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Updated: Jan 19, 2026

Developing a Rat Model for Bipolar Disorder
Published on: May 2, 2025
Longitudinal analysis of cognitive performances in recent-onset and late-life Bipolar Disorder: A systematic review
Alejandro Szmulewicz1,2,3, Marina P Valerio2,4, Diego J Martino4,5
1Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Objectives:
Neurocognitive deficits have been widely reported in euthymic Bipolar Disorder (BD) patients and contribute to functional disability. However, the longitudinal trajectory of these deficits remains a subject of debate. Although most research to this date shows that neurocognitive deficits tend to be stable among middle-age BD patients, it remains plausible that deterioration occurs at either early or late stages of this condition.
Methods:
We conducted a comprehensive meta-analysis of studies that reported longitudinal neurocognitive performance among individuals with BD either within the year of their diagnosis or among late-life BD patients. Pooled effects of standardized mean differences (SMDs) for changes in neuropsychological scores over follow-up were estimated using random effects model. We also examined effect moderators, such as length of follow-up, mood state, or pharmacological load.
Results:
Eight studies met inclusion criteria for recent-onset and four studies for late-life BD analysis. No evidence for a deterioration in neurocognitive functioning was observed among recent-onset BD patients (8 studies, 284 patients, SMD: 0.12, 95% CI -0.06 to 0.30, mean follow-up: 17 months) nor for late-life BD patients (4 studies, 153 patients, SMD: -0.35, 95% CI -0.84 to 0.15, mean follow-up: 33 months). None of the moderators were shown to be significant.
Conclusions:
These results, when appraised together with the findings in middle-life BD patients and individuals at genetic risk for BD, suggest that neurodevelopmental factors might play a significant role in cognitive deficits in BD and do not support the notion of progressive cognitive decline in most patients with BD.
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