By Maria R. Restivo , Margaret C. McKinnon, Benicio N. Frey, Geoffrey B. Hall, Wasimuddin Syed, Valerie H. Taylor

In a research article published in the Open Access journal PLOS, researchers concluded that in individuals with Major Depressive Disorder (MDD), the impact of concomitant obesity may be significant.

Background

Evidence suggests obesity exerts a negative impact on cognition. Major Depressive Disorder (MDD) is also linked to problems in cognitive functioning. Obesity is highly prevalent in individuals with MDD and is linked to a failure to return to a full level of functioning. The study’s objective was to investigate the effect of obesity on cognitive impairment in participants with MDD.

Methods

This study compared cognitive performance in obese individuals with MDD and two control populations (obese individuals without a psychiatric illness and non-obese controls). A standardized battery of neuropsychological tests specifically designed to assess performance in declarative memory, executive functioning, processing speed and attention was administered. Mood ratings, physical measurements, nutritional and health questionnaires were also completed.

Results

We observed a consistent pattern across measures of memory, executive functioning, attention and processing speed. Whereas healthy controls performed better than both bariatric groups across the majority of measures administered, bariatric controls tended to outperform bariatric MDD patients.

Limitations

The overall sample size of our study was small and thus largely explorative in nature. However, it provides compelling results (while controlling for extraneous variables such as medication load, nutritional status and common metabolic comordidities) that strongly urges for further investigation and study replication with larger sample sizes.

Conclusions

We found obesity has a subtle impact on cognition in obese individuals, and when obesity is present in individuals with MDD, this impact may be significant. It is important to minimize all modifiable variables that can add to cognitive burden in this population.

Introduction

Obesity is associated etiologically with cardiovascular disease, in part due to its contribution to risk factors such as dyslipidemia, hypertension and type II diabetes (T2D) [1]. As a consequence, public health interest in obesity prevention and treatment has been significant [2]. This effort has begun to target specific populations, as there is an inherent increased vulnerability towards weight gain associated with mental illness. Individuals with major depressive disorder (MDD), an illness predicted to be the main cause of disability worldwide by 2020 [3], have a 21% higher risk of developing obesity than the general population according to the National Comorbidity Survey-Replication (NCS-R) [4]. The deleterious effects of obesity on peripheral systems have been well elucidated but its impact on central brain function remains much less well understood [5]. An emerging area of investigation suggests that adiposity may negatively impact cognitive functioning [6–8]. For example, studies of obese adults seeking bariatric surgery have shown significant impairment on measures of executive functioning in particular prior to surgical intervention [6, 9]. Although executive functioning (higher-order cognitive processing) is the cognitive domain most often affected, performance on tasks of memory also point towards a potential negative association with obesity [10].

The impact of obesity among individuals with mental health conditions and, in particular, MDD, may be particularly problematic. Here, individuals with depression show impairment relative to matched healthy controls across multiple cognitive domains, including memory, processing speed, and cognitive flexibility [11–16]. Additional studies point towards alterations in performance on executive functioning tasks involving the selection, timing, monitoring and interpretation of behavior, and on measures of working memory and selective attention [11, 17, 18].

Despite clear links between obesity, and cognitive functioning and MDD, the extent to which obesity impacts cognitive functioning in individuals with MDD is absent from the literature. Even with the greater prevalence of overweight or obese individuals in the MDD population [19–21], participant weight is not routinely reported as a demographic characteristic or potential covariate in reviews on cognition in this population [11, 15, 22–26]. Given that impaired cognition is often linked with a failure to return to full functioning, despite a remission in other symptoms [12, 27, 28] and that obesity is a potentially preventable or modifiable risk factor, there is an urgent need to explore this association.

We aimed to examine the impact of obesity and MDD on cognitive function in an adult population (age 18–60). Cognitive performance was assessed in obese individuals seeking bariatric surgery, with and without MDD, and compared to healthy control (non-depressed, normal body mass index [BMI)]) individuals. Here, we hypothesized that healthy controls would outperform both bariatric (obese) participant groups on measures of cognitive performance. We also postulated that depression would have an additive effect, wherein bariatric participants with MDD would perform more poorly than bariatric controls (free of psychiatric illness). In addition, we examined how important potential confounding variables not routinely investigated in previous studies, such as nutritional intake and the presence of medical illnesses commonly co-morbid with obesity, might impact these associations.

Demographic

Age at time of neuropsychological testing, years of education, sex, marital status and ethnicity was collected for each participant (see Table 2). The Cognitive Failure Questionnaire (CFQ) [38] was used to assay subjective sense of cognitive dysfunction, while the Sheehan Disability Scale (SDS) was used to quantify functional impairment across 3 life domains (Work/School, Social Life, and Family Life/Home Responsibilities) [39].

Psychiatric

Mood rating questionnaires were administered on the day of testing or within 2 weeks of the study visit. The Beck Depression Inventory (BDI) [40] and Hamilton Rating Scale for Depression-17 (HAMD-17) [41] were used to examine depressive symptoms while the Altman Rating Scale for Mania (ARSM) [42] and Young Mania Rating Scale (YMRS) [43] were used to control for mania symptoms. Additionally, the Childhood Trauma Questionnaire was administered to control for previous trauma exposure [44] (a potential confounder in MDD populations). Current and past psychiatric morbidities were captured through the SCID-I, and additional information regarding MDD illness burden including illness age of onset and number of episodes was also obtained (clinical characteristics listed in Table 2).

Discussion

To our knowledge, this is the first study to attempt to examine the potentially deleterious effects of obesity, its comorbidities, and depression on cognitive performance. It is also the first to attempt to control for variables such as medication load, nutritional status and medical illness burden in a systematic way. Provocatively, although healthy controls often outperformed bariatric controls and bariatric controls often outperformed bariatric MDDs (with regards to raw test scores), these differences in cognitive performance did not generally reach significance until comparing performance between healthy controls and bariatric MDDs. This suggests that MDD and obesity may have an additive effect on cognition that leads to measurable deficits in cognitive performance on neuropsychological measures.

Our work adds to the growing number of studies linking obesity to poor cognitive performance [56] and illustrates how even subtle changes in weight can be clinically relevant in populations with preexisting vulnerability. Although obesity may not have a perceptible effect on cognitive performance in psychologically healthy individuals, it may be an issue in patients already susceptible to cognitive dysfunction such as those with MDD.

Consistent with previous studies who have found an effect of obesity on cognition, the majority of our reported findings of cognitive impairment in the bariatric MDD group were on measures of executive functioning, attention, and processing speed, capacities shown to be affected by both obesity and MDD individually [17, 26, 57, 58]. Further, when comparing performance patterns across groups, MDD (including both past and current diagnosis) seemed to have an additive negative effect on cognition in the presence of obesity, with comparisons between bariatric MDD and healthy controls resulting in significantly different levels of performance on several cognitive tasks (differences were generally not seen as significant when contrasting bariatric MDD and bariatric controls). However, it is possible that subtle differences in group performances that do not meet the threshold for statistical significance may still result in clinically significant impact. This has important ramifications on both clinical practice and theoretical research.

Clinically, many psychotropic medications are associated with problematic metabolic side effects, including increased weight gain [59, 60]. A common complaint of MDD patients is cognitive impairment [15]; in line with this, the MDD sample in our study reported high levels of subjective cognitive impairment on the CFQ. Current clinical treatment guidelines do not factor in tolerability when suggesting first and second line options, but knowing metabolic changes can impact cognitive functioning (an outcome used as a measure of remission of psychiatric symptomatology) may impact stratification of medication recommendations, especially given the emphasis on functional recovery [27]. Given an option between several first-line treatment options for MDD, physicians may want to therefore consider a psychotropic medication with a smaller likelihood of significant weight gain, as well as implementing a weight management or monitoring strategy with medication-treated patients.

While it is known that MDD is associated with impairment on tests of memory, attention, executive function and processing speed [11, 12, 26] few studies investigating interactions between MDD and cognitive impairment report on, or account for, the possible confounding effects of obesity. In our study, we found that an additive effect of MDD and obesity reached significance on measures of processing speed and executive function. One can therefore speculate that some of the cognitive impairment traditionally attributed to the presence of a mood disorder may be associated with obesity and/or its related metabolic comorbidities and further work is needed to articulate this linkage.

Limitations

Although a consistent group performance pattern was seen across almost all measures, results may have failed to achieve significance on certain measures due to our study’s modest sample size limitation. Also, due to the absence of a non-bariatric MDD study group, we are unable to draw complete conclusions regarding the independent effects (and interactions) between MDD and obesity on cognition. However, our exploratory yet compelling results (while controlling for extraneous variables such as medication load, nutritional status and common metabolic comordidities) strongly urge for further investigation and study replication with larger sample sizes (along with the addition of a non-bariatric MDD group).

Conclusion

We observed an overall consistent pattern across several neuropsychological wherein healthy controls consistently achieved higher scores than both bariatric groups (BC and MDD-B) across the majority of test measures, while the BC group tended to outperform the MDD-B group. This indicates that obesity may partially contribute to the negative impairment associated with MDD. Further work is needed to expand on these provocative findings to clarify the directionality between obesity and cognitive impairment and to further disentangle the interactive effects of mood disorder diagnosis, obesity and cognitive performance. The work to date, however, indicates that obesity may impact cognitive performance in individuals with preexisting vulnerability, such as those with MDD, and weight management is especially important in this population in order to ensure the best outcomes.

Acknowledgments

We extend our sincere appreciation to Hayley Jones, Jordyn Vernon, Dr. Alex Kiss and the Bariatric Registry Study for their assistance in the preparation of the manuscript.

Citation: Restivo MR, McKinnon MC, Frey BN, Hall GB, Syed W, Taylor VH (2017) The impact of obesity on neuropsychological functioning in adults with and without major depressive disorder. PLoS ONE 12(5): e0176898. https://doi.org/10.1371/journal.pone.0176898