RNA-seq analysis of amygdala tissue reveals characteristic expression profiles in schizophrenia

Abstract

The amygdala brain region has been implicated in the pathophysiology of schizophrenia through emotion processing. However, transcriptome messages in the amygdala of schizophrenia patients have not been well studied. We used RNA sequencing to investigate gene-expression profiling in the amygdala tissues, and identified 569 upregulated and 192 downregulated genes from 22 schizophrenia patients and 24 non-psychiatric controls. Gene functional enrichment analysis demonstrated that the downregulated genes were enriched in pathways such as 'synaptic transmission' and 'behavior', whereas the upregulated genes were significantly over-represented in gene ontology pathways such as 'immune response' and 'blood vessel development'. Co-expression-based gene network analysis identified seven modules including four modules significantly associated with 'synaptic transmission', 'blood vessel development' or 'immune responses'. Taken together, our study provides novel insights into the molecular mechanism of schizophrenia, suggesting that precision-tailored therapeutic approaches aimed at normalizing the expression/function of specific gene networks could be a promising option in schizophrenia.

Beyond C4: Analysis of the complement gene pathway shows enrichment for IQ in patients with psychotic disorders and healthy controls

“…Using a shRNA‐mediated knock‐out of SERPING1 to silence the gene expression, a recent study suggests knock‐out of this gene impairs neuronal migration and affects brain development . Preliminary evidence in a study of complement genes in twins with SZ implicated peripheral expression of C5 and SERPING1 to be associated with cortical thinning in the superior frontal region; SERPING1 has also been found to be overexpressed in the amygdala of patients with SZ . In animal studies, C1 inhibitor created by SERPING1 attenuated acute neurobehavioral deficits, ischemic volume, and neurodegeneration .…”

“…40 Preliminary evidence in a study of complement genes in twins with SZ implicated peripheral expression of C5 and SERPING1 to be associated with cortical thinning in the superior frontal region 4 ; SERPING1 has also been found to be overexpressed in the amygdala of patients with SZ. 42 In animal studies, C1 inhibitor created by SERPING1 attenuated acute neurobehavioral deficits, ischemic volume, and neurodegeneration. 43 Therefore, SER-PING1 is a gene pivotal to inflammatory response regulation, neural development, and a key contributor to complement cascade activation.…”

Reelin Supplementation Into the Hippocampus Rescues Abnormal Behavior in a Mouse Model of Neurodevelopmental Disorders

“…In particular, synaptoporin, which is exclusively enriched in granule cell axons, is a synaptic vesicle marker for hippocampal mossy fibers ( Romer et al, 2011 ). Patients with schizophrenia have both decreased synaptoporin levels ( Guillozet-Bongaarts et al, 2014 ; Chang et al, 2017 ) and mossy fiber deficits ( Kolomeets et al, 2007 ), indicating that synaptoporin expression may be a good marker for hippocampal synaptic disturbances in schizophrenia. In the presents study, we demonstrated synaptoporin deficit in MIA offspring, even in the absence of gross anatomical alterations in the brain or neuronal loss.…”

nMAGMA: a network enhanced method for inferring risk genes from GWAS summary statistics and its application to schizophrenia

“…At last, a total of 16 modules were detected across the four tissues as shown in Table 3. The functional terms enriched in the 16 modules were detected with the Database for Annotation, Visualization and Integrated Discovery (DAVID, version 6.8) [52], where only the most enriched term was shown for each module in Table 3 where pathways associated with ribosome and immune response were also enriched [57,58]. Another, the functional component of lipid droplet in Small Bowel (p=5.8110 -8 , module 1) is a main organelle that has important roles in regulating lipid metabolism [59].…”