Preliminary study on cerebrospinal fluid proteomics of Erxian Decoction against neurogenesis impairment in late-onset depression / 中国中药杂志

This study aims to elucidate the underlying mechanism of Erxian Decoction(EXD) against neurogenesis impairment in late-onset depression(LOD) rats based on cerebrospinal fluid(CSF) proteomics. A total of 66 20-21-month-old male Wistar rats were randomized into naturally aged(AGED) group, LOD group, and EXD group. All rats received chronic unpredictable mild stress(CUMS) for 6 weeks for LOD modeling except for the AGED group. During the modeling, EXD group was given EXD(ig, twice a day at 4 g·kg~(-1)) and other groups received equivalent amount of normal saline(ig). After modeling, a series of behavioral tests, such as sucrose preference test(SPT), open-field test(OFT), forced swimming test(FST), and Morris water maze test(MWMT) were performed. Immunofluorescence method was used to detect the number of Ki-67/Nesti-positive cells and BrdU/DCX-positive cells in the hippocampal DG area of each group. High-concentration corticosterone(CORT) was combined with D-galactose(D-gal) to simulate the changes of LOD-related stress and aging and the proliferation and differentiation of primary neural stem cells of hippocampus in each group were observed. Data independent acquisition(DIA)-mass spectrometry(MS) was used to analyze the differential proteins in CSF among groups and bioinformatics analysis was performed to explore the biological functions of the proteins. Behavioral tests showed that sucrose consumption in SPT, total traveling distance in OFT, and times of crossing the platform in MWMT were all reduced(P<0.01) and the immobility time in FST was prolonged(P<0.01) in the LOD group compared with those in the AGED group, suggesting that LOD rats had developed depression symptoms such as anhedonia, decreased locomotor activity ability, and cognitive dysfunction. Behavioral abnormalities were alleviated(P<0.01, P<0.05) in the EXD group as compared with those in the LOD group. Immunofluorescence results demonstrated that Ki-67/Nesti-positive cells and BrdU/DCX-positive cells in the hippocampal DG area were fewer(P<0.05) in LOD group than in the AGED group, and the positive cells in the EXD group were more(P<0.05) than those in the LOD group. In vitro experiment showed that the proliferation and differentiation of primary hippocampal neural stem cells under the CORT+D-gal treatment were reduced(P<0.01). The proliferation rate of neural stem cells decreased(P<0.05) in CORT+D-gal+LOD-CSF group but increased(P<0.01) in CORT+D-gal+EXD-CSF group compared with that in the CORT+D-gal group. A total of 2 620 proteins were identified from rat CSF, with 135 differential proteins between the LOD group and AGED group and 176 between EXD group and LOD group. GDF11, NrCAM, NTRK2, and GhR were related to neurogenesis and 39 differential proteins were regulated by both LOD and EXD. EXD demonstrated obvious anti-LOD effect, as it improved the locomotor activity ability and cognitive function of LOD rats and protected the proliferation and differentiation of hippocampal neural stem cells. EXD exerts anti-LOD effect by regulating the proteins related to neurogenesis in CSF, such as GDF11, NrCAM, NTRK2, and GhR and maintaining hippocampal neurogenesis.

Correlation analysis of depression severity and neurocognitive function in patients with late-onset depression / 预防医学

Objective@#To explore the correlation between depression severity and neurocognitive function in patients with late-onset depression .@*Methods@#The patients with late-onset depression treated in Jinhua Second hospital from February 2015 to December 2017 were assigned into the mild,moderate and severe groups according to the severity of depression assessed by the Hamilton Depression Scale-17（HAMD-17）. At the same time,some healthy persons were selected as the control group. Wisconsin Card Sorting Test（WCST）,Verbal Fluency Test（VFT）and Stroop Test were carried out,and the scores of these tests were compared in the four groups. The correlations of WCST, VFT, Stroop Test and HAMD-17 scores were analyzed .@*Results@# There were 32,28,35 and 35 subjects involved in the mild,moderate,severe and control group,respectively. The subjects of the mild group,moderate group and severe group had more total errors,perseverative responses and perseverative errors than the control group,and less percent conceptual level responses than the control group （all P<0.05）. The total errors,perseverative responses,perseverative errors and percent perseverative errors increased and the percent conceptual level responses decreased gradually with the severity of depression（all P<0.05）. The correct numbers of Stroop-consistent group and VFT in the severe group were less than those in the control,mild and moderate group（all P<0.05）,which was significantly different between the mild,moderate and control group （P>0.05）. The HAMD-17 scores were negatively correlated with the correct numbers of Stroop congruent group（r=-0.448,P<0.001）and VFT（r=-0.401,P<0.001）,and were positively correlated with perseverative responses in the WCST（r=0.784,P<0.001） .@*Conclusion@#The neurocognitive impairment in patients with late-onset depression aggravated with the severity of depression.

The effects of the age onset on cognitive function in late life depression / 中国神经精神疾病杂志

Objective To investigate the cognitive characteristics and vascular risk factor between early onset de?pression and late onset depression in late life depression and provide a clue to elucidate the cause of cognitive impairment in late life depression. Method Fifty-six late life depression patients were recruited in our hospital, including 29 early on?set depression patients and 27 late onset depression patients. 25 controls were recruited from Guangzhou community. Cog?nitive evaluation were conducted in all the patients and controls, including MMSE, memory, attention, language, visuospa?tial abilities,executive function and Framingham vascular risk assessment, and analyze the cognitive and vascular risk be?tween the patients. Result There were statistically significant differences in overall cognitive assessment MMSE(24.8 ± 2.9,22.8±3.5,P=0.030), symbol digit modalities test(SDMT)(29.8±10.5, 22.9±11.8, P=0.028), clock drawing test(CDT) (3.6 ± 0.8, 2.9 ± 1.3, P=0.006) and trail making test(TMT) (60.4 ± 20.6, 74.7 ± 28.8, P=0.027) between late onset depression and early onset depression. In addition, the score of vascular risk assessment was significant between late onset depression and early onset depression(14.6±2.7,12.3±2.2,P=0.001). Conclusion Compare with early onset depression, late onset de?pression has much severe cognitive impairments and increased vascular risk factors.

The Relationship between Late-Onset Depression and Alzheimer's Disease

OBJECTIVES: With the elderly population rising sharply, there is a rising interest in dementia, and recently researches on risk factors for dementia, particularly of Alzheimer's disease have been actively conducted. The purpose of this research is to examine the effect of the late-onset depression as a risk factor for Alzheimer's disease. METHODS: The subjects were divided into the group of the patients who were diagnosed with depression in the National Health Insurance Corporation Ilsan Hospital from March 1, 2000 to December 31, 2009 and the corresponding control group, which was the group of the patients who were diagnosed with osteoarthritis for the same period. Of the above patients, the following cases were excluded from the final analysis. The excluded cases were those who were first diagnosed with either of the two diseases at the age of less than 50, and those who were diagnosed with major psychiatric disorder or neurologic disorder. As a result, a total of 5,347 people, made up of 1,697 depression patients and 3,650 osteoarthritis patients, were selected. Two groups were compared through survival analysis. RESULTS: Form the Log-Rank tests, it could be confirmed that there were significant differences (p<0.01) among the two groups. Even when many confounding factors including age and gender were controlled, the degree of occurrence of Alzheimer's disease was found to be higher in the group of late-onset depression patients than in the group of osteoarthritis patients (HR : 2.53-2.80). CONCLUSION: The late-onset depression can become independently the risk factor for Alzheimer's disease. Therefore it can be expected that the rate of occurrence of Alzheimer's disease may be reduced through active medical treatment of depression.

Inhibitory control dysfunction of late-onset depression: an event-related fMRI study / 中华行为医学与脑科学杂志

Objective To investigate the neural circuit of inhibitory control in late-onset depressed patients(LOD) by functional magnetic resonance imaging(fMRI). Methods Fourteen late-onset depressed patients (LOD group) and thirteen elderly healthy subjects( control group) were recruited. The two groups were age, gender, and education matched. All the subjects performed a visual Go/Nogo task during the fMRI scan. Erect or inverted isosceles triangular figures were used for stimuli. The two groups were instructed to press a button as quickly and correctly as possible when the erect triangular figures(Go) were presented, but not to response when the inverted triangular figures(Nogo) were presented. The differences of brain activation between the two groups were compared. Results ( 1 ) During Go trials, there were no significant differences in reaction time and hit rate between the two groups (P ＞ 0.05 ). During Nogo trials, however, the late-onset depressed patients showed much higher false alarm rate(0.09 ±0.06) compared with control group(0.04 ±0.02) (P＜0.05＝. (2) During Go trials , LOD group showed significantly greater activity in left postcentral gyrus, left inferior parietal lobule, right precentral gyrus, left paracentral lobule, right inferior parietal lobule, right anterior cingulate cortex, left middle frontal gyrus, right middle frontal gyrus, right superior frontal gyrus compared with the control group. Whereas during Nogo trials, LOD group exhibited greater activity in left inferior parietal lobule and left middle frontal gyrus compared with the control group. Conclusion This study suggests that inhibitory control dysfunction in late-onset depressed patients may be closely related to frontostriatal circuit impairment. Over activation in left middle frontal gyrus, right middle frontal gyrus and right anterior cingulate cortex may contribute to the pathogenesis of late-onset depression.

Comparison of Clinical Symptoms between Early and Late Onset Depression in Elderly Depressive Patients in Korea

OBJECTIVES: Clinical differences between elderly patients with early and late onset depression have been described although these have been inconsistent. We aimed to compare differences of clinical symptoms using the 17 items Hamilton Rating Scale for Depression(HAM-D-17) between two groups. METHODS: Data of 175 elderly patients with a diagnosis of major depressive disorder according to DSM-IV from January 2005 to November 2009 were collected. Seventy five patients were early onset depression and one hundred patients were late onset depression. Depressive symptoms were assessed by the 17-item Hamilton Rating Scale for depression. RESULTS: There were some differences in HAM-D-17 scores between early and late onset depression. Early onset depression patients scored significantly higher in retardation(t = 2.41, p = 0.017) and somatic symptoms( general)(t = 2.37, p = 0.019) than late onset depression patients. CONCLUSION: We concluded that early onset depression patients have more severe psychomotor retardation and general somatic symptoms than late onset depression patients in Korea. Because of some limitations of this study, further investigations will be needed to validate this study results.

Vascular Depression

This article reviews the recent literature of 'vascular depression' hypothesis. The 'vascular depression' hypothesis is supported by the evidence for associations between vascular disease and late-onset depression and between ischemic brain lesions and distinctive depressive symptoms. Patients with vascular depression is characterized by late-onset, absence of family history of mood disorders, evidence of vascular disease or vascular risk factors, cognitive impairment, psychomotor retardation, limited depressive ideation, poor insight, and disability. Vascular depression may be the entity suitable for studies of mechanism of depression. Depression in later life is often under-diagnosed and under-treated. Drugs used in the prevention and treatment of cerebrovascular disease may be shown to be beneficial influences for the prevention of vascular depression. Combined treatment with antidepressant and cognitive-behavioral rehabilitation will be more helpful. In the future, developments in structural and functional imaging, electrophysiology, chronobiology, and genetics will permit the knowledge of the association between mood disorders and brain lesions.