•We surveyed the use of machine learning to inform predictive models in mood disorders.•We include studies that use machine learning algorithms to identify predictors of therapeutic outcomes in ...uni/bipolar depression.•Classification algorithms informed by neuroimaging, phenomenological, and genetic data were able to predict therapeutic outcomes with an overall accuracy of 0.82.•Predictive models integrating multiple data types performed better when compared to models with single lower-dimension data types (p <0.01).•Machine learning provides opportunity to parse clinical heterogeneity and characterize moderators of disease risk and trajectory.
No previous study has comprehensively reviewed the application of machine learning algorithms in mood disorders populations. Herein, we qualitatively and quantitatively evaluate previous studies of machine learning-devised models that predict therapeutic outcomes in mood disorders populations.
We searched Ovid MEDLINE/PubMed from inception to February 8, 2018 for relevant studies that included adults with bipolar or unipolar depression; assessed therapeutic outcomes with a pharmacological, neuromodulatory, or manual-based psychotherapeutic intervention for depression; applied a machine learning algorithm; and reported predictors of therapeutic response. A random-effects meta-analysis of proportions and meta-regression analyses were conducted.
We identified 639 records: 75 full-text publications were assessed for eligibility; 26 studies (n=17,499) and 20 studies (n=6325) were included in qualitative and quantitative review, respectively. Classification algorithms were able to predict therapeutic outcomes with an overall accuracy of 0.82 (95% confidence interval CI of 0.77, 0.87). Pooled estimates of classification accuracy were significantly greater (p < 0.01) in models informed by multiple data types (e.g., composite of phenomenological patient features and neuroimaging or peripheral gene expression data; pooled proportion 95% CI = 0.930.86, 0.97) when compared to models with lower-dimension data types (pooledproportion=0.680.62,0.74to0.850.81,0.88).
Most studies were retrospective; differences in machine learning algorithms and their implementation (e.g., cross-validation, hyperparameter tuning); cannot infer importance of individual variables fed into learning algorithm.
Machine learning algorithms provide a powerful conceptual and analytic framework capable of integrating multiple data types and sources. An integrative approach may more effectively model neurobiological components as functional modules of pathophysiology embedded within the complex, social dynamics that influence the phenomenology of mental disorders.
Cognitive dysfunction is a symptomatic domain identified across many mental disorders. Cognitive deficits in individuals with major depressive disorder (MDD) contribute significantly to occupational ...and functional disability. Notably, cognitive subdomains such as learning and memory, executive functioning, processing speed, and attention and concentration are significantly impaired during, and between, episodes in individuals with MDD. Most antidepressants have not been developed and/or evaluated for their ability to directly and independently ameliorate cognitive deficits. Multiple interacting neurobiological mechanisms (eg, neuroinflammation) are implicated as subserving cognitive deficits in MDD. A testable hypothesis, with preliminary support, posits that improving performance across cognitive domains in individuals with MDD may improve psychosocial function, workplace function, quality of life, and other patient-reported outcomes, independent of effects on core mood symptoms. Herein we aim to (1) provide a rationale for prioritizing cognitive deficits as a therapeutic target, (2) briefly discuss the neurobiological substrates subserving cognitive dysfunction, and (3) provide an update on current and future treatment avenues.
•Numerous studies indicate that probiotics have anti-inflammatory effects.•Immune-inflammatory modulation may mediate the antidepressant effects of probiotics.•Probiotics may be more effective in ...depressed subgroups with elevated inflammation.•Future studies should parse out the heterogeneous effects of different probiotics.
During the past decade, there has been renewed interest in the relationship between brain-based disorders, the gut microbiota, and the possible beneficial effects of probiotics. Emerging evidence suggests that modifying the composition of the gut microbiota via probiotic supplementation may be a viable adjuvant treatment option for individuals with major depressive disorder (MDD). Convergent evidence indicates that persistent low-grade inflammatory activation is associated with the diagnosis of MDD as well as the severity of depressive symptoms and probability of treatment response. The objectives of this review are to (1) evaluate the evidence supporting an anti-inflammatory effect of probiotics and (2) describe immune system modulation as a potential mechanism for the therapeutic effects of probiotics in populations with MDD. A narrative review of studies investigating the effects of probiotics on systemic inflammation was conducted. Studies were identified using PubMed/Medline, Google Scholar, and clinicaltrials.gov (from inception to November 2017) using the following search terms (and/or variants): probiotic, inflammation, gut microbiota, and depression. The available evidence suggests that probiotics should be considered a promising adjuvant treatment to reduce the inflammatory activation commonly found in MDD. Several controversial points remain to be addressed including the role of leaky gut, the role of stress exposure, and the role of blood-brain-barrier permeability. Taken together, the results of this review suggest that probiotics may be a potentially beneficial, but insufficiently studied, antidepressant treatment intervention.
Major Depressive Disorder (MDD) is a prevalent, chronic, disabling, and multidimensional mental disorder. Cognitive dysfunction represents a core diagnostic and symptomatic criterion of MDD, and is a ...principal determinant of functional non-recovery. Cognitive impairment has been observed to persist despite remission of mood symptoms, suggesting dissociability of mood and cognitive symptoms in MDD. Recurrent impairments in several domains including, but not limited to, executive function, learning and memory, processing speed, and attention and concentration, are associated with poor psychosocial and occupational outcomes. Attempts to restore premorbid functioning in individuals with MDD requires regular screenings and assessment of objective and subjective measures of cognition by clinicians. Easily accessible and cost-effective tools such as the THINC-integrated tool (THINC-it) are suitable for use in a busy clinical environment and appear to be promising for routine usage in clinical settings. However, antidepressant treatments targeting specific cognitive domains in MDD have been insufficiently studied. While select antidepressants, e.g., vortioxetine, have been demonstrated to have direct and independent pro-cognitive effects in adults with MDD, research on additional agents remains nascent. A comprehensive clinical approach to cognitive impairments in MDD is required. The current narrative review aims to delineate the importance and relevance of cognitive dysfunction as a symptomatic target for prevention and treatment in the phenomenology of MDD.
Anhedonia is a common, persistent, and disabling phenomenon in treated adults with Major Depressive Disorder (MDD). Hitherto, relatively few antidepressant agents have been evaluated with respect to ...their effect on anhedonia in MDD.
This is a
analysis of a primary study that sought to evaluate the sensitivity to change of the THINC-integrated tool (THINC-it) in MDD (ClinicalTrials.gov Identifier: NCT03053362). Adults meeting DSM-5 criteria for MDD with at least moderate depressive symptom severity i.e., Montgomery Åsberg Depression Rating Scale (MADRS) total score ≥20 were eligible. Subjects were recruited between October 2017 and August 2018 in Toronto, Ontario at the Brain and Cognition Discovery Foundation. All subjects received open-label vortioxetine (10-20 mg/day, flexibly-dosed) for 8 weeks. Herein, the primary outcome of interest was the change from baseline to endpoint in the Snaith-Hamilton Pleasure Scale (SHAPS) total score, as well as the MADRS anhedonia factor. The mediational effects of improvements in anhedonia on general function and quality of life, as measured by the Sheehan Disability Scale (SDS) and the 5-Item World Health Organization Well-Being Index (WHO-5), were secondarily assessed.
A total of 100 subjects with MDD were enrolled in the primary study and began treatment with vortioxetine. Vortioxetine significantly improved anhedonia as evidenced by significant baseline to endpoint improvements in SHAPS and MADRS anhedonia factor scores (
< 0.0001). Improvements in the SHAPS and the MADRS anhedonia factor correlated with improvements in general function (i.e., SDS) and quality of life (i.e., WHO-5) (
< 0.0001). Notably, improvements in anhedonia were found to mediate the association between improvements in overall depressive symptom severity (i.e., MADRS total score) and social functioning (i.e., social life component of the SDS) (
= 0.026).
The unmet need in depression is to improve patient functioning and other patient-reported outcomes (e.g., quality of life). Antidepressant interventions capable of attenuating anhedonia as well as cognitive dysfunction in MDD may help in this regard, as improvement in these domains have been associated with improvement in psychosocial function and quality of life.
It is well established that deficits in motivation, reward, and cognition are common during and in between syndromal episodes of depression as part of Major Depressive Disorder (MDD). Informed by ...evidence indicating functional and structural interconnectivity between cognitive and reward brain circuits, we preliminarily evaluate the association between measures of cognitive performance and reward/motivation.
This is a post-hoc analysis of a primary study (i.e. the THINC-it sensitivity to change study). Adults (18–65 years of age) meeting DSM-5 criteria for MDD, single-episode or recurrent confirmed by M.I.N.I. with moderate severity or greater (i.e. Montgomery Asberg Depression Rating Scale ≥20). All eligible subjects received vortioxetine 10–20 mg open-label for 8 weeks. The Effort Expenditure Reward Task (EEfRT) was the principal measure of motivation and reward. We directly compare the effects of cognitive measures and depressive symptoms on effort-based decision-making using the THINC-it composite score and MADRS total score.
Twenty-one participants with MDD (Mean age = 38.47, SD = 12.85) and 20 healthy volunteers (Mean age = 41.50, SD = 14.21) completed the optional EEfRT task. Amongst individuals with MDD, performance in processing speed, executive function (i.e. Trails B) and overall composite cognitive score was positively associated with the proportion of hard-task choices in the high reward condition (i.e. greater reward valuation). Across both groups, a greater probability (χ2 = 1.137) and magnitude of reward (χ2 = 0.045) was associated with increased effort (i.e. choosing the hard task more frequently). Using fully factored GEE models, we observed a positive association between performance on the Trails test (β = 2.223, SE = 0.928, p = 0.017) as well as the composite score (β = 0.978, SE = 0.0.459, p = 0.033), and greater effort for high rewards. In addition, it was observed that a positive association (i.e. greater effort for reward in higher probability) was observed with depressive symptoms and overall cognitive measures.
Herein, we observed that an association exists between overall cognitive function, notably processing speed and executive function and reward function. Specifically, a greater effort for hard task rewards (using the EEfRT task) was manifested in individuals exhibiting higher levels of cognitive performance in a well-characterized sample of MDD treated with Vortioxetine.
•Cognitive function highly correlates with measures of reward and motivation in adults with major depressive disorder (MDD)•Processing speed, executive function and overall cognition was positively associated with greater reward valuation•Overall cognition positively correlated (i.e. greater effort for reward in higher probability) with depressive symptoms•Self-reported measures of anhedonia and reward valuation are distinct domains of psychopathology in those with MDD
Herein, we sought to determine the sensitivity to change in cognitive function, as measured by the THINC-it tool, in a sample of adults with major depressive disorder (MDD) receiving standardized ...antidepressant therapy.
Adults meeting the DSM-5 criteria for MDD with at least moderate depressive symptom severity
, Montgomery Åsberg Depression Rating Scale (MADRS) total score ≥ 20 were treated with open-label vortioxetine (10-20 mg/day, flexibly-dosed) for 8 weeks. The previously validated THINC-it tool was the primary dependent measure. The THINC-it tool was validated against the paper and pencil version of the Digit Symbol Substitution Test (DSST) and the Trails Making Test B (TMTB).
After 8 weeks of treatment, adults with MDD exhibited improvement in cognitive function relative to healthy controls (
, processing speed) (p = 0.031). A subdomain measure of working memory (
, symbol check; SC) exhibited significant improvement at Weeks 2 and 8 in latency (p = 0.032), SC accuracy (p = 0.046), and objective z-score (p = 0.001) independent of depressive symptoms. A linear regression analysis determined that the THINC-it tool measures of processing speed, as well as executive function were significantly associated with changes observed on the pencil and paper version the Digit Symbol Substitution Test (DSST) (p = 0.002) and in Trails Making Test B (TMTB) (p = 0.003), respectively.
The THINC-it tool demonstrates sensitivity to change in adults with MDD and is highly correlated with improvements on pencil and paper versions of DSST and TMTB.
ClinicalTrials.gov, identifier NCT03053362.
•Childhood maltreatment is an important stressor associated with stress & depression.•Stress- and depression-associated changes were mostly found in NRC31 and SLCA4.•Epigenetic changes occurring at ...different loci may have variable downstream effects.•Most studies measured epigenetic changes using peripheral tissue samples.•Future studies should evaluate epigenetic effects of psychotropic medication use.
Environmental stressors, such as childhood maltreatment, have been recognized to contribute to the development of depression. Growing evidence suggests that epigenetic changes are a key mechanism by which stressors interact with the genome leading to stable changes in DNA structure, gene expression, and behaviour. The current review aimed to evaluate the relationship between stress-associated epigenetic changes and depression. Human studies were identified via systematic searching of PubMed/Medline from inception to February 2018. Seventeen articles were identified. Stress-associated epigenetic changes in the following genes were correlated with depression: NRC31, SLCA4, BDNF, FKBP5, SKA2, OXTR, LINGO3, POU3F1 and ITGB1. Epigenetic changes in glucocorticoid signaling (e.g., NR3C1, FKBP5), serotonergic signaling (e.g. SLC6A4), and neurotrophin (e.g., BDNF) genes appear to be the most promising therapeutic targets for future research. However, continued research is warranted due to inconsistent findings regarding the directionality of epigenetic modification. Future studies should also aim to control for the use of psychotropic agents due to their widespread use in depressed populations and established effects on DNA methylation.
•Depressive symptoms are lower than baseline beyond 2 years post-surgery.•The post-surgery course of anxiety symptoms is more variable.•Pre-surgery anxiety/depressive symptoms do no predict ...post-surgery BMI.•Bariatric surgery is associated with long-term psychological improvements.
No previous review has comprehensively assessed long-term changes in anxiety and depressive symptoms in bariatric surgery patients. This systematic review assessed the effects of bariatric surgery on long-term reductions (≥ 24 months) in anxiety and depressive symptom severity in morbidly obese (≥ 35 BMI kg/m2) participants. Short term effects (< 24 months) are briefly reviewed for context.
PsychINFO, Google Scholar and PubMed databases were systematically searched for prospective cohort studies published from inception to 14 June 2018 that evaluated long-term (≥ 24 months) changes in anxiety and depressive symptom severity in bariatric surgery patients with a BMI ≥ 35 kg/m2 using a combination of the following search terms: bariatric surgery (and surgical approaches included under this term), obesity, depression, depressive disorder, anxiety, anxious, psychiatric disorders, mood disorders.
We reviewed 2058 articles for eligibility; 14 prospective studies were included in the systematic review. 13 studies (93%) reported significant reductions in depressive symptom severity 2–3 years after bariatric surgery. However, all studies recorded statistically significant reductions in depressive symptoms at the conclusion of the study. Similarly, there were reductions in overall anxiety symptom severity at ≥ 24 months follow-up (k = 8 studies, n = 1590 pooled). Pre-operative anxiety or depression scores did not predict outcomes of post-operative BMI. Similarly, post-surgery weight loss did not predict changes in anxiety symptoms.
Very few studies assessed anxiety or depression as a primary outcome. Therefore, we cannot suggest bariatric surgery as a stand-alone therapeutic tool for anxiety and depression based on our findings.
Currently available evidence suggests that bariatric surgery is associated with long-term reductions in anxiety and depressive symptoms. This supports existing literature showing that metabolic treatments may be a viable therapeutic intervention for mood disorders.
Anhedonia is defined as a diminished ability to experience interest or pleasure, and is a critical psychopathological dimension of major depressive disorder (MDD). The purpose of the current ...systematic review is to evaluate the therapeutic efficacy of pharmacological treatments on measures of anhedonia in adults with MDD. Electronic databases Cochrane Library (CENTRAL), Ovid MEDLINE, PubMed, PsycINFO, and Google Scholar were searched from inception to June 1, 2018 for longitudinal studies utilizing pharmacotherapy for the treatment of anhedonia in patients with MDD. A total of 17 eligible studies were identified (i.e., evaluated the effects of pharmacotherapy on a measure of anhedonia). Among the identified studies, the efficacy of 14 different pharmacotherapies on measures of anhedonia were evaluated, including melatonergic agents (i.e. agomelatine), monoaminergic agents (i.e. moclobemide, clomipramine, bupropion, venlafaxine, fluoxetine, amitifadine and levomilnacipran, escitalopram, and sertraline), glutamatergic agents (i.e., ketamine and riluzole), stimulants (i.e., methylphenidate), and psychedelics (i.e., psilocybin). Based on the available evidence, most antidepressants demonstrated beneficial effects on measures of anhedonia as well as the other depressive symptoms. Only escitalopram/riluzole combination treatment was ineffective in treating symptoms of anhedonia in MDD. Continued research is warranted to further support the efficacy of mechanistically-distinct antidepressants in treating symptoms of anhedonia in MDD. Future research should also aim to parse out the heterogeneous effects of different pharmacotherapies on anhedonic symptoms.
•Majority of antidepressants do not show pronounced collinear improvements in anhedonia and other depressive symptoms.•Therapies targeting melatonergic receptors and circadian rhythm imbalances are more direct targets for treating anhedonia.•Ketamine may be faster acting of anti-anhedonia due to direct effect on mitochondrial energy metabolism.
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