The clinical symptoms of HIV may at first seem like major depression or
classic subcortical dementia, said Francisco Fernandez, M.D. (left), who
spoke, along with Mordecai Potash, M.D., at APA's Institute on Psychiatric
Services in October.
Credit: Ellen Dallager
The mental health consequences of HIV infection, recognized since the early
days of the epidemic, are still not entirely known, two psychiatrists said at
APA's Institute on Psychiatric Services in New Orleans last month.
Epidemiological studies suggest that up to 60 percent of people infected
with HIV will also experience at least one major psychiatric disorder during
the course of infection.
Understanding how HIV infection disrupts the central nervous system has
grown steadily over the last two decades, but the psychiatric consequences
will also grow more prominent in the future as life expectancy for HIV/AIDS
patients increases with better treatments, said Francisco Fernandez, M.D., and
Mordecai Potash, M.D.
Early in the course of the epidemic, many scientists thought that
neurocognitive effects would crop up overnight, compromising the ability of
HIV-infected individuals working in critical fields such as health care,
engineering, or the armed forces to do their jobs, said Potash, an associate
professor of clinical psychiatry at Tulane University School of Medicine.
Paradoxically, the common wisdom also held that central nervous system (CNS)
symptoms occurred only after the individual progressed from HIV infection to
clinically manifested AIDS.
However, that is not always the case, said Fernandez, professor and chair
of the Department of Psychiatry and Behavioral Medicine and director of the
Institute for Research in Psychiatry at the University of South Florida School
"HIV invades the CNS early in the infectious process, and psychiatric
manifestations may be subtle or profound," said Fernandez, who is chair
of the APA Committee on AIDS and a member of the Psychiatric News
Editorial Advisory Board. "The acute stage of the initial infection,
during the first three to six weeks, may produce cognitive or psychotic
symptoms but not a decrement in function."
The risk factors run in both directions, said Potash. Not only can HIV
affect the brain, but people with psychotic illnesses may underestimate their
risk of infection or engage in risky behaviors that increase their chance of
The effects of HIV infection occur in at least four ways. The virus may
invade and damage CNS cells directly. Viral yield is low in neurons but higher
in macrophages, microglia, astrocytes, or other support cells. Acting
indirectly, the virus can also activate an immune cascade that can harm
neurons secondarily. Finally, the immunosuppressive action of the infection
can open the door to numerous infectious diseases such as toxoplasmosis,
cryptococcal meningitis, tuberculous meningitis, HSV1 encephalitis, and
primary CNS lymphoma.
In the earliest, asymptomatic stage, abnormalities may show up in cognitive
abilities evaluated during neuropsychiatric testing but not necessarily as
impairments in clinical or role functioning.
As infection proceeds to the early symptomatic stage, both tests and
clinical observation provide evidence of declining function. Careful medical
and neurobehavioral evaluation can help rule out primary—and
treatable—nervous system diseases.
A National Institute of Mental Health consensus conference in 1989 declared
that "significant impairment" occurs when tests of speed of
information processing, verbal memory, or other nonlanguage tests fall two
standard deviations below the mean of an HIV-negative subject. That cutoff,
however, does not imply either a clinical disorder or that a dementing
syndrome is present, Fernandez explained.
However, in late symptomatic infection, CNS impairment may occur in up to
60 percent of patients, either as minor cognitive-motor disease or as
The clinical presentation of HIV in the CNS resembles classic subcortical
dementing processes: motor impairment, cognitive disturbance, and a
predominance of apathy over depression, said Fernandez.
"This early presentation of HIV-1-associated dementia may look like
major depressive disorder, with symptoms like lethargy and social withdrawal,
forgetfulness, poor concentration, an unsteady gait, and difficulty with
once-familiar tasks," he said.
Antiretroviral treatment—sometimes with "industrial-grade
doses"—may not only reduce symptoms "below the neck"
but also help with CNS function, especially if started early to minimize CNS
damage. Other drugs may be effective, too. Methylphenidate, for example, can
improve reaction time and performance tasks and aid memory, although it should
be avoided in patients with a history of psychotic symptoms or seizures, said
Potash also suggested caution in the use of antipsychotic drugs for
patients with HIV.
"The destruction by the virus of cells in the basal ganglia appears
to prime the brain for increased extrapyramidal side effects following use of
typical antipsychotics," he said. "I suggest using atypical
antipsychotics as first-line therapies, starting with low doses. Treat
patients for as short a time as possible—only as long as symptoms
Knowledge of the interplay between HIV and psychosis is still incomplete
and is likely to change quickly as research in neuropsychiatry, pharmacology,
and infectious diseases progresses, said Potash. The work of individual
psychiatrists with even one or two patients can contribute to this development
and stimulate research if communicated to the field through case reports to
journals, he concluded. ▪