Neuropsychological and behavioral alterations from comorbid Alcohol Dependence (AD) and Major Depressive Disorder (MDD) are likely more than additive. These findings were published in HELIYON.

Outpatients (N=60) were recruited at the Instituto Nacional de Psiquiatía (National Institute of Psychiatry) in Mexico City, Mexico. Participants were evaluated for AD and MDD and were assessed using the 21-item Hamilton Depression Scale (HAMD), Montgomery-Åsberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI), Alcohol Dependence Scale (ADS), and Obsessive-Compulsive Drinking Scale (OCDS) instruments and for neuropsychological measurements, event-related brain potentials (ERP), and electroencephalogram (EEG) at baseline and 8 weeks after fluoxetine treatment (MDD and AD-MDD groups).

The AD-MDD (n=17), MDD (n=14), AD (n=17), and control (n=17) cohorts were made up of men aged mean 43, 33, 44, and 37 years (P ≤.05). They had 2, 2, 1, and 0 previous depressive episodes (P ≤.01) respectively, and they started consuming alcohol at 15, 17, 15, and 17 years of age, respectively.

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Significant group differences were observed for ADS (F, 20.7; P ≤.01), HAMD (F, 59.1; P ≤.01), MADRS (F, 44.5; P ≤.01), BDI (F, 29.5; P ≤.01), and HAS (F, 29.3; P ≤.01) instruments.

Compared with controls, individuals with AD or AD-MDD had lower execution on logic, verbal, and visual tasks as well as slower processing speed in Diller’s Single Letter Cancellation Test (LCT) and performed more poorly on the California Verbal learning test. Patients with AD-MDD had the poorest performance in the memory test, Digits Symbols task, and LCT.

A significant stimulus-by-anterior-posterior-by-diagnosis interaction was observed during ERP assessment at baseline (F, 3.70; P <.009). Compared with controls, the AD, MDD, and AD-MDD groups had detriments in the amplitude of the parietal and frontal zones during low cognitive demand tasks.

The reaction time to infrequent stimulus during low cognitive demand was lowest for controls (mean, 467 ms), followed by MDD (mean, 479 ms), AD (mean, 481 ms), and AD-MDD (mean, 552 ms). The AD-MDD cohort did not display the anticipated Stroop effect.

After treatment, symptoms of depression and anxiety significantly improved.

At 8 weeks there were significant time (F, 5.37; P =.03), time-by-anterior-posterior (F, 17.6; P ≤.01), and time-by-anterior-posterior-by-lateral (F, 3.2; P =.045) effects during P200 ERP. For P300, time (F, 6.61; P ≤.01) and time-by-anterior-posterior-by-diagnosis (F, 0.83; P =.05) were significant. No significant effects were observed for N450 ERP in the post hoc analysis.

The major limitation of this study was the small sample size.

The study authors concluded, “The results of the neuropsychological evaluation and electrophysiological recordings do not support the notion that AD and MDD in comorbidity are merely the consequence of the sum of the negative contributions of the single clinical entities. More important, these findings could have encouraging clinical implications for alcohol disorders treatment, where a therapeutic intervention should consider the presence or absence of affective comorbidity. One can envision, for example, that an adequate neurocognitive adjustment might impinge on beneficial learning responses, promoting a better pharmacological adherence and psychotherapy attachment.”


Flores-Medina Y, Rodríguez-Agudelo Y, Bernal-Hernández J, Cruz-Fuentes CS. Cognitive impairment in the co-occurrence of alcohol dependence and major depression: neuropsychological assessment and event-related potentials analyses. Heliyon. 2022;8(7):e09899. doi:10.1016/j.heliyon.2022.e09899