The Polygenetic Basis of Mutations in the Development of Schizophrenia
Schizophrenia is a mental disorder often presented in patients by abnormal thought processes, impaired emotional responses, and negative symptoms. As a chronic disorder that affects ~1% of all people, schizophrenia can be have debilitating effects on patients, especially on their social lives. Due to the lack of knowledge on its pathophysiology and also the heterogeneity of the symptoms, it has been increasingly important to understand the genetics of schizophrenia.
Due to the marked reduction in fecundity seen in schizophrenic patients, the high heritability of the disorder pointed to the possibility that genetic alleles that were risk factors might occur as de novo mutations. Previous exome sequencing studies showed no promising results, but the inconclusive results were likely due to small sample size and a narrow focus on target genes. Two recent studies, the largest of their kind, gathered data from nearly 7000 people (nearly 3500 patients) from Sweden and Bulgaria, and showed that genetic effects on schizophrenia seemed to be very complex. Specifically, both papers published in Nature reflected on the implication of genetic mutations in clusters of specific proteins that governed signaling networks dealing with learning and memory. The studies identified the presence of de novo mutations, often nonsense mutations, notably in genes related to the PSD (post-synaptic density of dendrites), the calcium channels, the postsynaptic ARC complex, and the NMDA receptors.
Going on vacation with my family for thirteen days was both exciting and daunting. The West Coast adventure was extremely appealing and I couldn’t wait to see the Grand Canyon, explore Yosemite National Park, and drive a convertible down the Pacific Coast Highway. But where was I going to get my brain fix? The Scientific American issue I bought for the flight to Phoenix wasn’t doing it for me. Some hope was gained at The Exploratorium, a hands-on science museum in San Francisco that managed to convince my thirteen-year-old sister that neuroscience might be almost potentially cool, but it wasn’t until a trip to Sonoma County that my curiosity was finally piqued.
Tiger the horse and I were riding along on a vineyard tour and I was talking to the tour guide about school. I’ve got yet another new response to “I’m studying neuroscience”: the tour guide told me about his son’s mysterious mental illness that may or may not be schizophrenia and we rode through wine country discussing psychiatrists, Thorazine, thought disorders and SSRIs. All in all, a good day.
This conversation got me wondering about the kinds of challenges psychologists and psychiatrists face when having to diagnose patients with schizophrenia. All the clinicians have to go on are whatever behavioral abnormalities make themselves apparent. But how do you weed out schizophrenia from other kinds of psychosis (some of which may respond to the typical treatment for schizophrenia)? More