| Objectives:To investigate the cognitive impairment characteristics and related factors in first-episode, treatment-naive patients with major depressive disorder (MDD), and explore brain functional and structural pathological mechanisms of cognitive impairment in MDD by analyzing the brain gray matter, white matter, resting state brain activity and the default state network and the correlation with the severity of disease and cognitive functionMethods:46first-episode MDD (according to diagosis critietia of DSM-Ⅳ) and46healthy controls were assessed by17-item Hamilton Depression Rating Scale (HAMD-17), Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Hamilton anxiety scale (HAMA). HAMD-17scores were requested≥17in patients and≤7in controls. The neuropsychological tests including Wisconsin Card Sorting Test (WCST), Stroop Color Word Test (SCWT), Continuous Performance Test (CPT) and Trail making test (TMT) were used to assess the cognitive function. Then,30patients and30controls were obtained by MRI scan ordering to T1structure, three-dimensional structure of imaging(3D), resting state fMRI and diffusion tensor imaging (DTI). Finally, statistical analysis was carried out for exploring the difference in the brain gray matter density, fractional anisotropy (FA) valus, regional homogeneity (ReHo) valus and functional connectivity within default state network (DMN) between the depression and controls, and correlation analysis between these different brain regions and the cognitive function.Results:46depressed patients and46controls completed the neuropsychological tests,30patients and30controls group finished MRI scan. Some data were excluded by head movements.Data could be analyzed finally including26patients and26controls in3D and resting state fMRI,25patients and25controls in DTI.(1) The total number of errors, number of perseverative errors, random errors of WSCT in the depressive group were significantly more than that in the control group(P＜0.05), the correct trials and categories were significantly less than that in the control group (P＜0.05), the correct trials of CPT2was less than that in the control group (P>0.05), the completion time in the TMT-A and TMT-B was longer than that in the control group (P＜0.05).There was a significant positive correlation between total number of errors and random errors of WSCT, the completion time in the TMT-B and age (repectively, r=0.313, P=0.034; r=0.322, P=0.029; r=0.615, P=0.000), and a significant negative correlation between the correct trials, categories of WSCT and age in patients (repectively, r=-0.381, P=0.009; r=-0.418, P=0.004). In addition, there was a significant positive correlation between the correct trials in WSCT and CPT2and education (repectively, r=0.364, P=0.013; r=0.370, P=0.011), and a significant negative correlation between the completion time in the TMT-A and the TMT-B and education (repectively, r=-0.308, P=0.038; r=-0.482, P=0.001).No correlation was found between abnormal cognitive function and duration and severity of disease in MDD patients (P>0.05).(2) MDD patients showed significant less gray matter volumns than healthy controls in frontal lobe (right precentral gyrus, bilateral superior frontal gyrus and right middle frontal gyrus), parietal lobe(left postcentral gyrus, left paracentral lobule, bilateral precuneus), temporal lobe (right superior temporal gyrus), occipital lobe (left superior occipital gyrus)(P<.O.05).There was a significant negative correlation between left postcentral gyrus and left superior occipital gyrus gray matter density and the TMT-B completion time (repectively, r=-0.462, P=0.017; r=-0.448, P=0.022).No correlation was found between abnormal gray matter density and duration and severity of disease in MDD patients (P>0.05).(3) Compared with controls, MDD patients exhibited significant decrease FA values in frontal lobe(right superior frontal gyrus, bilateral precentral gyrus), temporal lobe (left middle temporal gyrus), right occipital lobe, left thalamus, and bilateral cerebelum(P<0.01).There was a significant positive correlation between four areas FA values in left cerebelum and the correct trials of WSCT (repectively, r=0.589, P=0.002; r=0.455, P=0.022; r=0.478, P=0.016; r=0.513, P=0.009), and a significant positive correlation between FA valus in left cerebelum and the categories of WSCT (r=0.564, P=0.003).There was a significant negative correlation between FA values in left cerebelum and duration (r=-0.411, P=0.041). No correlation was found between abnormal FA valus and severity of disease in MDD patients (P>0.05). (4) Compared with controls, MDD patients exhibited significant decrease ReHo values in frontal lobe (left superior frontal gyrus, left inferior frontal gyrus), temporal lobe (left superior temporal gyrus), occipital lobe (left middle occipital gyrus) and limbic system (bilateral posterior cingulate gyrus), and significant increase ReHo values in frontal lobe (right medial superior frontal gyrus, right middle frontal gyrus), limbic system (left parahippocampal gyrus, left anterior cingulate gyrus, bilateral hypothalamus) and cerebellum (right cerebellum, bilateral cerebellar tonsil).The ReHo values in left inferior frontal gyrus was positively correlated with the correct trials of WSCT(r=0.442, P=0.024), and negatively with the TMT-B completion time(r=-0.556, P=0.032). The ReHo value in left anterior cingulate gyrus was positively correlated with the total number of errors and perseverative errors of WSCT(repectively, r=0.450, P=0.021; r=0.411, P=0.037), and negatively with the correct trials of WSCT(r=-0.405, P=0.040). The ReHo values in left parahippocampal gyrus was negatively correlated with the correct trials of CPT2(r=-0.523, P=0.006).No correlation was found between abnormal ReHo values and duration and severity of disease in MDD patients (P>0.05).Compared with controls, MDD patients showed significantly increased functional connectivity in left ventral anterior cingulate gyrus and medial prefrontal cortex within DMN (P<0.05). There was a significant negitive correlation between functional connectivity values in left ventral anterior cingulate gyrus and medial prefrontal cortex and the correct trials of WSCT(r=-0.398, P=0.044).Conclusions:(1)The first-episode, treatment-naive MDD patients exhibiteded a wide range of cognitive impairment, especially in executive function and attention function. It showed that some cognitive function indicators were associated with age and education. No correlation was found between abnormal cognitive function and duration and severity of disease in MDD patients.(2) MDD patients showed significant lower gray matter density than healthy controls in frontal lobe, parietal lobe, temporal lobe, occipital lobe. Decreased gray matter density in left postcentral gyrus and left superior occipital gyrus may be invovled in the executive dysfunction. Lower gray matter density increase the risk of MDD episode, however, no correlation with the duration and severity of disease.(3) It showed that the white matter microstructure abnormalities in frontal lobe, temporal lobe, occipital lobe, thalamus, cerebelum in first-episode, treatment-naive MDD patients, suggesting that the abnormalities of brain white matter may be present early in the course of MDD. Abnormal fibers were involved in the cognitive and affective neural circuit including the prefrontal and limbic system. There were a wide range of upstream projection fibers from the cerebelum to the frontal lobe and limbic system.The white matter microstructure abnormalities may disrupt the neural circuit and thus contribute to the pathophysiology of MDD. It also found that the decreased white matter integrity in left cerebelum may be associated with progressed with the illness course, and thus be invovled in the the pathophysiology of executive function.(4) It showed that the abnormal brain activity in MDD in resting state fMRI. It found that ReHo abnormalities mainly in the frontal lobe, temporal lobe, occipital lobe, limbic system and cerebellum may disrupt the neural circuit and thus contribute to the pathophysiology of MDD. The study found that the existence of asymmetry in the basic state left and right prefrontal cortex, especially increased activity in the prefrontal dorsolateral local neuronal activity (DLPFC) and decresed activity in right DLPFC may be involved in the pathophysiology of MDD. In addition, the dysfunction in prefrontal function may conctribute to the neuropathology of executive impairment.(5)The first-episode, treatment-naive MDD patients showed the abnormal resting state DMN. The increased functional conneetivity in left ventral anterior cingulate gyrus and medial prefrontal cortex within DMN may conctribute to the neuropathology of executive impairment. |
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