Differential Relationships Among C-Reactive Protein, Attention Functioning, and Brain Structure in Bipolar Offspring With and Without Subthreshold Mood Symptoms

Wenjin Zou, MD; Robin Shao, PhD; Weicong Lu, MD; Ruoxi Zhang, MD; Suk-Yu Yau, PhD; Ningning Chen, MD; Guiyun Xu, PhD, MD; Kwok-Fai So, PhD; Kangguang Lin, MD, PhD

J Clin Psychiatry 2022;83(6):21m14113

ABSTRACT

Background: Bipolar disorder (BD) is a highly heritable mood disorder. Activated low-grade inflammation may not only play an adverse role in the pathophysiology of BD, but also contribute to a resilience process. The neuroinflammatory processes may underlie the attention deficit and alteration of gray matter volume (GMV) in the early stage and premorbid period of BD. Also, the differential inflammation-brain relationship may be identified as biological markers for BD pathology or resilience.

Methods: The present data were collected between March 2013 and June 2016. Sixty-four offspring of BD patients were recruited and subdivided into asymptomatic (n = 33, mean age = 17.8 years) and symptomatic (n = 31, mean age = 16.2 years) groups according to whether they manifested subthreshold mood symptoms. The diagnosis of BD was confirmed according to DSM-IV criteria. C-reactive protein (CRP) level, attention functioning, and GMV data were measured by ELISA, the Continuous Performance Test-Identical Pair test (CPT-IP), and 3.0 T magnetic resonance imaging, respectively. Their relationships were examined with mediation and moderation analyses.

Results: We observed a higher level of CRP and poorer attention in the symptomatic group than the asymptomatic group and found a significant group × CRP interactive effect on GMV in regions spanning right precentral and postcentral gyri (P = .043). CRP levels negatively mediated the relationship between the group and CPT-IP scores, and the group marginally moderated the relationship between pre/postcentral gyri volumes and CPT-IP scores (P = .05).

Conclusions: Symptomatic and asymptomatic bipolar offspring manifested differential inflammation-GMV-attention relationships, which may represent, respectively, an endophenotype or a resilience process for BD.

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