Structural brain imaging correlates of schizophrenia symptomatology and their genetic background
Human Genetics
Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry
Human Cognitive and Systems Neuroscience
Final Report Abstract
The research objectives of this project were to investigate distinct symptoms of schizophrenia and their brain-based and genetic correlates. The overall aim was to shed light into etiological factors and underlying pathological processes by reducing the considerable variability of cognitive and clinical symptoms. In detail, two studies were proposed to investigate a) the structural correlates of negative and positive symptomatology – core symptoms of schizophrenia - and b) the genetics behind both symptom classes and related brain structures. Demographic, clinical, genetic and structural imaging data from the Neuro Imaging Genetics Through Meta-Analysis (ENIGMA) consortium was analyzed including 17 international sites with data of almost 2000 patients with schizophrenia. In study 1, meta-analytical results indicated that left, but not right, medialorbitofrontal cortex thickness was negatively correlated with negative symptom severity, even after controlling for age, gender or overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness attenuated the link between negative symptoms and left medialorbitofrontal cortex thickness. Positive symptom severity was negatively associated with superior temporal gyrus thickness in both hemispheres after covarying for age, gender, duration of illness, antipsychotic medication or handedness. In comparison, the association of positive symptoms with superior temporal gyrus thickness was much more robust compared to the link between negative symptoms and medialorbitofrontal cortex thickness, both with respect to hemispheric differences and to the potentially confounding effects of duration of illness, antipsychotic medication or handedness. Considering the stability of negative symptoms, but the rather fluctuating patterns of positive symptoms across the course of the disease, these findings were somewhat unexpected. This suggests that reduced cortical thickness might be a promising brain-based correlate for positive symptoms, but less so for negative symptoms. The genetic analyses, planned to be carried out in the second year of the fellowship, were not carried out due to a career progression. Combining imaging and meta-analytical approaches helped to gain insight into more specific and causal neurobiological mechanisms of schizophrenia.
Publications
- (2017) Positive symptoms associate with cortical thinning in the superior temporal gyrus via the ENIGMA Schizophrenia consortium. Acta psychiatrica Scandinavica 135 (5) 439–447
Walton E, Hibar D, van Erp TGM, et al.
(See online at https://doi.org/10.1111/acps.12718) - (2018) Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium. Psychological medicine 48 (1) 82–94
Walton, E.; Hibar, D. P.; van Erp, T. G. M.; Potkin, S. G.; Roiz-Santiañez, R.; Crespo-Facorro, B.; Suarez-Pinilla, P.; van Haren, N. E. M.; Zwarte, S. M. C. de; Kahn, R. S.; Cahn, W.; Doan, N. T.; Jørgensen, K. N.; Gurholt, T. P.; Agartz, I.; Andreassen,
(See online at https://doi.org/10.1017/S0033291717001283)
