Case group: The out-patients or in-patients with schizophrenia were recruited from the Department of Psychiatry in Huai’an No. 3 People's Hospital from June 2017 to May 2019. Inclusion criteria: ① The diagnosis meets the criteria for schizophrenia based on the International Classification of Diseases-10 (ICD-10); ② The DS meets the diagnostic criteria of the Chinese version of the schedule for the deficit syndrome (SDS).; ③ The patient’s age is between 18 and 60 years. Exclusion criteria: ① Pregnant or lactating women; ② Patients with mental retardation or epilepsy, brain tumors, and psychoactive substance abuse.
After adjusting for the selection criteria, a total of 30 cases were recruited into the study (20 males and 10 females), with an average age of 34±12 years. 17 cases were single and 13 were married, and the duration of education was (12±4) years. The average age of onset was (27±9) years, the time from onset of disease to first treatment was (12±3) months, and the duration of illness was (78±12) months.
Control group: The outpatients or inpatients diagnosed as NDS were evaluated by the SDS scale and the DS patients were excluded during the same period. In addition to the inclusion criteria ② of the DS patients, other inclusion criteria and exclusion criteria are the same as the case group. There were 30 cases, including 21 males and 9 females, the average age was (35±11) years. 15 cases were single, 15 married, and the duration of education was (13±3) years. The average age of onset was (30±9) years, the time from onset to first treatment was (9±2) months, and duration of illness was (56±11) months.
This study was approved by the Ethics Committee of Huai'an No. 3 People's Hospital of . Before the commencement of the study, the research purpose, method, and possible risks were explained to the subjects and their guardians. Also, written informed consent was obtained from the subjects and/or their guardians.
Assessment of socio-demographic and general information
A self-designed questionnaire was used to collect the gender, age, education duration, marital status, and other sociodemographic characteristics such as the age of onset, duration of illness, time from onset of disease to first treatment, hospitalization frequency, name and dose of antipsychotics and use of anticholinergic drugs, and other general clinical data. The positive and negative syndrome scale (PANSS) was used to assess the current severity.
The dose of antipsychotics was converted to the equivalent dose of chlorpromazine for comparison. The specific conversion method is as follows: chlorpromazine 600mg= clozapine 600mg = risperidone 6mg = aripiprazole 30mg = olanzapine 20mg = quetiapine 750mg = sulpiride 1200mg = amisulpride 1200mg. As the maximum therapeutic dose of each drug is considered to be the equivalent of the conversion dose, it was further converted according to the dose that was actually administered.
Assessment of Deficit schizophrenia and non-defective schizophrenia
The deficit syndrome (SDS) was conducted by the Chinese version of the schedule, which was compiled by Brian Kirkpatrick and translated into Chinese by Xiang Wang under the guidance of the original author. It consists of two parts. The first includes six aspects: emotion limitation, poor speech, narrow range of emotion, decreased interest, decreased purpose, and lack of social drive. The severity, primary and stability of negative symptoms were assessed. The severity was assessed on a scale of 5 from 0 to 4, and the primary and stability of symptoms were scored according to answer "yes" or "no". The second part summarizes the results of the first part to evaluate whether the clinical manifestations of the patients meet the four aspects of the DS diagnostic criteria. This scale has been verified in the Chinese population and has good reliability and validity. Finally, patients with DS and NDS were classified according to the SDS scale.
DS diagnostic criteria: ① Met the diagnostic criteria of ICD-10 schizophrenia; ② At least two of the six negative symptoms on the SDS scale were moderate or above; ③ The presence of symptoms that lasted longer than a year and persisted even in clinical remission; ④ It was the primary negative symptom, or negative symptoms secondary to psychiatric symptoms such as paranoia. Depression and anxiety were excluded, and negative symptoms secondary to extrapyramidal reactions, psychoactive substances, and mental retardation were also excluded.
Assessment of white matter
DTI data were collected using 1.5T magnetic resonance imaging (MRI) scanner(produced by the United Imaging company). Conventional brain scan sequences of the MRI included T1WI, T2WI, FLAIR T2WI, and DWI sequences, while the organic lesions of the whole brain were excluded. The DTI scan was performed using the spin-echo echo plane imaging (SE-EPI) sequence (TR=4600ms, TE=106.4ms, FOV read at 230mm, FOV phase 220mm, read at 128 resolution, phase resolution 100). A total of 30 continuous layers were scanned with a slice thickness of 4.0mm, a diffusion sensitivity gradient direction of 24, a diffusion sensitivity coefficient b of 1000s/mm2, and a scanning time of 5 mins 45s. Conventional MRI scan and DTI scan covered the whole brain.
For data processing, the tract-based spatial statistics (TBSS) method in the FSL (FMRIB Software Library, http://www.fmrib.ox.ac.uk/fsl) software package was used to analyze the DTI images of the white matter. Firstly, the eddy current correction was used to generate the whole brain mask before obtaining the individual FA figure. Then, the FA images of each subject were standardized to a spatial template of the standard brain atlas at the Montreal Neurological Institute (MNI) to make the average FA template and extract the tract skeleton. The white matter fibers of each of the subjects were registered to the tract skeleton, thus, completing the spatial normalization of the FA images. Finally, for each of the subjects in each group the average FA skeleton diagram (white matter skeleton diagram) calculated and the FA image was projected to the average white matter skeleton diagram for inter-group comparison.
SPSS 19.0 was used for statistical analysis. The measured data were expressed as x±s and the independent sample t-test was used for comparison between the groups. The categorical variable was expressed by frequency and percentage, and the chi-square test was used for comparison. Spearman correlation analysis was used to compare the FA values in the white matter difference area between the two variables, and p<0.05 was considered to be statistically significant.