2.1. Subject
We recruited 136 schizophrenia patients from the Department of psychiatry at Xijing Hospital and 146 healthy control through advertising. All subjects signed informed consent. The study was approved by the Xijing Hospital Institutional Ethics Committee and followed the principles in the Declaration of Helsinki. All subjects were Han and right-handed. Exclusion criteria include (1) organic lesions of the central nervous system; (2) history of congenital brain development or head trauma, epilepsy; (3) other types of mental disorders (such as obsessive-compulsive disorder, depression, anxiety disorder, etc.); (4) severe unstable somatic diseases (such as coronary heart disease, systemic lupus erythematosus, thyroid disease, hypertension, etc.); (5) substance abuse or substance dependence; (6) pregnancy or preparation for pregnancy, lactation; (7) Contraindications for MRI examination (e.g., pacemaker and other metal implants, etc.). A full description of the sample is available in the study by Li et al[8].
The diagnosis of schizophrenia patients is in accordance with the schizophrenia diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)[18]. Two experienced clinical psychiatrists reached an agreement after an independent diagnosis. The severity of patients' symptoms was evaluated by using the Positive and Negative Symptom Scale (PANSS)[19]. Scale assessment and MRI scans were completed on the same day.
2.2. Cognitive Assessment
We assessed the cognition of subjects with the digit span (forward, backward) and digit symbol coding task in the Wechsler Adult Intelligence Scale-Revised in China (WAIS-RC). The forward digit span task consists of up to 12 digits while the backward digit span task consists of up to 10 digits, with each part arranged from easy to difficult. Any string is repeated correctly, then proceed to the next string. If there is an error, run a second test with a new string of the same length, stop the test for the part that all fails and record the string's length. In the digit symbol coding task, the number 0 to 9 corresponds to a specified symbol, and the subject is required to quickly fill in the corresponding symbol in the space under each number from left to right and should not jump the space. Subjects started with the practice program with the formal test time limit of 90 seconds. Ultimately, we obtained data on digit symbol and digit span from 132 patients and 56 healthy controls.
2.3. Image acquisition
Resting-state fMRI and structural T1 scans were collected for each subject on a General Electric (GE) Discovery MR750 3.0 T MR. During acquiring the images, participants were asked to lie flat, remain still, close eyes, not fall asleep, and use custom head ring pads and ear plugs to reduce head movement and weaken the noise of the scanner.
2.4. Data preprocessing
Same as in the previous study, we processed the data through the Data Processing Assistant for Resting-State fMRI Advanced Edition (DPARSFA) V4.4[8]. The steps are as follows: (1) convert DICOM image format to NIfTI. (2) remove the first ten time points for each subject. (3) slice timing correction. (4) realignment were performed. (5) regression covariates, including global mean signal, six head motion parameters, white matter signal, and cerebrospinal fluid signals. (6) coregister the T1-weighted images to the functional images. (7) normalize coregistration images to the Montreal Neurological Institute space. (8) smooth.
2.5. ALFF calculation
TheALFF of the BOLD signal was performed using DPARSFA V4.4 to identify regional brain function[20]. For ALFF, the data were filtered by bandpass (0.01–0.08 Hz). Then, the fraction amplitude of fALFF is obtained by calculation.
2.6. Gene expression
We searched through a web Allen Human Brain Atlas (http://human.brain-map.org/), and we acquired the genes differentially expressed in IPL. Then, we compared the transcriptome-wide association study (TWAS) results of schizophrenia[21] and our TWAS results with the genes differentially expressed in IPL .
2.7. Statistical analysis
We use WAIS-RC scores to describe cognitive grouping, a cutoff of scores of < − 1.0 SD to describe the group with cognitive impairment, and scores of ≥ − 0.5 SD to describe a group with normal cognitive function[22]. Then compare whether there are differences between the two groups in fALFF and diacylglycerol kinase ζ (DGKζ) gene expression, and analyze the correlation between gene expression and fALFF. In addition, we made the correlation analysis between ALFF of the left IPL of patients and healthy controls and digit symbol task score, forward digit span task score and backward digit span task score.