Is It All in Your Head?

Table of Contents

• HIV and the Brain
• HIV and Emotions
• Neuropsychiatric Disorders
• Depression
• Substance Use and Abuse
• Psychological Issues
• Goals of Treatment
• References
• Tables

People living with HIV, not surprisingly, commonly experience concerns, and even disorders, that affect their mental health. The same is true for people at high risk of infection.

While anyone who engages in unprotected sex or shares needles is at risk to contract HIV, people with pre-existing psychiatric disorders (including addictive substance use) are at increased risk for behaviors that transmit HIV.

In addition, HIV-positive people are at increased risk for mood, anxiety, substance use, and cognitive disorders.

HIV and the Brain

HIV invades the central nervous system (CNS -- the brain and spine) at the time of initial infection. During the acute period of infection, in addition to symptoms of an acute viral infection throughout the body, a substantial proportion of people experience the impact of HIV in the central nervous system, such as confusion, disorientation, slowness of thinking, and changes in mood.

Most of the time, however, the infection of the CNS goes unnoticed. Whether or not a particular individual develops symptoms of CNS disturbance depends on a variety of factors including, but not limited to: the particular strain of HIV, viral load, immunological response, inflammatory response in the body and brain, and current medical or psychiatric problems.

HIV and Emotions

Aside from the initial impact of HIV in the brain and body, there is an ongoing emotional adjustment to becoming positive. Incorporating an HIV-positive status into one's identity may include managing information about one's health with both health care providers and other relationships, and adjusting to medical care and lifestyle changes to reduce risks to health.

There is a great range of reactions and accommodations to becoming positive and adjusting one's view of the self and of one's relationship to the world. These emotional and psychological reactions may change throughout a changing course of illness.

Emotional support is often very helpful, particularly from experienced therapists or members of HIV-positive support groups who are negotiating this process of integrating the reality of being HIV-positive into their future.

The interaction of HIV on the body, brain, and mind is complex. Symptoms that seem to arise in one area often impact all the others.

Whatever the symptom, a thorough evaluation and assessment must be done to ensure the correct diagnosis and treatment. This is most comprehensively accomplished using a bio-psycho-social-cultural-spiritual model.

For example, a complaint of fatigue or lack of energy may be a symptom of depression, but may also be explained by a disturbance in sleep, endocrine function (such as adrenal insufficiency,^{1, 2} low thyroid, or low testosterone in both males and females³), anemia due to HIV or medications, or poor pulmonary function due to lack of exercise or some lung infection. Alternatively, low energy or fatigue may be a reaction to an existential crisis around fear of dying, losing relationships, being rejected, or a manifestation of guilt or shame about sexuality, drug use, or other concerns.

To assess a particular symptom or set of symptoms requires medical providers to take time not only to evaluate the physical aspects of having HIV, but the emotional aspects caused by living with a chronic condition that is uncertain, may progress, and cause premature functional impairment.

In other words, every biological aspect of living with HIV is accompanied by a psychological response. People with HIV can use positive coping strategies to diminish the impact of changes in physical or mental well-being. Quality of life, and the maintenance of overall function, should be the focus of treatment for anyone living with HIV. A coordinated, collaborative approach among all providers is essential to maximize the individual's capacity to function at the highest possible level for as long as possible.

While living longer with HIV is now the norm rather than the exception, there are adjustments in function and lifestyle that must be anticipated, and discussed openly between patient and provider.

Neuropsychiatric Disorders

Over the past decade, evidence has mounted that HIV in the central nervous system (CNS) causes variable degrees of inflammation that manifests itself in a variety of ways, including

• mood disorders (depression and mania),
• anxiety,
• sleep disturbances, and
• cognitive impairment

See Table I for early and late signs of cognitive deficits.

Surviving longer with HIV, independent of viral load and CD4 count, increases the likelihood of some impairments of cognitive function. People at greatest risk for cognitive changes are those whose CD4 counts dropped to below about 200-300 before responding to HIV meds, and those with the highest viral loads in both the cerebral spinal fluid that bathes the brain and in the blood.

The chances of developing cognitive impairments increase with

• advancing age,⁴
• co-infection with hepatitis C,
• the use of toxic substances such as methamphetamine,
• cognitive changes early in the course of infection, and
• depression.⁵

Changes in personality are also common in people with mild cognitive impairments, and the inability to function as well as expected can cause significant fear, depression, and anxiety. Advancing cognitive impairment may lead to impulsivity, poor adherence to both medications and protective sexual behaviors, and hopelessness, including suicidal thoughts and attempts.

Cognitive disorders may be due to primary HIV in the brain, or secondary dysfunction due to metabolic, endocrine, infectious, or neoplastic effects on the CNS. Medications, herbal remedies, excessive vitamins, and substances of abuse are also frequently associated with cognitive impairment.^{6, 7} HIV antiretrovirals (ARVs) may also cause neuropsychological impairment, and head trauma may also contribute to CNS dysfunction.

Classification of primary HIV cognitive impairment is based on criteria having to do with the presence or absence of symptoms and the degree of functional impairment. HIV Associated Neurocognitive Disorder (HAND) (see Table II) classifies impairment under three categories:

1. asymptomatic neurocognitive impairment (ANI) with evidence upon neuropsychological testing of cognitive deficits;
2. mild neurocognitive disorder (MND) with some functional limitations due to the cognitive domains affected; and
3. the often progressive and disabling HIV-associated dementia (HAD) that always requires significant impairment for diagnosis.⁸

As ARVs have been more widely prescribed, the incidence of HAD has declined from the number of cases seen before these medications arrived,⁹ but as HIV-positive people live longer, there are increasing rates of MND and ANI being diagnosed.

In spite of the fact that ARVs may slow the development of illness, and have almost eliminated the appearance of diseases that were so common before ARVs, there is evidence that the impact of HIV in the brain may cause mild to moderate cognitive impairment as people live longer and age with HIV.5 The prevalence rates of primary HIV mild neurocognitive disorder may range from 20-60%.

The most common symptoms include:

• short-term memory loss,
• problems with attention, concentration, multitasking, and word finding, and
• motor slowing.

No single rapid screening tool currently has been validated to diagnose MND, but there are a couple of screening tests that have been shown to correlate with the more advanced form of cognitive impairment, HAD. Providers can ask a few questions of every HIV-positive patient to get a sense of cognitive concerns. (See Table III.) The treatment of cognitive disorders in HIV includes ARVs,¹⁰ psychostimulants, and cognitive rehabilitative strategies for compensating for deficits and enhancing mental function. (See Table IV.)

As people live longer with HAD and MND, the range of symptoms may vary more than previously thought.¹¹ There are many co-morbid conditions that can contribute to CNS dysfunction that require a comprehensive medical workup. (See Table V.)

In an aging HIV-positive population, there are also increased risks for other types of non-HIV-related cognitive disorders that may synergistically cause cognitive impairment, such as hypertension, cerebrovascular disease, depression, and diabetes.

Depression

Depression is the most common psychiatric problem in the HIV-positive population, affecting as many as 50% of primary care HIV patients. HIV-negative gay men have been reported to have rates of depression 2-3 times that of heterosexual men, and gay men with HIV appear to have higher rates than HIV-negative gay men. Women have higher rates of depression than men in both the general and HIV populations, and untreated depression in HIV is associated with increased risk of dying.

The treatment of depression in HIV-positive people has been shown to be most effective when combining antidepressant medications and psychotherapy. While acute anxiety, shock, fear, and sadness are common initial reactions to discovering HIV-positivity, depression is not a normal reaction to illness, and should be treated aggressively to prevent decreased adherence to medications and protective sexual practices.

Depression must be distinguished from sadness, grief, fear, and existential concerns such as a fear of dying or losing one's health. Since so many people with HIV may have some of the symptoms of depression due to the medical illness, it is important to look at the more emotional and less biological aspects of depression, such as loss of interest in self or others, a sense of hopelessness, and guilt for behaviors or thoughts that are unacceptable to the person.

For example, a mother who is fatigued and cannot muster the energy to play with her children, but wants to, may not be depressed compared to a mother who becomes hopeless and disinterested in doing so.

When diagnosed in a patient with co-existing substance use, depression and the substance use disorder must both be treated in a comprehensive model.

Substance Use and Abuse

There is growing evidence in the research that certain legal substances, as well as drugs of abuse, vary in their toxicity in the CNS. Alcohol, nicotine, and excessive vitamins like B6 are all legal but potentially toxic to brain function.

Episodic binge drinking is likely more toxic to brain function compared to small amounts of alcohol on a daily basis, but any alcohol with certain medications may be detrimental to brain function and may affect blood levels of medications.

Illicit drugs have varying degrees of toxicity. Additionally, the brain is more vulnerable to the effects of such drugs depending on the presence of a co-existing psychiatric disorder or previous delirium. Some illicit drugs, more than others, have direct effects on nerve development in the CNS.

Methamphetamine appears to be the most neurotoxic of all illicit substances, even in small doses, causing loss of actual nerve tissue and function in the brain. Methamphetamine is not only rapidly addictive, but also very resistant to treatment and has very high relapse rates. To date, no medication is clearly beneficial in the treatment of methamphetamine addiction. Behavioral treatments have been shown to help in some situations, but the relapse rates are very high relative to the treatment for other addictive behaviors. The long-term cure for methamphetamine addiction may be as low as 10%.

HIV infection rates are significantly increased in methamphetamine users and secondary transmission is high, as judgment and impulse control are impaired with methamphetamine use.

For an informative summary on methamphetamine effects and treatment, see www.ncjrs.gov/ondcppubs/publications/drugfact/methconf/appen-b3.html.

Other illicit drugs such as marijuana, cocaine, ecstasy, GHB, and ketamine may also have neurotoxic effects, and may disrupt or deplete neurotransmitters that are essential for a well-functioning brain.

Psychological Issues

Mental health issues are best addressed in the context of a professional relationship with a provider who is non-judgmental, open, and able to formulate a psychological understanding of behavior and the resistance to change.

Primary care and mental health providers must stay collaborative and vigilant for changes in mental status, and for interactions between medications, especially in the context of recreational substances. There are phases to the psychological adjustment of becoming HIV-positive, even when there is awareness that one has put oneself at risk for infection. Research shows that sero-conversions most often occur in the context of sexual encounters under the influence of substances. Occasional use, as well as addiction, can reduce the capacity for using condoms. Depression, cognitive impairment, intoxication, and impulsive personality traits can reduce executive function of the frontal lobes that control rational thinking and behavior.

Additionally, there is growing evidence that previous sexual abuse and trauma are highly correlated with risky behaviors. The psychological impact of sexual or emotional trauma can reduce an individual's capacity to insist on condom use, or to refrain from undesired sexual or drug use behaviors.

Couples in which one partner is positive and one negative may experience a variety of emotional responses. Fear of infecting a partner, or being infected, can precipitate a loss of intimacy, a change in sexual function, or an increase in pre-existing psychiatric symptoms.

Psychosocial support has been shown to be very important to sustaining adherence to antiretroviral medications and dealing with side effects.

Attention should also be paid to the impact of bodily changes due to HIV or its treatment. Body image can impact a sense of self-worth, cause one to be stigmatized, and can affect one's sense of sexual attractiveness and desirability.

With the promise of a longer life now possible with good medication adherence, HIV-positive people are often interested in starting or maintaining sexual relationships, and often feel hesitant, or afraid of being rejected. Many HIV-related problems (such as neuropathy, metabolic syndrome, and renal or liver disease) can cause sexual dysfunction in both men and women.

Additionally, many of the medications used for cardiovascular disease or hypertension (beta blockers), as well as many psychiatric meds (antidepressants and antipsychotics) can cause sexual side effects.

Most importantly, providers must create a safe environment in which expressing concerns about sexuality is welcomed.

Goals of Treatment

The most important mental health issues facing people who are HIV-positive today include maintaining excellent adherence to antiretroviral medications, avoiding toxic substances that impair brain function, preventing co-infection with other strains of HIV (to prevent resistance to medications that are suppressing viral replication), being treated for underlying psychiatric symptoms and disorders, and dealing with subtle changes in brain function over time. All of the above factors affect each other. Preserving brain function is at least as important as preserving liver, lung, and cardiac function. Living longer with greater quality of life should be the focus of treatment. Finding purpose and community can provide the impetus for self-care and hope.

Marshall Forstein, M.D., is Director of Training for the Division of Adult Psychiatry at The Cambridge Hospital, and an Associate Professor of Psychiatry at Harvard Medical School. He teaches medical students and is a core faculty member in the Division of Palliative Care at Harvard Medical School. Dr. Forstein has been a principal investigator on an HIV Education and Training Grant through the federal Center for Mental Health Services, and teaches and has published on the neuropsychiatry and psychosocial aspects of HIV/AIDS. He is a Distinguished Fellow of the American Psychiatric Association and is currently serving on the Residency Review Committee for Psychiatry of The Accreditation Council for Graduate Medical Education.

References

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Tables