White Matter Abnormalities and Cognitive Impairment in Early-Onset Schizophrenia-Spectrum Disorders

Abstract

OBJECTIVE To characterize white matter abnormalities in adolescents with early onset schizophrenia (EOS) relative to three comparison groups (adolescents at clinical high risk for developing schizophrenia [CHR], adolescents with cannabis use disorder [CUD], and healthy controls [HC]), and to identify neurocognitive correlates of white matter abnormalities in EOS. METHOD We used diffusion tensor imaging and tractography methods to examine fractional anisotropy (FA) of the cingulum bundle, superior longitudinal fasciculus, corticospinal tract (CST), inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF), and uncinate fasciculus in adolescents with EOS (n=55), CHR (n=21), CUD (n=31), and HC (n=55). FA in tracts that were significantly altered in EOS was correlated with neurocognitive performance. RESULTS EOS and CHR groups had significantly lower FA than HC in four tracts: bilateral CST, left ILF, and left IFOF. CUD had lower FA than HC in left IFOF. Lower FA in left IFOF and left ILF predicted worse neurocognitive performance in EOS. CONCLUSIONS This study identified left ILF and left IFOF as possible biomarkers of vulnerability for developing schizophrenia. Lower FA in these tracts may disrupt functioning of ventral visual and language streams, producing domain-specific neurocognitive deficits that interfere with higher order cognitive abilities.

Frontal fasciculi and psychotic symptoms in antipsychotic-naive patients with schizophrenia before and after 6 weeks of selective dopamine D2/3 receptor blockade

“…47 Our observation of FA reductions in the right CT is in line with findings in patients with early-onset schizophrenia and in individuals at high risk for psychosis. 48 However, deficits in this region are less frequently observed in later stages of illness, suggesting that FA changes in the CT may be more prominent at the time of illness onset.…”

Prefrontal cortex and the dysconnectivity hypothesis of schizophrenia

“…Decreased FA in the left IFOF predicts worse neurocognitive performance both in never-medicated chronic schizophrenia [46] and in adolescents with earlyonset schizophrenia [47] , as well as predicting empathic impairments in patients with schizophrenia [48] . Other whitematter fiber tracts related to the PFC in schizophrenia include the anterior limb of the internal capsule, the medial portion of which includes the anterior thalamic radiation linking the thalamus and the PFC [49,50] , the genu of the corpus callosum linking the bilateral PFCs [51,52] , and deep white matter within the PFC [53] .…”

White matter microstructural deficits in 22q11.2 deletion syndrome

“…DTI facilitates the in vivo study of brain white matter (WM) microstructure (Mori et al, 2008), and typical DTI measures include fractional anisotropy (FA), mean (MD), axial (AD) and radial diffusivity (RD). Alterations in these metrics are reported in 22q11DS (Barnea-Goraly et al, 2003; da Silva Alves et al, 2011; Deng et al, 2015; Kates et al, 2015; Kikinis et al, 2012; Martin et al, 2014; Ottet et al, 2013; Padula et al, 2015; Radoeva et al, 2012; Scariati et al, 2016; Sundram et al, 2010; Villalon-Reina et al, 2013), and some of the patterns observed are similar to deficits in SZ (Kyriakopoulos et al, 2008; Roalf et al, 2015; Thomason and Thompson, 2011), adolescents with psychosis (Davenport et al, 2010; White et al, 2007) and youth at risk for developing psychosis (Epstein et al, 2013; Lee et al, 2013). In contrast to structural gray matter findings, DTI results in 22q11DS are more inconsistent.…”

“…Patients with 22q11DS who develop schizophrenia have similar symptoms compared to patients with idiopathic schizophrenia (Murphy et al, 1999). Indeed, both 22q11DS and idiopathic schizophrenia share brain morphological changes (Eliez et al, 2001; Eliez et al, 2000; Glahn et al, 2008; Jalbrzikowski et al, 2013; Schaer et al, 2006), including alterations in WM structure and organization (Asami et al, 2014; Epstein et al, 2013; Kyriakopoulos et al, 2008; Lee et al, 2013; Roalf et al, 2013b). Thus, direct comparison of WM differences between 22q11DS patients with and without psychotic symptoms may elucidate deficits specific to psychosis.…”