Eighty percent of all patients suffering from major depressive disorder (MDD) relapse at least once in their lifetime. Thus, understanding the neurobiological underpinnings of the course of MDD is of utmost importance. A detrimental course of illness in MDD was most consistently associated with superior longitudinal fasciculus (SLF) fiber integrity. As similar associations were, however, found between SLF fiber integrity and acute symptomatology, this study attempts to disentangle associations attributed to current depression from long-term course of illness.

A total of 531 patients suffering from acute (N = 250) or remitted (N = 281) MDD from the FOR2107-cohort were analyzed in this cross-sectional study using tract-based spatial statistics for diffusion tensor imaging. First, the effects of disease state (acute v. remitted), current symptom severity (BDI-score) and course of illness (number of hospitalizations) on fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity were analyzed separately. Second, disease state and BDI-scores were analyzed in conjunction with the number of hospitalizations to disentangle their effects.

Disease state (pFWE < 0.042) and number of hospitalizations (pFWE < 0.032) were associated with decreased FA and increased MD and RD in the bilateral SLF. A trend was found for the BDI-score (pFWE > 0.067). When analyzed simultaneously only the effect of course of illness remained significant (pFWE < 0.040) mapping to the right SLF.

Decreased FA and increased MD and RD values in the SLF are associated with more hospitalizations when controlling for current psychopathology. SLF fiber integrity could reflect cumulative illness burden at a neurobiological level and should be targeted in future longitudinal analyses.

Schizotypy is a putative risk phenotype for psychosis liability, but the overlap of its genetic architecture with schizophrenia is poorly understood.

We tested the hypothesis that dimensions of schizotypy (assessed with the SPQ-B) are associated with a polygenic risk score (PRS) for schizophrenia in a sample of 623 psychiatrically healthy, non-clinical subjects from the FOR2107 multi-centre study and a second sample of 1133 blood donors.

We did not find correlations of schizophrenia PRS with either overall SPQ or specific dimension scores, nor with adjusted schizotypy scores derived from the SPQ (addressing inter-scale variance). Also, PRS for affective disorders (bipolar disorder and major depression) were not significantly associated with schizotypy.

This important negative finding demonstrates that despite the hypothesised continuum of schizotypy and schizophrenia, schizotypy might share less genetic risk with schizophrenia than previously assumed (and possibly less compared to psychotic-like experiences).