By Andrew Porterfield
Just from a look at the number of drugs available to treat schizophrenia, bipolar disorder, and other mental illnesses, the disorders hardly seem like an unmet medical need. However, the number of available antipsychotic drugs also indicates how stubborn these disorders can be. For some patients, one drug may work and another may not. Dosage also plays an important role, and for other patients, no available treatment is effective and tolerable.
One barrier to combating mental illness is that we have yet to arrive at an understanding of how these diseases are caused. This knowledge gap has alarming consequences for pharmaceutical development. Two British scientists wrote recently (PDF) that:
Despite considerable advances in neuroscience, there have been few if any notable advances in pharmacotherapy, and as a consequence of this and the perceived challenges in the field, many pharmaceutical companies are discontinuing research in neuroscience and psychiatry.
This issue may get help from genetics.
Just last year, the largest study ever of the genetics of schizophrenia was conducted. The numbers were impressive: more than 300 scientists conducted a genome-wide association study (GWAS) on 37,000 people who had the disease and 113,000 who didn’t, and found 128 genetic variants (including but not limited to mutations) that showed up more often in schizophrenia than in non-schizophrenics.
This marked a good start, but other studies have discovered genes that overlap certain mental disorders, indicating either that symptoms are shared among separate disorders, or that the disorders themselves need to be redefined, more closely following the genetics underlying each disease.
Symptom overlap in mental disorders has been known to psychiatrists for some time. For example, patients have been diagnosed with both schizophrenia and bipolar disorder. But psychiatric treatments of these disorders have not overlapped, leading psychiatry to establish a hierarchy of diagnoses (PDF). For at least a century, patients with symptoms of multiple disorders were diagnosed with the highest “ranked” disorder. So, in the case of schizophrenia and bipolar disorder in the same person, that person was diagnosed with only schizophrenia, and treated accordingly.
While this practice may have boosted the failure rate of psychiatric treatments, it may yet lead to better definitions of mental disorders, based on genetics and biological mechanisms.
In 2013, the first of many studies traced five major mental and neurodevelopmental illnesses (schizophrenia, bipolar disorder, depression, ADHD, and autism) to the same gene variations, shared on four chromosomes. Genome wide association studies (GWAS) determined that these genetic variations explained between 17–28 percent of the risk of getting any of these illnesses. On the other hand, twin studies showed 81 percent heritability in schizophrenia.
Since then, studies have shown (PDF) single nucleotide polymorphisms that each contained some effect on the risk of mental disorder. Scientists have also found alleles over-represented in schizophrenia were also over-represented in bipolar disorder and ADHD, but not in autism. Other studies have found copy number variations may increase the risk of certain disorders, but in other cases may protect against them. Still more work has found that genes involved in synaptic transmission, specific nerve cell receptor channels, the ability of synapses to “rebound” and change, signal transduction and nerve cell structure were altered in cases of mental illness.
The study of genes in mental illness may be comparable to the state of cancer biology. As oncology has been progressing from classifying tumors based on location to classifying them based on genetics, so too may mental illness change its diagnostic and treatment bases. But we’ll have to identify the right genes first.