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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.
The pathophysiological role of neural autoantibodies in acute psychotic disorders is receiving increased attention. However, there is still an ongoing debate, whether predominantly psychotic manifestations of autoimmune encephalitides exist that may remain undetected and, thus, untreated. Furthermore, it is discussed if such conditions can be diagnosed based on serum antibody results or if a reliable diagnosis requires additional cerebrospinal fluids (CSF) results. In this study, we screened pairs of serum and CSF samples from antipsychotic-naïve individuals with first-episode schizophrenic psychosis (FEP, n = 103), clinical high risk for psychosis (CHR, n = 47), and healthy volunteers (HV, n = 40) for eight different antibodies against various antigens that have been shown to be associated with autoimmune encephalitides: N-methyl-D-aspartate receptor (NMDAR, NR1 subunits only), glutamic acid decarboxylase (GAD65), leucine-rich glioma inactivated protein 1 (LGI1), contactin-associated protein-like 2 protein (CASPR2), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit 1, AMPAR subunit 2, γ-aminobutyric acid-B receptors (GABABR), and glycine receptors. All patients were within the norm with regards to a careful neurological examination, a magnetic resonance imaging (MRI) of the brain, an electroencephalogram (EEG), and routine blood pathology. All CSF samples were autoantibody-negative. In three serum samples of individuals with FEP, we detected low-titer CASPR2 immunoglobulin (Ig) G antibodies (≤1:160, n = 2) and non-IgG antibodies against NMDAR (n = 1) (overall serum-autoantibody prevalence in FEP: 2.91%). However, the IgG titers were below the laboratory cut-off defined for positivity, and non-IgG antibodies are of no clinical relevance. This suggests that there were no cases of autoimmune encephalitis in our cohort. Our results highlight the importance and the high specificity of CSF analysis to reliably detect autoantibodies. They confirm the hypothesis that pure psychotic manifestations of antibody-associated autoimmune encephalitides without any additional neuropsychiatric findings are very rare. However, special attention must be paid to those presenting with atypical mental illnesses with additional neurological symptoms, evidence of clinically-significant cognitive involvement, profound sleep-wake perturbations, seizures, electroencephalographic, or magnetic resonance imaging pathologies to be able to identify cases with autoimmune-mediated psychiatric syndromes.