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Letters to the Editor
Published Online: 1 July 2016

Response to Sarpal et al.: Importance of Neuroimaging Biomarkers for Treatment Development and Clinical Practice

To the Editor: The letter by Sarpal et al. reviews recent work from their group that supports ideas presented in our Review and Overview Article regarding progress and future directions for neuroimaging studies in early-course schizophrenia (1). We and others have conducted resting state (24) and task-based functional magnetic resonance imaging (fMRI) (5) studies to examine antipsychotic treatment effects on functional brain systems in first-episode schizophrenia, and have linked MRI measures to symptom severity and clinical changes following treatment initiation (6). The recent work by Sarpal and colleagues (as part of a randomized clinical trial) extended this line of work by providing evidence that specific fMRI abnormalities in frontostriatal circuitry can be useful for both tracking and predicting outcomes from acute antipsychotic pharmacotherapy.
Sarpal et al. have reported two major findings. First, they reported that corticostriatal functional connectivity was increased by antipsychotic therapy (7). We have previously reported that altered frontostriatal connectivity is a common alteration across psychotic disorders (8), but we have observed a general reduction in corticostriatal connectivity with treatment (6), as did Anticevic et al. (9), who related this change to clinical outcome. In contrast, Sarpal et al. observed increased connectivity in frontostriatal circuits but decreased parietostriatal connectivity following antipsychotic treatment of schizophrenia (7). A number of possibilities might account for these differences, including medication selection, treatment duration, and technical factors, which clearly require further study. Secondly, and of particular clinical interest, Sarpal et al. reported that pretreatment MRI alterations could predict acute treatment outcome (10). Thus, their findings provide important continuing support for the potential predictive value of pretreatment alterations in functional brain connectivity in relation to acute treatment outcomes. This finding contrasts with our 1-year follow-up study in which pretreatment resting state fMRI data did not predict long-term clinical outcome. Thus, resting state fMRI data may be more useful in predicting acute treatment effects than longer-term role function and persistent residual symptom severity. Importantly, and perhaps not surprisingly, fMRI seems more useful for predicting and tracking clinically relevant acute treatment outcomes than anatomic imaging. Acute anatomic changes in the striatum and other regions have been reported (11, 12) but often in different brain regions from those where functional alterations have been observed. The reasons for these dissociations and their mechanisms require further study in patients and in animal models so that the relative clinical utility of anatomic and functional changes can be evaluated and best exploited.
The broader message of the letter from Sarpal et al. is its emphasis on the promise of MRI data to provide useful biomarkers for psychotic disorders. In this sense, their work supports a primary argument of our article (1), on which this commentary was addressed. The critical need for brain-based biomarkers is an urgent one in our field for treatment development and in the longer term for clinical practice. This prospect is consistent with the broad aims of the Research Domain Criteria project from the National Institute of Mental Health. Similarly, there is increasing interest within radiology in the potential of applying quantitative MRI methods in the clinical evaluation of psychiatric patients. The work from Dr. Sarpal’s group contributes meaningful foundational support for ongoing efforts to move forward in this area. Biomarkers that can predict treatment response could potentially help stratify patients in clinical trials, determine whether antipsychotic treatment is indicated in prodromal and early-course patients, elucidate the distinct subgroups of patients with psychotic disorders having distinct pathophysiological alterations (13), and predict response to different therapeutic strategies based on individual patient characteristics. Evidence continues to accumulate indicating that MRI studies of connectivity, anatomy, and chemistry may be useful for such purposes in ways that could significantly improve personalized medicine for patients suffering from psychotic disorders.

References

1.
Gong Q, Lui S, Sweeney JA: A selective review of cerebral abnormalities in patients with first-episode schizophrenia before and after treatment. Am J Psychiatry 2016; 173:232–243
2.
Lui S, Deng W, Huang X, et al: Association of cerebral deficits with clinical symptoms in antipsychotic-naive first-episode schizophrenia: an optimized voxel-based morphometry and resting state functional connectivity study. Am J Psychiatry 2009; 166:196–205
3.
Li F, Lui S, Yao L, et al: Longitudinal changes in resting-state cerebral activity in patients with first-episode schizophrenia: a 1-year follow-up functional MR imaging study. Radiology (Epub ahead of print, Jan 26, 2016)
4.
Kraguljac NV, White DM, Hadley N, et al: Aberrant hippocampal connectivity in unmedicated patients with schizophrenia and effects of antipsychotic medication: a longitudinal resting state functional MRI study. Schizophr Bull (Epub ahead of print, Feb 12, 2016)
5.
Keedy SK, Rosen C, Khine T, et al: An fMRI study of visual attention and sensorimotor function before and after antipsychotic treatment in first-episode schizophrenia. Psychiatry Res 2009; 172:16–23
6.
Lui S, Li T, Deng W, et al: Short-term effects of antipsychotic treatment on cerebral function in drug-naive first-episode schizophrenia revealed by “resting state” functional magnetic resonance imaging. Arch Gen Psychiatry 2010; 67:783–792
7.
Sarpal DK, Robinson DG, Lencz T, et al: Antipsychotic treatment and functional connectivity of the striatum in first-episode schizophrenia. JAMA Psychiatry 2015; 72:5–13
8.
Lui S, Yao L, Xiao Y, et al: Resting-state brain function in schizophrenia and psychotic bipolar probands and their first-degree relatives. Psychol Med 2015; 45:97–108
9.
Anticevic A, Hu X, Xiao Y, et al: Early-course unmedicated schizophrenia patients exhibit elevated prefrontal connectivity associated with longitudinal change. J Neurosci 2015; 35:267–286
10.
Sarpal DK, Argyelan M, Robinson DG, et al: Baseline striatal functional connectivity as a predictor of response to antipsychotic drug treatment. Am J Psychiatry 2016; 173:69–77
11.
Keshavan MS, Bagwell WW, Haas GL, et al: Changes in caudate volume with neuroleptic treatment. Lancet 1994; 344:1434
12.
Ren W, Lui S, Deng W, et al: Anatomical and functional brain abnormalities in drug-naive first-episode schizophrenia. Am J Psychiatry 2013; 170:1308–1316
13.
Sun H, Lui S, Yao L, et al: Two patterns of white matter abnormalities in medication-naive patients with first-episode schizophrenia revealed by diffusion tensor imaging and cluster analysis. JAMA Psychiatry 2015; 72:678–686

Information & Authors

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Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 733 - 734
PubMed: 27363556

History

Accepted: April 2016
Published online: 1 July 2016
Published in print: July 01, 2016

Authors

Details

Qiyong Gong, M.D., Ph.D.
From Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China.

Funding Information

The author’s disclosures accompany the original article.

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