Cascade Biotechnology INC | Complement Therapeutics; novel approach to CNS/PNS disease management using the innate complement system.
Cognitive Disorders: Schizophrenia
Schizophrenia is a life long psychiatric disorder that often strikes in the late teens or early twenties.
There is strong genetic component that is also significantly shaped by environmental factors.
The disease often involves excessive loss of gray matter (Cannon TD, et al. (2002) Cortex mapping reveals regionally specific patterns of genetic and disease- specific gray-matter deficits in twins discordant for schizophrenia. Proceedings of the National Academy of Sciences of the United States of America. 2002; 99:3228–32332) (Cannon TD et al.,(2015) Progressive reduction in cortical thickness as psychosis develops: a multisite longitudinal neuroimaging study of youth at elevated clinical risk. Biol Psychiatry Jan 15;77(2):147-57. doi: 10.1016/j.biopsych.2014.05.023) and reduced numbers of synaptic structures on neurons, (Garey LJ, et al. Reduced dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia. J Neurol Neurosurg Psychiatry. 1998; 65:446–453).
Schizophrenia is associated with decreased dendritic spine density on prefrontal cortical pyramidal neurons (Glausier JR, Lewis DA. Dendritic spine pathology in schizophrenia. Neuroscience. 2013; 251:90– 107).
Consequently cognition, memory and perception are often impaired.
Psychotic symptoms (positive which are: hallucinations, delusions, thought disorders and paranoia, even movement disorders: negative which are: flat affect, lack or loss of emotion and speech, reduced sense of pleasure, difficultly initiation, maintaining activity) of schizophrenia are treated medicinally with varying degrees of success.
The cause and mechanisms involved with schizophrenia are not well understood.
Significant effort has been put forth to understand the genetic basis of schizophrenia.
More than 100 loci in the human genome contain SNP haplotypes that associate with risk of schizophrenia (Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014; 511:421–427).
There is an association between schizophrenia and genetic markers across the Major Histocompatibility Complex (MHC) locus.
The MHC locus is known for its role in immunity, containing highly polymorphic human leukocyte antigen (HLA) genes that encode many antigen-presenting molecules. Autoimmune diseases may have genetic associations at the MHC locus that arise from alleles of HLA genes. Schizophrenia’s association to the MHC is not yet explained.
Studies have shown that strongly associated markers are near a complex, multi-allelic, and partially characterized form of genome variation that affects the C4 gene encoding complement component 4. Schizophrenia is associated to CSMD16,10, which encodes a regulator of C413. (Sekar. et al., (2016) Schizophrenia risk from complex variation of complement component 4 Nature. February 11; 530(7589): 177–183).
In addition, very recently C5 levels in CSF were abnormally high in several psychiatric disorders, including bipolar disorder and schizophrenia. (Ishii T et al. (2018) Increased cerebrospinal fluid complement C5 levels in major depressive disorder and schizophrenia.Biochem Biophys Res Commun. Mar 4;497(2):683-688).