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Recent-onset schizophrenia and adolescent cannabis use: MRI evidence for structural hyperconnectivity?

B. Peters, Lieuwe de Haan, E. Vlieger, Charles B.l.m. Majoie, Gerard J. den Heeten, Don H. Linszen

Psychopharmacology Bulletin August 12, 2025 DOI: 10.64719/pb.4310 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Case-control study Peer reviewed
Sample size 56
Population 35 male recent-onset schizophrenia patients (with and without cannabis use before age 17) and 21 matched healthy comparison men without illicit drug use
Measures diffusion tensor imaging (DTI)
Topics Cannabis
Key findings Patients with cannabis use before age 17 showed increased directional coherence in the bilateral uncinate fasciculus, anterior internal capsule, and frontal white matter compared with controls, while patients without early cannabis use showed no such abnormalities. The authors propose these patients may represent a subgroup with structural hyperconnectivity, in contrast with most DTI studies reporting hypoconnectivity in schizophrenia.

Abstract

There is growing evidence that brain white matter abnormalities are implicated in the pathophysiology of schizophrenia. Cannabis use is an independent risk factor for schizophrenia.We tested the hypothesis that cannabis use during early adolescence is associated with white matter abnormalities in schizophrenia patients. Thirtyfive male recent-onset schizophrenia patients, with and without a history of cannabis use before age 17, and twenty-one matched healthy comparison men without illicit drug use were assessed with diffusion tensor imaging (DTI).White matter regions of interest were examined in co-registered DTI images. Compared to controls, patients with cannabis use before age 17 showed increased directional coherence in the bilateral uncinate fasciculus, anterior internal capsule and frontal white matter. These abnormalities were absent in patients without cannabis use before age 17. The abnormalities were not related to lifetime doses of cannabis or other illicit drugs.We could not exclude confounding effects of other illicit drugs. Recent-onset schizophrenia patients with start of cannabis use during early adolescence use may represent a subgroup of schizophrenia patients with increased white matter directional coherence, which may reflect structural hyperconnectivity. This is in contrast with most DTI studies in schizophrenia, which have produced evidence for hypoconnectivity. Further studies are necessary to assess the effect of adolescent cannabis and other illicit drug use on brain white matter in schizophrenia.

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