Abstract
White matter (WM) abnormalities are commonly reported in psychiatric disorders. Whether peripartum insufficiencies in brain oxygenation, known as birth asphyxia, are associated with WM of patients with severe mental disorders is unclear. To examine the association between birth asphyxia and WM in adult patients with schizophrenia and bipolar disorders (BDs) compared with healthy adults. In this case-control study, all individuals participating in the ongoing Thematically Organized Psychosis project were linked to the Medical Birth Registry of Norway (MBRN), where a subset of 271 patients (case group) and 529 healthy individuals (control group) had undergone diffusion-weighted imaging (DWI). Statistical analyses were performed from June 16, 2020, to March 9, 2021. Birth asphyxia was defined based on measures from standardized reporting at birth in the MBRN. Associations between birth asphyxia and WM regions of interest diffusion metrics, ie, fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD), were compared between groups using analysis of covariance, adjusted for age, age squared, and sex. Of the 850 adults included in the study, 271 were in the case group (140 [52%] female individuals; mean [SD] age, 28.64 [7.43] years) and 579 were in the control group (245 [42%] female individuals; mean [SD] age, 33.54 [8.31] years). Birth asphyxia measures were identified in 15% to 16% of participants, independent of group. The posterior limb of the internal capsule (PLIC) showed a significant diagnostic group × birth asphyxia interaction (F(1, 843) = 11.46; P = .001), reflecting a stronger association between birth asphyxia and FA in the case group than the control group. RD, but not AD, also displayed a significant diagnostic group × birth asphyxia interaction (F(1, 843) = 9.28; P = .002) in the PLIC, with higher values in patients with birth asphyxia and similar effect sizes as observed for FA. In this case-control study, abnormalities in the PLIC of adult patients with birth asphyxia may suggest a greater susceptibility to hypoxia in patients with severe mental illness, which could lead to myelin damage or impeded brain development. Echoing recent early-stage schizophrenia studies, abnormalities of the PLIC are relevant to psychiatric disorders, as the PLIC contains important WM brain pathways associated with language, cognitive function, and sensory function, which are impaired in schizophrenia and BDs.
Highlights
radial diffusivity (RD), but not axial diffusivity (AD), displayed a significant diagnostic group × birth asphyxia interaction (F(1, 843) = 9.28; P = .002) in the posterior limb of the internal capsule (PLIC), with higher values in patients with birth asphyxia and similar effect sizes as observed for fractional anisotropy (FA). In this case-control study, abnormalities in the PLIC of adult patients with birth asphyxia may suggest a greater susceptibility to hypoxia in patients with severe mental illness, which could lead to myelin damage or impeded brain development
Echoing recent early-stage schizophrenia studies, abnormalities of the PLIC are relevant to psychiatric disorders, as the PLIC contains important white matter (WM) brain pathways associated with language, cognitive function, and sensory function, which are impaired in schizophrenia and bipolar disorder (BD)
Clinical and Demographic Variables Of the 850 adults included in the study, 271 were in the case group (140 [52%] female individuals; mean [showed higher mean (SD)] age, 28.64 [7.43] years) and 579 were in the control group (245 [42%] female individuals; mean [SD] age, 33.54 [8.31] years)
Summary
Widespread white matter (WM) abnormalities in schizophrenia and bipolar disorder (BD) support the dysconnectivity hypothesis, which involves dysfunctional communication between brain regions[1,2,3,4] and disturbances in WM microstructural organization.[5,6] oligodendrocyte and myelin abnormalities in patients with schizophrenia and BD are commonly reported.[7,8,9] Since premyelinating oligodendrocytes are key cellular targets in hypoxic brain injury,[10,11] previous findings of WM abnormalities in patients might be partly accounted for by having experienced birth asphyxia. Birth asphyxia is a condition in which affected newborns experience a peripartum deficiency in brain oxygenation. This can cause hypoxic injury and, in severe cases, lead to permanent brain damage or death in offspring. A history of severe birth asphyxia often leads to cerebral palsy with or without cognitive deficit and has been associated with increased risk of developing schizophrenia (odds ratio, 4.4)[13] and BD (hazard ratio, 5.3),[14] but so have other serious obstetric complications (OCs).[15]
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