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Abnormal Frontocortical Thinning Observed in Patients With Bipolar Disorder
In the conclusion of this Q&A, Christophe Abé, PhD, Quantify Research, Stockholm, Sweden, is joined by co-author Mikael Landén, MD, PhD, Department of Medical Epidemiology and Biostatistics and the Karolinska Institute, Stockholm, Sweden, where they discuss the unexpected outcomes and clinical implications of their study, "Longitudinal Structural Brain Changes in Bipolar Disorder: A Multicenter Neuroimaging Study of 1232 Individuals by the ENIGMA Bipolar Disorder Working Group."
The study examined structural brain changes over time in bipolar disorder using longitudinal magnetic resonance imaging (MRI) and clinical data and also highlighted the importance of mania prevention in treatment.
>>READ Part 1: Study Highlights Mania Prevention Importance in Bipolar Disorder Treatment
Q: Were any outcomes different than you expected?
Mikael Landén: Yes, first, it seems that abnormal cortical changes are coupled to mood episodes and may not [be] an inevitable progressive phenomenon. Second, our findings also suggest that the structural changes are reversible if patients stay well.
Dr Christoph Abé: In addition, while most findings were in line with our hypotheses, the finding that bipolar disorder patients showed slower thinning of the cortex in some brain areas compared with healthy individuals was somewhat unexpected. One possibility to explain this finding is that lithium, a medication used to treat bipolar disorder, is known to have neuroprotective effects and could bolster cortical thickness. However, more research is needed to clarify this.
Q: In what ways does this study highlight the importance of mania prevention in bipolar disorder (BD) treatment and are there any other practical applications of your findings for clinicians treating patients with BD?
Dr Landén: The findings stress the importance of preventing mood episodes in bipolar disorder. One might argue that we do not need brain imaging studies to do that. But the fact that severe mood episodes entail structural brain changes underlines the gravity of these events. The findings might also help to explain the clinical observation that the recovering phase extends beyond the period of elated mood, where cognitive impairment might linger for months.
Dr Abé: Our study highlights the impact mania may have on the brain, thus, it emphasized that mania prevention is a very important aspect in treatment of bipolar disorder. The treatment of other mood episodes, such as depression, is of course as important, as they can also have severe consequences.
Another implication is that we learned more about the disorder, which is an important step toward improving treatments in the future.
For example, our study indicates that bipolar disorder may have neuroprogressive features, at least for some patients. It also suggests that we should focus on understanding the underlying processes on a mechanistic level and identify potential risk factors, ie. patient characteristics that may increase the risk of, eg, mania-related cortical decline. These could include biochemical, lifestyle, or genetic factors that predispose an individual. Understanding these details is essential for the improvement of treatment options that aim at the prevention of mood episodes and ultimately improve [the] quality of life of affected individuals.
Q: Are you conducting any more research in this area, and/or are there any other studies you feel are needed? Any final thoughts pertaining to this research?
Dr Abé: The St. Göran project, based in Stockholm and Göteborg, Sweden, which is led by principal investigator Professor Mikael Landén is currently investigating disease mechanisms on many different levels. This includes long-term prospective studies, where patients are followed over 14 years. Currently, there are also several ongoing large-scale ENIGMA studies focusing on various aspects of the disease. All these efforts are aimed at providing more refined insights into the mechanisms underlying bipolar disorder.
Dr Landén: As is often the case in research, the results prompt new questions [such as the following]: What are the mechanisms driving the brain changes during mood episodes? (Clarifying the mechanisms might open ways to prevent this from happening.) Moreover, do these imaging findings correspond to symptoms that matter for patients? Speculation would be that brain changes confer cognitive sequelae, but that remains to be shown.
Mikael Landén, MD, PhD, is a professor in the Department of Medical Epidemiology and Biostatistics and the Karolinska Institutet in Stockholm, Sweden. He is also chief physician of the Department of Psychiatry and Neurochemistry in the Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Sweden.
Christoph Abé, PhD, obtained his PhD in biophysics from the University of Osnabrueck, Germany, in 2010. From 2011 to 2012, he was employed as postdoc at the University of California San Francsico (UCSF) at the Department of Radiology and Biomedical Imaging, where he conducted research in substance use disorders using neuroimaging. From 2013 to 2017, he was postdoc at Karolinska Institutet (KI), Stockholm, Sweden (Dept. of Clinical Neuroscience, CNS), where he performed neuroimaging research in psychiatric disorders with a focus on bipolar disorder. From 2017 tp 2021, he was employed as assistant professor in neuroimaging psychiatric disorders at KI, CNS. Currently, he is the lead analysist at Quantify Research, Stockholm, and affiliated to research at Karolinska Institutet (CNS).
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