Changes in White Matter Organization in Adolescent Offspring of Schizophrenia Patients

Abstract

Schizophrenia is associated with frontostriatal network impairments underlying clinical and cognitive symptoms. We previously found disruptions in anatomical pathways, including the tract connecting the left nucleus accumbens and left dorsolateral prefrontal cortex (DLPFC). Similar deficits are observed in unaffected siblings of schizophrenia patients, indicating that these deficits are linked to a genetic vulnerability for the disorder. Frontostriatal tract disruptions may arise during adolescence, preceding the clinical manifestation of the disorder. However, to date, no studies have been performed to investigate frontostriatal tract connections in adolescents who are at increased familial risk for schizophrenia. In this study, we investigate the impact of familial risk on frontostriatal tract connections using diffusion tensor imaging in 27 adolescent offspring of schizophrenia patients and 32 matched control adolescents, aged 10-18 years. Mean fractional anisotropy (FA) was calculated for the tracts connecting the striatum (caudate nucleus, putamen, nucleus accumbens) and frontal cortex regions (DLPFC, medial orbital frontal cortex, inferior frontal gyrus). As expected, based on siblings data, we found an impact of familial risk on frontostriatal development: schizophrenia offspring showed increased FA in the tracts connecting nucleus accumbens and DLPFC as compared with control adolescents. Moreover, while FA increased across age in control adolescents, it did not in schizophrenia offspring. We did not find differences in FA in other frontostriatal tracts. These results indicate altered development of white matter in subjects who are at familial risk for schizophrenia and may precede frontostriatal white matter alterations in adult schizophrenia patients and siblings.

White matter abnormalities in 22q11.2 deletion syndrome patients showing cognitive decline

“…Furthermore, our findings are consistent with several studies in UHR samples reporting increased FA compared to healthy controls (Hoptman et al 2008; Bloemen et al 2010; O'Hanlon et al 2015; de Leeuw et al 2017). Specifically, we found that FA was both globally and locally increased and that local WM regions overlap with WM tracts found to be affected in schizophrenia and individuals with 22q11DS and psychosis.…”

Towards an integrated account of the development of self-regulation from a neurocognitive perspective: A framework for current and future longitudinal multi-modal investigations

“…In the brain, the further development of self-regulation, and thus the rise of strategic control, has been theorized to co-occur with the vast improvement of the quality of connections between cortical and subcortical regions ( Casey et al, 2019 ; Cools, 2011 ; Padmanabhan et al, 2011 ; Vink et al, 2014b ). This is facilitated at the onset of adolescence by the increase in myelination of white-matter tracts connecting these regions ( Asato et al, 2010 ; De Leeuw et al, 2017 ; Ladouceur et al, 2012 ), allowing for faster and more precise neural signalling. Such anatomical changes directly affect brain function and hence behaviours linked to improvements in self-regulation.…”

Emerging psychopathology and clinical staging in adolescent offspring of parents with bipolar disorder or schizophrenia—A longitudinal study

“…In total, 58 SZo (38 families), 94 BDo (60 families), and 56 Co (34 families), aged 8–18 years old, were included between 2010 and 2017. Data at baseline has been partly presented before 33–35 . Figure S1 presents detailed recruitment and drop‐out characteristics.…”

“…Data at baseline has been partly presented before. [33][34][35] Figure S1 presents detailed recruitment and drop-out characteristics. Overall, 88.5% of the offspring participated at 4-year follow-up: 51 SZo (87.9%), 84 BDo (89.4%), and 49 Co (87.5%).…”