Zika virus infection followed by a first episode of psychosis: another flavivirus leading to pure psychiatric symptomatology

Zika virus (ZIKV), a flavivirus primarily transmitted by Aedes mosquitoes, represents a major public health concern. ZIKV infection, previously considered a self-limited febrile exanthematic disease, leads to serious neurologic complications.1

Microcephaly and extensive brain damage can result from congenital ZIKV infection. An association with Guillain-Barre Syndrome was suggested after the French Polynesia outbreak,2 and reports from endemic areas suggest that acute ZIKV infection leads to numerous central nervous system (CNS) complications. Considering the complexity of CNS function, we can expect a variety of clinical manifestations, even purely psychiatric symptoms.

A 17-year-old boy was transferred to our psychiatric emergency ward for evaluation of a first-episode psychosis (FEP). He had no significant health history or previous psychiatric history. Ten days prior to admission, he suddenly presented paranoid delusions and vivid auditory, somatic and olfactory hallucinations. He showed intense anxiety and panic-like symptoms, alternating with moments of inadequate behavioral disinhibition. Symptoms also included sleeplessness, increased speech production, vocal mannerisms and refusal to eat. A distinct period of altered mood was negated. Upon admission he was fully conscious with no attention deficits, disoriented about the time and place, afraid, suspicious and speaking incoherently. Physical and neurological exams were otherwise normal. Initial workup included hematological, toxicological, neuroradiologic and electroencephalographic assessments, which were all within normal range. A febrile rash – followed by pruritus, myalgia, arthralgia, periocular pain and posterior cervical adenopathy, which began 14 days before the onset of the behavioral symptoms and remitted after a week – was then reported by his parents.

We extended the investigation to rule out other medical conditions leading to the psychotic episode. All CSF parameters were within the normal range. In peripheral blood we detected positive dengue virus (DENV) in ELISA, IgM, and IgG tests; the NS1 antigen was undetectable and RT-PCR was negative for DENV. RT-PCRs for ZIKV resulted positive in multiple blood samples. An intense cross-reaction was observed across DENV and ZIKV ELISA titers,3,4 leading us to conclude that this was the case. After five days of Haloperidol with no response, the prescription was changed to Risperidone 2 mg/day and remission was achieved in three days. The patient was discharged and medication was tapered off after 3 weeks. No relapse in symptoms was noted during one year of follow-up in our specialized FEP outpatient service.

To the best of our knowledge, this is the first report in which psychiatric symptoms were the only complication of acute ZIKV infection. There is much evidence of psychiatric symptomatology in viral infections. Dengue-related manic and psychotic episodes have been described in which symptoms suggesting encephalitis or encephalopathy were not seen – thus supporting flavivirus’ role in inducing purely behavioral symptoms. Cases in which DENV infections have led to neuropsychiatric complications are numerous, well established in the literature and more commonly diagnosed than in regular clinical practice.5

Neuroimmune mechanisms leading to psychosis during acute CNS stress is an open and prolific field for research. On the clinical front, mental health professionals dealing with emergency psychiatry and FEP must have a high grade of suspicion to avoid underrecognizing particular – and self-limited – conditions.

Disclosure

The authors report no conflicts of interest.