Response to stress can cause lasting changes in the function of the HPA axis possibly disrupting the negative feedback mechanism, homeostasis, and the regulation of emotion leading to altered behaviors.The question of how schizophrenia could be primarily genetically influenced, given that people with schizophrenia have lower fertility rates, is a paradox. It is expected that genetic variants that increase the risk of schizophrenia would be selected against due to their negative effects on reproductive fitness. A number of potential explanations have been proposed, including that alleles associated with schizophrenia risk confers a fitness advantage in unaffected individuals. While some evidence has not supported this idea, others propose that a large number of alleles each contributing a small amount can persist.A meta-analysis found that oxidative DNA damage was significantly increased in schizophrenia. Environmental
Environmental factors, each associated with a slight risk of developing schizophrenia in later life include oxygen deprivation, infection, prenatal maternal stress, and malnutrition in the mother during prenatal development. A risk is associated with maternal obesity, in increasing oxidative stress, and dysregulating the dopamine and serotonin pathways. Both maternal stress and infection have been demonstrated to alter fetal neurodevelopment through an increase of pro-inflammatory cytokines. There is a slighter risk associated with being born in the winter or spring possibly due to vitamin D deficiency or a prenatal viral infection. Other infections during pregnancy or around the time of birth that have been linked to an increased risk include infections by Toxoplasma gondii and Chlamydia. The increased risk is about five to eight percent.
Drugs may also be used as coping mechanisms by people who have schizophrenia, to deal with depression, anxiety, boredom, and loneliness. The use of cannabis and tobacco are not associated with the development of cognitive deficits, and sometimes a reverse relationship is found where their use improves these symptoms. However, substance use disorders are associated with an increased risk of suicide, and a poor response to treatment.Cannabis use may be a contributory factor in the development of schizophrenia, potentially increasing the risk of the disease in those who are already at risk. The increased risk may require the presence of certain genes within an individual. Its use is associated with doubling the rate. Mechanism
The mechanisms of schizophrenia are unknown, and a number of models have been put forward to explain the link between altered brain function and schizophrenia.The prevailing model of schizophrenia is that of a neurodevelopmental disorder, and the underlying changes that occur before symptoms become evident are seen as arising from the interaction between genes and the environment. Extensive studies support this model. Maternal infections, malnutrition and complications during pregnancy and childbirth are known risk factors for the development of schizophrenia, which usually emerges between the ages of 18–25, a period that overlaps with certain stages of neurodevelopment. Gene-environment interactions lead to deficits in the neural circuitry that affect sensory and cognitive functions.The common dopamine and glutamate models proposed are not mutually exclusive; each is seen to have a role in the neurobiology of schizophrenia.