Effects of age on white matter integrity and negative symptoms in schizophrenia

Abstract

The current study examined the relationship between white matter integrity as indexed by diffusion tensor imaging and negative symptom severity in schizophrenia. The current study included statistical controls for age effects on the relationship of interest, a major weakness of the existing literature on the subject. Participants included 59 chronic schizophrenia patients, and 31 first-episode schizophrenia patients. Diffusion-weighted neuroimaging was used to calculate fractional anisotropy (FA) in each major brain region (frontal, temporal, parietal, and occipital lobes). Negative symptoms were measured using the Scale for the Assessment of Negative Symptoms (SANS) in all schizophrenia patients. Significant bivariate correlations were observed between global SANS scores and global FA, as well as in most brain regions. These relationships appeared to be driven by SANS items measuring facial expressiveness, poor eye contact, affective flattening , inappropriate affect, poverty of speech, poverty of speech content, alogia, and avolition. However, upon addition of age as a covariate, the observed relationships became non-significant. Further analysis revealed very strong age effects on both FA and SANS scores in the current sample. The findings of this study refute previous reports of significant relationships between DTI variables and negative symptoms in schizophrenia, and they suggest an important confounding variable to be considered in future studies in this population.

Integrity of the arcuate fasciculus in patients with schizophrenia with auditory verbal hallucinations: A DTI-tractography study

“…The observed increase in FA within the left arcuate fasciculus seems to be specifically associated with AVH severity since no significant relationship was observed between FA (right and left) and total PANSS score. We ensured that our results were not influenced by individual characteristics that are known to influence FA values in patients with schizophrenia by introducing age (Mori et al, 2007, Voineskos et al, 2010, Bijanki et al, 2015) as a covariate in our analysis. Moreover, we ensured that AVH + and no-AVH groups were not different for illness duration, gender and medication (Minami et al, 2003, Okugawa et al, 2004, Takase et al, 2004).…”

“…As a trend toward a significant difference in age was observed between groups (p = 0.06) and since age is known to influence FA values (Voineskos et al, 2010, Bijanki et al, 2015), age was added as covariate in the analysis. For each hemisphere, FA values of the arcuate fasciculus were compared between AVH + and no-AVH patients using an ANCOVA with age as covariate.…”

White matter microstructure in schizophrenia: Associations to neurocognition and clinical symptomatology

“…In general, negative symptoms, in addition to age, are considered to be the best predictors of white matter change in schizophrenia (Mitelman et al, 2007; Wolkin et al, 2003). However, a recent finding suggests that age may be the driving force of these effects (Bijanki et al, 2014). Negative symptoms in schizophrenia are related to structural brain abnormalities (Sigmundsson et al, 2001), including deficits in WM regions (Nestor et al, 2008; Skelly et al, 2008) and lower FA values (Mitelman et al, 2009; Mitelman et al, 2006; Sigmundsson et al, 2001; Wible et al, 2001).…”

A combined VBM and DTI study of schizophrenia: bilateral decreased insula volume and cerebral white matter disintegrity corresponding to subinsular white matter projections unlinked to clinical symptomatology

“…Most of the DTI studies focused on FA values conducting voxel-based analysis of FA only (30,31). In whole brain analysis studies, even early cases of schizophrenia showed bilaterally decreased FA values, which may be associated with illness duration (32,33).…”