Polygenic risk scores mediating functioning outcomes through cognitive and clinical features in youth at family risk and controls.

Schizophrenia and bipolar disorder exhibit substantial clinical overlap, particularly in individuals at familial high risk, who frequently present sub-threshold symptoms before the onset of illness. Severe mental disorders are highly polygenic traits, but their impact on the stages preceding the manifestation of mental disorders remains relatively unexplored. Our study aimed to examine the influence of polygenic risk scores (PRS) on sub-clinical outcomes over a 2-year period in youth at familial high risk for schizophrenia and bipolar disorder and controls.

Effects of the PAM of mGluR2, JNJ-46356479, on brain apoptotic protein levels in a mouse model of schizophrenia.

Current treatment for schizophrenia (SZ) ameliorates the positive symptoms, but is inefficient in treating the negative and cognitive symptoms. The SZ glutamatergic dysfunction hypothesis has opened new avenues in the development of novel drugs targeting the glutamate storm, an inducer of progressive neuropathological changes. Positive allosteric modulators of metabotropic glutamate receptor 2 (mGluR2), such as JNJ-46356479 (JNJ), reduce the presynaptic release of glutamate, which has previously been demonstrated to attenuate glutamate- and dopamine-induced apoptosis in human neuroblastoma cell cultures.

Gene expression imputation provides clinical and biological insights into treatment-resistant schizophrenia polygenic risk.

Genome-wide association studies (GWAS) have revealed the polygenic nature of treatment-resistant schizophrenia TRS. Gene expression imputation allowed the translation of GWAS results into regulatory mechanisms and the construction of gene expression (GReX) risk scores (GReX-RS).  In the present study we computed GReX-RS from the largest GWAS of TRS to assess its association with clinical features.

The polygenic basis of relapse after a first episode of schizophrenia.

Little is known about genetic predisposition to relapse. Previous studies have linked cognitive and psychopathological (mainly schizophrenia and bipolar disorder) polygenic risk scores (PRS) with clinical manifestations of the disease. This study aims to explore the potential role of PRS from major mental disorders and cognition on schizophrenia relapse.

Exploration of cannabis use and polygenic risk scores on the psychotic symptom progression of a FEP cohort.

Cannabis use is highly prevalent in first-episode psychosis (FEP) and plays a critical role in its onset and prognosis, but the genetic underpinnings promoting both conditions are poorly understood. Current treatment strategies for cannabis cessation in FEP are clearly inefficacious. Here, we aimed to characterize the association between cannabis-related polygenic risk scores (PRS) on cannabis use and clinical course after a FEP.