Major depression is the most common mental disorder and a leading cause of years lived with disability. In addition to the burden attributed to depressive symptoms and reduced daily life functioning, ...people with major depression are at increased risk of premature mortality, particularly due to cardiovascular diseases. Several studies point to a bi-directional relation between major depression and cardiovascular diseases, thereby indicating that both diseases may share common pathophysiological pathways. These include lifestyle factors (e.g. physical activity, smoking behavior), dysfunctions of endocrine systems (e.g. hypothalamus-pituitary adrenal axis), and a dysbalance of pro- and anti-inflammatory factors. Furthermore, recent research point to the role of epigenomic and proteomic factors, that are reviewed here with a particular focus on the mitochondrial energy metabolism.
•Major depression and cardiovascular diseases share several pathophysiological pathways.•These include lifestyle factors, stress system activation, immune dysregulation, epigenomic and metabolomics alterations.•Both disorders share genes involved in energy metabolism, stress system, circadian rhythm, inflammation, neurotransmission.•Central metabolic pathways for ATP production are disturbed in major depression and cardiovascular disease.•This points to the role of mitochondrial dysfunction and dysfunction of glucose transporter proteins.•These results are promising factors to stimulate further research in energy metabolism dysfunction in both disorders.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The current article discusses assertiveness training, a once highly popular area of investigation that has been neglected in recent years by the field of psychotherapy. A substantial body of research ...indicates that assertiveness is a relevant factor associated with a variety of clinical problems, populations, and contexts, and that assertiveness training is a valuable transdiagnostic intervention. Despite its demonstrated importance, research on assertiveness and assertiveness training as a stand‐alone treatment within clinical psychology has diminished drastically. We review the history of assertiveness training, revisit early research evidence for assertiveness training in treating various clinical problems, discuss the current status of assertiveness training, consider issues of clinical implementation, and comment on how the variables accounting for unassertiveness map onto the NIMH RDoC funding priorities.
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BFBNIB, CEKLJ, FFLJ, FZAB, GIS, IJS, KILJ, NLZOH, NUK, ODKLJ, OILJ, PEFLJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background:
Findings of substantial remaining morbidity in treated major depressive disorder (MDD) led us to review controlled trials of treatments aimed at preventing early relapses or later ...recurrences in adults diagnosed with MDD to summarize available data and to guide further research.
Methods:
Reports (n = 97) were identified through systematic, computerized literature searching up to February 2015. Treatment versus control outcomes were summarized by random-effects meta-analyses.
Results:
In 45 reports of 72 trials (n = 14 450 subjects) lasting 33.4 weeks, antidepressants were more effective than placebos in preventing relapses (response rates RR = 1.90, confidence interval CI: 1.73–2.08; NNT = 4.4; p < 0.0001). In 35 reports of 37 trials (n = 7253) lasting 27.0 months, antidepressants were effective in preventing recurrences (RR = 2.03, CI 1.80–2.28; NNT = 3.8; p < 0.0001), with minor differences among drug types. In 17 reports of 22 trials (n = 1 969) lasting 23.7 months, psychosocial interventions yielded inconsistent or inconclusive results.
Conclusions:
Despite evidence of the efficacy of drug treatment compared to placebos or other controls, the findings further underscore the substantial, unresolved morbidity in treated MDD patients and strongly encourage further evaluations of specific, improved individual and combination therapies (pharmacological and psychological) conducted over longer times, as well as identifying clinical predictors of positive or unfavorable responses and of intolerability of long-term treatments in MDD.
•We identified 84 diverse psychopathological features during prodromes.•Prevalence of 19 prodromal factors appeared to differ among final diagnoses.•Seven factors significantly distinguished subjects ...with psychotic MDD vs. BD-I.•Nine features distinguished subjects with SzAffD vs. psychotic MDD or BD-I.•Early psychopathology predicted final diagnosis of psychotic affective and SzAffD.
Study aims were to analyze psychopathological details of prodromes leading to first-lifetime psychotic episodes and apply them to improve prediction of final diagnoses.
Comprehensive records of subjects with final diagnoses of bipolar I (BD-I; n = 216), schizoaffective (SzAffD; n = 71), or psychotic major-depressive (MDD; n = 42) disorders in the Harvard-McLean First-Psychotic Episode Project were analyzed to identify psychopathological details of prodromes leading to first-lifetime episodes with psychotic features and their ability to predict final diagnoses tested with multivariable logistic regression modeling.
While held blind to final diagnoses, we identified 84 distinct psychopathological characteristics of prodromes to first-psychotic episodes, including perceptual disturbances, affective symptoms, sleep disturbances, onset rate, and duration. Prevalence of 19 factors appeared to differ among final diagnoses, and were tested with multivariable regression modeling. Significantly and independently more associated with final diagnoses of MDD than BD-I were 7 features: suicidal ideation, somatic delusions, anorexia, lack of insomnia, older presenting age, depressive symptoms, and lack of impulsivity; 9 others were associated more with later SzAffD than MDD or BD-I: lack of insomnia, homicidal behavior, lack of excitement, visual hallucinations, command hallucinations, longer prodrome, male sex, responding to internal stimuli, and younger age at presentation.
Historical-retrospective and prospective assessments may have misidentified some prodromal features, and subjects with final psychotic-MDD diagnosis were relatively few.
Psychopathological features identified during prodromes leading to first-episodes with psychotic features predicted and distinguished among final diagnoses of MDD, BD-I, and SzAffD. The findings add to growing impressions that early psychopathology has value in predicting final diagnoses of major affective and schizoaffective disorders.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Major depressive disorders have a significant impact on children and adolescents, including on educational and vocational outcomes, interpersonal relationships, and physical and mental ...health and well‐being. There is an association between major depressive disorder and suicidal ideation, suicide attempts, and suicide. Antidepressant medication is used in moderate to severe depression; there is now a range of newer generations of these medications.
Objectives
To investigate, via network meta‐analysis (NMA), the comparative effectiveness and safety of different newer generation antidepressants in children and adolescents with a diagnosed major depressive disorder (MDD) in terms of depression, functioning, suicide‐related outcomes and other adverse outcomes. The impact of age, treatment duration, baseline severity, and pharmaceutical industry funding was investigated on clinician‐rated depression (CDRS‐R) and suicide‐related outcomes.
Search methods
We searched the Cochrane Common Mental Disorders Specialised Register, the Cochrane Library (Central Register of Controlled Trials (CENTRAL) and Cochrane Database of Systematic Reviews (CDSR)), together with Ovid Embase, MEDLINE and PsycINFO till March 2020.
Selection criteria
Randomised trials of six to 18 year olds of either sex and any ethnicity with clinically diagnosed major depressive disorder were included. Trials that compared the effectiveness of newer generation antidepressants with each other or with a placebo were included. Newer generation antidepressants included: selective serotonin reuptake inhibitors; selective norepinephrine reuptake inhibitors (SNRIs); norepinephrine reuptake inhibitors; norepinephrine dopamine reuptake inhibitors; norepinephrine dopamine disinhibitors (NDDIs); and tetracyclic antidepressants (TeCAs).
Data collection and analysis
Two reviewers independently screened titles/s and full texts, extracted data, and assessed risk of bias. We analysed dichotomous data as Odds Ratios (ORs), and continuous data as Mean Difference (MD) for the following outcomes: depression symptom severity (clinician rated), response or remission of depression symptoms, depression symptom severity (self‐rated), functioning, suicide related outcomes and overall adverse outcomes. Random‐effects network meta‐analyses were conducted in a frequentist framework using multivariate meta‐analysis. Certainty of evidence was assessed using Confidence in Network Meta‐analysis (CINeMA). We used "informative statements" to standardise the interpretation and description of the results.
Main results
Twenty‐six studies were included. There were no data for the two primary outcomes (depressive disorder established via clinical diagnostic interview and suicide), therefore, the results comprise only secondary outcomes. Most antidepressants may be associated with a "small and unimportant" reduction in depression symptoms on the CDRS‐R scale (range 17 to 113) compared with placebo (high certainty evidence: paroxetine: MD ‐1.43, 95% CI ‐3.90, 1.04; vilazodone: MD ‐0.84, 95% CI ‐3.03, 1.35; desvenlafaxine MD ‐0.07, 95% CI ‐3.51, 3.36; moderate certainty evidence: sertraline: MD ‐3.51, 95% CI ‐6.99, ‐0.04; fluoxetine: MD ‐2.84, 95% CI ‐4.12, ‐1.56; escitalopram: MD ‐2.62, 95% CI ‐5.29, 0.04; low certainty evidence: duloxetine: MD ‐2.70, 95% CI ‐5.03, ‐0.37; vortioxetine: MD 0.60, 95% CI ‐2.52, 3.72; very low certainty evidence for comparisons between other antidepressants and placebo).
There were "small and unimportant" differences between most antidepressants in reduction of depression symptoms (high‐ or moderate‐certainty evidence).
Results were similar across other outcomes of benefit.
In most studies risk of self‐harm or suicide was an exclusion criterion for the study. Proportions of suicide‐related outcomes were low for most included studies and 95% confidence intervals were wide for all comparisons. The evidence is very uncertain about the effects of mirtazapine (OR 0.50, 95% CI 0.03, 8.04), duloxetine (OR 1.15, 95% CI 0.72, 1.82), vilazodone (OR 1.01, 95% CI 0.68, 1.48), desvenlafaxine (OR 0.94, 95% CI 0.59, 1.52), citalopram (OR 1.72, 95% CI 0.76, 3.87) or vortioxetine (OR 1.58, 95% CI 0.29, 8.60) on suicide‐related outcomes compared with placebo. There is low certainty evidence that escitalopram may "at least slightly" reduce odds of suicide‐related outcomes compared with placebo (OR 0.89, 95% CI 0.43, 1.84). There is low certainty evidence that fluoxetine (OR 1.27, 95% CI 0.87, 1.86), paroxetine (OR 1.81, 95% CI 0.85, 3.86), sertraline (OR 3.03, 95% CI 0.60, 15.22), and venlafaxine (OR 13.84, 95% CI 1.79, 106.90) may "at least slightly" increase odds of suicide‐related outcomes compared with placebo.
There is moderate certainty evidence that venlafaxine probably results in an "at least slightly" increased odds of suicide‐related outcomes compared with desvenlafaxine (OR 0.07, 95% CI 0.01, 0.56) and escitalopram (OR 0.06, 95% CI 0.01, 0.56). There was very low certainty evidence regarding other comparisons between antidepressants.
Authors' conclusions
Overall, methodological shortcomings of the randomised trials make it difficult to interpret the findings with regard to the efficacy and safety of newer antidepressant medications. Findings suggest that most newer antidepressants may reduce depression symptoms in a small and unimportant way compared with placebo. Furthermore, there are likely to be small and unimportant differences in the reduction of depression symptoms between the majority of antidepressants. However, our findings reflect the average effects of the antidepressants, and given depression is a heterogeneous condition, some individuals may experience a greater response. Guideline developers and others making recommendations might therefore consider whether a recommendation for the use of newer generation antidepressants is warranted for some individuals in some circumstances. Our findings suggest sertraline, escitalopram, duloxetine, as well as fluoxetine (which is currently the only treatment recommended for first‐line prescribing) could be considered as a first option.
Children and adolescents considered at risk of suicide were frequently excluded from trials, so that we cannot be confident about the effects of these medications for these individuals. If an antidepressant is being considered for an individual, this should be done in consultation with the child/adolescent and their family/caregivers and it remains critical to ensure close monitoring of treatment effects and suicide‐related outcomes (combined suicidal ideation and suicide attempt) in those treated with newer generation antidepressants, given findings that some of these medications may be associated with greater odds of these events. Consideration of psychotherapy, particularly cognitive behavioural therapy, as per guideline recommendations, remains important.
Abstract Background Cognitive models predict that vulnerability to major depressive disorder (MDD) is due to a bias to blame oneself for failure in a global way resulting in excessive self-blaming ...emotions, decreased self-worth, hopelessness and depressed mood. Clinical studies comparing the consistency and coherence of these symptoms in order to probe the predictions of the model are lacking. Methods 132 patients with remitted MDD and no relevant lifetime co-morbid axis- I disorders were assessed using a phenomenological psychopathology-based interview (AMDP) including novel items to assess moral emotions ( n =94 patients) and the structured clinical interview-I for DSM-IV-TR. Cluster analysis was employed to identify symptom coherence for the most severe episode. Results Feelings of inadequacy, depressed mood, and hopelessness emerged as the most closely co-occurring and consistent symptoms (≥90% of patients). Self-blaming emotions occurred in most patients (>80%) with self-disgust/contempt being more frequent than guilt, followed by shame. Anger or disgust towards others was experienced by only 26% of patients. 85% of patients reported feelings of inadequacy and self-blaming emotions as the most bothering symptoms compared with 10% being more distressed by negative emotions towards others. Limitations Symptom assessment was retrospective, but this is unlikely to have biased patients towards particular emotions relative to others. Conclusions As predicted, feelings of inadequacy and hopelessness were part of the core depressive syndrome, closely co-occurring with depressed mood. Self-blaming emotions were highly frequent and bothering but not restricted to guilt. This calls for a refined assessment of self-blaming emotions to improve the diagnosis and stratification of MDD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Novel antidepressants are predominantly evaluated preclinically in rodent models of chronic stress in which animals experience a single prolonged exposure to chronic stress prior to treatment. Rodent ...models of a single episode of chronic stress translate poorly to human depressive disorders, which are commonly marked by recurring depressive episodes. Intravenous administration of Reelin has previously been shown to resolve immobility in the forced swim test of rats exposed to a single prolonged exposure to chronic stress. To determine whether Reelin has antidepressant-like properties in a model of recurring depressive episodes, Long-Evans rats (N = 57) were exposed to multiple cycles of chronic stress and stress-free periods before the administration of a single injection of Reelin during the final cycle of chronic stress. The animals then performed in the forced swim test and open field test before the post-mortem evaluation of Reelin cell counts in the sub-granular zone of the dentate gyrus to determine the impact of treatment on hippocampal Reelin levels and spleen white pulp to evaluate the role of Reelin treatment in peripheral inflammation. The results show a single Reelin injection reversed elevated levels of immobility in the forced swim test in both male and female subjects exposed to the cyclic chronic stress model of recurring depressive episodes. Treatment with Reelin also restored Reelin-positive cell counts in the dentate gyrus sub-granular zone and reversed atrophy of spleen white pulp. The results shown here indicate that treatment with Reelin could effectively resolve alterations in forced swim test behavior caused by the cyclic corticosterone model of recurring depressive episodes and that Reelin homeostasis is important for regulating stress-related inflammation. Future preclinical antidepressant research should incorporate models of multiple depressive episodes to improve the translation of preclinical rodent research to human depressive disorders.
Objective: Digital delivery of mindfulness-based cognitive therapy through the Mindful Mood Balance (MMB) program is clinically effective (Segal et al., 2020); however, the mechanisms through which ...this program delivers its benefits have not been established. Method: This study investigates the differential impact of the MMB program paired with usual depression care (UDC) compared to UDC alone on the putative targets of self-reported mindfulness, decentering, and rumination and the extent to which change in these targets mediates subsequent depressive relapse among a sample of predominantly White, female participants, with residual depressive symptoms. Results: The MMB program relative to UDC was associated with a significantly greater rate of change in decentering (t = 4.94, p < .0001, d = 0.46), mindfulness (t = 6.04, p < .0001, d = 0.56), and rumination (t = 3.82, p < .0001, d = 0.36). Subsequent depressive relapse also was mediated by prior change in these putative targets, with a significant natural indirect effect for decentering, χ2(1) = 7.25, p < .008, OR = 0.57; mindfulness, χ2(1) = 9.99, p < .002, OR = 0.50; and rumination, χ2(1) = 12.95, p < .001, OR = 0.35. Conclusions: These findings suggest the mechanisms of MMB are consistent with the conceptual model for mindfulness-based cognitive therapy and depressive relapse risk and that such processes can be modified through digital delivery.
What is the public health significance of this article?
Evidence for putative target engagement and mediation is critical to identifying proximal markers of long-term benefit and guidance for the measurement and design of digital interventions for depression.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
Depression is one of the most common psychiatric disorders in today's society. The therapeutic effects of Lavandula angustifolia Mill. (Lamiaceae) (L. angustifolia) and Dracocephalum ruyschiana L. ...(Lamiaceae) (D. ruyschiana) have been demonstrated in the treatment of several disorders.
The present study aimed to evaluate the therapeutic effect of L. angustifolia and D. ruyschiana extracts on patients with mild to moderate depression under treatment with sertraline.
This study was experimental with a pretest-posttest control group design. Seventy individuals with major depressive disorder were randomly allocated into two groups. The first group received a dose of 100 mg sertraline tablet per day with placebo syrup three times a day. The second group was treated with the same dose of sertraline plus the herbal syrup containing two units of the extract of L. angustifolia and one unit of the D. ruyschiana three times a day. The unit dose was the same as defined in traditional medicine. Data were collected using the Structured Clinical Interview for DSM-IV (SCID-IV) and Beck Depression Inventory (BDI) and analyzed using appropriate statistical methods.
The mean scores for depression by BDI in the two groups were not significantly different before the intervention (P > 0.05). Six weeks after the intervention the mean scores of depression in the experimental group were significantly lower than in the control group (P = 0.02).
Simultaneous use of L. angustifolia and D. ruyschiana extracts alongside sertraline has beneficial effects in decreasing depression and confers a promising herbal medication in treating such patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The diagnosis of major depressive disorder (MDD) is commonly based on the subjective evaluation by experienced psychiatrists using clinical scales. Hence, it is particularly important to find more ...objective biomarkers to aid in diagnosis and further treatment. Alpha-band activity (7-13 Hz) is the most prominent component in resting electroencephalogram (EEG), which is also thought to be a potential biomarker. Recent studies have shown the existence of multiple sub-oscillations within the alpha band, with distinct neural underpinnings. However, the specific contribution of these alpha sub-oscillations to the diagnosis and treatment of MDD remains unclear.
In this study, we recorded the resting-state EEG from MDD and HC populations in both open and closed-eye state conditions. We also assessed cognitive processing using the MATRICS Consensus Cognitive Battery (MCCB).
We found that the MDD group showed significantly higher power in the high alpha range (10.5–11.5 Hz) and lower power in the low alpha range (7–8.5 Hz) compared to the HC group. Notably, high alpha power in the MDD group is negatively correlated with working memory performance in MCCB, whereas no such correlation was found in the HC group. Furthermore, using five established classification algorithms, we discovered that combining alpha oscillations with MCCB scores as features yielded the highest classification accuracy compared to using EEG or MCCB scores alone.
Our results demonstrate the potential of sub-oscillations within the alpha frequency band as a potential distinct biomarker. When combined with psychological scales, they may provide guidance relevant for the diagnosis and treatment of MDD.
•MDD group showed significantly higher power in the high alpha range and lower power in the low alpha range.•High alpha power in the MDD group is negatively correlated with working memory performance in MCCB.•Combining alpha oscillations with MCCB scores as features yielded the highest classification accuracy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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