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Ren W, Lui S, Deng W, Li F, Li M, Huang X, Wang Y, Li T, Sweeney JA, Gong Q. Anatomical and Functional Brain Abnormalities in Drug-Naive First-Episode Schizophrenia. Am J Psychiatry. 2013 Jun 4 ; Pubmed Abstract

Comments on News and Primary Papers

Primary Papers: Anatomical and Functional Brain Abnormalities in Drug-Naive First-Episode Schizophrenia.

Comment by:  Lei Wang
Submitted 17 July 2013
Posted 17 July 2013

There are two important contributions that this study brings to the field: 1) it has one of the largest samples of antipsychotic-na´ve individuals at the early stages of schizophreniaŚwhile most of the published studies on first-episode schizophrenia/psychosis are of small sample size (Radua et al., 2012), with 100 patients and 100 matched controls, this study provides good statistical power; and 2) it uses multimodal imaging. Although more and more studies have collected multimodal imaging data in an attempt to directly study relationships between brain structure and brain function (Schultz et al., 2012), there exists a dearth of information with regard to the direct relationship between structural changes and changes in resting-state functional connectivity, especially in treatment-na´ve patients.

The study also invokes new questions on the neurobiology of treatment-na´ve schizophrenia. For example, findings of the study suggest that in drug-naive first-episode schizophrenia patients, abnormal changes of neural structure and neural oscillation occur in different brain networks, independent of each other. The study also found, somewhat surprisingly, that a set of gray matter structures was enlarged after psychosis onset. One wonders if these brain structures, including the thalamus and anterior cingulate cortex (ACC), would also show signs of ôneuronal overgrowth or a deficit in normal pruning during neurogenesisö before onset. Looking further back into prodromal periods may offer some clues. However, studies of clinically high-risk patients have found decreases in gray matter but not increases prior to psychosis onset (Pantelis et al., 2009; Wood et al., 2013).

Therefore, taking into account that recruitment, population with regard to patient subtypes, or image analysis methodology may differ across studies, multiple neural mechanisms may be at play around the period of the psychosis onset: While many gray matter regions are on a progressively decreasing trajectory, others, including the thalamus and ACC, follow a trajectory of decrease during prodrome, increase shortly after onset, and continuous decrease thereafter, and while some brain networks undergo neural structural changes, others undergo neuronal oscillation changes, both of which are fundamental to normal functioning. All of this causes us to wonder what these different models are reflections of and what the different driving forces are behind them.


Pantelis C, YŘcel M, Bora E, Fornito A, Testa R, Brewer WJ, Velakoulis D, Wood SJ. Neurobiological markers of illness onset in psychosis and schizophrenia: The search for a moving target. Neuropsychol Rev . 2009 Sep ; 19(3):385-98. Abstract

Radua J, Borgwardt S, Crescini A, Mataix-Cols D, Meyer-Lindenberg A, McGuire PK, Fusar-Poli P. Multimodal meta-analysis of structural and functional brain changes in first episode psychosis and the effects of antipsychotic medication. Neurosci Biobehav Rev . 2012 Nov ; 36(10):2325-33. Abstract

Schultz CC, Fusar-Poli P, Wagner G, Koch K, Schachtzabel C, Gruber O, Sauer H, Schl÷sser RG. Multimodal functional and structural imaging investigations in psychosis research. Eur Arch Psychiatry Clin Neurosci . 2012 Nov ; 262 Suppl 2():S97-106. Abstract

Wood SJ, Reniers RL, Heinze K. Neuroimaging findings in the at-risk mental state: a review of recent literature. Can J Psychiatry . 2013 Jan ; 58(1):13-8. Abstract

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