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Abstract
In psychiatry, there has been a growing focus on identifying at-risk populations. For schizophrenia, these efforts have led to the development of early recognition and intervention measures. Despite a similar disease burden, the populations at risk of bipolar disorder have not been sufficiently characterized. Within the BipoLife consortium, we used magnetic resonance imaging (MRI) data from a multicenter study to assess structural gray matter alterations in N = 263 help-seeking individuals from seven study sites. We defined the risk using the EPIbipolar assessment tool as no-risk, low-risk, and high-risk and used a region-of-interest approach (ROI) based on the results of two large-scale multicenter studies of bipolar disorder by the ENIGMA working group. We detected significant differences in the thickness of the left pars opercularis (Cohen’s d = 0.47, p = 0.024) between groups. The cortex was significantly thinner in high-risk individuals compared to those in the no-risk group (p = 0.011). We detected no differences in the hippocampal volume. Exploratory analyses revealed no significant differences in other cortical or subcortical regions. The thinner cortex in help-seeking individuals at risk of bipolar disorder is in line with previous findings in patients with the established disorder and corresponds to the region of the highest effect size in the ENIGMA study of cortical alterations. Structural alterations in prefrontal cortex might be a trait marker of bipolar risk. This is the largest structural MRI study of help-seeking individuals at increased risk of bipolar disorder.
Highlights
In recent years, there has been an increasing effort to define and characterize individuals at risk for psychiatric disorders
region-of-interest approach (ROI) based primary analyses of left pars opercularis and hippocampus We detected a significant difference in the mean thickness of the left pars opercularis [F(2, 245) = 4.475, p = 0.024 (FDR-corrected)] between the bipolar-risk groups (Fig. 1 and Table 2) with medium effect size (Cohen’s d = 0.47)
In this study of help-seeking individuals at risk of bipolar disorder, we detected a significantly thinner left inferior frontal gyrus—pars opercularis in the high-risk individuals compared to the no-risk individuals
Summary
There has been an increasing effort to define and characterize individuals at risk for psychiatric disorders. These efforts gave rise to specialized early recognition services, which provide risk-stratifications and targeted interventions for helpseeking individuals at risk [1, 2]. Cumulative evidence from epidemiological, genetic, neuroimaging, and interventional studies led to the establishment of the psychosis risk syndrome, which is included as a diagnostic category in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) [3]. Bipolar disorder has been associated with brain structural alterations. The ENIGMA group performed two large-scale multicenter studies, which analyzed structural differences between individuals with bipolar disorder and healthy participants [9, 10], thereby
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