News|Articles|September 8, 2026

Isotretinoin for Adolescent Acne Shows No Cognitive Impairment Despite Rise in Internalizing Symptoms

Author(s)Marie Bosslett, Assistant Editor

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Key Takeaways

A 3-month isotretinoin course reduced acne severity without measurable deterioration in memory, learning, or executive performance on neuropsychological testing in adolescents.
Internalizing symptom scores increased on standardized scales, but changes were modest, did not meet diagnostic thresholds, and were not accompanied by suicidality or emergent psychiatric diagnoses.
Causal modeling suggested increased internalizing symptoms after covariate adjustment in imputed analyses, whereas completer-only results were nonsignificant, implicating attrition and missingness.
Peripheral inflammatory indices (NLR, PLR) were not associated with psychiatric or cognitive outcomes, consistent with limited relevance of systemic markers to CNS-related symptomatology.
Interpretability is constrained by single-arm design, high loss to follow-up, exclusion of adolescents with active psychopathology, and potential confounding from retesting effects and developmental maturation.

Study tracks teens on isotretinoin, finding stable cognition but modest rises in depression and anxiety symptoms, reinforcing the need for ongoing mental health monitoring.

A new prospective cohort study found no evidence that 3 months of isotretinoin treatment impaired neuropsychological functioning in adolescents with severe or treatment-resistant acne vulgaris, although measures of internalizing symptoms, including depression and anxiety-related symptoms, increased during treatment.¹ The findings support continued psychiatric monitoring during isotretinoin therapy while suggesting that cognitive functioning was not adversely affected in the study population.

Study Design

The single-center study included 78 adolescents aged 13 to 18 years, 62.8% of whom were female. Most participants had nodulocystic or papulopustular acne, with the majority classified as having severe to very severe disease. Participants underwent psychiatric and neuropsychological assessments before starting isotretinoin and after 3 months of treatment. Psychiatric status was evaluated using the Kiddie Schedule for Affective Disorders and Schizophrenia and the Revised Children’s Anxiety and Depression Scale-Child Version.² Neuropsychological testing included measures of interference control, memory, and learning. Acne severity and the inflammatory markers neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were also assessed.

Among the 78 enrolled participants, 31 completed the 3-month follow-up assessment. Isotretinoin treatment was associated with a significant reduction in acne severity. Neuropsychological testing did not demonstrate a decline in overall performance. In fact, measures of resistance to interference showed improvement, although this finding did not remain statistically significant among treatment completers after correction for multiple comparisons. The authors noted that potential explanations for the improvement included reduced acne-related stress, practice effects from repeated testing, and cognitive maturation.

Psychiatric Outcomes and Internalizing Symptoms

Psychiatric outcomes showed a different pattern. In the imputed analysis, scores for social phobia, panic disorder, and major depressive disorder increased significantly during treatment. Among treatment completers, major depressive disorder scores increased before correction for multiple comparisons, but this finding did not retain significance after correction. The authors emphasized that the increases represented modest changes in mean symptom scores rather than transitions across established clinical thresholds. No participant developed a new psychiatric diagnosis on the structured interview, reported suicidal ideation or self-harm behavior, or required urgent psychiatric intervention during the study period.

Causal analyses using a directed acyclic graph found a significant increase in internalizing symptoms in the imputed dataset after adjustment for acne severity, acne duration, age, sex, and BMI. However, the effect was not significant among treatment completers, raising the possibility that missing data or selective loss to follow-up influenced the findings. No consistent neuropsychological decline was identified, while a potential improvement in interference control was observed.

Data Limitations and Monitoring Recommendations

The study also found no significant associations between NLR or PLR and psychiatric or neuropsychological outcomes. The authors noted that peripheral inflammatory markers may not reflect inflammation relevant to cognitive or psychiatric functioning.

The findings should be interpreted cautiously because the study lacked a control group, had substantial loss to follow-up, excluded adolescents with current psychopathology, and may have been underpowered to evaluate inflammatory markers. The authors also noted that repeated testing, cognitive maturation, changes in acne severity, and unmeasured factors could have influenced outcomes.

Overall, 3 months of isotretinoin treatment was not associated with measurable neuropsychological impairment in this adolescent cohort. However, the increase in internalizing symptoms supports monitoring psychiatric symptoms during treatment and informing adolescents and their parents about potential mood changes.

References

1. Genişoğlu, HBO, Akıncı B, Sezer T, et al. Neuropsychological and Psychiatric Outcomes During Isotretinoin Treatment in Adolescents With Acne Vulgaris: A Single-Arm Prospective Cohort Study. Dermatologic Therapy, 2026, 3463004, 10 pages, 2026. doi:10.1155/dth/3463004

2. Kaufman J, Birmaher B, Brent D, et al. Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry. 1997;36(7):980-988. doi:10.1097/00004583-199707000-00021