New research seeks to shed light on inhibitory control in bipolar patients

Inhibitory control in bipolar disorder (BD), as measured by antisaccade performance, is influenced by valence and attentional modulation much in the same way as individuals without BD, according to a new study published in Psychiatry Research. The researchers attempted to characterize inhibitory control within both “hot and cold” emotional contexts in individuals with BD relative to psychiatrically healthy controls. The findings were not what they were expecting.The authors wrote that BD is associated with inhibitory control impairments. However, traditional inhibitory control tasks may be confounded by reading ability. This occurs in some patients with BD. Eye-movement tasks assessing antisaccade performance may help avoid these limitations. Yet, few studies have examined inhibitory control in BD using such tasks, particularly those modulating valence and attention.“At this stage, the findings don’t have clear clinical relevance, but they do help us to better describe a cognitive profile for people with bipolar disorder and understand nuances regarding the aspects of cognition that are and aren’t impaired,” said study first author Tamsyn Van Rheenen, a principal research fellow and associate professor the Oceania Regional Director at International Society for Bipolar Disorders (ISBD) at the University of Melbourne in Australia.The team used eye-tracking with 44 euthymic BD patients and 30 controls to measure antisaccade performance on tasks using emotional "hot" and nonemotional "cold" stimuli. Attentional modulation was examined by comparing performance across step and gap trials. The MINI Neuropsychiatric Interview (M.I.N.I. Bipolar 5.0.0) was used to confirm a diagnosis of BD. None of the patients had a mood episode at the time of assessment, and none reported that they had experienced a mood episode in the three weeks prior to entering the study. In the BD arm, 28 participants (64 %) had a history of psychosis. Unexpectedly, no significant between-group differences were seen in antisaccade error rate. The same was true for latency for neutral or emotionally charged stimuli. Inhibitory control is a core component of executive function and it contributes to cognitive, emotional and social development. It is theorized inhibitory control may be central to many of the classic symptoms of BD, such as impulsivity, risk taking, substance misuse and mood dysregulation. A trend in the BD group toward longer latencies for negative compared to positive stimuli in the gap condition was observed in the study. However, this effect did not survive correction for multiple comparisons. Dr. Michael Ziffra, a psychiatrist at Northwestern Medicine in Chicago, said the current study is an interesting effort to try to better understand how inhibitory control, one important measure of cognitive function, may differ in patients with BD. “This study is a variant of previous studies that have already demonstrated evidence of patients with bipolar disorder experiencing deficits in inhibitory control. These deficits in inhibitory control may partially explain a number of the symptoms we see in bipolar disorder. Unfortunately, much of the data did not support the authors’ original hypotheses,” Dr. Ziffra told the Medical Post. Most of the parameters showed no large differences between the BD group and the control group. Subsequently, the findings raise more questions than answers. “The results of this particular study did not add much more to the existing knowledge about inhibitory control deficits in bipolar disorder. I did find this somewhat surprising. Given that we already know of clear deficits experienced by patients with bipolar disorder in terms of inhibitory control, I would have expected this study to produce findings consistent with prior research,” said Dr. Ziffra.The authors write that there are no published studies examining the difference between step and gap condition on antisaccade performance in patients with BD and the few antisaccade studies that examined hot inhibitory control produced mixed results. The current study was designed to overcome these issues. “While the study itself and the results are interesting, they would not largely impact current clinical management of individuals with bipolar disorder. It is possible that future research on this topic will give us a better sense of the neurochemical basis of cognitive symptoms in patients with bipolar disorder, and that may eventually lead to new therapeutics to target those particular symptoms. However, this would likely be many years away,” said Dr. Ziffra.This is the largest hot antisaccade study in a cohort of predominantly non-symptomatic patients with BD. However, the sample size is still modest, limiting its statistical power. “The study is too small to detect modest and relatively small differences in processing affectively charged material, so a false negative finding is quite possible,” said Dr. Michael Thase, a professor of psychiatry at the University of Pennsylvania in Philadelphia. “Medication effects could also have a confounding effect. But, in the end, no meaningful differences were found between people with bipolar disorder and those who appear to have no mood disorder.”The lack of significant group differences in these direct comparisons contradicts previous findings. The authors theorized it might be explained by methodological differences between the current study and previous studies or other factors such as age. “It is also possible that this eye-tracking task is not sensitive enough to pick up cognitive control impairments in people with bipolar disorder or that it measures aspects of cognitive control that are not problematic for people with bipolar disorder,” Van Reeeren told the Medical Post.Clinical studies are warranted to more comprehensively explore whether there are other variables moderating antisaccade performance in patients with BD. “Future work explicitly designed to understand the cognitive processes associated with gap and step performance are needed in BD to explore more comprehensively whether the less exaggerated gap effect is a result of reduced variation between working memory and attentional domains in these patients,” wrote the authors.

New research seeks to shed light on inhibitory control in bipolar patients

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