•Schizophrenia, thought by many to be a genetic disorder, was specifically targeted for study by the Human Genome Project.•Extensive genetic studies have identified almost 300 risk genes but no ...causal gene.•NIMH invested extensive resources in this research with little to show for it and at the expense of alternative research projects.•Since schizophrenia does not appear to be a genetic disorder, NIMH's research portfolio should be reviewed.
The Human Genome Project was undertaken primarily to discover genetic causes and better treatments for human diseases. Schizophrenia was targeted since three of the project`s principal architects had a personal interest and also because, based on family, adoption, and twin studies, schizophrenia was widely believed to be a genetic disorder. Extensive studies using linkage analysis, candidate genes, genome wide association studies GWAS, copy number variants, exome sequencing and other approaches have failed to identify causal genes. Instead, they identified almost 300 single nucleotide polymorphisms SNPs associated with altered risks of developing schizophrenia as well as some rare variants associated with increased risk in a small number of individuals. Risk genes play a role in the clinical expression of most diseases but do not cause the disease in the absence of other factors. Increasingly, observers question whether schizophrenia is strictly a genetic disorder. Beginning in 1996 NIMH began shifting its research resources from clinical studies to basic research based on the promise of the Human Genome Project. Consequently, three decades later NIMH's genetics investment has yielded almost nothing clinically useful for individuals currently affected. It is time to review NIMH`s schizophrenia research portfolio.
Religions and mythologies from around the world teach that God or gods created humans. Atheist, humanist, and materialist critics, meanwhile, have attempted to turn theology on its head, claiming ...that religion is a human invention. In this book, E. Fuller Torrey draws on cutting-edge neuroscience research to propose a startling answer to the ultimate question.Evolving Brains, Emerging Godslocates the origin of gods within the human brain, arguing that religious belief is a by-product of evolution.Based on an idea originally proposed by Charles Darwin, Torrey marshals evidence that the emergence of gods was an incidental consequence of several evolutionary factors. Using data ranging from ancient skulls and artifacts to brain imaging, primatology, and child development studies, this book traces how new cognitive abilities gave rise to new behaviors. For instance, autobiographical memory, the ability to project ourselves backward and forward in time, gaveHomo sapiensa competitive advantage. However, it also led to comprehension of mortality, spurring belief in an alternative to death. Torrey details the neurobiological sequence that explains why the gods appeared when they did, connecting archaeological findings including clothing, art, farming, and urbanization to cognitive developments. This book does not dismiss belief but rather presents religious belief as an inevitable outcome of brain evolution. Providing clear and accessible explanations of evolutionary neuroscience,Evolving Brains, Emerging Godswill shed new light on the mechanics of our deepest mysteries.
This open access book analyzes the evidence linking Toxoplasma gondii to the increasing incidence of schizophrenia and bipolar disorder in the United States. Initially establishing that infectious ...agents are regularly transmitted from animals to humans, lead to human disease, and that infectious agents can cause psychosis, it then examines the protozoan parasite Toxoplasma gondii in detail. Infecting 40 million Americans, Toxoplasma gondii is known to cause congenital infections, eye disease, and encephalitis for individuals who are immunosuppressed. It has also been shown to change the behavior of nonhuman mammals, as well as to alter some personality traits in humans. After discussing the clinical evidence linking Toxoplasma gondii to human psychosis, the book elucidates the epidemiological evidence further supporting this linkage; including the proportional increase in incidence of human psychosis as cats transitioned to domestication over 800 years. Finally, the book assesses the magnitude of the problem and suggests solutions. Parasites, Pussycats and Psychosis: The Unknown Dangers of Human Toxoplasmosis provides a comprehensive review of the evidence linking human psychosis in the United States to infections of Toxoplasma gondii. It will be of interest to infectious disease specialists, general practitioners, scientists, historians, and cat-lovers.
Highlights • The annual environmental deposit of cat feces in the US is 1.2 million tons. • Toxoplasma gondii oocysts may remain viable for several years and thus accumulate. • In favored cat ...defecation sites, oocysts may accumulate in very high numbers. • The accumulation of T. gondii oocysts may be a major public health problem.
Environmental toxicants are thought to play a major role in the pathogenesis of Parkinson’s disease. In reviewing the literature on heavy metals known to be toxicants, we noted several recent studies ...on mercury suggesting a possible role in the etiology of some cases of this disease. We therefore undertook a review of this association, focusing especially on peer-reviewed articles to avoid the bias inherent in much of the literature regarding mercury. For most people, our contemporary exposure to mercury comes from dental amalgam tooth restorations and from eating fish contaminated with mercury. In both cases, mercury is known to get into the brain in utero and at all ages. It remains in the brain for many years and is known to produce permanent neuropsychological deficits. Mercury toxicity can produce tremors and other Parkinsonian clinical symptoms. It can also produce neurochemical and neuropathological changes similar to those found in Parkinson’s disease, including the loss of dopamine neurons, degeneration of tubulin and axons, dysfunction of mitochondria, and the aggregation of alpha-synuclein. Relatively few studies have assessed mercury in parkinsonian patients, but almost all reported a statistically significant association. Published studies suggest some promising leads in the relationship between mercury exposure and Parkinson’s disease. However, studies of patients are relatively few, and the need for research is clear. A search of Parkinsonian research studies currently funded by the US National Institutes of Health, Parkinson’s Foundation, and the Michael J Fox Foundation yielded no studies on mercury. We believe such studies should be supported.
Abstract Objective Studies of the neuroanatomical localization of schizophrenia have not given sufficient attention to the inferior parietal lobule (IPL). Methods A search of the medical literature ...was carried out for links between schizophrenia and the IPL. Results Structural differences in the IPL in schizophrenia were reported by 10 recent neuroimaging studies, although the studies did not all agree with each other. Functional differences in the IPL in schizophrenia have been prominently reported in four areas: sensory integration, body image, concept of self, and executive function. Conclusion The IPL appears to be an important, but relatively neglected, component of the frontal–limbic–temporal–parietal neural network involved in the schizophrenia disease process. To encourage histopathological research of this area, the Stanley Medical Research Institute is making available a new collection of sucrose-fixed IPL tissue from 25 individuals with schizophrenia and 25 matched controls. Additional imaging and functional studies are needed to better define the network and role of the IPL.
•Genetic research on schizophrenia has been disappointing.•The heritability of schizophrenia has been over-estimated.•What appears to be genetic may be infectious.•For patients this is good news ...since treatment of non-genetic causes is more feasible.
In recent years schizophrenia has been assumed to be largely a genetic disease with heritability estimates, derived primarily from family and twin studies, of 80%–85%. However, the results of genetic research on schizophrenia have not yielded results consistent with that estimate of heritability. In particular, extensive genetic studies have not led to new methods for diagnosis and treatment. An examination of the twin studies on which heritability is based shows why such studies exaggerate the genetic component of schizophrenia. In addition, the effects of infectious agents such as Toxoplasma gondii and the composition of the microbiome can produce a clinical picture that would also appear to be largely genetic due to familial aggregation and a role for a partial genetic contribution to the immune system. It is concluded that the genetic component of schizophrenia may have been overestimated and an increased focus on gene-environmental interactions is likely to accelerate research progress on this disease.
What Shaped My Career Torrey, E. Fuller
Psychiatric services (Washington, D.C.),
10/2019, Letnik:
70, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Torrey offers insights about his life and what shapes his career as psychiatrist. According to him, his life and career were largely shaped by four seminal experiences. He recounts the psychotic ...breakdown of his sister in 1957 at the age of 18, his experiences spending two years in Ethiopia as a Peace Corps physician prior to my training in psychiatry, and his affiliation at the National Institute of Mental Health (NIMH) in 1970 after completing my psychiatric residency.
The failure to find genes of major effect in schizophrenia has refocused attention on nongenetic, including infectious factors. In a previous study, antibodies to Toxoplasma gondii were found to be ...elevated in 23 studies of schizophrenia (OR 2.73; 95% CI 2.10-3.60). The current study replicates this finding with 15 additional studies (OR 2.71; 95% CI 1.93-3.80) and compares this with other identified schizophrenia risk factors. The highest risk factors are having an affected mother (relative risks RR 9.31; 95% CI 7.24-11.96), father (RR 7.20; 95% CI 5.10-10.16), or sibling (RR 6.99; 95% CI 5.38-9.08) or being the offspring of immigrants from selected countries (RR 4.5; 95% CI 1.5-13.1). Intermediate risk factors, in addition to infection with T. gondii, include being an immigrant from and to selected countries (RR 2.7; 95% CI 2.3-3.2), being born in (RR 2.24; 95% CI 1.92-2.61) or raised in (RR 2.75; 95% CI 2.31-3.28) an urban area, cannabis use (OR 2.10-2.93; 95% CI 1.08-6.13), having minor physical anomalies (OR 2.23; 95% CI 1.42-3.58), or having a father 55 or older (OR 2.21-5.92; 95% CI 1.46-17.02). Low-risk factors include a history of traumatic brain injury (OR 1.65; 95% CI 1.17-2.32), sex abuse in childhood (OR 1.46; 95% CI 0.84-2.52), obstetrical complications (OR 1.29-1.38; 95% CI 1.00-1.84), having a father 45 or older (OR 1.21-1.66; 95% CI 1.09-2.01), specific genetic polymorphisms (OR 1.09-1.24; 95% CI 1.06-1.45), birth seasonality (OR 1.07-1.95; 95% CI 1.05-2.91), maternal exposure to influenza (RR 1.05; 95% CI 0.98-1.12), or prenatal stress (RR 0.98-1.00; 95% CI 0.85-1.16).
Stigma against mentally ill persons is a major problem and has increased in incidence. Multiple studies have suggested that the perception of violent behavior by seriously mentally ill individuals is ...an important cause of stigma. It is also known that treating seriously mentally ill people decreases violent behavior. Therefore, the most effective way to decrease stigma is to make sure that patients receive adequate treatment.
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