Cortical thickness, volume and surface area in patients with bipolar disorder types I and II

Cortical thickness, volume and surface area in patients with bipolar disorder types I and II

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J Psychiatry Neurosci 2016;41(4):240-250

Christoph Abé, PhD; Carl-Johan Ekman, MD; Carl Sellgren, MD, PhD; Predrag Petrovic, MD, PhD; Martin Ingvar, MD, PhD; Mikael Landén, MD, PhD


Background: Bipolar disorder (BD) is a common chronic psychiatric disorder mainly characterized by episodes of mania, hypomania and depression. The disorder is associated with cognitive impairments and structural brain abnormalities, such as lower cortical volumes in primarily frontal brain regions than healthy controls. Although bipolar disorder types I (BDI) and II (BDII) exhibit different symptoms and severity, previous studies have focused on BDI. Furthermore, the most frequently investigated measure in this population is cortical volume. The aim of our study was to investigate abnormalities in patients with BDI and BDII by simultaneously analyzing cortical volume, thickness and surface area, which yields more information about disease- and symptom-related neurobiology.

Methods: We used MRI to measure cortical volume, thickness and area in patients with BDI and BDII as well as in healthy controls. The large study cohort enabled us to adjust for important confounding factors.

Results: We included 81 patients with BDI, 59 with BDII and 85 controls in our analyses. Cortical volume, thickness and surface area abnormalities were present in frontal, temporal and medial occipital regions in patients with BD. Lithium and antiepileptic drug use had an effect on the observed differences in medial occipital regions. Patients with the subtypes BDI and BDII displayed common cortical abnormalities, such as lower volume, thickness and surface area than healthy controls in frontal brain regions but differed in temporal and medial prefrontal regions, where only those with BDI had abnormally low cortical volume and thickness.

Limitations: The group differences can be explained by progressive changes, but also by premorbid conditions. They could also have been influenced by unknown factors, such as social, environmental or genetic factors.

Conclusion: Our findings suggest diagnosis-related neurobiological differences between the BD subtypes, which could explain distinct symptoms and point to potential biomarkers that could inform the subtype diagnosis of BD.

Submitted Mar. 25, 2014; Revised July 27, 2015; Accepted Aug. 21, 2015; Early-released Dec. 8, 2015

Acknowledgements: This research was supported by grants from the Swedish Medical Research Council (K2014-62X-14647-12-51 and K2010-61P-21568-01-4), the Swedish foundation for Strategic Research, the Swedish Brain foundation and the Swedish Federal Government under the LUA/ALF agreement (ALF 20130032, ALFGBG-142041). The authors thank the staff at the St. Göran bipolar affective disorder unit, including coordinator Martina Wennberg; study nurses Agneta Carlswärd-Kjellin, Lena Lundberg, Johanna Olofsson and Benita Gezelius; and Haydeh Olofsson and Mathias Kardell for database support. The authors thank Marie Tegnér and Yords Osterman for performing MRI scans and all the patients and controls who participated in this study.

Affiliations: From the Departments of Clinical Neuroscience (Abé, Ekman, Petrovic, Ingvar, Landén), Physiology and Pharmacology (Sellgren), and Medical Epidemiology and Biostatistics (Landén), Karolinska Institutet, Stockholm, Sweden; and the Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the Gothenburg University, Gothenburg, Sweden (Landén).

Competing interests: C.J. Ekman has received speaker honoraria from Medivir AB. M. Landén has received lecture honoraria from Biophausia, Servier Sweden, AstraZeneca, Bristol Myers-Squibb, and Bayer; and has served on the advisory board for Lundbeck pharmaceuticals. No other competing interests declared.

Contributors: C.J. Ekman, M. Ingvar and M. Landén designed the study. C.J. Ekman, C. Sellgren and M. Landén acquired the data, which C. Abé, P. Petrovic, M. Ingvar and M. Landén analyzed. C. Abé and M. Landén wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.150093

Correspondence to: C. Abé, Department of Clinical Neuroscience, Osher Center, Karolinska Institutet, Nobelsväg 9, 17177 Stockholm, Sweden;