), and suggests that reduced ventrolateral prefrontal cortex activity during emotion processing and emotion regulation may be a trait marker…”
The functional neuroanatomy of bipolar disorder: a consensus model
Strakowski, S. M., Adler, C. M., Almeida, J., Altshuler, L. L., Blumberg, H. P., Chang, K., DelBello, M. P., Frangou, S., McIntosh, A. M., Phillips, M. L., et al. (2012) · Bipolar Disorders · doi:10.1111/j.1399-5618.2012.01022.x · Cited by 555
“Indeed, other investigators have not observed increased amygdala activation during depression (26, 27) and have suggested that amygdala over-activation may be state dependent, as reviewed in this issue (1).”
BackgroundSelf-citationTreatment of depression with transcranial direct current stimulation (tDCS): A Review
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“This imbalance of activation is not restricted to the dorsolateral prefrontal cortex, but might affect also orbitofrontal areas (Altshuler et al., 2008).”
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A quantitative meta-analysis of fMRI studies in bipolar disorder
Chen, C., Suckling, J., Lennox, B., Ooi, C., & Bullmore, E. T. (2011) · Bipolar Disorders · doi:10.1111/j.1399-5618.2011.00893.x · Cited by 471
“Decreased activation in BD patients was shown in the IFG [reported by six studies (29, 34, 52, 60, 62, 67)], lingual gyrus [reported by six studies (33, 43, 50, 53, 66, 73], and putamen [reported by five studies (5, 36, 41, 58, 72)] (Table 3).”
BackgroundResultInfluential
Metadata
- Authors
- Altshuler, L., Bookheimer, S., Townsend, J., Proenza, M. A., Sabb, F., Mintz, J., & Cohen, M. S.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Altshuler, Lori
- Venue
- Bipolar Disorders
- Publisher
- Wiley
- Published
- 2008-08-18
- Volume
- 10
- Issue
- 6
- Pages
- 708-717
- ISSN
- 1398-5647 (ISSN-L)
- 1399-5618
- PMC
- PMC3260079
- OpenAlex
- W1964476186
- Cited by
- 135
- References
- 83
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 5 · 2021: 5 · 2020: 3 · 2019: 2 · 2018: 6 · 2017: 5 · 2016: 3 · 2015: 9 · 2014: 11 · 2013: 14 · 2012: 27
- FWCI
- 7.79
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Bipolar Disorders (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Simons Foundation
- Stanley Medical Research Institute
- National Alliance for Research on Schizophrenia and Depression
- Institut National de la Santé et de la Recherche Médicale
- National Institutes of Health
- National Institute of Mental Health (K24MH001848)
- National Institute on Drug Abuse (R01DA013054, DA13054)
- National Center for Research Resources (RR08655, P41RR013642, RR 13642, C06RR012169)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- bipolar I depression, bipolar disorder, prefrontal cortex, amygdala, orbitofrontal cortex, dorsolateral prefrontal cortex, brain activation, facial emotion recognition, negative affect
- MeSH terms
- Adult, Bipolar Disorder, Brain, Brain Mapping, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Oxygen, Pattern Recognition, Visual, Photic Stimulation, Reaction Time, Young Adult
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