Clinical and neuropsychological correlates of white matter abnormalities in recent onset schizophrenia

Philip R. Szeszko, Delbert G. Robinson, Manzar Ashtari, Joshua Vogel, Julia Betensky, Serge Sevy, Babak A. Ardekani, Todd Lencz, Anil K. Malhotra, Joanne McCormack, Rachel Miller, Kelvin O. Lim, Handan Gunduz-Bruce, John M. Kane, Robert M. Bilder

Research output: Contribution to journalArticlepeer-review

186 Scopus citations


The objective of this study was to investigate the clinical and neuropsychological correlates of white matter abnormalities in patients with schizophrenia studied early in the course of illness. A total of 33 (21 male/12 female) patients with recent onset schizophrenia and 30 (18 male/12 female) healthy volunteers completed structural and diffusion tensor imaging exams. Patients also received clinical and neuropsychological assessments. Fractional anisotropy (FA) maps were compared between groups in the white matter using a voxelwise analysis following intersubject registration to Talairach space and correlated with functional indices. Compared to healthy volunteers, patients demonstrated significantly (p<0.001, cluster size ≥100) lower FA within temporal lobe white matter regions corresponding approximately to the right and left uncinate fasciculus, left inferior fronto-occipital fasciculus, and left superior longitudinal fasciculus. There were no areas of significantly higher FA in patients compared to healthy volunteers. Lower FA in the bilateral uncinate fasciculus correlated significantly with greater severity of negative symptoms (alogia and affective flattening), and worse verbal learning/memory functioning. In addition, higher FA in the inferior fronto-occipital fasciculus correlated significantly with greater severity of delusions and hallucinations. White matter abnormalities are evident in patients with schizophrenia early in the course of illness, appearing most robust in left temporal regions. These abnormalities have clinical and neuropsychological correlates, which may be useful in further characterizing structure-function relations in schizophrenia and constraining neurobiological models of the disorder.

Original languageEnglish (US)
Pages (from-to)976-984
Number of pages9
Issue number5
StatePublished - Apr 2008

Bibliographical note

Funding Information:
This work was supported in part by grants from NARSAD (PRS) and the National Institute of Mental Health to Dr Szeszko (MH01990), Dr Bilder (MH60374), Dr Kane (MH60575), Dr Robinson (MH60004), and the NSLIJ Research Institute General Clinical Research Center (M01 RR018535).

Funding Information:
Anil K Malhotra, served as consultant, speaker and received grant support from Ortho-McNeil Janssen, Bristol-Myers Squibb, Pfizer, Clinical Data Inc., and AstraZeneca. Rachel Miller, received compensation from Healthed.


  • Diffusion tensor imaging
  • Neuropsychology
  • Schizophrenia
  • Symptoms
  • Temporal lobes
  • White matter

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