Two hit hypothesis

Nevertheless, there is strong evidence that some mental illnesses are partly inherited. One prevailing theory is the two hit hypothesis. The first of these two hits is a genetic trait that leaves one vulnerable to the illness. The second hit is some stressful life event or environmental insult (e.g., infection or toxic exposure) that triggers the onset of the illness in the vulnerable individual. 

Life Events and the Two-Hit Hypothesis of Psychiatric Disorders. One theory that tries to explain this combination of genetic vulnerabilities and environmental factors as the basis of many psychiatric disorders is the two-hit hypothesis. That is, in order to manifest an overt psychiatric disorder, one must not only sustain the first hit, namely all the critical genetic vulnerabilities, but one must also sustain a second hit of some type from the environment (Figs. 4-2 through 4-5). Thus, psychiatric disorders are increased in incidence in first-degree relatives of patients with a wide variety of psychiatric disorders but not to an extent that allows one to predict which specific individuals will or will not eventually develop a specific psychiatric disorder. 

Maynard TM, Sikich L, Lieberman JA, LaMantia A-S. 2001. Neural development, cell-signaling, and the two-hit hypothesis of schizophrenia. Schizophr Bull 27 457-476. McConnachie G, Langeberg LK, Scott JD. 2006. AKAP signaling complexes Getting to the heart of the matter. Trends Mol Med 12 317-323. 

The answer is b. (Murray, pp 787-811. Scriver, pp 521-528. Sack, pp 85-96. Wilson, pp 187-228.) The two-hit hypothesis was developed by Knudsen to explain why patients with hereditary retinoblastoma [germline mutations (180200)] have multiple, bilateral tumors while those with... 

As mentioned above (Section 34.3.4.2) there is growing evidence supporting the hypothesis that schizophrenia is caused by a combination of genetic or epigenetic factors that affect limbic brain structures in the last trimester of development and stress-induced envkonmental influences during the final maturation of these structures late in human adolescence. This two hit idea has led to research directed at two potential targets for cytokine action the effects of cytokines on the... 

Lewis wrote to Paul Ehrenfest that he thought he had "hit upon something pretty fundamental." But Lewis had difficulty publishing his paper, "On the Theory of Reaction Rate," which the editor and referees of the Journal of the American Chemical Society worried was too speculative and insufficiently oriented toward experimental verification.96 Lewis ended by rejecting the radiation hypothesis, even issuing a press release to announce that a decision now had been made between the two rival theories of violent collision and radiation absorption in favor of the former. 97... 

The first step to test this hypothesis is the division of the dataset into a training and a test dataset. Two-thirds (3685 compounds) of the entire dataset were assigned to the training dataset and the remaining third (1828 compounds) to the test dataset by a random selection with the restriction that the ratio of hits to non-hits in the entire dataset is preserved in both the training and test dataset. 

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