In a recent article published in Issues in Science and Technology, neuroanatomy professor Jonathan Leo combs through the findings of the largest genetic investigation of any mental disorder, a multi-national genome-wide association study involving almost 37,000 persons diagnosed with schizophrenia and more than 113,000 controls: http://issues.org/32-2/the-search-for-schizophrenia-genes/ . The researchers identified 108 loci with statistically significant associations, yielding a risk score that could account for about 3.4% of the variance. That isn't a typo: https://dash.harvard.edu/bitstream/handle/1/13890642/4112379.pdf?sequence=1
Of course, it is true that the study design may have failed to capture some loci, perhaps even some important ones. Conversely, the miniscule risk score may even be falsely inflated due to the same (or different) flaws in the study's methodology. The authors reveal that of the 49 ancestry-matched case-control samples that were constructed, 46 were for people of European ancestry and 3 for East Asian ancestry. The 3 family-based samples were exclusively of European lineage. These omissions are highly interesting, possibly informative, given the well documented history of racism in the handing out of psychiatric diagnoses in Europe and the US, especially schizophrenia diagnoses given to people of African and Latino descent: http://pb.rcpsych.org/content/25/7/244 ; http://www.tandfonline.com/doi/abs/10.1080/09540269974429?journalCode=iirp20 ; http://tps.sagepub.com/content/33/3/297.abstract ; https://www.amazon.com/Protest-Psychosis-Schizophrenia-Became-Disease/dp/0807001279 . Examining the records of 135,000 US veterans, Blow et al. found that, despite similar symptom presentations, African Americans were more than 4 times more likely than whites to be diagnosed with schizophrenia (instead of bipolar disorder), while Hispanic Americans were 3.15 times more likely to recieve a diagnosis of schizophrenia than whites: https://www.researchgate.net/profil..._psychoses/links/53d24ac30cf220632f3c898f.pdf As the article notes, people diagnosed with a psychotic disorder are treated quite differently than those given a mood disorder (bipolar) diagnosis. People diagnosed with a psychotic disorder are prescribed more toxic, more debilitating drugs and are more often subjected to forced drugging and confinement. The diagnosing of and prescribing "treatments" for mental disorders are obviously not scientific endeavors. Psychiatry is a system of social control, not a science.
In any case, it's difficult to imagine that discovery of any heretofore undiscovered genetic associations could possibly lead to the conclusion that genes are anything more than an insignificant contributor to the development of symptoms diagnosed as schizophrenia (or any other mental disorder). As professor Leo notes:
http://issues.org/32-2/the-search-for-schizophrenia-genes/
Leo proceeds to refer to the findings of the largest GWAS on people diagnosed with major depressive disorder, a 2013 mega-analysis involving more than 32,000 cases and 76,000 controls of European descent, the results of which the authors provide the definitive summary: “ . . . we were unable to identify robust and replicable findings.” http://neurogenetics.qimrberghofer.edu.au/papers/Ripke2013MolPsychiatry.pdf (However, a new, larger GWAS on depression was published a couple of days ago, a meta-analysis involving people who obtained their DNA profiles through 23andMe and reported a history of depression, treatment for depression or no history of depression, combined with samples from two previously published GWAS. The abstract, which is all I've read so far, announces finding 15 loci that reached genome-wide significance. But it does not report a risk score, and Figure 2 seems to show that the vast majority of the variance consists of principle components that are explained by geographical ancestry: http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.3623.html As the title of the paper notes, these findings were also limited to people of European descent. One can easily get the impression that researchers consider inclusion of people of non-European ancestry in GWAS on depression to just muddy the waters. It seems unlikely that the findings of this most recent study are generally applicable across cultures and races/ethnicities.)
Leo also explicates how the rationale for pharmacological regimens for mental disorders rests crucially on the assumption that the cause of mental disorders is largely genetic:
The irony of Faraone's statement here is that an honest discussion of the actual scientific findings on "the genetic etiology of ADHD" would begin and end with the fact that no such genetic etiology has been found: http://adhdnet.com/wp/wp-content/uploads/2014/10/Neale-2010-Meta-analysis-of-genome-wide-JAACAP.pdf , even when the sample is racially/ethnically limited: http://www.ncbi.nlm.nih.gov/pubmed/22012869 . Interestingly, after numerous failed attempts to find genetic associations, publication of GWAS on ADHD seem to have come to an abrupt halt around 2010. Leo notes the disturbing fact that 18 times more children are diagnosed with ADHD in the US than in France.
Of course, it is true that the study design may have failed to capture some loci, perhaps even some important ones. Conversely, the miniscule risk score may even be falsely inflated due to the same (or different) flaws in the study's methodology. The authors reveal that of the 49 ancestry-matched case-control samples that were constructed, 46 were for people of European ancestry and 3 for East Asian ancestry. The 3 family-based samples were exclusively of European lineage. These omissions are highly interesting, possibly informative, given the well documented history of racism in the handing out of psychiatric diagnoses in Europe and the US, especially schizophrenia diagnoses given to people of African and Latino descent: http://pb.rcpsych.org/content/25/7/244 ; http://www.tandfonline.com/doi/abs/10.1080/09540269974429?journalCode=iirp20 ; http://tps.sagepub.com/content/33/3/297.abstract ; https://www.amazon.com/Protest-Psychosis-Schizophrenia-Became-Disease/dp/0807001279 . Examining the records of 135,000 US veterans, Blow et al. found that, despite similar symptom presentations, African Americans were more than 4 times more likely than whites to be diagnosed with schizophrenia (instead of bipolar disorder), while Hispanic Americans were 3.15 times more likely to recieve a diagnosis of schizophrenia than whites: https://www.researchgate.net/profil..._psychoses/links/53d24ac30cf220632f3c898f.pdf As the article notes, people diagnosed with a psychotic disorder are treated quite differently than those given a mood disorder (bipolar) diagnosis. People diagnosed with a psychotic disorder are prescribed more toxic, more debilitating drugs and are more often subjected to forced drugging and confinement. The diagnosing of and prescribing "treatments" for mental disorders are obviously not scientific endeavors. Psychiatry is a system of social control, not a science.
In any case, it's difficult to imagine that discovery of any heretofore undiscovered genetic associations could possibly lead to the conclusion that genes are anything more than an insignificant contributor to the development of symptoms diagnosed as schizophrenia (or any other mental disorder). As professor Leo notes:
As more and more variants are implicated, the results become even more watered down. For instance, a recent algorithm to examine the polygenic risk of schizophrenia estimated that there are 20,000 single nucleotide polymorphisms (SNPs), or differences in single DNA components, implicated in schizophrenia. Commenting on these results, Alkes Price from the Harvard School of Public Health noted that because so many regions are implicated, there is the concern that “GWAS will ultimately implicate the entire genome, becoming uninformative.” A clinically useful signal appears impossible to distinguish from the noise.
Even if you completely agree with the 108 loci study’s methodology and all its inherent assumptions, there is no way to conclude that the researchers have discovered “schizophrenia genes.” In fact, they have disproved their existence. For each of the 108 loci there is a very small difference between the percent found in those diagnosed with schizophrenia and the control sample. Take the very first one: it’s found in 86.4 percent of the patients, and in 85 percent of the control group. This is a minor difference, and whether or not you have the variant tells you nothing about your risk of being diagnosed with schizophrenia. These genes are neither unique nor specific for people diagnosed with schizophrenia; many of the genes are scattered far and wide, and most of us carry at least some of them. As Kenneth Kendler, a psychiatry professor and geneticist at Virginia Commonwealth University, concluded in a recent paper, “All of us carry schizophrenia risk variants, and the vast majority of us carry quite a lot of them.” It is only by combining all the genetic markers into a single polygenic risk score that researchers can say that an individual has an increased risk of developing schizophrenia. However, even those individuals with a supposedly increased risk were more likely to not develop schizophrenia.
Even if you completely agree with the 108 loci study’s methodology and all its inherent assumptions, there is no way to conclude that the researchers have discovered “schizophrenia genes.” In fact, they have disproved their existence. For each of the 108 loci there is a very small difference between the percent found in those diagnosed with schizophrenia and the control sample. Take the very first one: it’s found in 86.4 percent of the patients, and in 85 percent of the control group. This is a minor difference, and whether or not you have the variant tells you nothing about your risk of being diagnosed with schizophrenia. These genes are neither unique nor specific for people diagnosed with schizophrenia; many of the genes are scattered far and wide, and most of us carry at least some of them. As Kenneth Kendler, a psychiatry professor and geneticist at Virginia Commonwealth University, concluded in a recent paper, “All of us carry schizophrenia risk variants, and the vast majority of us carry quite a lot of them.” It is only by combining all the genetic markers into a single polygenic risk score that researchers can say that an individual has an increased risk of developing schizophrenia. However, even those individuals with a supposedly increased risk were more likely to not develop schizophrenia.
http://issues.org/32-2/the-search-for-schizophrenia-genes/
Leo proceeds to refer to the findings of the largest GWAS on people diagnosed with major depressive disorder, a 2013 mega-analysis involving more than 32,000 cases and 76,000 controls of European descent, the results of which the authors provide the definitive summary: “ . . . we were unable to identify robust and replicable findings.” http://neurogenetics.qimrberghofer.edu.au/papers/Ripke2013MolPsychiatry.pdf (However, a new, larger GWAS on depression was published a couple of days ago, a meta-analysis involving people who obtained their DNA profiles through 23andMe and reported a history of depression, treatment for depression or no history of depression, combined with samples from two previously published GWAS. The abstract, which is all I've read so far, announces finding 15 loci that reached genome-wide significance. But it does not report a risk score, and Figure 2 seems to show that the vast majority of the variance consists of principle components that are explained by geographical ancestry: http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.3623.html As the title of the paper notes, these findings were also limited to people of European descent. One can easily get the impression that researchers consider inclusion of people of non-European ancestry in GWAS on depression to just muddy the waters. It seems unlikely that the findings of this most recent study are generally applicable across cultures and races/ethnicities.)
Leo also explicates how the rationale for pharmacological regimens for mental disorders rests crucially on the assumption that the cause of mental disorders is largely genetic:
It is impossible to separate genetic theories from the medicalization of psychological stress. The widespread use of psychiatric medications is based on the idea that schizophrenia and other psychological conditions arise, in part, from genetic defects that result in biological alterations such as reduced levels of neurotransmitters, or deficits in neuronal circuits, that need to be fine-tuned with medications. In general, higher genetic contributions to a disease equate to a stronger case for pharmacological treatment, while diseases with a higher environmental component are seen as better candidates for lifestyle changes and therapy. In 1996, in regards to ADHD, Stephen Faraone, a leading psychiatric genetic researcher, stated: “Many parents are reluctant for their children to take psychotropic medication and others find it difficult to maintain prescribed regimes. These problems are mitigated by discussing the genetic etiology of ADHD…” If parents really believe that their child has a measurable chemical imbalance, then just as they would treat their diabetic child, they would surely treat their child diagnosed with ADHD.
The irony of Faraone's statement here is that an honest discussion of the actual scientific findings on "the genetic etiology of ADHD" would begin and end with the fact that no such genetic etiology has been found: http://adhdnet.com/wp/wp-content/uploads/2014/10/Neale-2010-Meta-analysis-of-genome-wide-JAACAP.pdf , even when the sample is racially/ethnically limited: http://www.ncbi.nlm.nih.gov/pubmed/22012869 . Interestingly, after numerous failed attempts to find genetic associations, publication of GWAS on ADHD seem to have come to an abrupt halt around 2010. Leo notes the disturbing fact that 18 times more children are diagnosed with ADHD in the US than in France.
