Many important psychiatric issues are related to infectious diseases. Neuropsychiatric symptoms are a prominent part of the presentation of many systemic and central nervous system (CNS) infections, and psychologic factors influence the course of infectious diseases. Rapid cultural and economic changes have led to epidemics of new diseases and previously isolated diseases, requiring physicians to expand their knowledge. Infections contribute to the pathogenesis of some psychiatric disorders, although how much weight should be given to attributions of psychopathology to infectious pathophysiology is controversial.

A variety of host factors may influence the psychiatric manifestations of infectious diseases, including age, immune function, population exposure, and psychologic factors. For example, a simple upper respiratory or bladder infection may cause only discomfort in otherwise normal adults, but result in irritability, agitation, and frank delirium in the elderly, especially if the patient also suffers from dementia. Immune status can dramatically affect symptoms and signs of infection, since many are more a product of the immune system’s response to an organism rather than the organism itself. Symptoms of meningitis may be muted in very young children and immunosuppressed adults. Physicians must consider which infectious diseases are endemic in their areas of practice. Physicians should also consider where the patient has traveled or lived. Similar psychiatric symptoms might suggest Lyme disease in a hiker in the northeastern United States, but neurocysticerocosis in an immigrant from Central America. Psychologic factors may also affect the risk for or course of infectious diseases. This has been most studied with human immunodeficiency virus (HIV), but has also been shown for the common cold, pneumonia, genital herpes, hepatitis B and C, and recurrent urinary tract infections. This column will briefly discuss some illustrative examples of the important issues at the psychiatric-infectious disease interface, including pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS), neurosyphilis, Lyme disease, the common cold, Creutzfeldt-Jakob disease (CJD), neurocysticerocosis, and cerebral malaria. Fear of infectious diseases, psychiatric aspects of immunization, and psychiatric side effects of antibiotics will also be discussed. Fuller discussion of these and other infectious disease topics can be found in a review by Levenson and Schneider.¹

PANDAS

PANDAS is a fascinating autoimmune model for neuropsychiatric diseases. Investigators at the National Institute of Mental Health found an association between early-onset childhood obsessive-compulsive disorder (OCD) and a preceding Group A β-hemolytic streptococcal infection (GABHS).² PANDAS is characterized by the abrupt onset in early childhood of OCD and/or tic disorder associated with GABHS infection. The course of the disorder is typically episodic with varying symptom severity, and is commonly associated with neurologic signs. The association between recent GABHS infection and PANDAS symptoms is made apparent by a rapid rise in antistreptolysin-O titers associated with symptom onset or exacerbation, and a fall in titers associated with symptom resolution or improvement. Obtaining a throat culture is also recommended.

Children with strep infections who have been treated with antibiotics do not appear to be at increased risk for developing PANDAS.³ A small, randomized controlled trial in children with PANDAS found that antibiotic prophylaxis was effective in decreasing subsequent strep infections and neuropsychiatric symptoms.⁴
 

Syphilis

One hundred years ago, syphilis, caused by the spirochete Treponema pallidum, was the leading diagnosis in psychiatric inpatients. After many years of declining incidence, there has been an increase during the HIV era. Primary syphilis is manifested in a chancre. Secondary syphilis involves multiorgan spread and may include meningitis. Psychiatric symptoms are common in tertiary neurosyphilis, the most common forms of which are meningovascular (30.2%), meningeal (25.6%), and general paresis (25.6%).⁵ Patients with tertiary syphilis may show changes in memory, personality, psychosis, delirium, dementia, or seizures.⁶ Meningovascular syphilis can closely mimic atherosclerotic disease, resulting in changes in memory, personality, dizziness, transient ischemic attacks, and multi-infarct dementia.

While sporadic cases of neurosyphilis continue to be reported in psychiatric settings, it is not cost effective to screen all new psychiatric patients for syphilis (except in locales where syphilis is common). Screening for syphilis should focus on patients with unexplained cognitive dysfunction or other neurologic symptoms accompanying their psychopathology.

In serological testing of patients with suspected neurosyphilis, the venereal disease research laboratories (VDRL) test is not specific and has a sensitivity of only approximately 70% to 75%. The fluorescent treponemal antibody-absorption test (FTA-ABS) is more specific and has a sensitivity of 99%. In testing cerebral spinal fluid, the VDRL test is very specific but sensitivity is much lower (30% to 70%), while the FTA-ABS remains very sensitive.

Lyme Disease

Lyme disease is caused by a different spirochete, Borrelia burgdorfei, transmitted by deer ticks. The risk of a human getting infected even if bitten by an infected tick is <5%. More than 10,000 cases per year are reported in the US, with >90% of them from just eight states (Connecticut, Maryland, Minnesota, New Jersey, New York, Pennsylvania, Rhode Island, Wisconsin). Acutely, Lyme disease almost always (>90% of cases) includes the characteristic rash, erythema migrans. Chronic neuroborreliosis may develop years after the acute infection and may include mild sensory radiculopathy, cognitive dysfunction, fatigue, and depression. Nonspecific abnormalities occur in cerebrospinal fluid (CSF; >50% of cases), and magnetic resonance imaging (MRI; approximately 25%). The electroencephalograph (EEG) is usually normal, but neuropsychologic testing may demonstrate cognitive deficits.

It is important to recognize that Lyme disease is a clinical diagnosis. The results of serology may support but do not determine the diagnosis. As with HIV, serologic testing is a two-step process with an initial Elisa test, which, if positive, is confirmed by a Western Blot Test. There are limits to serological testing. First, there are often false negatives either in early infection or if the patient has received antibiotics early. Second, false positives are frequent with other infections or autoimmune diseases. As with serologic testing for Ebstein-Barr virus, a true positive is uncorrelated with the time of exposure or disease activity; it simply indicates the patient has at some point been exposed to the organism.

Neuroborreliosis has been overdiagnosed and overtreated. There have been many reported associations of psychopathology; however, association does not equal causality. Patients eager to find an “organic” explanation for fatigue or depression may now receive an inappropriate diagnosis of chronic Lyme disease. Depression and fatigue are common in patients who have been previously treated for proven Lyme disease. However, in patients without evidence of persisting infection, such symptoms are no more common than in control subjects.⁷ There has been no objective evidence of cognitive impairment in such patients. According to three randomized controlled trials examining whether such patients benefit from additional antibiotic therapy, no benefit was shown.^8,9

Common Cold (Rhinovirus)

The common cold has been the focus of interesting psychosomatic investigations. Susceptibility to colds is increased by chronic stress and decreased by positive emotional style, sociability, and moderate use of alcohol.¹⁰

Creutzfeldt-Jakob Disease

CJD is a transmissible spongiform encephalopathy caused by prions. It may be familial or occur sporadically. The initial presentation is nonspecific with one-third of patients presenting with behavioral or cognitive changes, one-third with neurologic symptoms, and one-third with general systemic symptoms like fatigue, insomnia, and anorexia. The development of diffuse myoclonic jerks is very suggestive of the diagnosis, and CJD typically progresses to mutism and death in a matter of months. Findings on MRI, EEG, and examination of the CSF can support the diagnosis but they have limited sensitivity and specificity.¹¹ Definitive diagnosis is established by brain biopsy.

New variant CJD is a form of the disease that occurs in younger patients (average 26 years of age vs. 60 years of age in regular CJD). In most cases of new variant CJD, psychiatric symptoms appear several months before any neurologic symptoms, including depression, irritability, anxiety, and apathy. New variant CJD is temporally and geographically linked to bovine spongiform encephalopathy.

Neurocysticercosis

NCC results from infection of the CNS by the larval form of Taenia solium, the pork tapeworm, which is endemic in developing nations. Cases in the US usually occur in immigrants from Latin America, but cysticercosis has also been transmitted by infected food handlers. NCC accounts for approximately 2% of the neurology and neurosurgery admissions in southern California. A high percentage of cases remain asymptomatic. Cerebral involvement may produce seizures, stroke, or hydrocephalus.¹² NCC is the leading cause of seizures in adults in Mexico and other endemic areas. Psychiatric symptoms are frequent, including depression, psychosis, catatonia, and cognitive decline.¹³ NCC is a common cause of a usually reversible dementia in the Third World, and has been reported to be a more common cause of dementia in India than Alzheimer’s disease.¹⁴

Malaria

Malaria, a relapsing fever with an accompanying delirium,  is endemic in tropical and subtropical areas. Plasmodia falciparium causes cerebral malaria and begins with disorientation, mild stupor, or even psychosis, and then rapidly progresses to seizures and coma with decerebrate posturing.¹⁵ Depression, irritability, anxiety, and personality change commonly occur after recovery from cerebral malaria, but cognitive dysfunction tends to persist.^16,17 When more severe symptoms like psychosis occur in fully recovered (aparasitemic) cerebral malaria, the symptoms are most likely due to antimalarial drugs.

Fear of Infectious Disease

Fear of infectious disease is a common symptom of OCD, and is one of the more common forms of delusional disorder. Unrealistic fears of infection are especially likely to focus on sexually transmitted diseases (especially HIV); serious epidemic outbreaks (eg, meningococcal meningitis on campus); and infectious threats given heavy media coverage, such as bacterial food contamination, bovine spongiform encephalopathy, severe acute respiratory syndrome (SARS), anthrax, or smallpox. Such fears are also a common form of mass conversion disorder in which a large number of individuals in proximity (eg, schools, military recruits) develop acute symptoms simultaneously. Societal hysterical responses fed by the media also occur, such as the widespread and inappropriate use of ciprofloxacin during the anthrax scare. Outbreaks of emerging lethal diseases can unleash phobic, hysterical, and paranoid anxiety, leading to overreaction, stigmatization, and discrimination. This, in turn, may lead those with such infections to delay seeking care and remain undetected, hindering public health measures.¹⁸

A recent example is the outbreak of SARS in which both those who were infected and those viewed at risk suffered stigma. Patients who were quarantined frequently also developed posttraumatic stress disorder (PTSD) and depression,¹⁹ and PTSD was even reported in the medical staff treating them.²⁰ Such reactions are not new. A 1905 editorial in the Journal of the American Medical Association²¹ noted:

Psychiatric Aspects of Immunization

Similar irrational fears of vaccination are also common.^22,23 There are no data supporting the widely publicized fears that the measles-mumps-rubella vaccination causes autism. There have been mass conversion disorder reactions in response to vaccination campaigns. Of course, there are real but rare serious adverse effects of immunization, including acute disseminated encephalomyelitis.

Psychiatric Side Effects of Selected Drugs for Infectious Diseases

Sometimes, psychiatric symptoms occuring in patients with infectious diseases are due to antibiotic treatment rather than the infection itself. Psychiatric side effects are common with a variety of antibacterial, antiviral, and antifungal drugs, particularly at very high doses. Those most commonly causing such adverse effects are shown in the Table.¹ PP

References

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