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Upper Respiratory Infections and Mood Disorders

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Upper Respiratory Infections and Mood Disorders Nothing to sneeze at: Upper respiratory infections and mood disorders URIs can destabilize mood disorders, and OTC cold/flu meds may increase risk of interactions cute upper respiratory infections (URIs) often lead to mild illnesses, but they can be severely destabilizing Afor individuals with mood disorders. Additionally, the medications patients often take to target symptoms of the common cold or influenza can interact with psychiatric medications to produce dangerous adverse events or induce further mood symptoms. In this article, we describe the rela- tionship between URIs and mood disorders, the psychiatric diagnostic challenges that arise when evaluating a patient with a URI, and treatment approaches that emphasize psycho education and watchful waiting, when appropriate. A bidirectional relationship VINE DIOMEDIA/BLEND RF/TERRY Acute upper respiratory infections are the most common Jeffrey J. Rakofsky, MD human illnesses, affecting almost 25 million people annually Assistant Professor in the United States.1 The common cold is caused by >200 Director, Medical Student Education different viruses; rhinovirus and coronavirus are the most Boadie W. Dunlop, MD, MS common. Influenza, which also attacks the upper respiratory Associate Professor Director, Mood and Anxiety Disorders Program tract, is caused by strains of influenza A, B, or C virus.2 The common cold may present initially with mild symptoms of • • • • headache, sneezing, chills, and sore throat, and then progress Department of Psychiatry and Behavioral Sciences to nasal discharge, congestion, cough, and malaise. When Emory University School of Medicine Atlanta, Georgia influenza strikes, patients may have a sudden onset of fever, headache, cough, sore throat, myalgia, congestion, weakness, anorexia, and gastrointestinal (GI) symptoms. Production of URI symptoms results from viral cytopathic activity along Disclosures Dr. Rakofsky receives grant/research support from the American Board of Psychiatry and Neurology, and Takeda. Dr. Dunlop receives grant/research support from Acadia, the National Current Psychiatry Institute of Mental Health, and Takeda, and is a consultant to Myriad Neuroscience. Vol. 18, No. 7 29 with immune activation of inflamma- 2.5 times greater for individuals with tory pathways.2,3 The incidence of colds is elevated scores on a depression symp- inversely correlated with age; adults aver- tom severity scale compared with those age 2 to 4 colds per year.4,5 Cold symptoms with lower scores.16 Because these studies peak at 1 to 3 days and typically last 7 to 10 were retrospective, recall bias may have days, but can persist up to 3 weeks.6 With impacted the results, as patients who are influenza, fever and other systemic symp- depressed are more likely to recall nega- Upper respiratory toms last for 3 days but can persist up to 8 tive recent events.17 infections days, while cough and lethargy can persist for another 2 weeks.7 Upper respiratory infections have the Proposed mechanisms potential to disrupt mood. Large studies Researchers have proposed several of psychiatrically-healthy undergraduate mechanisms to explain the association of students have found that compared with URIs with mood episodes. Mood disor- healthy controls, participants with URIs ders, such as bipolar disorder and major endorsed a negative affect within the first depressive disorder (MDD), are associated Clinical Point week of viral illness,8 and that the number with chronic dysregulation of the innate Mood disorders and intensity of URI symptoms caused immune system, which leads to elevated by cold viruses were correlated with the levels of cortisol and pro-inflammatory are associated degree of their negative affect.9 A few cytokines.18,19 Men with chronic low-grade with chronic case reports have documented instances inflammation are more vulnerable to all dysregulation of of individuals with no previous personal types of infection, including those that the innate immune or family psychiatric history develop- cause respiratory illnesses.20 High levels ing full manic episodes in the setting of of stress,21 a negative affective style,22 and system influenza.10-12 One case report described depression23 have all been associated with an influenza-induced manic episode in a reduced antibody response and/or cellular- patient with pre-existing psychiatric ill- mediated immunity following vaccina- ness.13 There are no published case reports tion, which suggests a possible mechanism of common cold viruses inducing a full for the vulnerability to infection found in depressive or manic episode. If cold symp- individuals with mood disorders. On the tom severity correlates with negative affect other hand, after influenza vaccination, among individuals with no psychiatric ill- patients with depression produce a greater ness, and if influenza can induce manic and more prolonged release of the cyto- episodes, then it is reasonable to expect kine interleukin 6, which perpetuates the that patients with pre-existing mood disor- state of chronic low-grade inflammation.24 ders could have an elevated risk for mood Additionally, patients with mood disor- disturbances when they experience a ders may engage in behaviors that reduce URI (Box, page 31). immune functioning, such as using illicit Mood disorders may also be a risk factor substances, drinking alcohol, smoking for contracting URIs. Patients with mood cigarettes, consuming an unhealthy diet, disorders are more likely than healthy con- or living a sedentary lifestyle. trols to be seropositive for markers of influ- Conversely, there are several mecha- enza A, influenza B, and coronavirus, and nisms by which a URI could induce a mood those with a history of suicide attempts are episode in a patient with a mood disorder. more likely to be seropositive for markers Animal studies have shown that a non- Discuss this article at of influenza B.14 In a community sample CNS viral infection can lead to depressive www.facebook.com/ of German adults age 18 to 65, those with behavior by inducing peripheral interferon- MDedgePsychiatry mood disorders had a 35% higher likeli- beta release. This signaling protein binds hood of having had a cold within the last to a receptor on the endothelial cells of the 12 months compared with those without blood-brain barrier, inducing the release a mood disorder.15 A survey of Korean of additional cytokines that affect neuro- employees found the odds of having had nal functioning.25 Among patients receiv- Current Psychiatry 30 July 2019 a cold in the last 4 months were up to ing interferon treatments for hepatitis C, a Box Case report: Unexplained recurrence of depression s. E is a 35-year-old financial analyst with of her annual goal to run a marathon, she MDedge.com/psychiatry Mbipolar disorder type I and alcohol use continues to train, albeit at a slower pace, and disorder in sustained remission. She had been has not had much time to rest because of her euthymic for the last 3 years, receiving weekly demanding job. psychotherapy and taking lamotrigine, 350 The psychiatrist explains to Ms. E that mg/d, lithium ER, 900 mg/d (lithium level: 1.0 an upper respiratory infection (URI) can mmol/L), lurasidone, 60 mg/d, and clonazepam, sometimes induce depressive symptoms. 1 mg/d. At her most recent quarterly outpatient Given the patient’s lengthy period of psychiatrist visit, she says her depression had euthymia and the absence of new medicines, returned. She reports 1 week of crying spells, dietary changes, or drug/alcohol intake, the initial and middle insomnia, anhedonia, feelings psychiatrist suspects that the cause of her of worthlessness, fatigue, poor concentration, mood episode recurrence is related to the and poor appetite. She denies having suicidal URI. Hearing this is a relief for Ms. E. She and ideation or manic or psychotic symptoms, the psychiatrist decide to refrain from making and she continues to abstain from alcohol, any medication changes with the expectation illicit drugs, and tobacco. She has been fully that the URI would soon resolve because adherent to her medication regimen and has it had already persisted for 1.5 weeks. The not added any new medications or made any psychiatrist tells Ms. E that if it does not and Clinical Point dietary changes since her last visit. She is her symptoms worsen, she should call him to puzzled as to what brought on this depression discuss treatment options. The psychiatrist GI symptoms such recurrence and says she feels defeated by the also encourages Ms. E to take a temporary bipolar illness, a condition she had worked break from training and allow her body to rest. as vomiting and tirelessly to manage. When asked about Three weeks later, Ms. E returns and diarrhea can reduce changes in her health, she reports that about reports that both the URI symptoms and the 1.5 weeks ago she developed a cough, nasal depressive symptoms lifted a few days after the absorption congestion, rhinorrhea, and fatigue. Because her last visit. of psychotropic medications history of depression increased their likeli- A diagnostic challenge hood of becoming depressed during their Making the diagnosis of a major depressive treatment course, which suggests people episode can be challenging in patients who with mood disorders have a sensitivity to present with a URI, particularly in those who peripheral cytokines.26 are highly vigilant for relapse and seek care Sleep interruptions from nighttime soon after mood symptoms emerge. Many coughing or nasal congestion can increase symptoms overlap between the conditions, the risk of a recurrence of hypomania or including insomnia, hypersomnia, reduced mania in patients with bipolar disorder,27 interest, anhedonia, fatigue, impaired con- or a recurrence of depression in a patient centration, and anorexia. Symptoms that with MDD.28 The stress that comes with are more specific for a major depressive epi- missed work days or the inability to take sode include depressed mood, pathologic care of other personal responsibilities due guilt, worthlessness, and suicidal ideation.
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