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We consider psychotic disorders to reside primarily in the domain of psychiatry. But primary care and other medical physicians almost always see these patients at some early point during their illness journey and can play a significant role in their care. By recognizing that your patient may have a psychotic disorder—or be in the process of developing one—early referral is possible. The duration of untreated psychosis is directly related to time to recovery.1 Hence, primary care physicians play a pivotal role in reducing the duration of untreated psychosis and modifying long-term outcome.2,3 Also, you can play a key role in co-managing, with a psychiatrist, patients’ often very prominent medical problems.

Unfortunately, there are many barriers to early recognition and treatment. First, “lack of insight,” which is perhaps the most frequent symptom of psychotic disorders, often delays seeking care by the patient.4 Second, self-stigma and societal stigma associated with the diagnosis of a psychiatric disorder, particularly a psychotic disorder, are prominent and difficult obstacles.4 Third, the customary separation of mental illness from general medicine means that medical clinicians are often unfamiliar with psychotic disorders, not considered part of their domain. Finally, substance use disorder is observed in 50% of patients presenting with early psychosis. This greatly impedes the diagnosis of a psychotic disorder, symptoms too readily ascribed to the substance use.5

Psychotic symptoms are experienced by 3% of the general population and up to 20% of patients seeking primary care.6,7 Further, up to a third of the general population will at some time during their lives experience psychotic symptoms.8 Worldwide, schizophrenia occurs in about 1% of the population, and it is the fifth (for men) and sixth (for women) leading cause of work disability.9

Neurobiological Basis

Our understanding of the neurobiological basis of psychotic disorders emerged in the 1950s following the serendipitous discovery of chlorpromazine. It became the first effective antipsychotic and dramatically transformed the lives of patients from sequestration in remotely-located institutions to recovery.10 It was discovered that antipsychotic agents work by blocking postsynaptic dopamine (D2) receptors in the mesolimbic pathway.10 The later discovery that amphetamines enhance the release of dopamine in this pathway and induce psychotic symptoms further corroborated this notion.11 This led to the “dopamine hypothesis.” The observation that psychotomimetic agents such as LSD and mescaline, which are serotonin 5-HT2A agonists, also induce psychotic symptoms, led to the “serotonin hypothesis” and the subsequent discovery of antipsychotic drugs targeting serotonin 5-HT2A receptors. Finally, the discovery that phencyclidine (PCP) induces the full spectrum of schizophrenic symptoms (positive, negative, and cognitive) led to the “glutamate N-methyl-D-aspartate (NMDA) receptor deficit hypothesis.”11

Key Symptoms

The symptoms of schizophrenia, the quintessential psychotic disorder, are generally classified as positive, negative, and ...

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