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Anhedonia and Cognitive Function in Adults With MDD: Results From the International Mood Disorders Collaborative Project

The International Mood Disorders Collaborative Project found a significant correlation between anhedonia and self-reported cognitive impairment in adults with major depressive disorder (MDD), which may help to identify individuals with MDD who are at higher risk of cognitive decline over time.

Kathleen T. McCoy, DNSc 

What do the results of this study mean for a practicing NP?

“This study found a significant correlation between symptoms of anhedonia and cognitive dysfunction in adults with major depressive disorder (MDD). More clinical focus on management that address these distinct, yet correlated domains may help patients living with MDD.”

NP Psych Navigator contributors are paid consultants of AbbVie Inc.

Anhedonia is observed across several neuropsychological disorders and serves as a core diagnostic criterion for major depressive episodes according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).1 It can often co-occur with deficits in cognitive function, suggesting that these 2 domains may share common neurobiological substrates. The International Mood Disorders Collaborative Project (IMDCP) aimed to assess the correlation between self-reported cognitive impairment and anhedonia in adults diagnosed with MDD.

Why was the research needed?

Anhedonia is exhibited when patients report markedly diminished interest or pleasure in most daily activities. It has been characterized as a reward system dysfunction that is observed in several neuropsychological conditions, including MDD, schizophrenia, and neurodegenerative disorders, and it serves as a core diagnostic criterion for major depressive episodes in the DSM-5.2

Impaired cognitive function is another diagnostic criterion for MDD (ie, diminished ability to think or concentrate, or indecisiveness).2 Cognitive impairment can be just as prominent and disabling as motivational and affective symptoms in psychiatric patients.3

Based on the view that anhedonia is not only prevalent across psychiatric disorders but also co-occurs alongside cognitive deficits in many individuals, the study authors sought to assess the correlation between anhedonia and impaired cognitive function for both clinical and heuristic applications.1

What did the researchers do?

The IMDCP was a multi-site, naturalistic, cross-sectional study conducted between January 2008 and July 2013 at specialized tertiary care centers at the University of Toronto’s Mood Disorders Psychopharmacology Unit and the Cleveland Clinic’s Center for Mood Disorders Treatment and Research.1

The analysis included a total of 369 adult patients who met the following inclusion criteria1:

  • A diagnosis of MDD as confirmed by the Mini-International Neuropsychiatric Interview for the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-4-TR)
  • A completed Montgomery–Åsberg Depression Rating Scale (MADRS)
  • A completed Adult Attention Deficit Hyperactivity Disorder (ADHD) Self-Report Scale (ASRS)
  • A completed Clinical Global Impression-Severity (CGI-S) scale

Anhedonia was assessed by measuring changes in item 8 of the MADRS (ie, inability to feel).1

Cognitive function was measured through the ASRS, which rates symptom severity in 2 domains: inattention and hyperactivity/impulsivity. Specifically, the inattention subscale was used to assess subjective cognitive symptoms in several dimensions that can be often impaired in adults with MDD (eg, executive function, memory, attention, information processing).1,2,4

The severity of MDD was determined using the CGI-S ratings by the treating physicians rather than another MADRS measure to avoid co-linearity.1

What were the key results of the study?

Patients in the IMDCP who met the inclusion criteria for this analysis had an average age of 40.3 years, and 63.4% were female. Of the 263 participants who reported their race, 87.1% were Caucasian, 4.6% were Asian, 4.2% were Black/African American, and 4.2% were other races. Of the 280 who reported employment status, 45.7% were employed, 35.7% were unemployed or disabled, 11.8% were students, and 6.8% were retired or homemakers.1

The study authors found that self-rated cognitive impairment significantly correlated with anhedonia (r = 0.131, p = 0.012). Cognitive dysfunction also correlated with total depression symptom severity as assessed by total MADRS score (r = 0.147, p = 0.005). Anhedonia and self-rated cognitive dysfunction remained significantly correlated after adjusting for illness severity (ie, CGI-S; r = 0.162, p = 0.007).1

The data from this study indicated that individuals with anhedonia were more likely to report deficits in measures of cognitive function. This relationship is dissociable from the overall severity of MDD since significant correlation remained even after adjusting for illness severity.1

Limitations

Study limitations included1:

  • Factors relevant to large, observational, cross-sectional cohorts (eg, absence of control for comorbidities, illness course, treatment assignments)
  • Missing data from participants
  • A lack of longitudinal follow-up
  • Utilization of the MADRS as a proxy for anhedonia in place of an independently validated measure
  • Self-reported cognitive measure in place of a comprehensive neuropsychological function assessment; however, the researchers note that the ASRS does subjectively evaluate cognitive function domains that are frequently reported as abnormal in MDD
  • Lack of a control group
  • Cohort of participants (ie, individuals using services at tertiary-based mood disorder centers) may limit generalizability; however, the researchers note that the subjects represent real patients seeking treatment for MDD since they were not selected based on any additional criteria

Why are these results important?

The results of this study provide preliminary clinical data supporting the hypothesis that anhedonia may correlate with cognitive dysfunction in MDD, independent of illness severity. This correlation was significant yet modest, indicating that they may be separate phenomena with genesis from common neurobiological systems. The potential relationship between these symptoms may help clinicians identify MDD patients who are at higher risk of cognitive decline over time.1

Across neuropsychological conditions, anhedonia is a challenging symptom that can be associated with poorer treatment response, illness chronicity, and increased suicide risk.5 Additionally, issues with cognition have been shown to play a major role in mediating the impact on functional impairment in MDD and other disorders.6

Focusing on both anhedonia and cognitive dysfunction may be an important MDD management goal that can help patients achieve better psychosocial outcomes, workplace functioning, and other patient-reported outcomes such as quality of life.7,8

What’s next?

Further studies using validated instruments are needed to better assess the overlap of anhedonia and cognitive function in patients with MDD. Additionally, examining the subdomains of anhedonia (eg, desire, anticipation, motivation, effort, pleasure, learning of stimulus-reward associations) could provide deeper insights.1,9

References

  1. McIntyre RS, Woldeyohannes HO, Soczynska JK, et al. Anhedonia and cognitive function in adults with MDD: results from the International Mood Disorders Collaborative Project. CNS Spectr. 2016;21(5):362-366. doi:10.1017/S1092852915000747
  2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Text Revision. American Psychiatric Association Publishing; 2022.
  3. Millan MJ, Agid Y, Brüne M, et al. Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy. Nat Rev Drug Discov. 2012;11(2):141-168. doi:10.1038/nrd3628
  4. Rhee TG, Shim SR, Manning KJ, et al. Neuropsychological assessments of cognitive impairment in major depressive disorder: a systematic review and meta-analysis with meta-regression. Psychother Psychosom. 2024;93(1):8-23. doi:10.1159/000535665
  5. Pizzagalli DA. Anhedonia: Preclinical, Translational, and Clinical Integration. Springer Nature; 2022.
  6. Buist-Bouwman MA, Ormel J, de Graaf R, et al. Mediators of the association between depression and role functioning. Acta Psychiatr Scand. 2008;118(6):451-458. doi:10.1111/j.1600-0447.2008.01285.x
  7. Pan Z, Park C, Brietzke E, et al. Cognitive impairment in major depressive disorder. CNS Spectr. 2018;24(1):22-29. doi:10.1017/S1092852918001207
  8. McIntyre RS, Lee Y, Carmona NE, et al. Characterizing, assessing, and treating cognitive dysfunction in major depressive disorder.  Harv Rev Psychiatry. 2018;26(5):241-249. doi:10.1097/HRP.0000000000000171
  9. Rizvi SJ, Pizzagalli DA, Sproule BA, Kennedy SH. Assessing anhedonia in depression: potentials and pitfalls. Neurosci Biobehav Rev. 2016;65:21-35. doi:10.1016/j.neubiorev.2016.03.004 

This summary was prepared independently of the study’s authors.

This resource is intended for educational purposes only and is intended for US healthcare professionals. Healthcare professionals should use independent medical judgment. All decisions regarding patient care must be handled by a healthcare professional and be made based on the unique needs of each patient. 

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