Identification of antisense lncRNAs targeting GSK3β as a regulator in major depressive disorder

Epigenomics ◽  
2020 ◽  
Vol 12 (19) ◽  
pp. 1725-1738
Author(s):  
Zhifen Liu ◽  
Xinrong Li ◽  
Chen Chen ◽  
Ning Sun ◽  
Yanfang Wang ◽  
...  

Aim: To identify lncRNAs targeting GSK3β in MDD. Materials & methods: The levels of GSK3β and its three targeting lncRNAs (gsk3β antisense AS1, AS2 and AS3) were detected in 52 patients with major depressive disorder (MDD) before and after 8 weeks of escitalopram treatment. The functional study was evaluated using the silence of lncR-gsk3βAS2/3. The correlation between lncRNA-gsk3β and 89 MDD patients was analyzed. Human neuron progenitor cells were used to investigate the functional role of lncRNA-gsk3β in MDD. Results: All three lncRNAs were downregulated in MDD patients but upregulated after treatment. Inhibition of gsk3βAS2/3 reduced GSK3β expression and its phosphorylation levels in the neuron progenitor cells. Conclusion: Our findings suggest that lncRNA-gsk3βAS3 regulates GSK3β activity in MDD and has potential as a novel therapeutic target.

Author(s):  
Priya Vishal Naik ◽  
Prachi Datta Dalvi U.

The WHO theme for the year 2017 is Depression. Depression (major depressive disorder) is a common and serious medical illness that negatively affects how a person feels, thinks and behaves. Psychotherapy if incorporated along with medications can be of substantial help in depression. It is also called ‘talking therapy’ and is based on personal interaction with the patient. Patients suffering from this disorder do not easily accept it and hence do not feel the need to seek medical intervention or counselling. In this process the symptoms might get aggravated and suicidal tendency (which is the worst effect of this disease) may develop. So it is extremely essential for the patient, family and society to accept, talk, discuss and seek treatment for this disease. This ‘talking therapy’ is of utmost importance in today’s life where concept of privacy is taking its toll. This therapy is mentioned in Ayurveda as Aashwasan Chikitsa. Aashwasan Chikitsa consists of good, pleasing and benevolent thoughts, spiritual ideas, positive attitude, ethics and communication with near ones. So in the treatment of psychological disorders, along with medications counselling therapy plays a very important role. Finally counselling can act as a part of preventive, curative therapy and also aids to avoid recurrence in the patients of depression.


2020 ◽  
Author(s):  
Samuel David Clark

AbstractThe kappa opioid receptor (KOR) and its endogenous ligands dynorphins (DYN) have been implicated in the development or symptomatology of a variety of neuropsychiatric disorders. This review covers a brief history of the development of KOR agonists and antagonists, their effects in healthy volunteers, and the potential role of DYN/KOR dysfunction in schizophrenia and major depressive disorder from a translational perspective. The potential role of DYN/KOR dysfunction in schizophrenia is based on several lines of evidence. Selective KOR agonists induce affective states in healthy volunteers with similarities to the symptoms of schizophrenia. Studies have shown increased DYN in patients with schizophrenia, although the data have been mixed. Finally, meta-analytic data have shown that opioid antagonists are associated with reductions in the symptoms of schizophrenia. The potential role of DYN/KOR dysfunction in major depressive disorder is also based on a combination of preclinical and clinical data. Selective KOR agonists have shown pro-depressive effects in human volunteers, while selective KOR antagonists have shown robust efficacy in several preclinical models of antidepressant activity. Small studies have shown that nonselective KOR antagonists may have efficacy in treatment-resistant depression. Additionally, recent clinical data have shown that the KOR may be an effective target for treating anhedonia, a finding relevant to both schizophrenia and depression. Finally, recommendations are provided for translating preclinical models for schizophrenia and major depressive disorder into the clinic.


2017 ◽  
Vol 41 (S1) ◽  
pp. S529-S529
Author(s):  
B. Grancini ◽  
B. Dell’Osso ◽  
L. Cremaschi ◽  
F. De Cagna ◽  
B. Benatti ◽  
...  

IntroductionMajor depressive disorder (MDD) is a prevalent burdensome disease, which frequently remains untreated. The duration of untreated illness (DUI) is modifiable parameter and a valid predictor of outcome. Previous investigation in patients with MDD revealed a DUI of different years, while recent reports have documented a reduction of DUI across time, in patients with different psychiatric disorders.Objectives/aimsThe present study was aimed to investigate potential differences in terms of DUI and related variables in patients with MDD across time.MethodsAn overall sample of 188 patients with MDD was divided in two subgroups on the basis of their epoch of onset (onset before and after year 2000). DUI and other onset-related variables were assessed through a specific questionnaire and compared between the two subgroups.ResultsThe whole sample showed a mean DUI of approximately 4.5 years, with a lower value in patients with more recent onset compared to the other subgroup (27.1 ± 42.6 vs. 75.8 ± 105.2 months, P < .05). Moreover, patients with onset after 2000 reported higher rates of onset-related stressful events and lower ones for benzodiazepines prescription (65% vs. 81%; P = 0.02; 47% vs. 30%; P = 0.02).ConclusionsThe comparison of groups with different epochs of onset showed a significant reduction in terms of DUI and benzodiazepines prescription, and a higher rate of onset-related stressful events in patients with a more recent onset. Reported findings are of epidemiologic and clinical relevance in order to evaluate progress and developments in the diagnostic and therapeutic pathways of MDD in Italian and other countries.Disclosure of interestThe authors have not supplied their declaration of competing interest.


2013 ◽  
Vol 37 (8) ◽  
pp. 1336-1345 ◽  
Author(s):  
Sandra Odebrecht Vargas Nunes ◽  
Heber Odebrecht Vargas ◽  
Eduardo Prado ◽  
Decio Sabbatini Barbosa ◽  
Luiz Picoli de Melo ◽  
...  

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