Multimodal assessment of white matter microstructure in antipsychotic-naïve schizophrenia patients and confounding effects of recreational drug use
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Multimodal assessment of white matter microstructure in antipsychotic-naïve schizophrenia patients and confounding effects of recreational drug use. / Raghava, Jayachandra M.; Mandl, René C.W.; Nielsen, Mette Ø.; Fagerlund, Birgitte; Glenthøj, Birte Y.; Rostrup, Egill; Ebdrup, Bjørn H.
I: Brain Imaging and Behavior, Bind 15, 2021, s. 36–48.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Multimodal assessment of white matter microstructure in antipsychotic-naïve schizophrenia patients and confounding effects of recreational drug use
AU - Raghava, Jayachandra M.
AU - Mandl, René C.W.
AU - Nielsen, Mette Ø.
AU - Fagerlund, Birgitte
AU - Glenthøj, Birte Y.
AU - Rostrup, Egill
AU - Ebdrup, Bjørn H.
PY - 2021
Y1 - 2021
N2 - Cerebral white matter (WM) aberrations in schizophrenia have been linked to multiple neurobiological substrates but the underlying mechanisms remain unknown. Moreover, antipsychotic treatment and substance use constitute potential confounders. Multimodal studies using diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI) may provide deeper insight into the whole brain WM pathophysiology in schizophrenia. We combined DTI and MTI to investigate WM integrity in 51 antipsychotic-naïve, first-episode schizophrenia patients and 55 matched healthy controls, using 3 T magnetic resonance imaging (MRI). Psychopathology was assessed with the positive and negative syndrome scale (PANSS). A whole brain partial least squares correlation (PLSC) method was used to conjointly analyze DTI-derived measures (fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), mode of anisotropy (MO)) and the magnetization transfer ratio (MTR) to identify group differences, and associations with psychopathology. In secondary analyses, we excluded recreational substance users from both groups resulting in 34 patients and 51 healthy controls. The primary PLSC group difference analysis identified a significant pattern of lower FA, AD, MO and higher RD in patients (p = 0.04). This pattern suggests disorganized WM microstructure in patients. The secondary PLSC group difference analysis without recreational substance users revealed a significant pattern of lower FA and higher AD, RD, MO, MTR in patients (p = 0.04). This pattern in the substance free patients is consistent with higher extracellular free-water concentrations, which may reflect neuroinflammation. No significant associations with psychopathology were observed. Recreational substance use appears to be a confounding issue, which calls for attention in future WM studies.
AB - Cerebral white matter (WM) aberrations in schizophrenia have been linked to multiple neurobiological substrates but the underlying mechanisms remain unknown. Moreover, antipsychotic treatment and substance use constitute potential confounders. Multimodal studies using diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI) may provide deeper insight into the whole brain WM pathophysiology in schizophrenia. We combined DTI and MTI to investigate WM integrity in 51 antipsychotic-naïve, first-episode schizophrenia patients and 55 matched healthy controls, using 3 T magnetic resonance imaging (MRI). Psychopathology was assessed with the positive and negative syndrome scale (PANSS). A whole brain partial least squares correlation (PLSC) method was used to conjointly analyze DTI-derived measures (fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), mode of anisotropy (MO)) and the magnetization transfer ratio (MTR) to identify group differences, and associations with psychopathology. In secondary analyses, we excluded recreational substance users from both groups resulting in 34 patients and 51 healthy controls. The primary PLSC group difference analysis identified a significant pattern of lower FA, AD, MO and higher RD in patients (p = 0.04). This pattern suggests disorganized WM microstructure in patients. The secondary PLSC group difference analysis without recreational substance users revealed a significant pattern of lower FA and higher AD, RD, MO, MTR in patients (p = 0.04). This pattern in the substance free patients is consistent with higher extracellular free-water concentrations, which may reflect neuroinflammation. No significant associations with psychopathology were observed. Recreational substance use appears to be a confounding issue, which calls for attention in future WM studies.
KW - Antipsychotic-naïve
KW - Diffusion tensor imaging
KW - Magnetization transfer
KW - MRI
KW - Schizophrenia
KW - White matter
U2 - 10.1007/s11682-019-00230-4
DO - 10.1007/s11682-019-00230-4
M3 - Journal article
C2 - 31909444
AN - SCOPUS:85077581036
VL - 15
SP - 36
EP - 48
JO - Brain Imaging and Behavior
JF - Brain Imaging and Behavior
SN - 1931-7557
ER -
ID: 250430647