Clinical and cognitive outcomes following gamma knife capsulotomy in treatment-resistant obsessive–compulsive disorder

Background: Treatment-resistant obsessive–compulsive disorder (OCD) is associated with substantial functional impairment and limited response to conventional pharmacological and psychotherapeutic interventions (1). For a subset of patients, neurosurgical approaches such as Gamma Knife capsulotomy represent a potential therapeutic option (2). While previous studies have demonstrated clinically meaningful symptom reduction following capsulotomy, concerns remain regarding possible adverse cognitive effects (2). Furthermore, the extent to which different cognitive domains are affected following this intervention remains insufficiently characterized.

Aims: To evaluate clinical outcomes and changes in cognitive functioning in patients with treatment-resistant OCD following Gamma Knife capsulotomy at 6-month follow-up.

Methods: This longitudinal observational study included 21 patients with treatment-resistant OCD undergoing bilateral anterior capsulotomy using Gamma Knife radiosurgery. Two 4-mm isocenters were placed at the mid-putaminal level of the anterior limb of the internal capsule bilaterally (maximum dose 140–180 Gy). Clinical assessments were conducted at baseline and 6 months post-intervention. Symptom severity was assessed using the Yale–Brown Obsessive Compulsive Scale (Y-BOCS), Hamilton Anxiety Rating Scale (HAM-A), and Hamilton Depression Rating Scale (HAM-D). Cognitive performance was evaluated across attention, executive functioning, and planning domains using the Stroop Test, Wisconsin Card Sorting Test (WCST), and Tower of Hanoi (TOH). Given the non-normal distribution of several variables, changes over time were analysed using Wilcoxon signed-rank tests, with effect sizes calculated as r. Associations between clinical and cognitive changes were explored using Spearman correlation analyses.

Results: The median age of the patients was 32 years (IQR 27–47), and the median duration of illness was 15 years (IQR 12–18). Y-BOCS scores significantly decreased at 6-month follow-up (Z = −4.03, p < 0.001, r = 0.88). Treatment response (≥35% reduction) was observed in 66.7% of patients, with all patients demonstrating some degree of symptom improvement. Anxiety and depressive symptoms also decreased significantly, as reflected by reductions in HAM-A (Z = −3.73, p < 0.001, r = 0.81) and HAM-D (Z = −3.75, p < 0.001, r = 0.82). Cognitive performance remained stable in attention-related domains, with no significant change in Stroop performance (Z = −0.37, p = 0.715, r = 0.08). In contrast, consistent improvements were observed in executive functioning, as indicated by reductions in perseverative errors (Z = −3.61, p < 0.001, r = 0.79) and perseverative error rates (Z = −2.73, p = 0.006, r = 0.59) on the WCST. Planning and problem-solving abilities also improved, with decreased deviation from optimal solutions on the TOH (Z = −3.56, p < 0.001, r = 0.78).

Conclusions: Gamma Knife capsulotomy was associated with significant clinical improvement in patients with treatment-resistant OCD without evidence of cognitive deterioration over a 6-month period. Improvements were observed in executive functioning and planning domains, suggesting that this intervention may have differential effects across cognitive systems. These findings support Gamma Knife capsulotomy as an effective and cognitively safe intervention in carefully selected patients, although confirmation in larger controlled studies is required.

References

1-McLaughlin, N.C.R., Magnotti, J.F., Banks, G.P. et al. Gamma knife capsulotomy for intractable OCD: Neuroimage analysis of lesion size, location, and clinical response. Transl Psychiatry 13, 134 (2023). https://doi.org/10.1038/s41398-023-02425-2 2- Zaed, I., Roumy, LG., Lozito, A. et al. Gamma Knife Surgery (GKS) for the Treatment of Obsessive-Compulsive Disorder (OCD) Refractory to Pharmacological Therapy: State of the Art and Review of the Literature. SN Compr. Clin. Med. 1, 944–951 (2019). https://doi.org/10.1007/s42399-019-00141-x