TO THE EDITOR
In the March, 2016 issue of the Journal, Gong et al. (1) selectively review the literature on treatment-related brain abnormalities in patients with first-episode schizophrenia. They emphasize the need for studies focused on patients early in their illness, as well the potential gains from neuroimaging biomarkers that track and predict treatment outcomes.
Supporting the growing literature of prospective studies in first-episode schizophrenia reviewed by Gong et al., we recently reported that longitudinal changes in striatal functional connectivity are associated with efficacious treatment by second-generation antipsychotic drugs (2). This work, conducted within a controlled clinical trial (NCT00320671) with pre- and post-treatment functional imaging revealed that efficacious treatment was associated with increased striatal functional connectivity with frontal and limbic brain regions mentioned in Gong et al., including the anterior cingulate, middle frontal gyrus, orbitofrontal cortex, and hippocampus. In addition, first episode patients with less improvement in psychosis demonstrated greater striatal connectivity with parietal regions. Another recent study applied longitudinal neuroimaging to examine abnormalities in large-scale functional networks in relation to treatment response in patients off medications, including a subset of treatment-naïve first-episode patients (3).
Moreover, in a paper published in the January, 2016 issue of the Journal (4), we reported that baseline functional connectivity of the striatum in first-episode patients with schizophrenia was predictive of the initial response to antipsychotic treatment. We derived an index of striatal connectivity that separated responders from non-responders in a discovery cohort, and tested our measure in a more chronic sample of patients undergoing treatment for acute psychosis. The sensitivity and specificity of this measure were 80% and 75%, respectively, in our replication. As highlighted by Gong et al., studies such as ours may be useful for guiding clinicians, while taking a step toward precision medicine approaches to the treatment of psychosis.
Our work supports the longitudinal and prognostic framework for studies described in Gong et al., and stresses the need for biomarker-based treatment trials that trace patient outcomes. Collectively, these results provide momentum toward discoveries that may shed light on the elusive biology that underlies the dynamic progression of schizophrenia.
Supplementary Material
Footnotes
Dr. Malhotra is a consultant to Genomind, Inc, FORUM Pharmaceuticals, and Takeda Pharmaceuticals. Dr. Lencz has been a consultant to Eli Lilly. Dr. Sarpal reports no financial relationships with commercial interests.
References
- 1.Gong Q, Lui S, Sweeney JA. Selective Review of Cerebral Abnormalities in Patients With First-Episode Schizophrenia Before and After Treatment. Am J Psychiatry. 2016;173:232–243. doi: 10.1176/appi.ajp.2015.15050641. [DOI] [PubMed] [Google Scholar]
- 2.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. doi: 10.1001/jamapsychiatry.2014.1734. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Kraguljac NV, White DM, Hadley JA, et al. Abnormalities in large scale functional networks in unmedicated patients with schizophrenia and effects of risperidone. Neuroimage Clin. 2015;10:146–158. doi: 10.1016/j.nicl.2015.11.015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.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. doi: 10.1176/appi.ajp.2015.14121571. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.