Dengtang LIU*, Yifeng XU, Kaida JIANG

•Review•

Advances in neuroimaging research of schizophrenia in China

Dengtang LIU*, Yifeng XU, Kaida JIANG

schizophrenia, magnetic resonance imaging, magnetic resonance spectroscopy, diffusion tensor imaging, China

Neuroimaging studies of schizophrenia include both structural and functional techniques.[1-3]The former include X-ray computed tomography (CT) and magnetic resonance imaging (MRI); the latter include singlephoton emission computed tomography (SPECT), positron emission tomography (PET), functional MRI (fMRI),and magnetic resonance spectroscopy (MRS).[1-12]Diffusion tensor imaging (DTI) is another functional technique that measures the structure and integrity of the white matter.[13,14]This review describes the evolution of the use of these techniques in the study of schizophrenia(not including molecular neuroimaging) from the perspective of the results generated by researchers in mainland China.

1. Structural neuroimaging studies of schizophrenia

Since the end of the 19th century, researchers seeking the biological basis of schizophrenia have focused on the structure and function of the brain. The earliest study may be the 1879 report by Crichton-Browne that the brains of deceased individuals with schizophrenia were lighter than those of individuals with mood disorders but heavier than those of individuals with dementia. This was followed by a series of neurological autopsy studies and neuropathology studies.[1,2]Pneumoencephalography was the earliest form of in vivo neuroimaging. In 1927, Jacobi and colleagues used pneumoencephalography and found enlarged ventricles and hydrocephalus among individuals with schizophrenia, the first report of structural changes associated with schizophrenia.[1,2,15]

The first contemporary brain structure study of schizophrenia was conducted in 1976 by Johnstone and colleagues[16]who assessed 17 individuals with schizophrenia using CT and found enlarged lateral ventricles and cortical encephalatrophy. Additionally,they found that the enlargement of the lateral ventricles was associated with cognitive impairment but unrelated to antipsychotic treatment.[16]The earliest CT study in China by Yu and colleagues in 1983[17]found that 30%of individuals with schizophrenia had encephalatrophy.A replication study by Wang and colleagues reported in 1986[18]also documented enlarged ventricles and widened sulus. The number of CT studies on schizophrenia in China grew significantly after 1987.[19-22]A 10-year follow-up study of their original sample by Wang and colleagues[23]found that the prevalence of encephalatrophy inthe patients had risen from 16 to 31% over the 10-year interval; they concluded that the structural abnormalities in schizophrenia were related to the duration of disease.

Table 1 lists MRI studies on schizophrenia in China.Early studies engaged relatively simple imaging sequences and low-frequency magnetic fields. The analysis and presentation of the results were relatively basic.They reported that approximately 30% of individuals with schizophrenia had encephalatrophy, which was identified as reduced volume of the brain, widened sulus, and enlarged third and lateral ventricles.[24-30]The emergence of high fields MRI (e.g., 3T) and voxel-based morphometry (VBM) in 2006 equipped researchers with improved technology that could objectively quantify the volume and density of the local gray matter. Using VBM, a series of studies in China found reductions in the gray matter in the frontal lobe, temporal lobe and its interior structures, anterior cingulate, insula, parietal lobe, and cerebellum,[31-38]results that were consistent with findings from other countries. For example,Williams reviewed MRI-VBM studies and concluded that major structural brain changes in chronic schizophrenia included decreased gray matter in the superior temporal lobe (reported by 81% of studies) and in the inferior frontal lobe, inferior frontal lobe, inferior temporal lobe, and insula (reported by 50 to 70% of studies).[39]In first-episode schizophrenia reductions of the gray matter in the anterior cingulate gyrus and in the right parietal lobe were reported by 15 to 25% of studies and reductions of the gray matter in the inferior frontal lobe and the medial prefrontal lobe were also reported.[39]After two to three years of follow-up of first-episode schizophrenia, progressive reductions of the gray matter in the prefrontal-temporal lobe were found, changes that converge with those seen among individuals with chronic schizophrenia.[39]

2. Functional neuroimaging studies of schizophrenia

2.1 Functional magnetic resonance imaging (fMRI)studies

Liu and colleagues discussed the use of MRI in psychiatric research in 2001[8]and conducted a series of studies on cognitive functioning among Chinese individuals without mental disorders.[40-42]In 2002, they reported results from a fMRI study on schizophrenia which found that treatment with antipsychotic medications(risperidone or chlorpromazine) can activate certain brain areas among patients with schizophrenia.[9]

Table 2 lists task-based fMRI studies on schizophrenia from China. Tasks used in these studies included basic cognitive functioning (e.g., working memory,[10,43,45,47,48-52]verbal functioning,[9,44]and executive functioning[46]) and social cognitive functioning(e.g., face recognition[48]). These studies found that patients with schizophrenia had impairment in the memorization of active information as well as in the management and execution of active information.[10,43,45,47,48-52]The Sternberg item recognition task is one of the most widely used tests for short-term memory; studies that use this test in conjunction with fMRI report that during the maintenance stage of the task individuals with schizophrenia had increased activity levels in the left motor cortex, dorsolateral prefrontal cortex (DLPFC),ventral prefrontal cortex (VPFC), and the right precuneus– this suggests reduced efficiency of these brain regions.[10,43-45]The n-back task is a commonly used task to evaluate the ability to manage and execute working memory; based on the results of this task, individuals with schizophrenia were found to have impairment in the prefrontal cortex.[47]The Stroop task evaluates selective attention and impulse control; using this test, distracted individuals with schizophrenia were found to have deactivation in the left middle frontal gyrus and the right anterior cingulate and increased activity in the temporal lobe and right superior frontal lobe.[46]Using the facial recognition task, which evaluates social cognitive function, individuals with schizophrenia exhibited deactivation of the bilateral fusiform gyrus, occipital gyrus, cingulate gyrus, middle frontal gyrus, inferior frontal gyrus and cerebellum, left superior frontal gyrus, superior parietal lobe and the thalamus, and the right inferior parietal lobe.[48]Using the Burke dysphagia screening test, Jiang and his team found that after eight weeks of treatment with risperidone (3.8 mg/d), patients with schizophrenia showed improved brain activities in the left superior frontal gyrus and the left VPFC; this suggests that antipsychotics can ameliorate defective working memory in schizophrenia.[10]

Resting-state fMRI (as opposed to task-based fMRI)refers to fMRI conducted under a completely relaxed state. Under the resting state, certain areas of the brain are actively performing important functions.[53]Liu and colleagues found decreased regional homogeneity in individuals with schizophrenia in the bilateral frontal lobes, temporal lobes, inferior cerebellum, right parietal lobe, and the left limbic lobe.[54]Jiang and colleagues studied a sample of individuals with early-onset schizophrenia (12-19 years of age) and found lower regional homogeneity in the bilateral medial prefrontal cortex (MPFC).[55]More recently, researchers used the amplitude of low frequency fluctuations (ALFF) to evaluate resting-state brain functions and found that among individuals with schizophrenia the ALFF was elevated in the right corpus callosum, occipital lobes, leftcerebellar lobe, superior frontal gyrus and precuneus,and the ALFF was decreased in the bilateral postcentral gyrus and left precuneus.[56]Huang and colleagues reported lower ALFF at the MPFC and higher ALFF at the bilateral putamina among those with drug-naïve schizophrenia.[57]The above studies provide supportive evidence about the role of a dysfunctional MPFC in the pathogenesis of schizophrenia. Lui and colleagues investigated the influence of antipsychotics on restingstate brain functions among patients with schizophrenia and found that after six weeks of treatment with atypical antipsychotic medications, patients with firstepisode schizophrenia showed higher ALFF at the

bilateral prefrontal cortex, parietal lobe, left superior temporal lobe, and the right caudate; moreover, this increase of ALFF was correlated with improvement of clinical symptoms.[58]

Table 1. Magnetic resonance imaging(MRI) studies of schizophrenia in China

Table 2. Task-based functional magnetic resonance imaging(fMRI) studies of schizophrenia in China

2.2 . Magnetic resonance spectroscopy (MRS) studies

Dopamine (DA) hyperfunction is an important hypothesis in the etiology of schizophrenia. It has been challenged in recent years due to the limited effectiveness of antipsychotic medications on negative symptoms and impaired cognition.[59]In its place the glutamate hypothesis has gained in popularity because it not only accounts for psychotic symptoms but it can provide a sensible explanation for the defective cognition in schizophrenia. This hypothesis postulates that individuals with schizophrenia have deactivated N-methyl-D-aspartic acid (NMDA) receptors, which results in a deficiency of gamma-aminobutyric acid(GABA) and disinhibition of glutamic acid. Some scholars consider the hyperfunction of DA a result of the deficiency of GABA.[59,60]Assessment of the glutamate hypothesis requires accurate measurement of GABA in the brains of individuals with schizophrenia.Magnetic resonance spectroscopy (1H-MRS) is the most common technique for measuring the level of GABA in combination with high-frequency (≥3T) MRI.[61,62]

Table 3 lists MRS studies in China which have been used to assess levels of N-acetylaspartic acid(NAA), creatine (Cr), and choline (Cho) in individuals with schizophrenia.[63-68]They have found a decreased NAA/Cr ratio in the prefrontal cortex among patients with schizophrenia.[64-67]Most studies found no significant changes in the Cho/Cr ratio,[64-66]but Gao and colleagues reported a decreased Cho/Cr ratio in the bilateral frontal cortex.[67]These findings support hypotheses about the early damage of neurons in the frontal cortex of individuals with schizophrenia. There have been contradictory results from MRS studies of the hippocampus: Wang and colleagues[63]found an increased Cho/Cr ratio but no changes in the NAA/Cr ratio among male patients with schizophrenia while Peng and colleagues[65]found a decreased NAA/Cr ratio among patients with first-episode schizophrenia. Chen and colleagues[64]explored the effect of antipsychotics on brain metabolism but found no changes in the NAA/Cr or CHO/Cr ratios at the bilateral frontal cortex with treatment, suggesting that short-term treatment with atypical antipsychotic medications may not affect metabolism in the frontal cortex.

2.3 Diffusion tensor imaging (DTI) studies

DTI, which produces images of brain white matter and fiber tracts, highlights structural and functional asymmetry in different parts of the brain. Normally both grey matter and white matter are asymmetric,[1,2]but several researchers have found that in schizophrenia the asymmetry is reduced or reversed. Wang and colleagues[70]found that the asymmetry of the anterior cingulate tract was reduced in patients with schizophrenia. Su and colleagues[80]found that the asymmetry of the bilateral frontal lobe disappeared inpatients with schizophrenia and that the laterality of the genu and the posterior limb of the internal capsule was reversed.

Table 3. Magnetic resonance spectroscopy (MRS) studies on schizophrenia in China

DTI research has found structural abnormalities in the corpus callosum of patients with both firstepisode and chronic schizophrenia. Most research on the corpus callosum of patients with schizophrenia reports decreased fractional anisotropy (FA) in the genu,[79,80,83,86]and some studies report abnormalities in the splenium[73,76,86]and the truncus[74,86]of the corpus callosum. Kong and colleagues[83]found a reduced FA value in the genu of chronic patients but not in firstepisode patients, suggesting that the abnormality in that area reflects progression of the disease. Li and colleagues[86]compared five areas of the corpus callosum (splenium, truncus, anterior genu, mid genu,and posterior genu) in patients with schizophrenia,patients with bipolar disorder, and healthy controls;they found that both patient groups had lower FA values in all areas than those of healthy controls but they did not differ significantly from each other—which suggests that abnormalities in the corpus callosum are a shared component in the pathogenesis of schizophrenia and bipolar disorder.

The internal capsule has also been extensively studied. The first study in China by Zhao and colleagues[72]did not find any abnormalities in the internal capsule of patients with schizophrenia but subsequent studies reported reduced FA in the anterior limb of the bilateral internal capsule,[75,80]anterior limb of the left internal capsule,[77]genu of the left internal capsule,[80]and genu of the right internal capsule.[84]

Other studies report changes in the white matter and fiber tracts in other brain regions including the cerebellar peduncle, cingulate tract, cerebral peduncle,corona radiate, frontal lobe, temporal lobe, parietal lobe, insula, hippocampus, frontotemporal junction,parieto-occipital fasciculus, longitudinal fasciculus,and external capsule.[69-73,76,78,80-82,84-85]The results of DTI studies about schizophrenia conducted in China are summarized in Table 4.

2.4 Brain network

Brain network is currently a popular field in brain imaging research of schizophrenia in China.[87,88]Structural brain network research employs MRI to assess complex structural human brain networks and DTI to assess the white matter fiber tracts that connect these networks.Functional brain network research employs resting-state fMRI, task-state fMRI, electroencephalography (EEG),and magnetoencephalography (MEG) to assess complex functional human brain networks.[87-91]

2.4.1 Structural brain network

In 2012, Zhang and colleagues[92]used structural MRI to collect morphological data of the brain, and used the Automated Anatomical Labeling atlas (ALL) template to divide the brain into 78 areas (nodes). They used the graph theory analytical method for complex networks to analyze the brain network based on the thickness of the cortices. They found that the ‘small world’ property of the brain network of patients with schizophrenia was abnormal: (a) compared to normal brains the characteristic path length and the clustering coefficient increased; (b) the nodes in some brain areas had decreased centrality and thinner cortices (especially the left parahippocampal gyrus, inferior temporal gyrus,angular gyrus, and right superior frontal gyrus, which are part of the default network); and (c) the nodes in other brain areas had increased centrality, including nodes in the primary cortex (bilateral precuneous, left precentral gyrus, postcentral gyrus, and right Heschl gyrus) and the paralymbic system (bilateral orbital frontal gyrus,temporal pole, right cingulate tract, and inferior parietal gyrus). These findings indicated that the characteristics of the topology of the brain network changed in patients with schizophrenia. In 2014, Zhang and colleagues[93]reported that patients with schizophrenia had decreased connectivity between the thalamus and the bilateral inferior frontal gyrus, left superior temporal gyrus, and right parieto-occipital regions. These findings indicated that schizophrenia is associated with the loss of brain connectivity.

Wang and colleagues[94]used the ALL template along with white matter fiber tracts data collected using DTI to map the brain into 90 areas, and analyzed the white matter fiber tracts network using fiber tracking technology and graph-theory-based complex network analysis. They found that the normal characteristics of the topography of the brain network changed in patients with schizophrenia, resulting in a significant decrease in global efficiency that was correlated with scores on the Positive and Negative Syndrome Scale (PANSS). They also found decreased regional efficiency of some hubs,including the joint frontal cortex, paralimbic system,limbic system, and left lentiform nucleus.

2.4.2 Functional brain network

Functional brain networks are constructed using time series data of functional brain activities. Brain networks are differentiated into brain networks based on regions of interest, brain networks with specific functions, and whole brain networks. Examples of brain networks based on regions of interest are the dorsal lateral prefrontal lobe network and the medial prefrontal lobe network. Examples of specific brain networks are the default mode network (DMN) and the fronto-parietal network (FPN).[91]

Zhou and colleagues[95]studied the functional connection of the bilateral dorsal lateral prefrontal cortex (DLPFC); they found that patients with schizophrenia had reduced functional connection between the DLPFC and the parietal lobe, post cingulate gyrus, thalamus and striatum, but increased functional connection between the left DLPFC and the left midanterior temporal lobe and paralimbic regions. Fan and colleagues[96]studied the functional connection of the vetromedial prefrontal cortex (vMPFC) in patients with schizophrenia; they found (a) decreased functional

connection between the vMPFC and the medial frontal lobe, right middle temporal gyrus, right hippocampus,parahippocampal gyrus and amygdale, (b) decreased strength of the negative correlation between the vMPFC and the bilateral DLPFC and anterior supplementary motor area, and (c) a positive correlation between the reduction in the vMPFC-DLPFC connection and the positive symptoms of schizophrenia.

Table 4. Diffusion tensor imaging (DTI)studies on schizophrenia in China

Tang and colleagues[97]studied the default mode network (DMN) in patients with early-onset schizophrenia (12 to 19 years old); they found increased functional connection between the ventromedial prefrontal lobe and the right inferior temporal gyrus,left angular gyrus, and dorsomedial prefrontal lobe,but decreased functional connection between the right angular gyrus and the cerebellar tonsil, left superior frontal gyrus and right inferior semilunar lobule. Chang and colleagues[98]studied the anterior and posterior DMN as well as the left lateral and right lateral frontopariental networks (FPN); they found (a) abnormal intranetwork connections in the anterior DMN and bilateral FPN in both patients with schizophrenia and their healthy siblings, (b) normal intra-network connection of the posterior DMN, (c) a positive association between the two networks in patients with schizophrenia, their healthy siblings, and healthy controls, and (d) a stronger functional connection between the right FPN and the anterior DMN in patients with schizophrenia than in healthy controls.

Other researchers studied schizophrenia from the perspective of inherent networks, and proposed that the inherent networks include a task-positive network(TPN) and a task-negative network (TNN). Kong and colleagues[99]found increased functional connection in the bilateral inferior temporal gyrus of the TNN among individuals with schizophrenia and their healthy siblings;they also found increased functional connection between the left DLPFC and the right inferior temporal gyrus of the TPN among individuals with schizophrenia.Zhou and colleagues[100]assessed the TNN and TPN in patients with paranoid schizophrenia and found abnormal TNN functional connections with the bilateral dorsomedial prefrontal cortex, lateral parietal lobe, and inferior temporal gyrus, and abnormal TPN functional connections with the DLPFC and the right dorsal premotor cortex.

Liang and colleagues[101]used the ALL template to divide the brain into 116 areas, and analyzed the whole brain network using a complex network analysis method based on graph theory. They found that the functional brain connection of patients with schizophrenia during the resting state showed a wide-spread decline. Ke and colleagues[102]compared the properties of the brain network of patients with schizophrenia who primarily have positive symptoms with that of patients who primarily have negative symptoms; they found that the decline in the ‘small-world’ network was more pronounced in the patients with negative symptoms.

Guo and colleagues[103]assessed first order symmetry(the strength of the functional connection between the same brain regions from opposite hemispheres) and second order symmetry (the functional connection between the same pairs of brain regions from opposite hemispheres). They found that patients with schizophrenia had significantly decreased first and second order symmetry: the decrease in the first order symmetry indicated a reduced synchronicity between the two hemispheres; the decrease in the second order symmetry indicated a pronounced difference between the functional networks in the two hemispheres. They then compared the brain areas that were connected by the corpus callosum (CC) and the anterior commissure(AC) in patients with schizophrenia, and found that first and second order symmetry decreased in brain areas connected by the CC, but only first order symmetry decreased in brain areas connected by AC.

Liu and colleagues[104]assessed the diagnostic distinctiveness of the resting-state whole brain network.They found an 80.4% accuracy in distinguishing patients with schizophrenia from healthy controls, a 77.6%accuracy in distinguishing patients with schizophrenia from their healthy siblings, and a 78.7% accuracy in distinguishing schizophrenia patients’ healthy siblings and healthy controls without relatives with schizophrenia. These results suggest that the restingstate brain network of the patients’ siblings without schizophrenia is also changed in ways that distinguish it both from the brain network of their ill siblings and from that of healthy controls without a family history of mental illness.

3. Conclusions and future directions

In the past 30 years, advances in imaging technology and data analysis techniques have transformed neuroimaging into an exciting field that is rapidly advancing our understanding of the normal and abnormal functioning of the brain. These methods have identified structural and functional abnormalities in the brains of individuals with schizophrenia that confirm the biological basis of the disorder. However, much more multi-disciplinary work will be needed to integrate these findings into a comprehensive model of the etiology of this complex disorder. Chinese investigators have been and will continue to be enthusiastic participants in this global effort to understand, treat, and, hopefully,prevent this devastating condition.

Future neuroimaging research needs to overcome several central problems.

(a) Schizophrenia is highly heterogeneous, so dividing individuals with the clinical diagnosis into relatively homogeneous subgroups is essential to identifying distinct biological markers using neuroimaging techniques. The traditional methods of categorizing subtypes (paranoid,adolescent-onset, catatonic, simple, etc.) are obviously insufficient for research purposes. The dimensional approach based on rating the severity of 8 core symptoms of psychosis suggested in DSM-5[105]may be an improvement, but the utility of this method has not yet been assessed.

(b) There are some basic limitations to neuro-imaging that need to be overcome. Re-construction of images of white matter fiber tracts using DTI still has many methodological problems, including the false connections that can appear when reconstructing crossing fibers or longer fibers.[88]At present neuroimaging can only use MRI morphological data based on the population to construct a collective brain structural network; it cannot use data from a single participant to build an individualized brain structural network.

(c) Current brain network research is focused on the macro-level (whole brain or brain region)and relies on brain atlases (e.g., dividing the brain into 90 regions/nodes). Micro-level brain network research (neuron-level or voxellevel) may be more helpful for revealing the pathological mechanisms of a disorder, but such voxel-level studies will require much longer image processing time and more complex image analysis techniques.[87,88]Moreover, present brain network research describes associationsnotcause and effect relationships, so we do not know how the related brain areas work together to function effectively. Future research must construct directional networks that specify the directionality of the fiber connection between different brain regions and the causal relationship between neural activities.[87,88]

(d) More research in multi-modal imaging is needed to explore the potential benefits of combining methods. Many possible combinations are possible: structural MRI and resting-state fMRI;[106]resting-state fMRI and DTI;[107]neural imaging techniques based on MRI and EEG or MEG;[88]task-state fMRI and event-related potentials (ERP) or resting-state fMRI; and so forth. These multi-modal imaging methods can attain better results than single-mode methods by combining the complementary strengths of the different methods. For example, MRI has higher spatial resolution and EEG has better time resolution so combining the two methods provides a more multi-dimensional assessment.

(e) A parallel effort needs to be made in combining neuroimaging with genetics research[108,109]and with cognitive-behavioral research. Such a multi-disciplinary approach could reduce the necessary sample size of genetics research, help identify the genetic basis of the abnormal structure and function of the brain in schizophrenia, and clarify the link between altered genes, dysfunctional brains, and abnormal behavior.

Conflict of interest

The authors declare no conflict of interest related to this manuscript.

Funding

This review was funded by the National Science Foundation of China (81371479).

1. Xu YF, Liu DT. [Schizophrenia]. Beijing: People’s medical publishing house. 2012. Chinese

2. Liu TB, Zang DX. [Research progress of biological psychiatry in schizophrenia]. Wuhan: Hubei science and technology publishing house. 1994. Chinese

3. Malhi GS, Lagopoulos J. Making sense of neuroimaging in psychiatry.Acta Psychiatr Scand. 2008; 117: 100-117. doi:http://dx.doi.org/10.1111/j.1600-0447.2007.01111.x

4. Zhang WH, Zhou DF. [Advances of neuroimaging and neuropathology studies in schizophrenia].Zhonghua Jing Shen Ke Za Zhi. 2003; 36: 249-251. Chinese. doi: http://dx.doi.org/10.3760/j:issn:1006-7884.2003.04.025

5. Hao GF, Zhang ZJ, Hou G. [Progress of structural MRI in firstepisode schizophrenic patients].Guo Wai Yi Xue Jing Shen Bing Xue Fen Ce. 2005; 32: 125-128. Chinese

6. Zipursky RB, Meyer JH, Verhoeff NP. PET and SPECT imaging in psychiatric disorders.Can J Psychiatry. 2007; 52(3): 146-157

7. Pan J, Ouyang AM, Wang FS. [Research progress of positron emission tomography in schizophrenia].Jing Shen Yi Xue Za Zhi. 2008; 21: 311-313. Chinese. doi: http://dx.doi.org/10.3969/j.issn.1009-7201.2008.04.033

8. Liu DT, Jiang KD, Xu YF. [Functional magnetic resonance imaging in psychiatry].Zhong Hua Jing Shen Ke Za Zhi.2001; 34: 49-51. Chinese. doi: http://dx.doi.org/ 10.3760/j:issn:1006-7884.2001.01.031

9. Liu DT, Jiang KD, Xu YF, Zhuo S, Shi S, Wang L, et al. [A preliminary study of functional magnetic resonance imaging in first-episode schizophrenia].Shanghai Arch Psychiatry.2002; 14(4): 193-197. Chinese. doi: http://dx.doi.org/10.3969/j.issn.1002-0829.2002.04.001

10. Liu DT, Jiang KD, Xu YF, Zhu S, Shi S, Liu H, et al. [Functional magnetic resonance imaging of backward digit span task in first-episode schizophreniac patients before and after treatment].Zhong Hua Jing Shen Ke Za Zhi. 2004;37(2): 81-84. Chinese. doi: http://dx.doi.org/10.3760/j:issn:1006-7884.2004.02.006

11. Chen LJ, Xie SP. [Advances of magnetic resonance spectroscopy in schizophrenia].Guo Wai Yi Xue Jing Shen Bing Xue Fen Ce. 2005; 32: 28-32. Chinese

12. Zhang GF, Zhang YT. [MRS in Brain Research of Schizophrenia].Guo Wai Yi Xue Lin Chuang Fang She Xue Fen Ce. 2006; 29: 14-19. Chinese

13. Yang H, Zhou XP, Deng KH. [MR diffusion tensor imaging and its applications in schizophrenia].Lin Chuang Fang She Xue Za Zhi. 2006; 25: 785-787. Chinese. doi: http://dx.doi.org/10.3969/j.issn.1001-9324.2006.08.023

14. Xu YK, Yu CX, Wang CY. [Progress of tensor diffusion imaging in schizophrenia].Lin Chuang Fang She Xue Za Zhi. 2007;26: 194-196. Chinese. doi: http://dx.doi.org/10.3969/j.issn.1001-9324.2007.02.023

15. Gu NF, Xia ZY. [CT and schizophrenia].Zi Ran Za Zhi. 1984;7(8): 610-612. Chinese

16. Johnstone EC, Crow TJ, Frith CD, Husband J, Kreel L. Cerebral ventricular size and cognitive impairment in chronic schizophrenia.Lancet. 1976; 2(7992): 924-926. doi: http://dx.doi.org/10.1016/S0140-6736(76)90890-4

17. Yu QH, Chen PZ, Liu TS, Yin ZJ. [Preliminary report Schizophrenia decline brain CT and cognitive function test].Zhong Hua Shen Jing Jing Shen Ke Za Zhi.1983; 1: 42-45.Chinese

18. Wang XY, Li WT, Hu JR, Zhang XF, Liang EW, Quan CG, et al.[The relationship of CT and clinical characteristics: evidences from 73 patients with schizophrenia].Zhongguo Shen jing Jing Shen Ji Bing Za Zhi. 1986; 12(6): 345-347. Chinese

19. Yang ZJ, Hou Y. [Preliminary study of brain CT in 9 patients with schizophrenia].Beijing Yi Ke Da Xue Xue Bao. 1987;19(1): 53. Chinese

20. Gu NF, Yan HQ, Cai GJ, Lin ZG, Zhang MD, Xia ZY, et al. [The third ventriculars dilatation and schizophrenia].Zi Ran Za Zhi.1987; 1: 78-9. Chinese

21. Zhang LD, Zhang MY, Gu NF, Zhang YL, Yan HQ, Xia ZY, et al.[Brain CT study in first- episode schizophrenia].Shanghai Arch Psychiatry.1987; 01: 23-26. Chinese

22. Gu NF, Yan HJ, Cai GJ, Lin ZG, Zhang MD, Xia ZY, et al. [Brain CT study in schizophrenic patients and relatives].Shanghai Arch Psychiatry. 1987; 13(3): 93-99. Chinese

23. Wang XY, Wang SY, Li WT, Jiang T, Ma WY, Sun HX, et al. [10-year follow-up study of cerebral CT and clinical features of schizophrenia].Zhong Hua Jing Shen Ke Za Zhi. 1998;31(2): 111-113. Chinese. doi: http://dx.doi.org/10.3760/j:issn:1006-7884.1998.02.015

24. Shi XX, Jin WD, Sun GH, Yang JM. [The relationships of MRI and clinical characteristics in patients with schizophrenia].Zhong Yuan Jing Shen Yi Xue Za Zhi. 1996; 2(4): 208-209.Chinese

25. Chen Z, Chen H, Wu H, Hong QS, Wang HQ, Yu XY. [The corpus callosum study with MRI in 23 male patients with schizophrenia].Zhongguo Shen Jing Jing Shen Ji Bing Za Zhi.1997; 23(3): 29. Chinese

26. Wang KW, Xie SP, Kang B, Zhang XB, Yu XH, Liu H. [MRI abnormalities and psychiatric symptoms in schizophrenia].Lin Chuang Jing Shen Yi Xue Za Zhi. 1998; 8(1): 5-7. Chinese

27. Gan JL, Yang JM, Zhang WH, Sun GH, Lv CS, Wang JM, et al. [A study of global atrophy and its relative factors in schizophrenia].Sichuan Jing Shen Wei Sheng. Chinese. 2000;13(1): 6-8

28. Sui YX, Liu W, Li YP, Zhuo ST. [A study of brain structure in schizophrenia by magnetic resonance imaging].Lin Chuang Jing Shen Yi Xue Za Zhi. 2001; 11(3): 134-136. Chinese. doi:http://dx.doi.org/10.3969/j.issn.1005-3220.2001.03.003

29. Kang WH, Yu BL, Wang W, Chen C, Li Q, Ma XC, et al.[Correlation between MRI of temporal lobe morphology in patients with first-episode schizophrenia and pathopsychological factors].Xian Jiao Tong Da Xue Xue Bao(Yi Xue Ban). 2004; 25(1): 8-10. Chinese. doi: http://dx.doi.org/10.3969/j.issn.1671-8259.2004.01.003

30. Sui YX, Liu W, Fan JX, Zhuo ST. [Corpus callosum in schizophrenia: a magnetic resonance imaging study].Zhong Hua Jing Shen Ke Za Zhi. 2005; 2: 79-81. Chinese.

31. Wu DX, Yan LY, Tan CL, Hu DW, Yao SQ. [A voxel-based morphometric analysis of structural gray matter abnormality in schizophrenia].Zhongguo Yi Xue Ying Xiang Ji Shu.2007; 22(11): 1652-1655.1. Chinese. doi: http://dx.doi.org/10.3321/j.issn:1003-3289.2006.11.013

32. Lv S, Ouyang L, Huang XQ, Deng W, Tang HH, Jang LJ, et al.[An optimized voxel-based morphometry MRI study of the brain in patients with first episode schizophrenia].Zhong Hua Fang She Xue Za Zhi. 2007; 41(5): 495-498. Chinese. doi:http://dx.doi.org/10.3760/j.issn:1005-1201.2007.05.013

33. Zhou L, Den W, Ouyang L, Lv S, Huang XQ, Jiang LJ, et al. [A VBM study of the brain asymmetric changes in first-episode,antipsychotic-naive schizophrenia patients].Hua Xi Yi Xue.2008; 23(3): 442-444. Chinese

34. Lui S, Deng W, Huang XQ, Jiang LJ, Ouyang L, Stefan J, et al.Neuroanatomical differences between familial and sporadic schizophrenia and their parents: an optimized voxel-based morphometry study.Psychiatry Res. 2009; 171(2): 71-81.doi: http://dx.doi.org/10.1016/j.pscychresns.2008.02.004

35. Cui LQ, Li ML, Deng W, Guo WJ, Ma XH, Huang CH, et al.Overlapping clusters of gray matter deficits in paranoid schizophrenia and psychotic bipolar mania with family history.Neurosci Lett. 2011; 489(2): 94-98. doi: http://dx.doi.org/10.1016/j.neulet.2010.11.073

36. Lai YY, Yang L, Zhang XP, Chen L, Yu X, Hong N. [First-episode schizophrenia foot dome MRI findings].Zhongguo Yi Xue Ying Xiang Xue Za Zhi. 2012; 20(4): 263-267. doi: http://dx.doi.org/10.3969/j.issn.1005-5185.2012.04.007

37. Sheng JH, Zhu YK, Lu Z, Liu N, Huang N, Zhang ZW, et al.Altered volume and lateralization of language-related regions in first-episode schizophrenia.Schizophr Res.2013; 148(1): 168-174. doi: http://dx.doi.org/10.1016/j.schres.2013.05.021

38. Hu MR, Li J, Eyler L, Guo XF, Wei QL, Tang JS, et al. Decreased left middle temporal gyrus volume in antipsychotic drugnaive, first-episode schizophrenia patients and their healthy unaffected siblings.Schizophr Res. 2013; 144(1): 37-42. doi:http://dx.doi.org/10.1016/10.1016/j.schres.2012.12.018

39. Williams LM. Voxel-based morphometry in schizophrenia:implications for neurodevelopmental connectivity models,cognition and affect.Expert Rev Neurother. 2008; 8(7): 1049-1065. doi: http://dx.doi.org/10.1586/14737175.8.7.1049

40. Jiang KD, Liu DT, Wang ZY, Ling Z, Wu Y, Liu HQ, et al. [Brain activity during verbal fluency task in healthy volunteers: a functional magnetic resonance imaging study].Zhong Hua Jing Shen Ke Za Zhi. 2004; 37(3): 164-167. Chinese. doi:http://dx.doi.org/10.3760/j:issn:1006-7884.2004.03.010

41. Xu YF, Liu DT, Jang KD, Liu HQ, Yao ZY. [Functional magnetic resonance imaging studies of backward digit span task].Zhongguo Shen Jing Jing Shen Ji Bing Za Zhi. 2005;31(2): 133-135. Chinese. doi: http://dx.doi.org/10.3969/j.issn.1002-0152.2005.02.016

42. Zhu DM, Tang WJ, Yang ZL, Xu YF, Liu DT. [Functional magnetic resonance imaging studies of event-based prospective memory].Zhong Hua Xing Wei Yi Xue Yu Nao Ke Xue Za Zhi. 2012; 21(10): 924-926. Chinese. doi: http://dx.doi.org/10.3760/cma.j.issn.1674-6554.2012.10.019

43. Liu DT, Xu YF, Ling Z, Liu HQ, Yao ZY, Jiang KD. [FMRI of backward digit span task in first-episode schizophrenic patients].Shanghai Arch Psychiatry.2004; 5: 258-262.Chinese

44. Liu DT, Jiang KD, Wu Y, Liu HQ, Yao ZY, Xu YF, et al. [Functional magnetic resonance imaging of verbal fluency task in firstepisode schizophrenic patients].Zhong Hua Jing Shen Ke Za Zhi. 2005; 38(3): 138-141. Chinese. doi: http://dx.doi.org/10.3760/j:issn:1006-7884.2005.03.004

45. Wu DX, Tan CL, Yan LR, Hu DW, Wang X, Yao SQ. [The role of the prefrontal cortex in schizophrenia accompanied by dysexecutive syndromes during the double working memory tasks: an fMRI study].Zhongguo Yi Ke Da Xue Xue Bao. 2008;36(6): 737-740. Chinese. doi: http://dx.doi.org/10.3969/j.issn.0258-4646.2007.06.045

46. Liu J, Zhou SK, Mou YF, Xue ZM, Xiao EH, He Z. [Stroop test in patients with paranoid schizophrenia: an fMRI study].Zhongguo Yi Xue Ying Xiang Ji Shu. 2007; 23(3):349-352. Chinese. doi: http://dx.doi.org/10.3321/j.issn:1003-3289.2007.03.009

47. Wang X, Yan LR, Tan CL, Li YJ, Xia WW, Situ WJ. [Evidence for abnormal executive function in deficit and nondeficit schizophrenia: a preliminary fMRI study].Zhongguo Yi Xue Ying Xiang Ji Shu. 2007; 23(8): 1130-1133. Chinese. doi:http://dx.doi.org/10.3321/j.issn:1003-3289.2007.08.008

48. Zou LQ, Yuan HS, Dong WT, Pei XL, Xing W, Liu PC, et al. [An fMRI study of facial work memory in drug-naive schizophrenic patients].Zhongguo Yi Xue Ying Xiang Ji Shu. 2007; 23(8): 1134-1138. Chinese. doi: http://dx.doi.org/10.3321/j.issn:1003-3289.2007.08.009

49. Yang GF, Zhang Q, Zhang YT, Shen JH, Zhang XJ, Chen QG, et al. [An fMRI study of aberrant brain network in schizophrenia patients].Zhongguo Lin Chuang Xin Li Xue Za Zhi. 2009; 5:581-583. Chinese

50. Yang GF, Zhang Q, Zhang YT, Shen JH, Zhang XJ, Chen QG,et al. [An fMRI study for different cognition components of working memory in schizophrenia patients].Zhongguo Lin Chuang Yi Xue Ying Xiang Za Zhi. 2009; 20(10):758-761. Chinese. doi: http://dx.doi.org/10.3969/j.issn.1008-1062.2009.10.008

51. Gu Q, Sun XJ, Tian W, Mo Y, Liu W. [Functional MR study of task-induced deactivations in schizophrenic patients].Zhongguo Lin Chuang Yi Xue Ying Xiang Za Zhi. 2009;20(1): 13-16. Chinese. doi: http://dx.doi.org/10.3969/j.issn.1008-1062.2009.01.004

52. Zhang HR, Wei XM, Tao HJ, Mwansisya TE, Pu WD, et al.Opposite effective connectivity in the posterior cingulate and medial prefrontal cortex between first-episode schizophrenic patients with suicide risk and healthy controls.PloS One.2013; 8(5): e63477

53. Wang YC, Liu DT. [Research progress of the default mode of brain network in mental disorders].Jing Shen Yi Xue Za Zhi. 2012; 25(4): 314-317. Chinese. doi: http://dx.doi.org/10.3969/j.issn.1009-7201.2012.04.025

54. Liu H, Liu Z, Liang M, Hao Y, Tan L, Kuang F, et al. Decreased regional homogeneity in schizophrenia: a resting state functional magnetic resonance imaging study.Neuroreport.2006; 17(1): 19-22

55. Jiang SY, Zhou B, Liao YH, Liu WQ, Tang CL, Chen XG, et al. [Primary study of resting state functional magnetic resonance imaging in early onset schizophrenia using ReHo].Zhong Nan Da Xue Xue Bao (Yi Xue Ban). 2010;35(9): 947-951. Chinese. doi: http://dx.doi.org/10.3969/j.issn.1672-7347.2010.09.008

56. Liu H, Fan GG, Xu K, Li HH, Shao J. [Amplitude of lowfrequency fluctuation study of resting-state function MRI in schizophrenia].Zhongguo Yi Xue Ying Xiang Ji Shu. 2010;26(9): 1659-1662. Chinese

57. Huang X, Lui S, Deng W, Chan RCK, Wu Q, Jiang L, et al.Localization of cerebral functional deficits in treatmentnaive, first-episode schizophrenia using resting-state fMRI.Neuroimage. 2010; 49: 2901-2906. doi: http://dx.doi.org/10.1016/j.neuroimage.2009.11.072

58. Lui S, Li T, Deng W, Jiang J, Wu Q, Tang H, 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(8): 783-792. doi: http://dx.doi.org/10.1001/archgenpsychiatry.2010.84

59. Poels EMP, Kegeles LS, Kantrowitz JT, Slifstein M, Javitt DC,Lieberman JA, et al. Imaging glutamate in schizophrenia:review of findings and implications for drug discovery.Mol Psychiatry. 2014; 19: 20–29

60. Coyle JT, Basu A, Benneyworth M, Balu D, Konopaske G.Glutamatergic synaptic dysregulation in schizophrenia:therapeutic implications. In:M.A. Geyer and G. Gross(eds.), Novel Antischizophrenia Treatments, Handbook of Experimental Pharmacology 213. Berlin Heidelberg :Springer-Verlag. 2012

61. Bustillo JR. Use of proton magnetic resonance spectroscopy in the treatment of psychiatric disorders: a critical update.Pharmacology. 2013; 15(3): 329-337

62. Maddock RJ, Buonocore MH. MR spectroscopic studies of the brain in psychiatric disorders.Curr Topics Behav Neurosci. 2012; 11: 199–251. doi: http://dx.doi.org/10.1007/7854_2011_197

63. Wang F, Sun ZG, Ruan Y, Wang XL, Zhang HY, Cong Z, et al.[A H1magnetic resonance spectroscopy imaging study on hippocampus in male patients with schizophrenia].Zhong Hua Jing Shen Ke Za Zhi. 2004; 37(2): 78-80. Chinese. doi:http://dx.doi.org/10.3760/j:issn:1006-7884.2004.02.005

64. Chen LJ, Xie SP, Chen N. [Proton magnetic resonance spectroscopy study on frontal lobe in the first-episode male schizophrenic patients before and after two month antipsychotic treatment].Zhong Hua Jing Shen Ke Za Zhi. 2006; 39(3): 157-160. Chinese. doi: http://dx.doi.org/10.3760/j:issn:1006-7884.2006.03.008

65. Peng M, Guo QY, Han JY, Fan GG, Jin KH. [Proton magnetic resonance spectroscopy of brains in first-episode schizophrenic patients].Zhongguo Xin Li Wei Sheng Za Zhi. 2006; 20(6): 400-403. Chinese. doi: http://dx.doi.org/10.3321/j.issn:1000-6729.2006.06.018

66. Ma XC, Gao CG, Ding H, Yu BL. [Proton magnetic resonance spectroscopy imaging study on prefrontal cortex in first fit schizophrenia].Xi’an Jiao Tong Da Xue Xue Bao: Yi Xue Ban. 2006; 27(4): 394-396. Chinese. doi: http://dx.doi.org/10.3969/j.issn.1671-8259.2006.04.022

67. Gao JY, Sun XH, Su ZH, Chen YR, Hu XB, Wang GS, et al.[The fractional anisotropy of metabolites of the brain in first-episode patients with paranoid schizophrenia: a study of MRS].Shen Jing Ji Bing Yu Jing Shen Wei Sheng.2010; 2: 149-152. Chinese. doi: http://dx.doi.org/10.3969/j.issn.1009-6574.2010.02.011

68. Li XW, Du XJ, Zhang X. [MRS study in the first-degree relatives of schizophrenic patients with normal personality traits].Neimenggu Yi Xue Za Zhi. 2011; 43(3): 301-304. Chinese. doi:http://dx.doi.org/10.3969/j.issn.1004-0951.2011.03.015

69. Wang F, Sun ZG, Du XK, Wang XL, Cong Z, Zhang HY, et al.A diffusion tensor imaging study of middle and superior cerebellar peduncle in male patients with schizophrenia.Neurosci Lett. 2003; 348(3): 135-138. doi: http://dx.doi.org/10.1016/S0304-3940(03)00589-5

70. Wang F, Sun ZG, Cui LW, Du XK, Wang XL, Zhang HY, et al.Anterior cingulum abnormalities in male patients with schizophrenia determined through diffusion tensor imaging.Am J Psychiatry. 2004; 161(3): 573-5

71. Hao Y, Liu Z, Jiang T, Gong G, Liu H, Tan L, et al. White matter integrity of the whole brain is disrupted in first-episode schizophrenia.Neuroreport. 2006; 17(1): 23-26. doi: http://dx.doi.org/10.1097/01.wnr.0000195664.15090.46

72. Zhao RY, Xu XF, Yang JZ, Tian W, Bao YM. [The white matter and grey matter in the first episodic schizophrenia: a diffusion tensor imaging study].Zhong Hua Jing Shen Ke Za Zhi. 2006; 39(2): 69-72. Chinese. doi: http://dx.doi.org/10.3760/j:issn:1006-7884.2006.02.002

73. Wu T, Liu W, Cai ZY. [Study of white matter microstructure in schizophrenia by MR diffusion tensor imaging].Zhongguo Yi Xue Ying Xiang Ji Shu. 2006; 22(7): 978-980. Chinese. doi:http://dx.doi.org/10.3321/j.issn:1003-3289.2006.07.004

74. Li Y, Liu W, Sui MX, Wu T. [Corpus callosum in first-episode patients with schizophrenia: a magnetic resonance diffusion tensor imaging study].Sichuan Jing Shen Wei Sheng. 2006;22(7): 978-980. Chinese. doi: http://dx.doi.org/10.3969/j.issn.1007-3256.2008.02.002

75. Zou LQ, Yuan HS, Pei XL, Dong WT, Liu PC, Xie JX. [Diffusion tensor imaging study of the anterior limb of internal capsules in neuroleptic-naive schizophrenia].Zhongguo Yi Xue Ying Xiang Ji Shu. 2008; 24(1): 27-29. Chinese. doi: http://dx.doi.org/10.3321/j.issn:1003-3289.2008.01.008

76. Li XL, Huang XQ, Jun QY, Lv S, Deng W, Zhang TJ, et al. [Neural substrate of schizophrenia revealed by combining voxelbased morphometry and diffusion tensor imaging].Hua Xi Yi Xue. 2008; 23(3): 435-437. Chinese. doi: http://dx.doi.org/10.3969/j.issn.1002-0179.2008.03.004

77. Zou LQ, Pei XL, Yuan HS, Dong WT, Liu PC, Xie JX. [Diffusion tensor imaging of the anterior limb of internal capsule in male schizophrenic patients before neuroleptic therapy].Radiologic Practice. 2009; 24(7): 704-707. Chinese. doi:http://dx.doi.org/10.3969/j.issn.1000-0313.2009.07.003

78. Hao YH, Yan Q, Liu HH, Lin X, Xue ZM, Song XQ, et al.Schizophrenia patients and their healthy siblings share disruption of white matter integrity in the left prefrontal cortex and the hippocampus but not the anterior cingulate cortex.Schizophr Res. 2009; 114(1): 128-135. doi: http://dx.doi.org/10.1016/j.schres.2009.07.001

79. Su ZH, Chen YR, Wang GS, Sun XH, Hu XB, Gao JY, et al.[The abnormalities of microstructure in corpus callosum in the first -episode patients with paranoid schizophrenia:a study of DTI and MRS].Jing Shen Yi Xue Za Zhi.2009;5: 325-327. Chinese. doi: http://dx.doi.org/10.3969/j.issn.1009-7201.2009.05.002

80. Su ZH, Chen YR, Wang GS, Sun XH, Hu XB, Gao JY, et al.[The DTI study of white matter fractional anisotropy in the first-episode patients with paranoid schizophrenia].Zhongguo Shen Jing Jing Shen Ji Bing Za Zhi. 2010;4: 233-236. Chinese. doi: http://dx.doi.org/10.3969/j.issn.1002-0152.2010.04.011

81. Li HH, Liu H, Sun WG, Fan GG, Xu K, Tang YQ, et al. [A stuty of cereballar structure in schizophrenia patients by combining voxel-based morphometry and diffusiong tensor imaging].Jie Pou Ke Xue Jin Zhan. 2011; 17(6): 541-544. Chinese

82. Cui L, Chen ZF, Deng W, Huang, XQ, Li ML, Ma XH, et al.Assessment of white matter abnormalities in paranoid schizophrenia and bipolar mania patients.Psychiatry Res.2011; 194(3): 347-353. doi: http://dx.doi.org/10.1016/j.pscychresns.2011.03.010

83. Kong XQ, Ouyang X, Tao HJ, Liu HH, Li L, Zhao JP, et al.Complementary diffusion tensor imaging study of the corpus callosum in patients with first-episode and chronic schizophrenia.J Psychiatry Neurosci. 2011; 36(2): 120-125.doi: http://dx.doi.org/10.1503/jpn.100041

84. Guo WB, Liu F, Liu ZN, Gao KM, Xiao CQ, Chen HF, et al. Right lateralized white matter abnormalities in firstepisode, drug-naive paranoid schizophrenia.Neurosci Lett. 2012; 531(1): 5-9. doi: http://dx.doi.org/10.1016/j.neulet.2012.09.033

85. Chen LP, Chen XG, Liu WQ, Wang QF, Jiang TZ, Wang XY, et al.White matter microstructural abnormalities in patients with late-onset schizophrenia identified by a voxel-based diffusion tensor imaging.Psychiatry Res. 2013; 212(3): 201-207. doi:http://dx.doi.org/10.1016/j.pscychresns.2012.05.009

86. Li J, Elliot K, Chen KY, Tang YQ, Ouyang X, Jiang YF, et al.A comparative diffusion tensor imaging study of corpus callosum subregion integrity in bipolar disorder and schizophrenia.Psychiatry Res. 2014; 221(1): p. 58-62. doi:http://dx.doi.org/10.1016/j.pscychresns.2013.10.007

87. Jiang T, Zhou Y. Brainnetome of schizophrenia: focus on impaired cognitive function.Shanghai Arch Psychiatry.2012; 24(1): 3-10. doi: http://dx.doi.org/10.3969/j.issn.1002-08329.2012.01.001

88. Jiang T, Zhou Y, Liu B, Liu Y, Song M. Brainnetome-wide association studies in schizophrenia: the advances and future.Neurosci Biobehav Rev. 2013; 37(10): 2818-2835.doi: http://dx.doi.org/10.1016/j.neubiorev.2013.10.004

89. Jiang TZ, Liu Y, Li YH. [Brain networks: from anatomy to dynamics].Sheng Ming Ke Xue. 2009; 2: 181-188. Chinese

90. Liang X, Wang JH, He Y. [Human connectome: Structural and functional brain networks].Ke Xue Tong Bao. 2010; 16:1565-1583. Chinese

91. Jiang T. Brainnetome: A new -ome to understand the brain and its disorders.Neuroimage. 2013; 80: 263-272. doi:http://dx.doi.org/10.1016/j.neuroimage.2013.04.002

92. Zhang Y, Lin L, Lin C, Zhou Y, Chou K, Lo C, et al. Abnormal topological organization of structural brain networks in schizophrenia.Schizophr Res. 2012; 141(2-3): 109-118. doi:http://dx.doi.org/10.1016/j.schres.2012.08.021

93. Zhang Y, Su T, Liu B, Zhou Y, Chou K, Lo C, et al. Disrupted thalamo-cortical connectivity in schizophrenia: A morphometric correlation analysis.Schizophr Res. 2014;153(1-3): 129-135. doi: http://dx.doi.org/10.1016/j.schres.2014.01.023

94. Wang Q, Su T, Zhou Y, Chou K, Chen I, Jiang T, et al.Anatomical insights into disrupted small-world networks in schizophrenia.Neuroimage. 2012; 59(2): 1085-1093. doi:http://dx.doi.org/10.1016/j.neuroimage.2011.09.035

95. Zhou Y, Liang M, Jiang T, Tian L, Liu Y, Liu Z, et al. Functional dysconnectivity of the dorsolateral prefrontal cortex in firstepisode schizophrenia using resting-state fMRI.Neurosci Lett. 2007; 417(3): 297-302. doi: http://dx.doi.org/10.1016/j.neulet.2007.02.081

96. Fan F, Tan S, Yang F, Tan Y, Zhao Y, Chen N, et al. Ventral medial prefrontal functional connectivity and emotion regulation in chronic schizophrenia: a pilot study.Neurosci Bull. 2013; 29(1): 59-74. doi: http://dx.doi.org/10.1007/s12264-013-1300-8

97. Tang JS, Chen XG, Zhou B, Liao YH, Liu WQ, Tang CL, et al.[Default mode network analysis in early onset schizophrenia using functional magnetic resonance imaging].Lin Chuang Jing Shen Yi Xue Za Zhi. 2010; 20(5): 289-292. Chinese

98. Chang X, Shen H, Wang L, Liu l, Xin W, Hu D, et al. Altered default model and fronto-parietal network subsystems in patients with schizophrenia and their unaffected siblings.Brain Res. 2014; 1562: 87-99. doi: http://dx.doi.org/10.1016/j.brainres.2014.03.024

99. Kong XJ, Li S, Liu HH, Liu ZN. [A magnetic resonance imaging study on the gray matter, white matter and intrinsic networks in schizophrenic patients]. ZhongguoLin Chuang Xin Li Xue Za Zhi. 2010; 4: 415-417. Chinese

100. Zhou Y, Liang M, Tian L, Wang K, Hao Y, Liu H, et al.Functional disintegration in paranoid schizophrenia using resting-state fMRI.Schizophr Res. 2007; 97(1-3): 194-205.doi: http://dx.doi.org/10.1016/j.schres.2007.05.029

101. Liang M, Zhou Y, Jiang T, Liu Z, Tian L, Liu H, et al. Widespread functional disconnectivity in schizophrenia with resting-state functional magnetic resonance imaging.Neuroreport. 2006;17(2): 209-213

102. Ke M, Zou R, Shen H, Liu ZN, Xue ZM, Hu DW. [A functional network analysis in schizophrenics with negative and positive symptoms].Zhongguo Lin Chuang Xin Li Xue Za Zhi.2009; 17(5): 575-578. Chinese

103. Guo S, Kendrick KM, Zhang J, Broome M, Yu R, Liu Z, et al.Brain-wide functional inter-hemispheric disconnection is a potential biomarker for schizophrenia and distinguishes it from depression.NeuroImage: Clinical. 2013; 2: 818-826

104. Liu M, Zeng L, Shen H, Liu Z, Hu D. Potential risk for healthy siblings to develop schizophrenia: evidence from pattern classification with whole-brain connectivity.Neuroreport.2012; 23(5): 265-269. doi: http://dx.doi.org/10.1097/WNR.0b013e32834f60a5

105. American Psychiatric Association.Diagnostic and Statistical Manual of Mental Health, Fifth Edition. Arlington, VA:American Psychiatric Association; 2013

106. Lui S, Deng W, Huang X, Jiang L, Ma X, Chen H, 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. doi:http://dx.doi.org/10.1176/appi.ajp.2008.08020183

107. Yan H, Tian l, Yan J, Sun W, Liu Q, Zhang Y, et al. Functional and anatomical connectivity abnormalities in cognitive division of anterior cingulate cortex in schizophrenia.PLoS One. 7(9): e45659. doi: http://dx.doi.org/10.1371/journal.pone.0045659

108. Liu B, Fan L, Cui Y, Zhang X, Hou B, Li Y, et al. DISC1 Ser704Cys impacts thalamic- prefrontal connectivity.Brain Struct Funct.2013. Epub 22 Oct 2013. doi: http://dx.doi.org/10.1007/s00429-013-0640-5

109. Wang F, Jiang T, Sun Z, Teng S, Luo X, Zhu Z, et al. Neuregulin 1 genetic variation and anterior cingulum integrity in patients with schizophrenia and healthy controls.J Psychiatry Neurosci. 2009; 34(3): 181-186

2014-08-07; accepted: 2014-08-20)

Dr. Dengtang Liu graduated from Wuhan University School of Medicine in 1996 with a bachelor’s degree and obtained a doctoral degree in medicine from Fudan University School of Medicine in 2003. He has been working at the Shanghai Mental Health Center affiliated with Shanghai Jiao Tong University School of Medicine since 2003 and is a chief psychiatrist. He conducts both basic science and clinic research on mental illnesses with a primary focus on cognitive functioning, neuroimaging and clinical intervention studies of schizophrenia.

中国精神分裂症的神经影像学研究进展

刘登堂, 徐一峰, 江开达

精神分裂症，磁共振成像，磁共振波谱，弥散张量成像，中国

Summary:Since Hounsfield’s first report about X-ray computed tomography (CT) in 1972, there has been substantial progress in the application of neuroimaging techniques to study the structure, function, and biochemistry of the brain. This review provides a summary of recent research in structural and functional neuroimaging of schizophrenia in China and four tables describing all of the relevant studies from mainland China. The first research report using neuroimaging techniques in China dates back to 1983, a study that reported encephalatrophy in 30% of individuals with schizophrenia. Functional neuroimaging research in China emerged in the 1990s and has undergone rapid development since. Recently, structural and functional brain networks has become a hot topic among China’s neuroimaging researchers.

[Shanghai Arch Psychiatry. 2014; 26(4): 181-193.

http://dx.doi.org/10.3969/j.issn.1002-0829.2014.04.002]

Division of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China*correspondence: erliu110@126.com

A full-text Chinese translation of this article will be available at www.saponline.org on September 25, 2014.

概述：自Hounsfield于1972年首次报道X线计算机断层扫描（CT）后，神经影像学技术应用持续发展，用于研究大脑结构、功能和生物化学等方面。本文就中国近年来对精神分裂症结构性和功能性神经影像学的研究做了一个概述并且用4个表格来描述中国大陆所有相关研究。国内在精神科领域使用神经影像学技术的首个研究报告可追溯至1983年，研究发现30%精神分裂症患者存在脑萎缩。上世纪90年代国内逐渐出现功能神经影像学研究，并且快速发展。近年来，脑结构网络和脑功能网络研究已成为中国神经影像学研究的一个热门话题。

本文全文中文版从2014年9月25日起在www.saponline.org可供免费阅览下载