Psychotic Disorders
Ewald Horwath
Francine Cournos
The association between psychotic disorders and human immunodeficiency virus (HIV) infection is complex. Psychotic disorders may precede HIV infection, a common etiologic factor may predispose to both HIV infection and psychosis, or HIV infection may play an etiologic role, either directly or indirectly, in the development of the psychosis. A solid understanding of the complex relationship between HIV and psychosis allows for better evaluation and more effective treatment for psychotic patients at risk for or infected with HIV.
Psychotic Disorders that Precede HIV Infection
Persons with severe and persistent mental illness, most of whom have psychotic disorders, are at risk to develop comorbid HIV infection and acquired immunodeficiency syndrome (AIDS). Published studies show that people with severe mental illness frequently engage in sexual and drug use behaviors that place them at risk for HIV infection and that they have substantial rates of HIV seropositivity, varying from 3% to 23%.1–3 The most common Axis I psychiatric diagnoses in this population are schizophrenia, schizoaffective disorder, and bipolar disorder, all of which have been shown to be highly comorbid with alcohol or other substance use disorders, which in turn strongly correlate with the likelihood of HIV infection.
Substance use alone can predispose people to both psychosis and HIV infection. Substances that can cause psychotic symptoms include amphetamines, methamphetamine (crystal meth), cannabis (especially high-dose forms such as hashish), cocaine (especially when smoked as crack, free-based, or injected intravenously), hallucinogens, phencyclidine (angel dust, PCP), and inhalants. Withdrawal from alcohol, sedative/hypnotics (especially barbiturates), and opiates can also produce psychotic symptoms. Substance use is often accompanied by unsafe sexual activities and/or use of nonsterile works for drug injection, activities that link these disorders to risk for HIV infection.
A growing literature documents the usefulness of HIV prevention and harm reduction techniques in reducing the acquisition of HIV infection in these populations, but evidence suggests that access to prevention services remains low in these groups.4
Etiology and Presentation of New-Onset Psychotic Disorders
Psychosis is more common among people with HIV infection than it is in the general population. Factors that may be associated with the onset of psychosis in HIV-positive people include the direct effects of HIV on the central nervous system (CNS), CNS opportunistic infections, CNS neoplasms, severe systemic illness, medical treatments, substance use disorders, and the psychological stresses of HIV infection, including deteriorating health and functional impairment.3 Symptoms of mania may or may not accompany these psychotic episodes. (For discussion of mania and its treatment, see Chapter 10.)
Several studies have evaluated small samples of HIV-positive subjects with and without psychotic symptoms. One study examined 20 HIV-infected psychotic men who had noniatrogenic psychosis without delirium, current substance abuse, or previous psychotic episodes and compared them with a group of 20 nonpsychotic HIV-infected men matched to the psychotic subjects with respect to age, race, years of education, and stage of HIV infection. The psychotic men differed from the nonpsychotic comparison group in having significantly higher rates of past stimulant and sedative/hypnotic abuse or dependence and, at follow-up, a higher rate of mortality. On autopsy three of the psychotic subjects had high HIV burdens in their brains and three had no detectable virus. The authors concluded that new-onset psychosis may be, at least in some cases, a manifestation of HIV-associated encephalopathy.5
Another study in an outpatient clinic compared 12 HIV-positive patients with new-onset psychosis to 15 matched nonpsychotic subjects, with a 2-year follow-up for 22 of the patients. The HIV-seropositive patients with new-onset psychosis more often had a positive past psychiatric history, no antiretroviral therapy, and a lower global cognitive performance than did the nonpsychotic HIV-seropositive patients. The authors concluded that antiretroviral therapy may play a preventive role for psychosis in some vulnerable patients.6
A third study evaluated 26 patients admitted to the hospital with HIV-associated psychosis and compared those who had opportunistic infections or metabolic encephalopathy to those without these conditions.7 The 13 patients with CNS opportunistic infections or with metabolic encephalopathy related to pulmonary, hepatic, or renal failure were defined as having “secondary psychosis,” and the other 13 patients were diagnosed with “primary psychosis” because they had no HIV-related CNS disease or acute metabolic disorder. Those patients with secondary psychosis were more likely to show disorders of consciousness, orientation, attention, and memory than those with primary psychosis.
The authors subdivided the secondary psychosis group on the basis of whether the patient had a focal brain lesion, defined as a space-occupying lesion visible on computed tomography (CT) scan. Six patients had a focal brain lesion, diagnosed as cerebral toxplasmosis (“lesional” secondary psychosis), and the remaining 7 had no space-occupying lesion (“nonlesional” secondary psychosis). When the lesional and nonlesional secondary psychosis groups were considered separately and compared with the primary psychosis group, only the scores on consciousness, orientation, attention, and memory for the nonlesional patients were significantly higher than those for the primary patients. All of the nonlesional psychotic patients died within a short time (mean = 31 days); patients in the focal brain lesion group recovered from their psychotic episode with antipsychotic treatment, but died months later (mean 158 days), similar in course to the primary psychotic group (mean survival 160 days). The authors concluded that psychotic symptoms in some HIV-seropositive patients are related to the systemic and cerebral complications of HIV infection, and given the difference between the groups in mean survival time, that the distinction between lesional secondary, nonlesional secondary, and primary psychosis may have important prognostic value.7
A common clinical feature noted in new-onset psychosis in HIV-infected patients is the acute or subacute onset of symptoms, including delusions, hallucinations, bizarre behavior,
and mood or affective disturbances, accompanied by memory disturbance or cognitive impairment. Some patients, especially those with an abnormal CT image and electroencephalogram at the time of presentation with psychosis, tend to have a relatively rapid deterioration in cognitive and medical status.8
and mood or affective disturbances, accompanied by memory disturbance or cognitive impairment. Some patients, especially those with an abnormal CT image and electroencephalogram at the time of presentation with psychosis, tend to have a relatively rapid deterioration in cognitive and medical status.8
The following case provides an example of a psychotic episode occurring along with HIV- associated dementia in a patient with typical radiologic findings of dilated lateral ventricles and hypodensity of the subcortical white matter, but no other evidence of CNS disease.
A 33-year-old African-American woman with AIDS and a history of cocaine abuse and heroin dependence presented to an emergency room with altered mental status and inability to care for herself in the community. Her CT scan showed prominent dilated lateral ventricles and hypodensity of the subcortical white matter, with no focal intracranial lesions. Cerebrospinal fungal, acid-fast bacillus, and bacterial cultures and cryptococcal antigen were negative. Her CD4 count was 160 cells/ml, hemoglobin was 9 g/dl, and hematocrit was 27 ml/dl. The urine toxicology was positive for cocaine. Although she was alert, she had profound poverty of speech and answered questions with one- or two-word responses. She was able to state her name, but could not identify the hospital, city, date, month or year. She reported auditory hallucinations of frightening voices, often appeared quite frightened, and intermittently picked at her clothing. Her behavior included occasional agitation and piercing screams for no apparent reason. She could not ambulate. The hallucinations, picking behavior, and agitation resolved with the addition of quetiapine up to 150 mg/day in divided doses. The cognitive and motor impairment persisted even after several months of highly active antiretroviral therapy (HAART), at which time the CD4 count was 506 cells/ml and the viral load was less than 75 copies/ml.
In this case the psychosis responded to treatment with an atypical antipsychotic, but the dementia did not improve in response to an otherwise effective course of antiretroviral therapy.
Several authors have reported new-onset cases of psychosis in HIV-infected individuals in the absence of concurrent substance use, iatrogenic causes, CNS opportunistic infection, CNS neoplasm, or detectable cognitive impairment. It is possible that new-onset psychotic symptoms also may occur as a manifestation of HIV-associated encephalopathy in the absence of frank HIV-associated dementia.3 One author has hypothesized, on the basis of a review of 14 cases of mania in the English language literature, that AIDS-related mania and agitated psychosis may be related to increased intracellular free calcium.9 On the other hand, because teenagers and young adults are the age-groups at greatest risk for HIV infection, as well as for the onset of a major mental illness, the two disorders may also co-occur entirely independently of one another.
Psychotic Disorder Associated with HIV-Related Medical Conditions
Mental status may be altered by CNS opportunistic diseases, including cerebral toxoplasmosis, cryptococcal meningitis, herpes encephalitis, progressive multifocal leukoencephalopathy (PML), neurosyphilis, tuberculous meningitis, and CNS neoplasms, such as lymphoma or Kaposi’s sarcoma. An acute mental status change may also be the presenting sign of systemic illness such as diarrhea, dehydration, electrolyte disturbances, fever, pneumonia, and septicemia. Although psychosis is not the most common psychiatric problem seen in these conditions, it can accompany any of them.
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