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Cell Jan 2022Psychiatric disease is one of the greatest health challenges of our time. The pipeline for conceptually novel therapeutics remains low, in part because uncovering the...
Psychiatric disease is one of the greatest health challenges of our time. The pipeline for conceptually novel therapeutics remains low, in part because uncovering the biological mechanisms of psychiatric disease has been difficult. We asked experts researching different aspects of psychiatric disease: what do you see as the major urgent questions that need to be addressed? Where are the next frontiers, and what are the current hurdles to understanding the biological basis of psychiatric disease?
Topics: Animals; Antidepressive Agents; Data Science; Depression; Depressive Disorder; Genomics; Humans; Neurons; Precision Medicine; Prefrontal Cortex; Translational Research, Biomedical; Treatment Outcome
PubMed: 34995512
DOI: 10.1016/j.cell.2021.12.010 -
Translational Psychiatry Sep 2023Treatment response and resistance in major depressive disorder (MDD) are suggested to be heritable. Due to significant challenges in defining treatment-related...
Treatment response and resistance in major depressive disorder (MDD) are suggested to be heritable. Due to significant challenges in defining treatment-related phenotypes, our understanding of their genetic bases is limited. This study aimed to derive a stringent definition of treatment resistance and to investigate the genetic overlap between treatment response and resistance in MDD. Using electronic medical records on the use of antidepressants and electroconvulsive therapy (ECT) from Swedish registers, we derived the phenotype of treatment-resistant depression (TRD) and non-TRD within ~4500 individuals with MDD in three Swedish cohorts. Considering antidepressants and lithium are first-line treatment and augmentation used for MDD, respectively, we generated polygenic risk scores (PRS) of antidepressants and lithium response for individuals with MDD and evaluated their associations with treatment resistance by comparing TRD with non-TRD. Among 1778 ECT-treated MDD cases, nearly all (94%) used antidepressants before their first ECT and the vast majority had at least one (84%) or two (61%) antidepressants of adequate duration, suggesting these MDD cases receiving ECT were resistant to antidepressants. We did not observe a significant difference in the mean PRS of antidepressant response between TRD and non-TRD; however, we found that TRD cases had a significantly higher PRS of lithium response compared to non-TRD cases (OR = 1.10-1.12 under various definitions). The results support the evidence of heritable components in treatment-related phenotypes and highlight the overall genetic profile of lithium-sensitivity in TRD. This finding further provides a genetic explanation for lithium efficacy in treating TRD.
Topics: Humans; Depressive Disorder, Major; Lithium; Antidepressive Agents; Electroconvulsive Therapy; Depressive Disorder, Treatment-Resistant
PubMed: 37770441
DOI: 10.1038/s41398-023-02602-3 -
NeuroImage. Clinical 2022A significant proportion of patients with major depressive disorder are resistant to antidepressant medication and psychological treatments. A core symptom of...
BACKGROUND
A significant proportion of patients with major depressive disorder are resistant to antidepressant medication and psychological treatments. A core symptom of treatment-resistant depression (TRD) is anhedonia, or the inability to feel pleasure, which has been attributed to disrupted habenula function - a component of the reward network. This study aimed to map detailed neural circuitry architecture related to the habenula to identify neural mechanisms of TRD.
METHODS
35 TRD patients, 35 patients with treatment-sensitive depression (TSD), and 38 healthy controls (HC) underwent resting-state functional magnetic resonance imaging. Functional connectivity analyses were performed using the left and right habenula as seed regions of interest, and the three groups were compared using whole-brain voxel-wise comparisons.
RESULTS
The TRD group demonstrated hyperconnectivity of the left habenula to the left precuneus cortex and the right precentral gyrus, compared to the TSD group, and to the right precuneus cortex, compared to the TSD and HC groups. In contrast, TSD demonstrated hypoconnectivity than HC for both connectivity measures. These connectivity values were significantly higher in patients with a history of suicidal ideation.
CONCLUSIONS
This study provides evidence that, unlike TSD, TRD is characterized by hyperconnectivity of the left habenula particularly with regions of the default mode network. An increased interplay between reward and default mode networks is linked to suicidality and could be a possible mechanism for anhedonia in hard to treat depression.
Topics: Anhedonia; Case-Control Studies; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Habenula; Humans; Magnetic Resonance Imaging; Suicidal Ideation
PubMed: 35305499
DOI: 10.1016/j.nicl.2022.102990 -
BMC Psychiatry Nov 2023Specifiers for a major depressive disorder (MDE) are supposed to reduce diagnostic heterogeneity. However, recent literature challenges the idea that the atypical and...
OBJECTIVES
Specifiers for a major depressive disorder (MDE) are supposed to reduce diagnostic heterogeneity. However, recent literature challenges the idea that the atypical and melancholic specifiers identify more homogenous or coherent subgroups. We introduce the usage of distance metrics to characterize symptom heterogeneity. We attempt to replicate prior findings and explore whether symptom heterogeneity is reduced using specifier subgroups.
METHODS
We used data derived from the National Epidemiological Survey on Alcohol and Related Conditions (NESARC Wave I; N = 5,749) and the Sequenced Treatment Alternatives to Relieve Depression study (STAR*D; N = 2,498). We computed Hamming and Manhattan distances from study participants' unique symptom profiles. Distances were standardized from 0-1 and compared by their within- and between-group similarities to their non-specifier counterparts for the melancholic and atypical specifiers.
RESULTS
There was no evidence of statistically significant differences in heterogeneity for specifier (i.e., melancholic or atypical) vs. non-specifier designations (i.e., non-melancholic vs. non-atypical).
CONCLUSION
Replicating prior work, melancholic and atypical depression specifiers appear to have limited utility in reducing heterogeneity. The current study does not support the claim that specifiers create more coherent subgroups as operationalized by similarity in the number of symptoms and their severity. Distance metrics are useful for quantifying symptom heterogeneity.
Topics: Humans; Depressive Disorder, Major; Depression; Psychopathology; Diagnostic and Statistical Manual of Mental Disorders
PubMed: 38037069
DOI: 10.1186/s12888-023-05377-5 -
Medicina (Kaunas, Lithuania) Dec 2023: This study investigated the differences in syntactic errors in older individuals with and without major depressive disorder and cognitive function disparities between...
: This study investigated the differences in syntactic errors in older individuals with and without major depressive disorder and cognitive function disparities between groups. We also explored the correlation between syntax scores and depression severity. : Forty-four participants, assessed for dementia with the Mini-Cog, completed the 15-item Geriatric Depression Scale (TGDS-15) and specific language tests. Following a single-anonymized procedure, clinical psychologists rated the tests and syntax scores. : The results showed that the depressive disorders group had lower syntax scores than the non-depressed group, primarily on specific subtests. Additionally, cognitive test scores were generally lower among the depressed group. A significant relationship between depression severity and syntax scores was observed (r = -0.426, 95% CI = -0.639, -0.143). : In conclusion, major depressive disorder is associated with reduced syntactic abilities, particularly in specific tests. However, the relatively modest sample size limited the sensitivity of this association. This study also considered the potential influence of cultural factors. Unique linguistic characteristics in the study's context were also addressed and considered as potential contributors to the observed findings.
Topics: Humans; Aged; Depressive Disorder, Major; Depression; Cognition Disorders; Neuropsychological Tests
PubMed: 38138236
DOI: 10.3390/medicina59122133 -
European Psychiatry : the Journal of... Jan 2023With almost one-third of patients with major depression not adequately responsive to treatments, the management of treatment-resistant depression (TRD) has continued to...
With almost one-third of patients with major depression not adequately responsive to treatments, the management of treatment-resistant depression (TRD) has continued to be challenging. Recently, an essential step was taken to replace TRD with difficult-to-treat depression (DTD), pointing to some drawbacks associated with this terminology and identifying addressable barriers. In line with the DTD concept, we discuss why terming this population of patients as TRD could be semantically and clinically misleading. We then suggest replacing TRD with quasi-tenacious depression (QTD), a model and terminology that are derived from a potentially measurable outcome, the tenacity index (TI). QTD predicts that in theory remission is achievable by providing suitable treatments at hand. QTD states that every patient with major depression (even those who respond well) has some degree of tenacity that needs to be overcome by the use of proper treatment modalities. Ergo, in patients with a higher TI, due to the dearth of available armamentaria, one might suffice to achieve a partial resolution of symptoms balanced with an optimal quality of life. However, QTD calls for an incessant pursuit of novel treatments and the identification of contributing factors leading to high TI. On a track toward personalized psychiatry, and in harmony with DTD, QTD embraces all key barriers leading to a failure to treatment response and tries to provide a measurable entity for a better clinical decision while conveying a dynamic positive outlook of the disorder for both patients and health care providers.
Topics: Humans; Depression; Quality of Life; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant
PubMed: 36632817
DOI: 10.1192/j.eurpsy.2022.2353 -
European Psychiatry : the Journal of... May 2023Major depressive disorder (MDD) is a leading cause of disability worldwide, and yet delivery of care for this illness is rife with gaps. The COVID-19 pandemic has had... (Review)
Review
BACKGROUND
Major depressive disorder (MDD) is a leading cause of disability worldwide, and yet delivery of care for this illness is rife with gaps. The COVID-19 pandemic has had far reaching implications for every facet of healthcare, and MDD is no exception. This scoping review aimed to ascertain the impacts of COVID-19 on the delivery of MDD care in Europe, as well as to evaluate any novel MDD care strategies trialled in this period.
METHODS
We searched the PubMed and PsycINFO databases up to January 2022 with a strategy centred around COVID-19 and MDD. Full texts of eligible studies examining working-age adults and conducted in Europe were evaluated against several criteria. All outcomes were then extracted and a narrative synthesis was constructed to summarise identified themes.
RESULTS
Of 1,744 records identified in our search, 11 articles were eligible for inclusion in the review. In general, these studies reported a decrease in treatment rates, access to care, and perceived access to care during the COVID-19 pandemic. In addition, digital interventions trialled during the pandemic were broadly well-received by users, though their efficacy in improving MDD care was ambiguous.
CONCLUSIONS
Despite a limited number of pertinent studies, this scoping review identified a trend of exacerbated treatment gaps in MDD care during the pandemic. Several of our pre-specified gaps, including delays to detection or treatment of depression and rates of follow-up contacts, remained unexplored in the context of COVID-19. This highlights the need for further investigation to obtain a full understanding of the relationship between COVID-19 and MDD care in Europe.
Topics: Humans; Adult; COVID-19; Depressive Disorder, Major; Pandemics; Delivery of Health Care; Europe
PubMed: 37170902
DOI: 10.1192/j.eurpsy.2023.2407 -
Cells Oct 2022Major depressive disorder (MDD) and bipolar disorder (BD) with melancholia and psychotic features and suicidal behaviors are accompanied by activated immune-inflammatory... (Meta-Analysis)
Meta-Analysis Review
The Tryptophan Catabolite or Kynurenine Pathway in a Major Depressive Episode with Melancholia, Psychotic Features and Suicidal Behaviors: A Systematic Review and Meta-Analysis.
Major depressive disorder (MDD) and bipolar disorder (BD) with melancholia and psychotic features and suicidal behaviors are accompanied by activated immune-inflammatory and oxidative pathways, which may stimulate indoleamine 2,3-dioxygenase (IDO), the first and rate-limiting enzyme of the tryptophan catabolite (TRYCAT) pathway resulting in increased tryptophan degradation and elevated tryptophan catabolites (TRYCTAs). The purpose of the current study is to systematically review and meta-analyze levels of TRP, its competing amino acids (CAAs) and TRYCATs in patients with severe affective disorders. Methods: PubMed, Google Scholar and SciFinder were searched in the present study and we recruited 35 studies to examine 4647 participants including 2332 unipolar (MDD) and bipolar (BD) depressed patients and 2315 healthy controls. Severe patients showed significant lower ( < 0.0001) TRP (standardized mean difference, SMD = -0.517, 95% confidence interval, CI: -0.735; -0.299) and TRP/CAAs (SMD = -0.617, CI: -0.957; -0.277) levels with moderate effect sizes, while no significant difference in CAAs were found. Kynurenine (KYN) levels were unaltered in severe MDD/BD phenotypes, while the KYN/TRP ratio showed a significant increase only in patients with psychotic features (SMD = 0.224, CI: 0.012; 0.436). Quinolinic acid (QA) was significantly increased (SMD = 0.358, CI: 0.015; 0.701) and kynurenic acid (KA) significantly decreased (SMD = -0.260, CI: -0.487; -0.034) in severe MDD/BD. Patients with affective disorders with melancholic and psychotic features and suicidal behaviors showed normal IDO enzyme activity but a lowered availability of plasma/serum TRP to the brain, which is probably due to other processes such as low albumin levels.
Topics: Albumins; Amino Acids; Depressive Disorder, Major; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Kynurenic Acid; Kynurenine; Quinolinic Acids; Suicidal Ideation; Tryptophan
PubMed: 36231075
DOI: 10.3390/cells11193112 -
Actas Espanolas de Psiquiatria Jul 2022Health care for depression is a major challenge. The aim of this review is to capture the status of the detection, diagno- sis and treatment of depression in the Spanish... (Review)
Review
Health care for depression is a major challenge. The aim of this review is to capture the status of the detection, diagno- sis and treatment of depression in the Spanish public health system. The data from the latest National Health Survey (ENSE 2017) have been analyzed and a non-systematic search for publications has been carried out in the PubMed and Scopus databases. We highlight the high specificity and low sensitivity in the detection of cases of major depression by Primary Care (PC) physicians in Spain. The detection of depression is supe- rior in specialized care compared to PC. The new healthcare systems based on the shared approach and the hierarchical model of screening, diagnosis and referral are reviewed and we present improvement proposals based on various programs and models of healthcare for depression.
Topics: Depressive Disorder, Major; Humans; Mass Screening; Primary Health Care; Spain
PubMed: 35867485
DOI: No ID Found -
Journal of Affective Disorders Oct 2023Debate is ongoing as to whether burnout can be differentiated from depression. This study evaluated whether burnout and depression could be distinguished using a new...
BACKGROUND
Debate is ongoing as to whether burnout can be differentiated from depression. This study evaluated whether burnout and depression could be distinguished using a new burnout measure and other variables.
METHODS
Scores on the Sydney Burnout Measure (SBM) were compared between participants with self-diagnosed burnout (BO-all group; n = 622) and clinically-diagnosed depression (DEP-all group; n = 90). The latter group was split into melancholic (DEP-mel; n = 56) and non-melancholic (DEP-nonmel; n = 34) depression subgroups for subsequent analyses. Differences in reporting of depressive symptoms and causal attributions were also evaluated.
RESULTS
While total SBM scores showed poor differentiation, the BO-all group had lower social withdrawal and higher empathy loss subscale scores than the depression groups. Odds ratios were significant for several of the depressive symptoms and causal attribution items when comparing the BO-all group to the DEP-all and DEP-mel groups, while only a few items were significant when comparing the BO-all and DEP-nonmel groups.
LIMITATIONS
Participants in the depression group were assigned by clinician-based depression diagnoses, rather than by a standardised diagnostic interview, and the group had a relatively small sample size. Participants in the burnout group were self-diagnosed and not assessed for comorbid psychiatric diagnoses.
CONCLUSIONS
There were some nuanced symptoms differences between burnout and depression, but many of the SBM symptoms were not specific to burnout. Results also suggested that burnout overlaps more with non-melancholic than melancholic depression, and that differentiation of burnout and depression may rely more on weighting causal factors over symptoms.
Topics: Humans; Depression; Depressive Disorder; Comorbidity; Burnout, Professional; Sample Size
PubMed: 37479038
DOI: 10.1016/j.jad.2023.07.095