White matter abnormalities in schizophrenia and schizotypal personality disorder

Abstract

Prior diffusion tensor imaging (DTI) studies examining schizotypal personality disorder (SPD) and schizophrenia, separately have shown that compared with healthy controls (HCs), patients show frontotemporal white matter (WM) abnormalities. This is the first DTI study to directly compare WM tract coherence with tractography and fractional anisotropy (FA) across the schizophrenia spectrum in a large sample of demographically matched HCs (n = 55), medication-naive SPD patients (n = 49), and unmedicated/never-medicated schizophrenia patients (n = 22) to determine whether (a) frontal-striatal-temporal WM tract abnormalities in schizophrenia are similar to, or distinct from those observed in SPD; and (b) WM tract abnormalities are associated with clinical symptom severity indicating a common underlying pathology across the spectrum. Compared with both the HC and SPD groups, schizophrenia patients showed WM abnormalities, as indexed by lower FA in the temporal lobe (inferior longitudinal fasciculus) and cingulum regions. SPD patients showed lower FA in the corpus callosum genu compared with the HC group, but this regional abnormality was more widespread in schizophrenia patients. Across the schizophrenia spectrum, greater WM disruptions were associated with greater symptom severity. Overall, frontal-striatal-temporal WM dysconnectivity is attenuated in SPD compared with schizophrenia patients and may mitigate the emergence of psychosis.

Keywords: DTI; MRI; cingulum; genu; inferior longitudinal fasciculus; psychosis; schizophrenia; schizotypal personality disorder; white matter.

Fig. 1.

Tract-based spatial statistics maps are shown comparing the 2 patient groups with the healthy control (HC) group. Compared with HCs, schizophrenia patients showed more marked white matter abnormalities in frontal, temporal, and frontal-striatal regions. In contrast, the schizotypal personality disorder (SPD) group only showed significantly reduced fractional anisotropy (FA) in the frontal lobe region (corpus callosum genu) and it was less marked than in the schizophrenia group. Note: the left hemisphere is shown on the right side of the images.

Fig. 2.

Compared with both the healthy control and schizotypal personality disorder groups, the schizophrenia patients showed significantly lower fractional anisotropy (FA) in the cingulum and inferior longitudinal fasciculus (ILF) and this was more marked in the left hemisphere, diagnostic group × white matter tract × hemisphere interaction, F[4,244] = 3.09, P < .02, Wilks.

Fig. 3.

Averaged across white matter tracts (CB, ILF, and ALIC), the schizophrenia patients showed lower fractional anisotropy (FA) in the left hemisphere compared with both the healthy control and schizotypal personality disorder (SPD) groups, diagnostic group × hemisphere interaction, F[2,123] = 5.79, P < .01, Wilks.

Fig. 4.

Scatterplots are shown for the relationship between fractional anisotropy (FA) in white matter tracts and clinical symptom severity. Among the schizophrenia patients, lower FA in the genu (top) and left inferior longitudinal fasiculus (middle) was associated with greater symptom severity measured with the 18-item BPRS. Among the schizotypal personality disorder (SPD) patients (bottom), lower FA in the genu was also associated with greater symptom severity (measured with a total severity score for the 9 DSM-IV criteria for SPD).