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Journal Digest
Published Online: 26 September 2019

Journal Digest: Visual Marker; Children With IBD; Weight-Loss; Postoperative Delirium; Early Parkinson’s; Opioid Receptors

Visual Marker May Help Identify Autism Severity

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Individuals with autism are slower at switching their focus between two competing images (known as binocular rivalry), and the degree of this switching delay correlates with the severity of autism symptoms, according to a study in Current Biology. This finding may some day lead to an objective test for autism that does not require any verbal communication.
Researchers at Dartmouth University and Johns Hopkins University tested the binocular rivalry of 18 adults with autism and 19 age- and IQ-matched adults without autism. The participants looked through a special prism so that each eye saw a unique image, and an electroencephalography (EEG) device measured their brain waves as the two images flickered on and off at different frequencies, causing the brain to continually shift its attention.
The EEG readings showed that the adults with autism were statistically slower at switching their focus between competing images compared with controls (about 21 perceptual switches per minute versus 24 per minute). On average, the participants with more severe autism symptoms (as assessed by the Autism Diagnostic Observation Schedule, second edition) had slower switching. Perceptual switching rates were independent of IQ scores.
The researchers noted that the adults with autism understood the nature of the test as well as the adults without autism, so that did not explain the differences.
Using purely the EEG data, the researchers were able to distinguish the participants with autism from controls with 87% accuracy.
A perception-based biomarker could be useful in several circumstances, the researchers noted. “These include assessments of preverbal infants or adults with minimal communication skills, who are estimated to represent 30% of the autism spectrum but are rarely included in research,” they noted.
Spiegel A, Mentch J, Haskins AJ, Robertson CE. Slower Binocular Rivalry in the Autistic Brain. Curr Biol. 2019; 29(17): 2948-2953.e3

Children With IBD Have Greater Risk of Psychiatric Problems

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Children who develop inflammatory bowel disease (IBD) are at an elevated risk for a range of psychiatric disorders and suicide attempts, according to a study appearing in JAMA Pediatrics.
A team led by researchers at Sweden’s Karolinska Institute used Swedish health registry data to identify all children born in the country between 1973 and 2013 who received an IBD diagnosis (such as ulcerative colitis or Crohn’s disease) before age 18. The analysis included 6,464 individuals with childhood-onset IBD, 6,999 siblings of these patients, and 323,200 unrelated individuals. (Children who had a psychiatric diagnosis prior to an IBD diagnosis and their siblings were excluded from the final sample.)
During the follow-up period (about nine years), 17.3% of the individuals with childhood-onset IBD received a diagnosis of a psychiatric disorder compared with 11.8% of the general population, corresponding to about a 60% increased risk of psychiatric disorders in individuals with childhood-onset IBD. A similar increased risk was seen when comparing the children with IBD with their siblings.
Risks of a psychiatric disorder were even higher for patients who received an IBD diagnosis before age 6 (140% increased risk), and those who required bowel or perianal surgery (100% increased risk). Individuals with childhood-onset IBD also had a 40% increased risk of suicide attempt.
“The highest risk of anxiety and mood disorders during the first year after a diagnosis of IBD suggests the need for psychological support for these patients,” the researchers concluded. “Particularly concerning is the increased risk of suicide attempt. Long-term psychological support should therefore be considered for patients with childhood-onset IBD.”
Butwicka A, Olén O, Larsson H, et al. Association of Childhood-Onset Inflammatory Bowel Disease With Risk of Psychiatric Disorders and Suicide Attempt. JAMA Pediatr. August 19, 2019. [Epub ahead of print]

Weight-Loss Program Benefits Patients on Psychotropics

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Individuals who are taking antidepressants and/or antipsychotics may benefit from participation in a weight-management program, according to a study published in Obesity.
Researchers at the University of Toronto and colleagues assessed the outcomes of 17,519 adults enrolled in a physician-guided weight-management program at the Wharton Medical Clinic (which has locations throughout Ontario) between July 2008 and July 2017. Of this group, 3,457 adults were taking an antidepressant, 172 were taking an antipsychotic, and 465 were taking both medications. The participants spent an average of 14 to 22 months in the program.
The researchers found that patients lost a significant amount of weight regardless of the psychiatric medications they were taking. Among men, those taking antidepressants lost slightly less weight in the program compared with patients not taking either medication after adjusting for differences in age, starting weight, and treatment time (average weight loss of 7 pounds compared with 9.5 pounds). Men taking antipsychotics or both medications lost similar amounts of weight as men taking neither medication. Among women, there were no adjusted differences in weight loss (average 6.5 pounds) among any of the four groups.
The researchers also found that both men and women taking an antidepressant and/or antipsychotic lost an equal amount of weight regardless of whether their medication was considered “weight-gaining.
Wharton S, Kuk JL, Petrova L, et al. Effectiveness of a Community-Based Weight Management Program for Patients Taking Antidepressants and/or Antipsychotics. Obesity (Silver Spring). 2019; 27(9):1539-1544

Regular Physical Activity Lowers Risk of Postoperative Delirium

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Add one more item to the list of health benefits conferred by regular physical activity: A study published in the Journal of the American Geriatrics Society found that older adults who are physically active prior to elective surgery are at reduced risk of postoperative delirium.
Investigators at the Albert Einstein College of Medicine in New York assessed 132 adults (aged 60 and older) without significant cognitive impairment who underwent elective orthopedic surgery. The participants completed a cognitive assessment and a physical activity questionnaire prior to the surgery. Of this group, 41 patients developed postoperative delirium. Overall, the participants who reported engaging in physical activity at least six days a week prior to surgery were 74% less likely to develop delirium. Women were especially likely to benefit from physical activity; active women were 86% less likely to develop delirium. There was no significant effect of physical activity on delirium risk when looking solely at men.
The effects of physical activity were independent of the patient’s cognitive scores. Thus, “[p]ersons with mild cognitive impairment or a relatively low level of participation in stimulating cognitive activities will likely still benefit from exercise, if tolerated,” the investigators wrote.
There was also some suggestion that regular physical activity lowered the severity of symptoms among patients who did develop postoperative delirium, but these findings were not statistically significant. The investigators suggested that a follow-up analysis in a larger population is warranted.
Lee SS, Lo Y, Verghese J. Physical Activity and Risk of Postoperative Delirium. J Am Geriatr Soc. August 1, 2019. [Epub ahead of print]

More Evidence Supports Depression as Marker for Early Parkinson’s

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A retrospective analysis of people in Bologna, Italy, provides further evidence that depression may be one of the early symptoms of Parkinson’s disease, prior to the more characteristic movement problems associated with this disorder.
A team at the Institute of Neurological Sciences in Bologna tracked a group of adults aged 35 and older from Bologna who did not have Parkinson’s disease. The researchers compared Parkinson’s disease diagnoses in study participants who took antidepressants for at least 180 consecutive days (considered a proxy for depression) with those who did not take antidepressants.
During roughly a decade of follow-up, 34,620 adults (totaling 199,093 person-years) were categorized as exposed to antidepressants, and 389,678 adults (totaling 4,286,470 person years) were considered not exposed.
The researchers found that patients exposed to antidepressants were 70% more likely to be diagnosed with Parkinson’s disease than those not exposed to antidepressants, and the diagnosis was made an average of three years after starting the medication.
The risks of Parkinson’s disease among individuals who took antidepressants were higher for men, for adults 65 and younger, and adults with fewer medical comorbidities. “[T]he fact that the risk of PD [Parkinson’s disease] is higher among patients without other physical conditions favoring depression confirms the link between depression itself and subsequent PD,” the investigators wrote. The article was published in the Journal of the Neurological Sciences.

Opioid Receptors May Mediate Ketamine’s Antisuicidality Effects

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Ketamine is known to reduce suicidal thoughts in people with severe depression. A study in Molecular Psychiatry now suggests ketamine’s antisucidality effects may be dependent on activation of the opioid system.
The findings come from a secondary analysis of a 14-person clinical trial by researchers at Stanford University and Palo Alto University. Patients received either naltrexone (a strong opioid receptor blocker used to treat opioid use disorder) or placebo prior to receiving intravenous ketamine (though each patient completed both arms of the study). The study participants were evaluated with the Hamilton Depression Rating Scale (HDRS), the Montgomery–Åsberg Depression Rating Scale (MADRS), and the Columbia Suicide Severity Rating Scale (CSSRS) throughout the two-week study.
The researchers found that patients reported less improvement on measures of suicidality (HRDS item 3, MADRS item 10, and CSSRS total score) after ketamine if they had taken naltrexone before the infusion compared with when taking placebo before the infusion.
A previous article for this trial reported that ketamine’s antidepressant effects were likely mediated by opioid receptors. The researchers noted that while the relative changes in patients’ depression and suicidality symptoms were similar in the first 24 hours, they diverged over the remaining 13 days. “Thus, similar to past reports, our current data support the hypothesis that the pharmacological mechanism through which ketamine reduces suicidality is partially independent from the mechanism through which it reduces depressive symptoms,” they wrote. ■
Williams NR, Heifets BD, Bentzley BS, et al. Attenuation of Antidepressant and Antisuicidal Effects of Ketamine by Opioid Receptor Antagonism. Mol Psychiatry. August 29, 2019. [Epub ahead of print]

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