Executive Function and its Relevant Factors in Patients with Major Depressive Disorders

Objective: To explore the characteristics of executive function and its relevant factors among Patients with Major Depressive Disorders (MDD). Methods: Two hundred and sixty-five patients with major depressive disorders were selected, who were admitted to the 4 th neurological department in Guangdong Sanjiu Brain Hospital from July 2018 to June 2020. They were administed with Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), Wisconsin Card Sorting Test (WCST) and a self-edited questionnaire on the personal general information. Result: The total score of HAMA, HAMD and WCST were (16.32±5.91), (34.67±8.72) and (1.97±1.94), respectively. Multiple linear regression analysis showed that the following 7 factors such as education, family monthly income, taking antidepressant drugs as prescribed, length of exercise per day, sleep quality, regular physical therapy, as well as understanding and support from relatives and friends were postively related with the total score of WCST (B= .137 ～ .522, all P<.05), and the total score of HAMD and HAMA, age, age of first episode, duration of depression, recurrent depression and family history of psychosis were negatively related with the total score of WCST (B= -.215 ～ -.711, all P<.05) . Conclusion: The MDD patients’ executive function has decreased significantly, which is closely related to such factors as the course of depression, severity of depression, the degree of brain function decline, treatment compliance, as well as family and social support. independent sample t-test and one-way ANOVA are used to explore the pairwise correlation among the variables; multiple linear regression is used to analyze the main related factors of WCST total score.

There are 14 items, which are divided into two factors: physical anxiety and mental anxiety. The higher the score, the more anxious the anxiety. The liketer 5-points scoring method is used to score from 0 to 4 points corresponding to (asymptomatic) -(very heavy). The clinical demarcation points are: If the total score <7, the patient is considered normal; If the total score is 7 to 13, the patient is possible anxiety; If the total score is 14-20, the patient is positive anxiety; If the total score is 21-28, the patient is obvious anxiety; And if the total score is more than 28, the patient is severe anxiety. In this study, Cronbach 'a coefficient of the total scale is 0.90, and Cronbach' a coefficient of each factor is 0.79-0.86, respectively.

Wisconsin Card Sorting Test (WCST):
It is compiled by Grant (1948) and revised by Tan Yunlong to Chinese version [17], which is used to test the abstract thinking ability of non-color blind people over 6 years old. There are 4 stimulus cards and 128 response cards, which are divided into 14 test indexes, namely Total Score (TS), number of Complete Categories (CC), Percentage of Conceptualization Level (RFP), Continuous Responses (RP), Continuous Error (RPE), non-continuous error (NRPE), total responses required to complete the test (RA), Correct Responses (RC), Correct Response Percentage (RCP), Wrong Responses (RE), the number of answers required to complete the first classification (RF), the Percentage Of Persistent Errors (RPEP), the number of incomplete classifications (FM), and the number of Learning to Learn (LL). In this study, the cronbach'a coefficient of the total scale is 0.91, and the cronbach'a coefficient of each dimension is 0.75-0.86.
Self-compiled questionnaire on personal general information: The CNKI, Wanfang database, VIP database, Baidu, Pubmed and other search engines are used to search the literatures about "related factors of executive function among major depressive disorder" (176 in Chinese and 4733 in foreign). Based on that, the basic content of the questionnaire is constructed, with a total of 17 items. Combined with the results of 3 collective discussions with 9 representatives of psychiatrists, 1 item is deleted, and 2 items are added. The final questionnaire for personal general information of MDD patients consists of 18 items, including age, gender, age of first episode, depression duration (months), whether anxiety is combined, education, occupation, whether psychological treatment has been received, monthly income of family, whether taking antidepressants according to the doctor's orders, whether exercise for more than 30 minutes every day, sleep quality, whether recurrence depression, with family history of mental diseases or not, with major negative life events within last 1 year or not, whether physical therapy (such as trams) was regularly accepted, what the attitude of relatives and friends towards your depression, and depression subtypes, etc.
Data processing SPSS 20.0 is used to analyze the effective data. Descriptive statistics are used to calculate the average score and standard deviation of each scale; Pearson product difference correlation, independent sample t-test and one-way ANOVA are used to explore the pairwise correlation among the variables; multiple linear regression is used to analyze the main related factors of WCST total score. It can be seen from Table 1 that the HAMD total score of this group reached the standard of (positive) depressive symptoms [9], HAMA total score reached the standard of (positive) anxiety symptoms [10], and WCST total score was significantly lower than that of normal people [17].

Correlation analysis of scores of each scale
From Table 2, there was a significant positive correlation between total scores of HAMD , HAMA and WCST.

Univariate analysis of demographic variables of executive function among MDD patients
Variable assignment: Firstly, the possible situations (alternative answers) of demographic classification variables and clinical related classification variables that may affect the total score of WCST are assigned. The results are shown in Table 3. Have you ever received regularly psychotherapy? 0 = none, 1 = yes 5

Multiple stepwise linear regression analysis of executive function related factors in patients with depression
Taking the total score of WCST as the dependent variable, and the above18 demographic variables, clinical related variables and HAMA, HAMD total scores as the independent variables, the multiple stepwise linear regression analysis is carried out within 95% confidence interval. It can be seen from Table 5 that education, family monthly income, taking antidepressants according to doctor's advice, daily exercise time, sleep quality, regular physical therapy, understanding and support from relatives and friends are positively correlated with the total score of WSCT (B=. 137 ~. 522, all P < 0.05). The total score of WSCT is negatively correlated with HAMD, HAMA, age, first-episode age, duration of depression, recurrent depression and family history of psychosis (B= -. 215 -. 711, all P < 0.05).

Discussion
The total score of WCST and the score of each factor in this group are significantly lower than the normal value [15], which is consistent with the results of previous studies [16][17][18][19][20], suggesting that the impairment of executive function is common in MDD patients, mainly in the aspects of individual inhibition, cognitive flexibility, planning, semantic fluency and set switching ability. Multiple stepwise linear regression shows that education, family monthly income, taking antidepressants as prescribed, daily exercise time, sleep quality, regular physical therapy, understanding and support of relatives and friends are positively correlated with WCST total score; HAMD total score, HAMA total score, age, firstepisode age, duration of depression, recurrent depression and psychotic family history were negatively correlated with WCST total score. Education and family monthly income positively predict the executive function of MDD patients, which is consistent with previous research results [21,22], suggesting that higher socioeconomic status can promote physiological and psychological functions. The "social causality theory" in the field of health [23] points out that people with lower socio-economic status (lower education level and lower per capita household consumption expenditure) are more likely to experience unfortunate life events (such as recent widowhood and death of children) Poor health level (such as malnutrition, disability, chronic diseases, infectious diseases, poor medical conditions, and so on), these factors will have a negative impact on brain function. At the same time, people with higher education level are more able to correctly understand depression and its treatment methods, more able to state their illness clearly to doctors, so that the diagnosis and treatment are more targeted, and they are more able to choose and adhere to the correct treatment methods.
Taking antidepressants according to the doctor's advice can help maintain executive function. It is consistent with the results of previous studies [21,24], suggesting that antidepressants can promote the affective disorder (such as depression) and cognitive

PPRS.000599. 4(5).2021
function (such as executive function) of MDD patients. Based on the existing theoretical hypothesis and clinical trial results, the occurrence of depression may be influenced by many factors, and each factor plays a role through different signal pathways and pathophysiological processes, which eventually leads to changes in the number and function of synapses [25], and damages synaptic plasticity. It can reduce the excitability of cerebral cortex [26], induce the occurrence of depression, and may be accompanied by cognitive decline [27]. Therefore, the improvement of synaptic plasticity can improve depressive symptoms and cognitive function. Although classical Selective Serotonin Reuptake Inhibitors (SSRI) and new antidepressants have different mechanisms of action, their antidepressant effects are related to the improvement of synaptic plasticity [27,28]. Rational administration can promote nerve regeneration in the Dentate Gyrus (DG) and other brain regions of patients [29], so it is also conducive to the maintenance of brain function. Sleep quality positively predicts executive function in patients with depression, which is consistent with the results of previous studies [21,29,30]. Sleep change is the most common circadian rhythm disorder in depression, about 80% of patients with depression will have sleep disorders [30], which main clinical manifestations are difficulty in falling asleep and shortened sleep duration. Sleep is the result of the balance of brain excitation and inhibition. The poor sleep quality can reflect the inflexibility of brain excitation and inhibition, that is, the poor executive function. On the other hand, poor sleep quality hinders the recovery of various physiological functions and has extensive damage to the regulatory function of the nervous system, especially the high-level nervous function responsible for the frontal lobe, such as executive function [31,32]. The duration of daily exercise and regular physical therapy (such as rTMS) positively predict the executive function of patients with major depressive disorder, which is consistent with the results of previous studies [21,[33][34][35][36]. It is suggested that moderate physical exercise and nerve stimulation have a positive effect on brain function. The most important clinical manifestation of depression is the decrease of mental activity, and its physiological mechanism is the decrease of synaptic number [25], function [26] and cortical excitability [26]. Experiments have shown that longterm and moderate physical exercise and regular physical therapy (such as rTMS) can increase the number of synapses [21,[32][33][34][35], improve the plasticity of synapses and the excitability of cortex, thus improving executive function.
The understanding and support of relatives and friends positively predicted the executive function of patients with depression, which was consistent with previous research results [21,36], suggesting that social support can maintain the executive function of MDD patients. Patients with high degree of social support can get more material support and spiritual encouragement, which makes them more confident to adhere to treatment and get more financial resources to comply with treatment. The total score of HAMD, HAMA, age, first-episode age, duration of depression, recurrent depression and family history of psychosis were negatively correlated with the total score of WCST. It is consistent with the previous research results [21,[37][38][39][40][41][42]. The above seven factors reflect the brain damage of patients and the negative impact of reduced plasticity on executive function from different perspectives.