text: It has been purported that there is a genetic risk factor for NMS. In one study, identical twins presented with NMS, and a mother and two of her daughters have presented with NMS in another case.
  Demographically, it appears that males, especially those under forty, are at greatest risk for developing NMS, although it is unclear if the increased incidence is a result of greater antipsychotic use in men under forty. It has also been suggested that postpartum women may be at a greater risk for NMS.
  An important risk factor for this condition is Lewy body dementia. These patients are extremely sensitive to antipsychotics. As a result, antipsychotics should be used cautiously in all cases of dementia.
  Pathophysiology
  The mechanism is commonly thought to depend on decreased levels of dopamine activity due to:
  Dopamine receptor blockade
  Genetically reduced function of dopamine receptor D2
  Sympathoadrenal hyperactivity and autonomic dysfunction
  It has been proposed that blockade of D2-like (D2, D3 and D4) receptors induce massive glutamate release, generating catatonia, neurotoxicity and myotoxicity. Additionally, the blockade of diverse serotonin receptors by atypical antipsychotics and activation of 5-HT1 receptors by certain of them reduces GABA release and indirectly induces glutamate release, worsening this syndrome.
  The muscular symptoms are most likely caused by blockade of the dopamine receptor D2, leading to abnormal function of the basal ganglia similar to that seen in Parkinson's disease.