Altered Cellular White Matter But Not Extracellular Free Water on Diffusion MRI in Individuals at Clinical High Risk for Psychosis.
OBJECTIVE
Detecting brain abnormalities in clinical high-risk populations before the onset of psychosis is important for tracking pathological pathways and for identifying possible intervention strategies that may impede or prevent the onset of psychotic disorders. Co-occurring cellular and extracellular white matter alterations have previously been implicated after a first psychotic episode. The authors investigated whether or not cellular and extracellular alterations are already present in a predominantly medication-naive cohort of clinical high-risk individuals experiencing attenuated psychotic symptoms.


METHODS
Fifty individuals at clinical high risk, of whom 40 were never medicated, were compared with 50 healthy control subjects, group-matched for age, gender, and parental socioeconomic status. 3-T multishell diffusion MRI data were obtained to estimate free-water imaging white matter measures, including fractional anisotropy of cellular tissue (FAT) and the volume fraction of extracellular free water (FW).


RESULTS
Significantly lower FAT was observed in the clinical high-risk group compared with the healthy control group, but no statistically significant FW alterations were observed between groups. Lower FAT in the clinical high-risk group was significantly associated with a decline in Global Assessment of Functioning Scale (GAF) score compared with highest GAF score in the previous 12 months.


CONCLUSIONS
Cellular but not extracellular alterations characterized the clinical high-risk group, especially in those who experienced a decline in functioning. These cellular changes suggest an early deficit that possibly reflects a predisposition to develop attenuated psychotic symptoms. In contrast, extracellular alterations were not observed in this clinical high-risk sample, suggesting that previously reported extracellular abnormalities may reflect an acute response to psychosis, which plays a more prominent role closer to or at onset of psychosis.
['Tang|Yingying|Y|', 'Pasternak|Ofer|O|', 'Kubicki|Marek|M|', 'Rathi|Yogesh|Y|', 'Zhang|Tianhong|T|', 'Wang|Junjie|J|', 'Li|Huijun|H|', 'Woodberry|Kristen A|KA|', 'Xu|Lihua|L|', 'Qian|Zhenying|Z|', 'Zhu|Anni|A|', 'Whitfield-Gabrieli|Susan|S|', 'Keshavan|Matcheri S|MS|', 'Niznikiewicz|Margaret|M|', 'Stone|William S|WS|', 'McCarley|Robert W|RW|', 'Shenton|Martha E|ME|', 'Wang|Jijun|J|', 'Seidman|Larry J|LJ|']
D001921:Brain D016022:Case-Control Studies D038524:Diffusion Magnetic Resonance Imaging D005110:Extracellular Space D005260:Female D006801:Humans D008297:Male D059906:Neuroimaging D011618:Psychotic Disorders D012307:Risk Factors D014867:Water D066127:White Matter D055815:Young Adult
White Matter Free Water Psychosis Clinical High-Risk Diffusion Tensor Imaging Neurodevelopment