Longitudinal diffusion weighted imaging of limbic regions in patients with major depressive disorder after 6 years and partial to full remission

2019 ◽  
Vol 287 ◽  
pp. 75-86 ◽  
Author(s):  
Kelly Doolin ◽  
Sinaoife Andrews ◽  
Angela Carballedo ◽  
Hazel McCarthy ◽  
Erik O'Hanlon ◽  
...  
2018 ◽  
Vol 31 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Michael Bauer ◽  
Nanco Hefting ◽  
Annika Lindsten ◽  
Mette Krog Josiassen ◽  
Mary Hobart

AbstractObjectiveTo evaluate brexpiprazole adjunctive to antidepressant therapies (ADTs) as maintenance treatment in patients with major depressive disorder with inadequate response to ADT, utilising a novel study design.MethodsThe study comprised an 8-week prospective treatment period with open-label ADT with double-blind placebo treatment and a 24-week randomised treatment period. Investigators and patients were blinded to treatment periods, randomisation criteria, and timing of randomisation. Patients with early response to open-label ADT were withdrawn at Week 6. Patients fulfilling criteria for inadequate response were randomised to ADT+brexpiprazole 1–3 mg/day, or ADT+placebo. The primary endpoint was full remission: Montgomery–Åsberg Depression Rating Scale (MADRS) total score ≤10 and ≥50% decrease from randomisation (i.e. baseline) in MADRS total score for at least 8 consecutive weeks.ResultsThe primary efficacy analysis failed to show a statistically significant difference between the proportions of patients on ADT+brexpiprazole (21.4%) and ADT+placebo (24.9%) achieving full remission; odds ratio: 0.83; p=0.2641. The secondary endpoint of change from baseline to Week 6 in MADRS total score showed no difference between ADT+brexpiprazole and ADT+placebo (−0.4; p=0.3259). The most frequent treatment-emergent adverse event (TEAE) in patients receiving ADT+brexpiprazole was weight increased (9.5% vs. 5.0% in ADT+placebo). The incidence of TEAEs leading to withdrawal in the randomised treatment period was 6.3% in the ADT+brexpiprazole group and 3.4% in the ADT+placebo group.ConclusionAdjunctive brexpiprazole did not differentiate from ADT+placebo on the primary endpoint of full remission. A number of design elements in this previously untried study design may have contributed to the study result. Brexpiprazole was well tolerated.


2019 ◽  
Vol 44 (6) ◽  
pp. 407-413 ◽  
Author(s):  
Jonathan Repple ◽  
Dario Zaremba ◽  
Susanne Meinert ◽  
Dominik Grotegerd ◽  
Ronny Redlich ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Jane A. Foster ◽  
Glen B. Baker ◽  
Serdar M. Dursun

Major depressive disorder (MDD) is a prominent cause of disability worldwide. Current antidepressant drugs produce full remission in only about one-third of MDD patients and there are no biomarkers to guide physicians in selecting the best treatment for individuals. There is an urgency to learn more about the etiology of MDD and to identify new targets that will lead to improved therapy and hopefully aid in predicting and preventing MDD. There has been extensive interest in the roles of the immune system and the gut microbiome in MDD and in how these systems interact. Gut microbes can contribute to the nature of immune responses, and a chronic inflammatory state may lead to increased responsiveness to stress and to development of MDD. The gut microbiome-immune system-brain axis is bidirectional, is sensitive to stress and is important in development of stress-related disorders such as MDD. Communication between the gut and brain involves the enteric nervous system (ENS), the autonomic nervous system (ANS), neuroendocrine signaling systems and the immune system, and all of these can interact with the gut microbiota. Preclinical studies and preliminary clinical investigations have reported improved mood with administration of probiotics and prebiotics, but large, carefully controlled clinical trials are now necessary to evaluate their effectiveness in treating MDD. The roles that several gut microbe-derived molecules such as neurotransmitters, short chain fatty acids and tryptophan play in MDD are reviewed briefly. Challenges and potential future directions associated with studying this important axis as it relates to MDD are discussed.


2006 ◽  
Vol 36 (6) ◽  
pp. 779-788 ◽  
Author(s):  
ULLA LESKELÄ ◽  
HEIKKI RYTSÄLÄ ◽  
ERKKI KOMULAINEN ◽  
TARJA MELARTIN ◽  
PETTERI SOKERO ◽  
...  

Background. Adverse life events and social support may influence the outcome of major depressive disorder (MDD). We hypothesized that outcome would depend on the level of depressive symptoms present at the outset, with those in partial remission being particularly vulnerable.Method. In the Vantaa Depression Study (VDS), patients with DSM-IV MDD were interviewed at baseline, and at 6 and 18 months. Life events were investigated with the Interview for Recent Life Events (IRLE) and social support with the Interview Measure of Social Relationships (IMSR) and the Perceived Social Support Scale – Revised (PSSS-R). The patients were divided into three subgroups at 6 months, those in full remission (n=68), partial remission (n=75) or major depressive episode (MDE) (n=50). The influence of social support and negative life events during the next 12 months on the level of depressive symptoms, measured by the Hamilton Rating Scale for Depression (HAMD), was investigated at endpoint.Results. The severity of life events and perceived social support influenced the outcome of depression overall, even after adjusting for baseline level of depression and neuroticism. In the full remission subgroup, both severity of life events and subjective social support significantly predicted outcome. However, in the partial remission group, only the severity of events, and in the MDE group, the level of social support were significant predictors.Conclusions. Adverse life events and/or poor perceived social support influence the medium-term outcome of all psychiatric patients with MDD. These factors appear to have the strongest predictive value in the subgroup of patients currently in full remission.


CNS Spectrums ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 64-77 ◽  
Author(s):  
Marie-Laure Cléry-Melin ◽  
Fabrice Jollant ◽  
Philip Gorwood

A lack of motivation and anhedonia represent frequent and pervasive symptoms in depression, although with poor specificity. Historically described as a response bias, reward-related impairments in depression may account for the important aspects of the cognitive impairments associated with diagnosis of major depressive disorder. Reward processing is a broad psychological construct that can be parsed into 3 distinct components known as “reinforcement learning” (learning), “reward responsiveness” (liking), and “motivation to obtain a reward” (wanting). Depressed patients respond hyposensitively to reward and maladaptively to punishment: this pattern is related to a dysfunction in the frontostriatal systems modulated by the monoamine systems; seems to be observed in medicated and unmedicated patients with depression and in healthy individuals with high levels of anhedonia; and could be observed in patients with a history of depression, even when in full remission. Considered to be cognitive impairments, reward-related-impairments may also constitute part of an underlying neurobiological vulnerability to major depressive disorder (MDD). For example, the reward-related impairment is state dependent and, more or less, correlated with symptom severity in some studies but has also been proposed as being trait like, with endophenotype characteristics, possibly contributing to the persistence of the disease or treatment resistance. The 3 core aspects of reward processing have specific neurobiological correlates that involve the ventral and dorsal striatum, lateral habenula, ventral tegmental area, orbitofrontal cortex, anterior cingulate cortex, and ventromedial and dorsolateral prefrontal cortex. These structures underline the important role of the dopaminergic mesolimbic pathway, but glutamate and serotonin could also have an important role, at least in some aspects of reward-related impairments.


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