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

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.

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.

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).

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.