Bipolar disorder (BD), including more specific classifications such as bipolar I and bipolar II disorders, is a condition characterized by episodes of mania, hypomania, and/or depression . It is thought to affect more than 1% of the world’s population and is considered a prominent cause of disability in young people . Although it remains unclear whether BD follows a primarily developmental versus progressive (i.e., neurodegenerative) disease course, what is apparent is that the likelihood of functional impairment increases over an individual’s lifetime [3, 4, 5]. Neurocognitive studies support at least a partial neuroprogressive contribution to BD, with cognitive dysfunction considered a well-documented feature of both symptomatic and euthymic states of the disorder [6, 7]. In the context of relatively preserved intellectual functioning, executive dysfunction and impairments in attention/working memory, processing speed, and verbal learning and memory are the most commonly cited impairments in euthymic BD individuals [6, 7, 8, 9].
While the relationship between cognitive impairment and BD is well established, the etiology and possible moderators of this dysfunction are less clear. This is further complicated by the high rate of comorbidities in this population that can also have a negative impact on cognition, such as substance use, poor treatment compliance, and compromised cardiovascular health [1, 10]. For example, while some meta-analyses report associations between cognitive impairment and BD severity variables (e.g., illness duration, number of manic episodes, number of hospitalizations), others find no such associations [6, 10, 11]. Specifically regarding antipsychotic medications, some authors report negative effects on cognition [6, 12], while those in favor of a neuroprogressive model of BD believe that medications (e.g., Lithium, valproic acid, and atypical antipsychotics) may in fact be neuroprotective in preventing biochemical causes of neuronal damage .
Both structural and functional neuroimaging studies have increased our general understanding the neurophysiology of BD, with changes in mood thought to result from structural and functional abnormalities within striatal–thalamic–prefrontal circuits . Structural neuroimaging studies provide insight specifically into potential sources of neurocognitive dysfunction, as certain structural abnormalities and reductions in gray matter volume (e.g., prefrontal, anterior cingulate, and subgenual regions) seem to become more evident over time [3, 4, 5, 13].
Future research directions regarding the relationship between cognitive dysfunction and BD include standardizing neuropsychological test procedures (e.g., The International Society for Bipolar Disorders–Battery for Assessment of Neurocognition; ISBD-BANC ), BD variables (e.g., the definition/criteria for euthymia), and cognitive impairment thresholds to reduce heterogeneity across studies . In addition, randomized control trials may yield additional information on the effects of drug treatment and other causal variables on cognition [6, 15]. Specifically, it remains unclear whether early and long-term treatment with medications such as lithium, observed to reduce cell death and increase gray matter volume, also enhances cognitive functioning over time [3, 4]. Finally, research on cognition in older adults with BD and prospective studies investigating patterns of cognitive impairment and decline across the lifespan are limited. A greater understanding of cognitive dysfunction in older adults, as well as the neuroprogressive features of BD, will be helpful in clinical settings for differentiating the source of cognitive impairment in older individuals diagnosed with BD.
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2. Grande, I., Berk, M., Birmaher, B., & Vieta, E. (2016). Bipolar disorder. The Lancet, 387(10027), 1561-1572. Link: https://www.ncbi.nlm.nih.gov/pubmed/26388529
3. Berk, M. (2009). Neuroprogression: pathways to progressive brain changes in bipolar disorder. International Journal of Neuropsychopharmacology, 12(4), 441-445. Link: https://www.ncbi.nlm.nih.gov/pubmed/18922203
4. Lim, C. S., Baldessarini, R. J., Vieta, E., Yucel, M., Bora, E., & Sim, K. (2013). Longitudinal neuroimaging and neuropsychological changes in bipolar disorder patients: review of the evidence. Neuroscience & Biobehavioral Reviews, 37(3), 418-435. Link: https://www.ncbi.nlm.nih.gov/pubmed/23318228
5. Savitz, J. B., Price, J. L., & Drevets, W. C. (2014). Neuropathological and neuromorphometric abnormalities in bipolar disorder: view from the medial prefrontal cortical network. Neuroscience & Biobehavioral Reviews, 42, 132-147. Link: https://www.ncbi.nlm.nih.gov/pubmed/24603026
6. Bourne, C., Aydemir, Ö., Balanzá‐Martínez, V., Bora, E., Brissos, S., Cavanagh, J. T. O., ... & Ferrier, I. N. (2013). Neuropsychological testing of cognitive impairment in euthymic bipolar disorder: an individual patient data meta-analysis. Acta Psychiatrica Scandinavica, 128(3), 149-162. Link:http://onlinelibrary.wiley.com/doi/10.1111/acps.12133/full
7. Quraishi, S., & Frangou, S. (2002). Neuropsychology of bipolar disorder: a review. Journal of affective disorders, 72(3), 209-226. Link:https://www.ncbi.nlm.nih.gov/pubmed/12450638
8. Robinson, L. J., Thompson, J. M., Gallagher, P., Goswami, U., Young, A. H., Ferrier, I. N., & Moore, P. B. (2006). A meta-analysis of cognitive deficits in euthymic patients with bipolar disorder. Journal of affective disorders, 93(1), 105-115. Link: https://www.ncbi.nlm.nih.gov/pubmed/16677713
9. Torres, I. J., Boudreau, V. G., & Yatham, L. N. (2007). Neuropsychological functioning in euthymic bipolar disorder: a meta‐analysis. Acta Psychiatrica Scandinavica, 116(s434), 17-26. Link: https://www.ncbi.nlm.nih.gov/pubmed/17688459
10. Cullen, B., Ward, J., Graham, N. A., Deary, I. J., Pell, J. P., Smith, D. J., & Evans, J. J. (2016). Prevalence and correlates of cognitive impairment in euthymic adults with bipolar disorder: A systematic review. Journal of Affective Disorders, 205, 165-181. Link: http://www.jad-journal.com/article/S0165-0327(16)30753-4/fulltext
11. Robinson, L. J., & Nicol Ferrier, I. (2006). Evolution of cognitive impairment in bipolar disorder: a systematic review of cross‐sectional evidence. Bipolar disorders, 8(2), 103-116. Link: http://onlinelibrary.wiley.com/doi/10.1111/j.1399-5618.2006.00277.x/abstract
12. Torrent, C., Martinez-Arán, A., Daban, C., Amann, B., Balanzá-Martínez, V., del Mar Bonnín, C., ... & Vieta, E. (2011). Effects of atypical antipsychotics on neurocognition in euthymic bipolar patients. Comprehensive psychiatry, 52(6), 613-622. Link: https://www.ncbi.nlm.nih.gov/pubmed/21295774
13. Strakowski, S. M., DelBello, M. P., DelBello, & Adler, C. M. (2005). The functional neuroanatomy of bipolar disorder: a review of neuroimaging findings.Molecular Psychiatry. 10, 105–116.
14. Yatham, L. N., Torres, I. J., Malhi, G. S., Frangou, S., Glahn, D. C., Bearden, C. E., ... & Ozerdem, A. (2010). The International Society for Bipolar Disorders–Battery for Assessment of Neurocognition (ISBD‐BANC). Bipolar disorders, 12(4), 351-363. Link: http://onlinelibrary.wiley.com/doi/10.1111/j.1399-5618.2010.00830.x/abstract
15. Arts, B., Jabben, N., Krabbendam, L., & Van Os, J. (2008). Meta-analyses of cognitive functioning in euthymic bipolar patients and their first-degree relatives. Psychological medicine, 38(06), 771-785. Link: https://www.ncbi.nlm.nih.gov/pubmed/17922938
Neuropsychological testing of cognitive impairment in euthymic bipolar disorder: an individual patient data meta-analysis (2013)
Background: Neurocognitive deficits are present in bipolar disorder (BD) patients and their unaffected (non bipolar) relatives, but it is not clear which domains are most often impaired and the extent of the impairment resulting from shared genetic factors. In this literature review, we address these issues and identify specific neurocognitive tasks most sensitive to cognitive deficits in patients and unaffected relatives.
Method: We conducted a systematic review in Web of Science, PubMed/Medline and PsycINFO databases.
Results: Fifty-one articles assessing cognitive functioning in BD patients (23 studies) and unaffected relatives (28 studies) were examined. Patients and, less so, relatives show impairments in attention, processing speed, verbal learning/memory, and verbal fluency.
Conclusion: Studies were more likely to find impairment in patients than relatives, suggesting that some neurocognitive deficits may be a result of the illness itself and/or its treatment. However, small sample sizes, differences among relatives studied (e.g., relatedness, diagnostic status, age), and differences in assessment instruments may contribute to inconsistencies in reported neurocognitive performance among relatives. Additional studies addressing these issues are needed.
Citation: Bourne, C., Aydemir, Ö., Balanzá‐Martínez, V., Bora, E., Brissos, S., Cavanagh, J. T. O., ... & Ferrier, I. N. (2013). Neuropsychological testing of cognitive impairment in euthymic bipolar disorder: an individual patient data meta-analysis. Acta Psychiatrica Scandinavica, 128(3), 149-162.
1. NAN Distance Recorded Webinar: The Clinical Utility of Neuropsychological Testing for Patients with Mental Disorders. Anthony C. Ruocco, Ph.D.
2. NAN Distance Recorded Webinar: Developmental Aspects of Bipolar Disorder in Children, Adolescents and Adults. Gabrielle A. Carlson, M.D.
1. PBS Special: Ride the Tiger: A Guide Through the Bipolar Brain (55 minutes)
“Nearly six million Americans have been diagnosed with the disorder and yet so little is known about how the illness manifests itself in our brains. Ride the Tiger is a one-hour documentary that tells the stories of highly accomplished individuals who have been diagnosed as bipolar.” – PBS