Cytokine alterations and cognitive impairment in major depressive disorder: From putative mechanisms to novel treatment targets

Author(s):  
Błażej Misiak ◽  
Jan Aleksander Beszłej ◽  
Kamila Kotowicz ◽  
Monika Szewczuk-Bogusławska ◽  
Jerzy Samochowiec ◽  
...  
Brain ◽  
2018 ◽  
Vol 141 (12) ◽  
pp. 3457-3471 ◽  
Author(s):  
Jiayuan Xu ◽  
Qiaojun Li ◽  
Wen Qin ◽  
Mulin Jun Li ◽  
Chuanjun Zhuo ◽  
...  

Abstract Depression increases the conversion risk from amnestic mild cognitive impairment to Alzheimer’s disease with unknown mechanisms. We hypothesize that the cumulative genomic risk for major depressive disorder may be a candidate cause for the increased conversion risk. Here, we aimed to investigate the predictive effect of the polygenic risk scores of major depressive disorder-specific genetic variants (PRSsMDD) on the conversion from non-depressed amnestic mild cognitive impairment to Alzheimer’s disease, and its underlying neurobiological mechanisms. The PRSsMDD could predict the conversion from amnestic mild cognitive impairment to Alzheimer’s disease, and amnestic mild cognitive impairment patients with high risk scores showed 16.25% higher conversion rate than those with low risk. The PRSsMDD was correlated with the left hippocampal volume, which was found to mediate the predictive effect of the PRSsMDD on the conversion of amnestic mild cognitive impairment. The major depressive disorder-specific genetic variants were mapped into genes using different strategies, and then enrichment analyses and protein–protein interaction network analysis revealed that these genes were involved in developmental process and amyloid-beta binding. They showed temporal-specific expression in the hippocampus in middle and late foetal developmental periods. Cell type-specific expression analysis of these genes demonstrated significant over-representation in the pyramidal neurons and interneurons in the hippocampus. These cross-scale neurobiological analyses and functional annotations indicate that major depressive disorder-specific genetic variants may increase the conversion from amnestic mild cognitive impairment to Alzheimer’s disease by modulating the early hippocampal development and amyloid-beta binding. The PRSsMDD could be used as a complementary measure to select patients with amnestic mild cognitive impairment with high conversion risk to Alzheimer’s disease.


2021 ◽  
Vol 73 (12) ◽  
pp. 786-792
Author(s):  
Doonyaporn Wongsawaeng ◽  
Orasa Chawalparit ◽  
Siriwan Piyapittayanan ◽  
Tanyaluck Thientunyakit ◽  
Weerasak Muangpaisan ◽  
...  

Objective: Depression among older adults is frequently an early symptom of cognitive decline, and is believed to be a risk factor for Alzheimer’s disease (AD). Hippocampal subfield volume loss is found in both mild cognitive impairment (MCI) and major depressive disorder (MDD). We aimed to investigate the potential of MR hippocampal subfield volumetry for discriminating among healthy older adults (HOA) and older adults with MCI or MDD. Materials and Methods: Seventy age-matched subjects (29 non-depressed MCI, 12 MDD, and 29 HOA) underwent 3-Tesla MR imaging (MRI) with high-resolution 3D-T1W-TFE whole brain. Hippocampal subfield volumetric measurements were performed using FreeSurfer software to distinguish among MCI, MDD, and HOA. Subgroup analysis with amyloid PET result was also performed.Results: Significantly smaller bilateral hippocampal tail volume was observed in MCI compared to HOA (p=0.004 and p=0.04 on the left and right side, respectively). The same comparative finding was observed at left HATA (hippocampus-amygdala-transition-area) of MCI (p=0.046). Other regions showed non-significantly smaller size in MCI than in HOA [left molecular layer HP (p=0.06), left whole hippocampus (p=0.06), and left CA1 (p=0.07)]. There was a non-significant trend toward smaller size in almost all 13 subfield hippocampal regions of MCI compared to MDD, even in subgroup analysis with amyloid PET result.Conclusion: MR hippocampal subfield volumetry may have value in routine clinical practice for screening individuals with MCI, and may be a valuable adjunct to amyloid PET study for very early-stage diagnosis of AD.


2018 ◽  
Vol 238 ◽  
pp. 228-232 ◽  
Author(s):  
Danielle S. Cha ◽  
Nicole E. Carmona ◽  
Nelson B. Rodrigues ◽  
Rodrigo B. Mansur ◽  
Yena Lee ◽  
...  

BJPsych Open ◽  
2020 ◽  
Vol 6 (4) ◽  
Author(s):  
Katie M. Douglas ◽  
Melissa Milanovic ◽  
Richard J. Porter ◽  
Christopher R. Bowie

Background Cognitive impairment is considered a core feature of major depressive disorder (MDD) and research into psychological treatments aiming to address cognitive impairment are gaining momentum. Compared with the well-established research base of cognitive treatment trials in schizophrenia, including meta-analyses, mood disorder research is much more preliminary. Aims To focus on identifying the important factors to consider in developing larger-scale psychological treatment trials targeting cognitive impairment in mood disorders. Trial design recommendations have been published for cognitive treatment trials in bipolar disorder. Method An in-depth discussion of methodological considerations in the development of cognitive treatment trials for MDD. Results Methodological considerations include: screening for, and defining, cognitive impairment; mood state when cognitive intervention begins; medication monitoring during cognitive interventions; use of concomitant therapy; level of therapist involvement; duration and dose of treatment; choice of specific cognitive training exercises; home practice; improving adherence; appropriate comparison therapies in clinical trials; and choice of primary outcomes. Conclusions As well as guidance for clinical trial development, this review may be helpful for clinicians wanting to provide cognitive interventions for individuals with MDD.


2017 ◽  
Vol 41 (S1) ◽  
pp. S143-S144
Author(s):  
S. Fedorová ◽  
M. Blažková ◽  
P. Humpolíček ◽  
R. Barteček

IntroductionCognitive impairment in patients with depressive disorder is a subject of intensive research.ObjectivesThis study deals with the cognitive impairment in patients with severe depressive episode with psychotic symptoms and patients with major depressive disorder during the acute state of illness.AimsThe aim was to define domains and the level of cognitive impairment in both groups of patients.The next aim was to compare profiles of cognitive impairment in both groups of patients.The last aim was to find out a relationship between cognitive performance and severity of depressive episode during the acute state of illness.MethodsWe have used neuropsychological test battery (Auditory–Verbal Learning Test, Rey-Osterrieth Complex Figure Test, Logical Memory, Digit span test, Trail making test, Verbal Fluency Test, Block Design and Benton Visual Retention Test) for the evaluation of the cognitive functions in patients with severe depressive episode with psychotic symptoms (n = 5) and patients with major depressive disorder (n = 8).ResultsWe found cognitive impairment in all examined domains in both groups of patients.More profound cognitive impairment was found in patients with severe depressive episode with psychotic symptoms, particularly in visual memory, visuo-constructive abilities, speed of cognitive processing and executive functions. We found no correlation between cognitive performance and severity of depressive episodes.ConclusionsOur findings suggest a strong correlation between psychotic symptoms in depression and cognitive performance.


2010 ◽  
Vol 32 (2) ◽  
pp. 64-64
Author(s):  
Diana Moitinho Bezerra ◽  
Quirino Cordeiro ◽  
Eduardo Yoshio Nakano ◽  
Homero Vallada ◽  
Cássio Machado de Campos Bottino

2021 ◽  
Vol 15 ◽  
Author(s):  
Yujiao Wen ◽  
Xuemin Zhang ◽  
Yifan Xu ◽  
Dan Qiao ◽  
Shanshan Guo ◽  
...  

The lifetime prevalence of major depressive disorder (MDD) in adolescents is reported to be as high as 20%; thus, MDD constitutes a significant social and public health burden. MDD is often associated with nonsuicidal self-injury (NSSI) behavior, but the contributing factors including cognitive function have not been investigated in detail. To this end, the present study evaluated cognitive impairment and psychosocial factors in associated with MDD with NSSI behavior. Eighteen and 21 drug-naïve patients with first-episode MDD with or without NSSI (NSSI+/– group) and 24 healthy control subjects (HC) were enrolled in the study. The Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Adolescent Self-injury Questionnaire, Beck Scale for Suicide Ideation–Chinese Version (BSI-CV), Shame Scale for Middle School Students, Sensation Seeking Scale (SSS) and Childhood Trauma Questionnaire (CTQ) were used to assess depression-related behaviors, and event-related potentials (ERPs) were recorded as a measure of cognitive function. The latency of the N1, N2, P3a, P3b, and P50 components of ERPs at the Cz electrode point; P50 amplitude and P50 inhibition (S1/S2) showed significant differences between the 3 groups. CTQ scores also differed across three groups, and the NSSI– and NSSI+ groups showed significant differences in scores on the Shame Scale for Middle School Students. Thus, cognitive function was impaired in adolescents with MDD with NSSI behavior, which was mainly manifested as memory decline, attention and executive function deficits, and low anti-interference ability. We also found that childhood abuse, lack of social support, and a sense of shame contributed to NSSI behavior. These findings provide insight into the risk factors for MDD with NSSI behavior, which can help mental health workers more effectively diagnose and treat these patients.


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