ID, mental health share complicated relationship

Research has shown a complicated and sometimes uncertain relationship between infectious diseases and mental health. The relationship is sometimes bidirectional, as in the case of HIV, which can be both the cause of neurocognitive disorders in infected patients and a consequence of risky behaviors associated with an already established mental illness. Infections also have been implicated as the root cause of mental health disorders such as Alzheimer’s disease, schizophrenia and bipolar disorder.

Photo courtesy of Cambridge Health Alliance

Despite these connections, few physicians feel comfortable taking care of mentally ill patients, said Marshall Forstein, MD, associate professor of psychiatry at Harvard Medical School and vice chair of the American Psychiatric Association’s council on medical education and lifelong learning. According to Forstein, there is a lack of psychiatry training in most medical specialties, leading to communication problems between patients and physicians and a potential gap in care.

“We don’t pay enough attention to mental function in any part of medicine, frankly,” Forstein told Infectious Disease News. “If you ask how many primary care doctors even have an ability to assess cognitive framework of their patients, most of them would say they don’t know how to do it.”

However, most medical schools include psychiatry in their curriculum across all 4 years, according to data Infectious Disease News obtained from the Association of American Medical Colleges (AAMC). Among schools requiring at least 1 week of psychiatry clerkships during the 2014-2015 academic year, the average length of these clerkships was 5.6 weeks per student. This is comparable to the training that medical students get in other core disciplines, according to Alison J. Whelan, MD, chief medical education officer for the AAMC.

“I think [psychiatry] is important and I think the AAMC data reflect that it is incorporated in medical school education,” Whelan said in an interview.

Infectious Disease News spoke with several experts to explore the intersection between infectious diseases and mental health, including the effect that mental health disorders have on treatment and the role stigma plays in the lives of patients.

A bidirectional relationship

Approximately one in five adults in the United States experience mental illness in any given year, according to the National Alliance on Mental Illness. This includes nearly one in 25, or about 10 million adults, who live with a serious mental illness, which increases the risk for various viral infections, including HIV and hepatitis C virus.

When it comes to such infections, the relationship with mental health is often bidirectional. In HIV, for example, the virus has a direct effect on the brain when it passes the blood-brain barrier into the central nervous system, causing neurocognitive disorders ranging from minor to severe. But the bidirectional relationship is more often seen in the way risky behavior and impulsivity — which are associated with a variety of mental health disorders — increase exposure to HIV.

According to Forstein, patients with a serious mental illness often have difficulties with impulse control and judgement and rarely have stable living conditions because of homelessness or inconsistent relationships with their families, leading to situations that may put them at risk for acquiring an infectious disease.

“There’s a problem in the vulnerability of mental illness,” Forstein said.

A direct causal relationship

Infections also may have a more direct causal relationship with some mental health conditions such as Alzheimer’s disease, depression, schizophrenia and bipolar disorder, although some of these links have been disputed and experts say more research is needed to explore them.

In the case of Alzheimer’s disease, the sixth-leading cause of death among Americans, Brian J. Balin, PhD, professor of microbiology and immunology and chair of the department of biomedical sciences at Philadelphia College of Osteopathic Medicine, and colleagues believe infection is the root cause of the progressive brain disorder — a controversial hypothesis in mainstream research.

Balin and colleagues drew attention to their hypothesis by publishing an editorial this year in the Journal of Alzheimer’s Disease that calls for further research into what they say is the long-neglected role of infectious agents such as herpes simplex virus type 1 (HSV-1) in the development of Alzheimer’s disease.

“I keep asking, ‘When will there be enough evidence? What do you need to see here?’ ” Balin told Infectious Disease News. “We have animal models, we have cell models, and we have identified these infectious agents in human brain tissue from people who have died from Alzheimer’s disease.”

WHO estimates that more than 3.7 billion people aged younger than 50 years worldwide are infected with HSV-1. Among older adults, Alzheimer’s disease is the most common cause of dementia, which affects more than 46 million people around the world. According to Balin and colleagues, HSV-1 has been linked to Alzheimer’s disease in about 100 studies, but explaining why the infection would be a factor in some people but not in others is difficult.

“We think there are other ingredients that have to be there in order to give the person the real risk; this is multifactorial” he said.

For example, the way apolipoprotein E is expressed in some people might aid carriage of HSV-1 and other microbes such as Chlamydia pneumoniae — present in the brain of 85% to 90% of patients who have died of Alzheimer’s disease — from the periphery of the body into the brain, increasing one’s susceptibility to infection. In basic terms, the infection may “piggyback” its way into cells.

“Because of that, if the virus or chlamydial bacterium gets into the brain, we know that it can set up shop and become chronic and initiate an immune response over time,” Balin said. “We’re not sure exactly why that’s happening in some people and not in others.”

According to the researchers, infections can cause cells in the brain to malfunction and produce too much waste, causing the buildup of tau and amyloid that is synonymous with Alzheimer’s disease. This buildup leads to an inflammatory response, cell death and cognitive and functional deficits. Thus, more research is needed to explore whether the hallmark signs of Alzheimer’s are causes or consequences of the disease, Balin and colleagues wrote.

Other pathogens have been directly linked to mental health disorders, including Toxoplasma gondii, a parasite found in undercooked meat and cat feces that is present in approximately one out of every three humans.

Click the image to enlarge.

A recent study showed that latent T. gondii (LTI) infection may change brain chemistry, leading to a risk for aggression in humans, although researchers are unclear whether the relationship is causal.

After a different study showed an association between LTI and neurocognitive impairment in HIV patients — leading to increases in impulsivity, aggression and suicide attempts — researchers called for further investigation into the role of neuroinflammation and neuronal injury in patients with LTI and for trials of anti-Toxoplasma therapy.

The link between T. gondii infection and brain and behavior impairments in humans was disputed by the results of a population-representative birth cohort that studied the association between the infection and four facets of human behavior.

A study this year demonstrated a potential link between Candida albicans yeast infections and certain mental health disorders. Data showed that men with schizophrenia or bipolar disorder were more likely to have a history of infection than men without these disorders. Women who had schizophrenia or bipolar disorder and who also tested positive for C. albicans were more likely to have delayed memory than women who had mental health disorders but no history of the yeast infection.

Autoimmune diseases and infections have been shown to increase the risk for mood disorders such as depression and bipolar disorder. For example, researchers reported in 2013 that hospital contacts with infections may account for up to 12% of these mental health disorders if the effect is causal.

According to a recent study in Denmark, hospitalized patients with infections were more likely to commit suicide than patients without infection. Although researchers did not determine if the link was causal, they wrote that infections may have a “relevant role in the pathophysiological mechanisms of suicidal behavior.”

The role of stigma

Around half of all Americans will meet the criteria for any mental health disorder in their lifetime, according to some estimates.

“Include substance abuse, and it’s normative. It’s more than half of the population,” Michael B. Blank, PhD, professor of psychology in psychiatry in the Perelman School of Medicine at the University of Pennsylvania, told Infectious Disease News. “We’ve got to be more accepting of the fact of our frailty and that encountering a problem like that sometime in our lives is more likely than not.”

Stigma plays a significant role in the lives of patients with infectious diseases and mental health disorders, and there is work to be done to figure out how to combat it, several experts said.

“Stigma is a social control mechanism that exists in society at every level and throughout the world. It’s a way of shunning undesirables,” Blank said. “How do we get over that? We need to understand how common mental illnesses are. Every family is affected by mental illness and substance abuse.”

According to Blank, who used HIV as an example, the stigmas associated with infectious diseases and mental health disorders are separate and unique.

“The stigma of mental health problems interferes with identification and treatment of mental health, and the stigma of HIV interferes with testing, diagnosis and adherence to treatment,” he said. “I think people with mental illnesses are additionally stigmatized by HIV and that people with HIV infections are additionally stigmatized by mental health problems.”

Illness evokes fear in the public, and fear augments stigma, Forstein said. This may be particularly true in infectious diseases that are visible, as in the case of leprosy or the Kaposi sarcoma lesions that were common early in the AIDS epidemic. Likewise, mental illness is not only stigmatized, it carries a significant risk for medical comorbidities, he said.

“People who are known to have a mental illness elicit fear because people don’t really know how to interact with them,” Forstein said. “In fact, most people with mental illness are quite easy to talk to. By talking to them, you feel more comfortable with them.”

The effect of mental health disorders on treatment

Further complicating the issue, mental health disorders may negatively influence the treatment of patients with infectious diseases, although anecdotal evidence suggests that such patients may adhere better than expected to antiretrovirals.

In the HIV clinic at the Cambridge Health Alliance co-founded by Forstein, approximately 60% of patients have a serious psychiatric disorder; 95% of them are virally suppressed on medication because of their consistent interaction with physicians, nurses and social service staff, he said.

“It really depends on the context in which people are getting their care. These are patients that need to be followed very closely with care providers who reach out to them,” Forstein said.

Daily dosing with a single pill for HIV has improved adherence, but serious mental health disorders can still make it more difficult for some to adhere to their medication.

“People with serious mental illness have trouble with routines and their lives are often chaotic, which interferes with administering ART with good regularity and adherence,” Blank said.

A systematic review of 82 studies demonstrated that inadequate treatment of depression in HIV patients can affect adherence to ART. However, the review concluded that more research is needed to address the impact of other mental health disorders.

Each patient is different, Forstein said.

“Someone who has a psychotic disorder who is having trouble just maintaining a sense of reality in the world is going to be different than someone with a serious depression disorder,” he said. “Many of those patients find it harder to maintain medications, putting them at risk for infections from other diseases, STDs and so forth. You also have patients with manic disorders where the hyperactivity can lead to excessive sexual behavior and lack of consistency taking their antiretrovirals.”

The importance of testing

Beyond training, the link between infectious diseases and mental health problems can be addressed at a clinical level by testing patients, according to Blank.

“There has to be an awareness about mental health problems,” he said.

Blank and colleagues emphasized the relationship between infections and mental health in a study published in the American Journal of Public Health that demonstrated the need to test patients for HIV at community mental health centers. Between January 2009 and August 2011, 4.8% of the more than 1,000 patients tested in three types of mental health care settings in Philadelphia and Baltimore were positive for HIV — about four times the overall rate of infection in those cities.

In patients with a serious mental illness, the estimated prevalence of HIV is as high as 23%.

“Where you live increases your risk and what you do increases your risk,” Blank said, “so we’ve been arguing that routine testing for HIV ought to be available at all community mental health centers. That’s something that doesn’t ordinarily happen right now.”

Blank said testing also should be done at infectious disease clinics to screen patients for mental health disorders such as depression, which affects 20% to 30% of patients living with HIV, according to various studies.

Depression comes up frequently in research linking infectious diseases with mental health disorders. According to one study, the lifetime rates of mental health disorders among patients with HCV are high, with depression being the most common of these disorders. The rates are even higher in patients who are coinfected with HIV. In fact, in a 2005 study of patients receiving care in the Department of Veterans Affairs, 76.1% of HIV/HCV–coinfected patients had a diagnosis of mental health illness compared with 63.1% among those who were infected with HIV alone. Specifically, the rate of major depression among HIV/HCV–coinfected patients was higher than those with HIV monoinfection — 56.6% to 45.8%.

“Any kind of chronic, life-threatening disease like HIV is associated with increased rates of depression,” Blank said, “so we recommend that screening for depression and other mental illnesses ought to be occurring in infectious disease clinics as well.”

Managing ID patients with mental health disorders

According to Whelan, the AAMC does not collect data at a granular level to show all the approaches that medical schools take to integrate each discipline, including psychiatry. However, she said a student’s exposure to psychiatry reflected in the AAMC data generally occurs in the third or fourth year at a clinical level, either in hospitals or in an outpatient setting.

“Some schools have begun to do more integrated clerkships, so those are harder to capture with data. But it’s pretty comparable to other core disciplines,” she said.

But Forstein believes medical students are ill-prepared after they graduate to manage patients who also have a mental health disorder.

“I think the question is more how psychiatry is taught and experienced by students,” Forstein said. “For example, psychiatry faculty should be present on all medical rounds, surgical rounds, etc, to discuss how the patient and their psychiatric disorder or personality affects how the illness may be diagnosed and treated and how adherence to treatment ... is dependent on the ability of the provider to establish and maintain a relationship with the patient. Much of what psychiatry has to offer is dealing with relationships with patients, as well as the specific medical aspects of their disorder.”

Integrated care may be one way to address the confluence of infectious diseases and mental health. For example, at the University of California, San Francisco (UCSF), the HIV clinic has an embedded psychiatrist on staff, according to Brian Schwartz, MD, associate professor in the UCSF School of Medicine. Schwartz told Infectious Disease News that he refers patients with psychiatric illnesses to a psychiatrist.

“Personally, I do not feel comfortable diagnosing and treating psychiatric illness as part of my practice,” he said.

Whelan, formerly a professor of medicine at Washington University in St. Louis, emphasized that medical school is only part of the continuum of education for physicians, and that students will continue to have more training in psychiatry and other disciplines as it relates to their work.

“I think people do realize the importance of psychiatry,” she said. “One of the challenges in physician education is continuing education. All of medicine — including our understanding of infectious diseases, psychiatry and behavioral medicine — is rapidly changing. For the practicing physician, it can be a challenge to keep up with the advances. Quality continuing medical education is critical and depends on the expertise of our psychiatry colleagues. Unfortunately, the clinical needs for psychiatrists are extraordinarily high, which can limit their ability to teach.”

Forstein thinks physicians across all specialties — not just infectious diseases — could benefit from better training in psychiatric disorders.

“There’s a lot of stigma within the medical profession itself that psychiatrists somehow are weird, or that they can read people’s minds. I’ve had doctors say, ‘Are you reading my mind?’ There’s a lot of ignorance about it. The medical profession just hasn’t done a very good job of mainstreaming psychiatry,” Forstein said. “If your brain isn’t working right, the rest is kind of moot, right?” – by Gerard Gallagher

• References:
• Backus LI, et al. AIDS. 2005;doi:10.1097/01.aids.0000192065.09281.01.
• Bengtson AM, et al. J Acquir Immune Defic Syndr. 2016;doi:10.1097/QAI.0000000000001131.
• Benrose ME, et al. JAMA Psychiatry. 2013;doi:10.1001/jamapsychiatry.2013.1111.
• Bharti AR, et al. Clin Infect Dis. 2016;doi:10.1093/cid/ciw655.
• Blank MB, et al. Am J Public Health. 2014;doi:10.2105/AJPH.2013.301633.
• Canli T, et al. Biol Mood Anxiety Disord. 2014;doi:10.1186/2045-5380-4-10.
• De Hert M, et al. World Psychiatry. 2011;10:52-77.
• Gaynes BN, et al. Gen Hosp Psychiatry. 2015;doi:10.1016/j.genhosppsych.2015.03.021.
• Hilsabeck RC, et al. Clin Infect Dis. 2005;doi:10.1086/429494.
• Itzhaki RF, et al. J Alzheimers Dis. 2016;doi:10.3233/JAD-160152.
• Kessler RC, et al. Arch Gen Psychiatry. 2005;doi:10.1001/archpsyc.62.6.593.
• Lund-Sorensen H, et al. JAMA Psychiatry. 2016;doi:10.1001/jamapsychiatry.2016.1594.
• Mayer EA, et al. J Neurosci. 2014;doi:10.1523/JNEUROSCI.3299-14.2014.
• NAMI. Mental health by the numbers. http://www.nami.org/Learn-More/Mental-Health-By-the-Numbers. Accessed November 21, 2016.
• Severance EG, et al. NPJ Schizophr. 2016;doi:10.1038/npjschz.2016.18.
• Springer SA, et al. AIDS Behav. 2012;doi:10.1007/s10461-012-0212-3.
• Sugden K, et al. PLoS One. 2016;doi:10.1371/journal.pone.0148435.

• For more information:
• Brian J. Balin, PhD, can be reached at brianba@pcom.edu.
• Michael B. Blank, PhD, can be reached at mblank2@mail.med.upen.edu.
• Marshall Forstein, MD, can be reached at mforsteinmd@gmail.com.
• Brian Schwartz, MD, can be reached at Brian.Schwartz@ucsf.edu.
• Alison J. Whelan, MD, can be reached at https://news.aamc.org/for-the-media.

Disclosures: Balin, Blank, Forstein, Schwartz and Whelan report no relevant financial disclosures.