monomers. such an increase in monomers may occur via the cooperativity mechanism which is responsible for d2high and d2low, the supersensitive and lowsensitivity states of the d2 dopamine receptor. more specifically, "an increase in monomers, may be one basis for dopamine supersensitivity". genetic and other biopsychosocial risk factors genetic evidence has suggested that there may be genes, or specific variants of genes, that code for mechanisms involved in dopamine function, which may be more prevalent in people experiencing psychosis or diagnosed with schizophrenia. advanced technology has led to the possibility of performing genome-wide association (gwa) studies. these studies identify frequently seen single nucleotide polymorphisms (snp) that are associated with common, yet complex disorders. genetic variants found due to gwa studies may offer insight concerning impairments in dopaminergic function. dopamine-related genes linked to psychosis in this way include comt, drd4, and akt1. while genetics play an important role in the occurrence of schizophrenia, other biopsychosocial factors must also be taken into consideration. while focusing on the risk of schizophrenia in second generation migrants, hennsler and colleagues relay that the dopamine hypothesis of schizophrenia may be an explanation. some migrants who have had adverse experiences in their host country, such as racism, xenophobia, and poor living conditions, were found to have high stress levels, which increased dopaminergic neurotransmission. this increase in dopaminergic neurotransmission can be seen in the striatum and amygdala, both of which are areas in the brain that process aversive stimuli. evidence against the dopamine hypothesis further experiments, conducted as new methods were developed (particularly the ability to use pet scanning to examine drug action in the brain of living patients) challenged the view that the amount of dopamine blocking was correlated with clinical benefit. these studies showed that some patients had over 90% of their d2 receptors blocked by antipsychotic drugs, but showed little reduction in their psychoses. this primarily occurs in patients who have had the psychosis for ten to thirty years. at least 90-95% of first-episode patients, however, respond to antipsychotics at low doses and do so with d2 occupancy of 60-70%. the antipsychotic aripiprazole occupies over 90% of d2 receptors, but this drug is both an agonist and an antagonist at d2 receptors. furthermore, although dopamine-inhibiting medications modify dopamine levels within minutes, the associated improvement in patient symptoms is usually not visible for at least several days, suggesting that dopamine may be indirectly responsible for the illness. similarly, the second generation of antipsychotic drugs – the atypical antipsychotics – were found to be just as effective as older typical antipsychotics in controlling psychosis, but more effective in controlling the negative symptoms, despite the fact that they have lower affinity for dopamine receptors than for various other neurotransmitter receptors. more recent work, however, has shown that atypical antipsychotic drugs such as clozapine and quetiapine bind and unbind rapidly and repeatedly to the dopamine d2 receptor. all of these drugs exhibit inverse agonistic effects at the 5-ht2a/2c receptors, meaning serotonin abnormalities are also involved in the complex constellation of neurologic factors predisposing one to the self reinforcing language-based psychological deficits found in all forms of psychosis. the excitatory neurotransmitter glutamate is now also thought to be associated with schizophrenia. phencyclidine (also known as pcp or "angel dust") and ketamine, both of which block glutamate (nmda) receptors, are known to cause psychosis at least somewhat resembling schizophrenia, further suggesting that psychosis and perhaps schizophrenia cannot fully be explained in terms of dopamine function, but may also involve other neurotransmitters. similarly, there is now evidence to suggest there may be a number of functional and structural anomalies in the brains of some people diagnosed with schizophrenia, such as changes in grey matter density in the frontal and temporal lobes. it appears, therefore, that there are multiple causes for psychosis and schizophrenia, including gene mutations and anatomical lesions. many argue that other theories concerning the cause of schizophrenia may be more reliable in some cases, such as the glutamate hypothesis, gaba hypothesis, dysconnection hypothesis, and bayesian inference hypothesis. psychiatrist david healy has argued that drug companies have inappropriately promoted the dopamine hypothesis of schizophrenia as a deliberate and calculated simplification for the benefit of drug marketing. relationship with glutamate research has shown the importance of glutamate receptors, specifically n-methyl-d-aspartate receptors (nmdars), in addition to dopamine in the etiology of schizophrenia. abnormal nmdar transmission may alter communication between cortical regions and the striatum. mice with only 5% of the normal levels of nmdar's expressed schizophrenic-like behaviors seen in animal models of schizophrenia while mice with 100% of nmdar's behaved normally. schizophrenic behavior in low nmdar mice has been effectively treated with antipsychotics that lower dopamine. nmdar's and dopamine receptors in the prefrontal cortex are associated with the cognitive impairments and working memory deficits commonly seen in schizophrenia. rats that have been given a nmdar antagonist exhibit a significant decrease in performance on cognitive tasks. rats given a dopamine antagonist (antipsychotic) experience a reversal of the negative effects of the nmdar antagonist. glutamate imbalances appear to cause abnormal functioning in dopamine. when levels of glutamate are low dopamine is overactive and results in the expression schizophrenic symptoms. combined networks of dopamine, serotonin, and glutamate psychopharmacologist stephen m. stahl suggested in a review of 2018 that in many cases of psychosis, including schizophrenia, three interconnected networks based on dopamine, serotonin, and glutamate - each on its own or in various combinations - contributed to an overexcitation of dopamine d2 receptors in the ventral striatum.