Schizophrenia is a complex brain and neurodevelopmental disorders associating with a wide range of clinical, cognitive and emotional manifestations. Although the clinical of schizophrenia is mainly leaned on the presence of psychotic symptoms known as positive symptoms (such as delusion and hallucination), the ultimate functional outcome or prognosis is mainly determined by negative symptoms (such as amotivation and anhedonia).

Negative symptoms are often persistent in the whole course of schizophrenia in a large number of patients and are resistant to treatment. Clinically, persistent negative symptoms (PNS) is characterized and defined by the presence and persistence of negative symptoms for at least 6 months with defined threshold levels of positive symptoms, and its resistance to treatment.

Therefore, PNS has long been one of the key target groups for clinicians and researchers in the field of schizophrenia research. However, it is still not fully known for the underlying brain structural and functional abnormalities in patients with PNS. 

Dr. Raymond Chan and his team from the Neuropsychology and Applied Cognitive Neuroscience (NACN) Laboratory, CAS Key Laboratory of Mental Health, Institute of Psychology of the Chinese Academy of Sciences, have recently conducted a meta-analysis to quantitatively examine the grey matter volume in patients with PNS.

Their findings showed that significant grey matter reduction in the PNS group relative to healthy controls was observed in the left caudate nucleus, the left precentral region, the left middle frontal region, the bilateral parahippocampal region, the left anterior cingulate region, the bilateral medial frontal gyrus, the thalamus and the insula.

In particular, the grey matter volume reduction in the caudate nucleus and the related cortico-striatal circuit abnormalities found in the present study are key hotspots of the reward system.

Evidence of deficits in these brain regions and neural network suggests that abnormality in reward processing may constitute the underlying mechanism of PNS in schizophrenia. This work has been published online in Schizophrenia Research.  

On the other hand, Schizophrenia Research has recently published two joint studies done by Dr. Chan and his international collaborators. One study was focusing on the dissociable working memory deficits in individuals with schizotypy and depressed mood, which was led by Dr. Weiwei Zhang’s team from University of California, Riverside.

They have specifically examined working memory and sensory memory performances in individual with schizotypy using a delayed colour estimation task and an immediate colour estimation task respectively.

They found that the schizotypal individuals retained less precise representations in working memory but without a reduction in the number of retained working representations (i.e., with an intact working memory capacity).

Given the lack of the significant correlations between the corresponding sensory memory precision and schizotypal traits, Drs. ZHANG and Chan argued that this working memory imprecision effect was probably not a result from imprecise sensory memory.

Moreover, they also found that depressed mood was inversely correlated with working memory capacity, but not with working memory precision. These findings suggested a dissociable working memory deficit in individuals with schizotypy and depressed mood.  

The other study, led by Dr. Henry Mak from the University of Hong Kong, was specifically examining the levels of GABA, Glx (summation of glutamate and glutamine) in patients with 19 first-episode schizophrenia and 14 healthy controls.

The team found that patents with first-episode schizophrenia exhibited reduced levels of GABA and myo-inositol(mI), and increased levels of Glx and choline(Cho), compared to healthy controls. Receiver operator characteristics analyses further showed that Glx had higher sensitivity and specificity (84.2%, 92.9%) compared to GABA (73.7%, 64.3%) for classifying schizophrenia patients from healthy controls. A final model combining GABA and Glx suggested the best sensitivity and specificity (89.5%, 100%).

Taken together, these findings showed patients with first-episode schizophrenia have already exhibited a reduction in GABA and elevation in Glx, and this might provide insights on explaining the disruption of modulation between GABAergic interneurons and glutamatergic neurons in this clinical group.   

The meta-analysis study was supported by a grant from the National Natural Science Fund China, the Beijing Training Project for the Leading Talents in Science and Technology, the Beijing Municipal Science and Technology Commission Grant, the "Strategic Priority Research Program (B)" of the Chinese Academy of Sciences, and the CAS Key Laboratory of Mental Health, Institute of Psychology.  

These studies are now published online in Schizophrenia Research.