MRI brain volume abnormalities in young, nonpsychotic relatives of schizophrenia probands are associated with subsequent prodromal symptoms

Abstract

Schizophrenia is characterized by subtle but well-replicated total and regional (frontal and temporal) brain tissue volume deficits. Studies of individuals at-risk for developing schizophrenia suggest that the onset of brain volume decrement may closely pre-date overt manifestations of schizophrenia, making brain volume abnormalities potential predictors for early identification. In an ongoing longitudinal morphometric MRI study of young, nonpsychotic first-or second-degree relatives of schizophrenia probands, we compared brain volumes in 46 relatives who are still within age range for developing schizophrenia against comparison groups of 46 schizophrenia patients and 46 healthy volunteers without family history of schizophrenia. Relatives had similar brain volume abnormalities as schizophrenia patients albeit less severe. Relatives had significantly larger whole brain, frontal, temporal and parietal gray matter (GM) volumes than patients. Relatives also had significantly smaller frontal GM volumes than healthy volunteers. Both relatives and patients had significantly larger whole brain WM (specifically parietal WM) volumes compared to healthy volunteers. Abnormally greater WM volumes in relatives and patients are suggestive of genetically-mediated dysmaturation of the age-expected myelination during adolescence through mid adulthood. On prodromal symptoms assessed in relatives one year after MRI brain scans, initial GM deficits as well as larger WM volumes correlated significantly with greater severity of subsequent prodromal symptoms. Together with previous genetic high-risk studies of adolescent or young adult relatives, these findings indicate that premorbid MRI brain abnormalities may be of predictive value for the early identification of schizophrenia.

Relationship between prefrontal gray matter volumes and working memory performance in schizophrenia: A family study

“…We also found nonpsychotic relatives of schizophrenia patients showed smaller prefrontal grey matter volumes than controls, reaching significance for the superior and inferior regions. Thus, aspects of reduced prefrontal gray matter volume may reflect genetic liability for schizophrenia (Bhojraj et al, 2011a; Cannon et al, 1998; Ho, 2007; Rosso et al, 2010); however, this is not a wholly consistent finding (Goghari et al, 2007a, b; Goldman et al, 2009). …”

COMT, neuropsychological function and brain structure in schizophrenia: a systematic review and neurobiological interpretation

“…120,121 Moreover, there is evidence of a negative correlation between grey matter volume and increasing genetic risk for schizophrenia. 122 Presence in unaffected relatives: Relatives of patients with schizophrenia show grey matter volume reductions in the total frontal lobe, 120 prefrontal cortex 123 and anterior cingulate gyrus 110,115,121 in comparison to healthy individuals. However, this finding has not been replicated in other studies.…”

Magnetic Resonance Imaging and Its Usage in Representative Areas of Neurobiological Research

“…In children with autism, an abnormal increase in white matter volume has often been associated with poor motor skills in behavioral tests [55] . Such increases in white matter as seen by MRI have also been found in the brains of schizophrenic patients and their relatives, which may be the result of dysmyelination between the stages of adolescence and adulthood [56] . Effects of prenatal maternal intake of drugs on the fetal or neonatal brain (whether of abusive agents or potentially damaging therapeutic drugs) have been outlined by MRI by quantitation of gray matter in the basal ganglia, hypothalamus and the frontal cortex [57][58][59] .…”