COVID-19 Has Numerous Neuropsychiatric Consequences, Report Finds

An article appearing today in the Journal of Neuropsychiatry and Clinical Neurosciences provides a comprehensive overview of the neurological and psychiatric impact of the COVID-19 pandemic.

“Although best known for its severe effects on respiratory function, SARS-CoV-2 produces a broad range of acute and chronic neurological and neuropsychiatric problems,” wrote Theodora Manolis, M.D., of Red Cross Hospital in Athens, Greece, and colleagues. “The COVID-19 pandemic has also had an important impact on the mental health of many individuals in the general population as a result of loss of loved ones, fear of calamity or death, financial hardships, social isolation resulting from government-mandated quarantine and social distancing requirements, and major disruptions of daily life and social connectedness.”

Manolis and colleagues compiled data from individual case reports, cohort studies, and meta-analyses on the neurological and psychiatric outcomes in patients with SARS-CoV-2 infection. Neurological problems in hospitalized COVID-19 patients are diverse and common, the authors noted, with one analysis finding that over 80% of these patients developed one neurologic condition over the course of the illness. While muscle pain, headache, and loss of taste/smell tend to be the most common neurologic symptoms in these patients, potentially fatal symptoms including stroke and encephalopathy were also reported among hospitalized patients.

“CNS infection combined with environmental stress caused by pandemic fear, social and financial restrictions, and ICU monitoring may result in the development of neuropsychiatric symptoms or syndromes, including depressive symptoms or episodes, manic or hypomanic symptoms or episodes, psychotic symptoms, obsessive-compulsive symptoms, and posttraumatic stress,” the authors added. They described several studies and case series that seem to suggest that patients hospitalized for COVID-19 may be at higher risk of depression and/or psychosis compared with those without COVID-19.

The range of acute and long-term neurological and psychiatric problems reflects the multipronged way the virus impacts the brain, the authors noted. This includes direct penetration of the nervous system through the nasal passage or circulatory system, indirect damage from the body’s immune response, and damage related to hypoxia or delirium.

Other topics explored in the article include the following:

• Impact of COVID-19 on neurodegenerative disorders
• Adverse neuropsychiatric effects of COVID-19 treatments
• Psychiatric impact of the pandemic on health care workers
• Maladaptive coping strategies and other psychosocial impacts of the pandemic

“There is an immediate need for interventions aimed at managing the psychosocial impact and mitigate the neuropsychiatric manifestations in addition to the other health and economic consequences of this unprecedented viral pandemic,” Manolis and colleagues concluded. “Protection of mental well-being can be accomplished by providing programs structured for psychosocial support to all those in need, such as health care workers, persons stricken by unemployment and financial hardship, families with COVID-19-affected members, older adults, and other vulnerable groups.”

To read more on this topic, see the Psychiatric News articles “Expect a ‘Long Tail’ of Mental Health Effects From COVID-19” and “Psychological Stress May Not Be Only Route Of COVID-19’s Psychiatric Burden.”

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Hyperactive Delirium May Be Common Among Critically Ill COVID-19 Patients

Critically ill COVID-19 patients who develop delirium are likely to become hyperactive and agitated, suggests a small study published today in the Journal of Neuropsychiatry and Clinical Neurosciences. In general, patients with delirium tend to be hypoactive, or show quiet confusion.

The study by Juan D. Velásquez-Tirado, M.D., of Clinica Universitaria Bolivariana in Medellín and colleagues involved 20 adult inpatients with COVID-19 who had delirium diagnosed by the Liaison Psychiatry Service at a hospital in Medellín, Colombia. Eighteen of these patients were in the intensive care unit (ICU) at the start of the study. A liaison psychiatrist evaluated the COVID-19 patients using DSM-5, the Delirium Diagnostic Tool-Provisional (DDT-Pro), Delirium Etiology Checklist (DEC), and Delirium Motor Subtype Scale-4 (DMSS-4).

At baseline, all the patients had multiple problems known to contribute to delirium, with the most common being organ failure (present in all 20 patients), systemic infection (present in all 20 patients), and metabolic disturbances (present in 19 patients). Half of the patients had DDT-Pro scores of 2 or less (which indicates significant cognitive and circadian impairment), including six patients with a score of 0. Patients with more severe COVID-19 were more likely to have lower DDT-Pro scores. In contrast, preexisting medical problems did not correlate with DDT-Pro scores.

According to DMSS-4 assessments, 15 of the 20 patients presented with only hyperactive delirium, whereas only three patients developed the more common hypoactive delirium and one patient fluctuated between hyperactive/hypoactive states. All the patients received frontline therapy with haloperidol or quetiapine; two patients who did not respond to haloperidol were switched to quetiapine while a third was switched to levomepromazine. Eight patients received adjunct trazodone to help with sleep.

Five of the 20 patients died, and the analysis suggested that lower baseline DDT-Pro scores was related to increased mortality risk.

“Although studies in larger samples are needed, more severe delirium on admission to ICU for COVID-19 may be a harbinger of mortality even in patients who did not have much preexisting medical comorbidity,” the authors wrote.

To read more on this topic, see the Psychiatric News article “Do Not Forget Delirium During the COVID-19 Scramble.”

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Loss of Consciousness, Confusion Following Mild TBI May Predict Delayed Recovery

Patients who lose consciousness and/or become dazed and confused following mild traumatic brain injury (mTBI) are less likely to fully recover within one month compared with mTBI patients without such symptoms, reports a study in the Journal of Neuropsychiatry and Clinical Neurosciences. Patients who experienced both loss of consciousness and a confused state had the highest risk of incomplete recovery one month after sustaining the injury. Among patients who had only one of these symptoms, loss of consciousness was a stronger indicator of incomplete recovery than a confused state.

These findings point to “additional risk factors for incomplete recovery post-mTBI, which will help identify patients who are in need of early psychosocial, rehabilitation, and psychiatric interventions,” wrote Durga Roy, M.D., of Johns Hopkins University School of Medicine and colleagues.

The findings come from an analysis of 407 adults who were admitted to either the Johns Hopkins Bayview Medical Center or Johns Hopkins Hospital emergency room for an mTBI due to blunt head trauma. Eighty-three of these adults lost consciousness (defined as complete or near-complete lack of responsiveness to people and other stimuli at the time of injury), 64 experienced an altered mental state (defined as being dazed, confused, or disoriented within 24 hours of injury), 127 experienced both, and 133 experienced neither. Functional recovery—which reflects how quickly and fully a patient resumes daily life activities, such as employment and social activities—was assessed via telephone or in-person interviews one, three, and six months after the head injury, using the Glasgow Outcome Scale–Extended (GOSE).

After one month, the odds of an incomplete recovery were 45% for patients who did not lose consciousness or have an altered mental state, 55% for patients who lost consciousness, 62% for patients with an altered mental state, and 70% for patients with both loss of consciousness and altered mental state. After adjusting for other clinical variables, Roy and colleagues calculated that loss of consciousness was associated with 2.17 times increased risk of incomplete functional recovery while an altered mental state was associated with 1.80 times increased risk of incomplete recovery after one month. Loss of consciousness also increased the risk of incomplete recovery at three months (though an altered mental state did not), and neither symptom increased the risk of incomplete recovery at six months.

For related information, see the Psychiatric News article “FDA Clears the Way for First Blood Test to Evaluate Head Injuries.”

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Physical Problems Exacerbate Severity of Post-Concussive Depression in Former NFL Players

A history of football-related concussions is more likely to lead to depression in former NFL players who also have physical problems such as body pain, headaches, and dizziness, reports a study published in the Journal of Neuropsychiatry and Clinical Neurosciences.

“These results suggest that medical professionals should be especially attentive to a retired athlete’s comorbid medical history and physically related conditions,” wrote Benjamin Brett, Ph.D., of the Vanderbilt Sports Concussion Center and colleagues. “If a retired athlete reports an extensive history of SRC [sport-related concussion] and somatic or depressive symptomatology, referral to a sports psychiatrist or clinical neuropsychologist is recommended for further assessment … and to differentiate depressive symptoms as purely somatic, psychiatric, or mixed.”

Brett and colleagues assessed data from 43 retired NFL players who had received comprehensive neuropsychological exams as part of a large neurological study. The exams included the Beck Depression Inventory II (BDI-II) to screen for depression and the Patient Health Questionnaire-15 (PHQ-15) to screen for somatic symptoms. The players self-reported an average of 8.7 sport-related concussions.

Of the 43 players, 29 reported minimal depressive symptoms, nine reported symptoms of mild depression (BDI-II score of 14 to 19), three reported symptoms of moderate depression (BDI-II score of 20 to 28), and two reported symptoms of severe depression (BDI-II score of 29 to 63). The average PHQ-15 score was 5.35.

Brett and colleagues found that there was no connection between concussion history and depressive symptoms in the players whose PHQ-15 scores were below average. In contrast, former players with average PHQ-15 scores did tend to have worse depression with greater somatic symptoms, and this association between concussion history and current depression was even greater among players with above-average PHQ-15 scores. The researchers also calculated that the presence of somatic symptoms contributed about twice as much to an individual’s depression as the concussions.

“Our results allow us to conclude that there are moderating factors that can affect the strength and nature of the relationship between [sport-related concussion] and depression,” the researchers concluded. “If somatic symptoms can be mitigated, it is possible that the risk and/or severity of depression may be decreased.”

For related information, see the Psychiatric News article “Can Sertraline Help Prevent Depression Following a TBI?”

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Individuals With Aggression-Related Diagnoses Are More Likely to Have Had Mild Head Injuries

Clinicians evaluating individuals with intermittent explosive disorder or self-directed aggression should be sure to ask them about a history of head injury, concluded a study published earlier this month in the Journal of Neuropsychiatry and Clinical Neurosciences.

Individuals with intermittent explosive disorder, as well as people with a history of suicidal or self-injurious behavior, were found to be twice as likely to have a history of mild traumatic brain injury (mTBI) than those with other psychiatric disorders or healthy controls, according data from a study by Emil F. Coccaro, M.D., of the University of Chicago and Caterina Mosti, Ph.D., of Drexel University.

Mild TBI is highly prevalent, with more than 1.3 million injuries occurring in the United States each year. Additionally, some 15% of returning military service personnel are estimated to have sustained an mTBI. Since many people who experience mild head injury do not seek medical treatment, this is likely a significant underestimation, the authors wrote. While the resulting cognitive, physical, and emotional consequences typically resolve within three months of the injury, a growing body of research suggests that 10% to 31% of those with mTBI injuries suffer lingering physical symptoms and mood disturbances.

To explore the relationship between history of mTBI and aggression, the researchers interviewed 1,634 physically healthy adults (this group included 695 participants with intermittent explosive disorder, 486 participants with a current/lifetime diagnosis of a psychiatric disorder that was not intermittent explosive disorder, and 453 with no psychiatric disorder). During these interviews, study participants were asked to report any history of mTBI (defined as a blow to the head associated with mild neurological symptoms including any of the following: dizziness, disorientation, memory difficulties lasting less than 24 hours, or loss of consciousness of less than 30 minutes). The participants were also asked questions about aggressive and impulsive behaviors.

Among patients who had a mTBI, 11% had no evidence of psychiatric disorder, 12% had a psychiatric or personality disorder (other than bipolar or schizophrenia/psychotic disorders), and 24% had intermittent explosive disorder. About 25% of those with mTBI had suicidal and/or self-injurious behavior. Participants reporting two or more loss of consciousness episodes had the highest aggression scores of all groups.

“On the basis of these data alone, we cannot say whether the presence of high trait impulsivity and aggression led IED [intermittent explosive disorder] participants to be in circumstances that increase risk for mTBI or whether history of mTBI altered the brains of mTBI participants, leading to an increase in aggressive and impulsive behavior post-mTBI,” the authors wrote. “That said, impulsive-aggressive behaviors are present from very early life, and individuals with this temperament are likely to place themselves in circumstances associated with bodily injury, including mTBI.”

For related information on aggression following TBI, see the Psychiatric News article “Amantadine May Reduce Aggression in TBI Patients.”

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Catatonia Often Goes Undiagnosed, Untreated in General Hospitals

Physicians fail to diagnose the majority of cases of catatonia in a general hospital setting, which may result in suboptimal treatment for these patients, according to an article in the Journal of Neuropsychiatry and Clinical Neurosciences. However, psychiatric consultation can significantly decrease the odds of failure to diagnose the condition, the study found.

Diagnosing catatonia is challenging because it requires clinical suspicion and physical examination, according to researchers Joan Roig Llesuy, M.D., of New York University School of Medicine and colleagues. While catatonia is often reversible when treated with lorazepam and/or electroconvulsive therapy (ECT), its underrecognition and subsequent lack of treatment might lead to dangerous medical complications, the authors wrote.

Moreover, failure to recognize catatonia may lead to improper treatment with antipsychotics, which can increase the risk for developing malignant catatonic features or neuroleptic malignant syndrome. “Thus, awareness about catatonia for all clinicians is relevant to improve patient care,” the authors wrote.

The study involved a retrospective chart review of adult inpatients at the University of Chicago general hospital between 2011 and 2013. The presence of three or more keywords in the chart describing catatonia-related signs was used to flag cases for review. Of 133 cases found meeting DSM-5 criteria for catatonia, 79 (nearly 60%) were not diagnosed with the condition.

Additional analysis revealed that patients meeting DSM-5 criteria for catatonia who underwent a psychiatric consultation during the admission process were more than 44 times as likely to be correctly diagnosed with catatonia, compared with those who did not receive a consultation. Still, more than one-third of undiagnosed patients (37%) had received a psychiatry consult, supporting “the need for greater recognition of catatonia across disciplines,” the researchers wrote.

Physicians may be unaware of the cluster of signs and symptoms that constitute catatonia: the presence of grimacing, agitation, or echolalia symptoms was associated with a 4 to 6 times greater likelihood that the catatonia would go undiagnosed.

Regardless of diagnosis of catatonia, none of the 133 subjects received ECT. Also, no differences were found in the rate of lorazepam treatment between diagnosed or undiagnosed patients: half of those with catatonia did not receive lorazepam. However, the total dose of lorazepam was significantly lower in the undiagnosed group, who received 0.4 mg a day on average versus those diagnosed with catatonia, who received an average of 1.3 mg a day. High doses of lorazepam for several days or longer might be needed to treat catatonia effectively, the researchers wrote.

“Improving detecting and treatment of catatonia could help improve clinical outcomes of patients with this reversible syndrome in the general hospital,” concluded the authors.

For related information, see the Journal of Neuropsychiatry and Clinical Neurosciences article “Suspected Delirium Predicts the Thoroughness of Catatonia Evaluation.”

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Transcranial Magnetic Stimulation May Reduce Cravings in People With Nicotine Use Disorder

Previous studies have found that repetitive transcranial magnetic stimulation (rTMS)—a noninvasive technique that stimulates targeted brain regions using magnetic pulses—reduces cravings in some patients with substance use disorder. A meta-analysis in the Journal of Neuropsychiatry and Clinical Neurosciences now suggests that the neuromodulatory tool may be particularly effective at cutting cravings in people with nicotine use disorder.

Researchers first performed a literature search of the MEDLINE and Cochrane databases for randomized, controlled trials and controlled clinical trials on transcranial magnetic stimulation (TMS) in patients with substance use disorder published up until 2015. Ten studies met the authors’ criteria for inclusion in the meta-analysis, including six on alcohol use disorder and four on nicotine use disorder that involved TMS stimulation to regions of the prefrontal cortex.

The meta-analysis revealed a significant effect size favoring active rTMS stimulation over sham stimulation in reducing craving in substance dependence. Active rTMS stimulation was found to be highly effective for nicotine use disorder in subgroup analysis, but it showed no favorable effect for alcohol use disorder.

“Stimulating DLPFC [dorsolateral prefrontal cortex] by rTMS has been postulated to reduce substance craving possibly by two mechanisms. ... [I]nterconnections of the DLPFC with the ventral tegmental area (VTA) increase dopamine excretion from the VTA to the ventral striatum, an area implicated in reward processing. ... [S]timulation of the DLPFC stimulates glutamate containing corticofugal fibers, which end on dopamine containing terminals in the ventral striatum, potentially increasing dopamine excretion and reducing craving,” wrote Rituparna Maiti, M.D., and colleagues at the All India Institute of Medical Sciences (AIIMS) in Bhubaneswar, India.

Based on the results of the meta-analysis, Maiti and colleagues recommended the adoption of a uniform rTMS treatment protocol for patients with nicotine use disorder. They also called for additional trials to examine the effectiveness of rTMS in patients with alcohol use disorder. “There is a need for further clinical trials with robust rTMS protocols and a greater number of treatment sessions to make a final conclusion on the anti-craving effects of rTMS in alcohol use disorder,” they concluded.

For related information, see the Psychiatric News article “Neuromodulation May Benefit Patients With Varying Psychiatric Illnesses,” by Andrew Leuchter, M.D., director of the Neuromodulation Division at the Semel Institute for Neuroscience and Human Behavior at the David Geffen School of Medicine at the University of California, Los Angeles.

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