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Case Report

HHV-6 and Schizophrenia: An Unusual Presentation or an Unproven Etiology?

Apoorva Deshpande, MDa,*; Zachary Herrmann, DOa; Jennifer Hsu, DOa; and A. John Rush, MDb,c,d

Published: January 6, 2022

Prim Care Companion CNS Disord 2022;24(1):21cr02944

To cite: Deshpande A, Herrmann Z, Hsu J, et al. HHV-6 and schizophrenia: an unusual presentation or an unproven etiology? Prim Care Companion CNS Disord. 2022;24(1):21cr02944.
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© Copyright 2022 Physicians Postgraduate Press, Inc.

aDepartment of Psychiatry, John Peter Smith Hospital, Fort Worth, Texas
bDuke—National University of Singapore (NUS), Singapore
cDepartment of Psychiatry and Behavioral Sciences, Duke University, School of Medicine, Durham, North Carolina
dDepartment of Psychiatry, Texas Tech Health Sciences Center, Odessa, Texas
*Corresponding author: Apoorva Deshpande, MD, 1617 Hemphill St, Fort Worth, TX 76104 (



Human herpesvirus-6 (HHV-6) is the etiologic agent of roseola infantum, a self-limited acute febrile illness of childhood. Infections in immunocompetent patients are rare and pose diagnostic challenges.1 Prior studies2,3 have suggested that central nervous system inflammation from an immune response to infectious agents can produce symptoms closely resembling schizophrenia. Further, studies4 have demonstrated a genetic co-susceptibility to some viral infections and schizophrenia. The potential medical causes of psychosis (secondary psychosis) are broad and are prone to be overlooked. Further complicating this situation is the lack of clinical practice guidelines for treating psychiatric symptoms of a specific secondary etiology. We present a case of HHV-6 infection with an unusual neuropsychiatric presentation in an immunocompetent patient.

Case Report

A 44-year-old Black man, who was an active military member, presented to the emergency department with a 1-day history of left-sided weakness and pain, severe intermittent headache, double vision, fever, and auditory hallucinations. He reported a history of auditory hallucinations resulting in a psychiatric inpatient hospitalization 3 months prior. While hospitalized, he was diagnosed with schizophrenia and stabilized on an unknown dose of haloperidol. He was informed of a potential medical cause; however, no further workup was completed. After discharge, he continued to experience waxing and waning symptoms but did not take the haloperidol. At the presenting visit, a lumbar puncture was performed and revealed neutrophilic pleocytosis. A provisional diagnosis of meningoencephalitis was made, and treatment was initiated with empirical antibiotics and an antiviral. The psychiatry department was consulted for concern of psychosis. Six days later, CSF PCR (cerebrospinal fluid polymerase chain reaction) came back positive for HHV-6. Since this is usually a self-limiting disease, the infectious disease consultant recommended discontinuation of antibiotics and the antiviral. He improved over the next few days with supportive treatment and was discharged with haloperidol 5 mg nightly and 2 mg daily as needed for auditory hallucinations. He was advised to follow up with the psychiatry department; however, he did not attend his follow-up appointment.


This case illustrates behavioral symptoms that can present with an underlying infection and the difficulties in diagnosing such a possible etiology. Interestingly, Niebuhr et al3 found a correlation between HHV-6 and schizophrenia among medically discharged military personnel. A large-scale genomic study by Nudel et al4 found evidence of the presence of a genetic risk for acquiring infections and a genetic correlation with mental disorders, as well as a high degree of comorbidity between them. Despite preliminary case-control and genomic studies suggesting an association between infection and schizophrenia, there remains a paucity of clinical information on how best to manage these cases. In our patient, HHV-6 was suspected as the etiology of symptoms that were originally diagnosed as schizophrenia. Given the severity of this diagnosis, patients would benefit from further exploration of this association to prevent misdiagnosis with a serious mental illness.

Primary psychosis is the result of an underlying psychiatric disorder, while secondary psychosis is due to a medical cause. In delineating the two disorders, history of the presenting problem, mental status examination, and collateral information are paramount.5 Primary disorders are likely to present in the adolescent and young adult population.6 A first break in a middle-aged or geriatric patient is suspicious for secondary causes. A subacute presentation would be suggestive of a medical cause.6 Our patient was older and exhibited a subacute presentation. Finally, his symptoms presented with nonpsychiatric symptoms, which should greatly raise the suspicion for secondary psychosis. Psychiatric diagnoses often indicate lifelong medication use. Given the inherent risks of medications and the potential for a medical etiology being left unexplored, it is imperative that a thorough workup for an underlying medical cause be completed when warranted.

Published online: January 6, 2022.
Potential conflicts of interest: Dr Rush has received consulting fees from Compass Inc, Curbstone Consultant LLC, Emmes Corp, Evecxia Therapeutics Inc, Holmusk, Johnson and Johnson (Janssen), Liva-Nova, Neurocrine Biosciences Inc, Otsuka-US, and Sunovion; speaking fees from Liva-Nova and Johnson and Johnson (Janssen); and royalties from Guilford Press and the University of Texas Southwestern Medical Center, Dallas, Texas (for the Inventory of Depressive Symptoms and its derivatives). He is also named co-inventor on 2 patents: US Patent No. 7,795,033: Methods to Predict the Outcome of Treatment With Antidepressant Medication, Inventors: McMahon FJ, Laje G, Manji H, Rush AJ, Paddock S, Wilson AS; and US Patent No. 7,906,283: Methods to Identify Patients at Risk of Developing Adverse Events During Treatment With Antidepressant Medication, Inventors: McMahon FJ, Laje G, Manji H, Rush AJ, Paddock S. Drs Deshpande, Herrmann, and Hsu report no conflicts of interest related to the subject of this report.
Funding/support: None.
Previous presentation: Poster presented at the 2020 JPS Research Symposium, Fort Worth, Texas; June 5, 2020, and poster presented at the Annual Meeting of the Academy of Consultation-Liaison Psychiatry Virtual Conference; November 12–13, 2020.
Additional information: Patient information has been de-identified to protect anonymity.

Volume: 24

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