Abnormal white matter connections between medial frontal regions predict symptoms in patients with first episode schizophrenia.
BACKGROUND
The medial orbitofrontal cortex (mOFC) and rostral part of anterior cingulate cortex (rACC) have been suggested to be involved in the neural network of salience and emotional processing, and associated with specific clinical symptoms in schizophrenia. Considering the schizophrenia dysconnectivity hypothesis, the connectivity abnormalities between mOFC and rACC might be associated with clinical characteristics in first episode schizophrenia patients (FESZ).


METHODS
After parcellating mOFC into the anterior and posterior part, diffusion properties of the mOFC-rACC white matter connections for 21 patients with FESZ and 21 healthy controls (HCs) were examined using stochastic tractography, one of the most effective Diffusion Tensor Imaging (DTI) methods for examining tracts between adjacent gray matter (GM) regions.


RESULTS
Fractional anisotropy (FA) reductions were observed in bilateral posterior, but not anterior mOFC-rACC connections (left: p < .0001; right: p < .0001) in FESZ compared to HCs. In addition, reduced FA in the left posterior mOFC-rACC connection was associated with more severe anhedonia-asociality (rho = -.633, p = .006) and total score (rho = -.520, p = .032) in the Scale for the Assessment of Negative Symptoms (SANS); reduced FA in the right posterior mOFC-rACC connection was associated with more severe affective flattening (rho = -.644, p = .005), total score (rho = -.535, p = .027) in SANS, hallucinations (rho = -.551, p = .018), delusions (rho = -.632, p = .005) and total score (rho = -.721, p = .001) in the Scale for the Assessment of Positive Symptoms (SAPS) in FESZ.


CONCLUSIONS
The observed white matter abnormalities within the connections between mOFC and rACC might be associated with the psychopathology of the early stage of schizophrenia.
Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; VA Boston Healthcare System, Boston, MA, USA; Safety and Health Organization, Chiba University, Chiba City, Chiba, Japan.
Toshiyuki
T
Ohtani
Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Sylvain
S
Bouix
Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Amanda E
AE
Lyall
Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; VA Boston Healthcare System, Boston, MA, USA; Tsuchida Hospital, Tokyo, Japan.
Taiga
T
Hosokawa
Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Neuropsychiatry, Kansai Medical University, Moriguchi City, Osaka, Japan.
Yukiko
Y
Saito
Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Eric
E
Melonakos
Surgical Planning Laboratory, MRI Division, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Carl-Fredrik
CF
Westin
Massachusetts Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Larry J
LJ
Seidman
Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Jill
J
Goldstein
Massachusetts Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
Raquelle
R
Mesholam-Gately
Stanley Center of Psychiatry Research, Broad Institute of MIT and Harvard, Boston, MA, USA; Psychiatry and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
Tracey
T
Petryshen
Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Joanne
J
Wojcik
Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; VA Boston Healthcare System, Boston, MA, USA. Electronic address: kubicki@bwh.harvard.edu.
Marek
M
Kubicki
D000293:Adolescent; D000328:Adult; D000339:Affect; D017668:Age of Onset; D059445:Anhedonia; D016880:Anisotropy; D014150:Antipsychotic Agents / Q000627:therapeutic use; D003702:Delusions / Q000209:etiology / Q000523:psychology; D056324:Diffusion Tensor Imaging; D005260:Female; D005625:Frontal Lobe / Q000473:pathology*; D066128:Gray Matter / Q000473:pathology; D006179:Gyrus Cinguli / Q000473:pathology; D006212:Hallucinations / Q000209:etiology / Q000523:psychology; D006801:Humans; D008297:Male; D011237:Predictive Value of Tests; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy / Q000473:pathology*; D012565:Schizophrenic Psychology; D012919:Social Behavior; D066127:White Matter / Q000473:pathology*; D055815:Young Adult
D014150:Antipsychotic Agents
Anterior cingulate cortex; First episode schizophrenia; Fractional anisotropy; Orbitofrontal cortex; White matter