Striatal and white matter volumes in chronic ketamine users with or without recent regular stimulant use.

Background: Previous studies found enlarged striatum and white matter in those with stimulants use disorders. Whether primarily ketamine users (Primarily-K) and ketamine users who co-used stimulants and other substances (K+PolyS) have abnormal brain volumes is unknown. This study aims to evaluate possible brain structural abnormalities, cognitive function and depressive symptoms, between Primarily-K and K+PolyS users.

Methods: Striatal and white matter volumes were automatically segmented in 39 Primarily-K users, 41 K+PolyS users and 46 non-drug users (ND). Cognitive performance in 7 neurocognitive domains and depressive symptoms were also evaluated.

Results: Ketamine users had larger caudates than ND-controls (Right: 1-way-ANCOVA-p=0.035; K+PolyS vs. ND, p=0.030; Linear trend for K+PolyS>Primarily-K>ND, p=0.011; Left: 1-way-ANCOVA-p=0.047, Primarily-K vs. ND p=0.051) and larger total white matter (1-way ANCOVA-p=0.009, Poly+K vs. Primarily-K, p=0.05; Poly+K vs. ND p=0.011; Linear trend for K+PolyS>Primarily-K >ND, p=0.004). Across all ketamine users, they performed poorer on Arithmetic, learning and memory tasks, and were more depressed than Non-users (p<0.001 to p=0.001). Greater lifetime ketamine usage correlated with more depressive symptoms (r=0.27, p=0.008). Larger white matter correlated with better learning across all participants (r=0.21, p=0.019), while larger right caudate correlated with lower depression scores in ketamine users (r=-0.28, p=0.013).

Conclusion: Ketamine users had larger caudates and total white matter than ND-controls. The even larger white matter in K+PolyS users suggests additive effects from co-use of ketamine and stimulants. However, across the ketamine users, since greater volumes were associated with better learning and less depressive symptom, the enlarged caudates and white matter might represent a compensatory response.