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Objectives To describe the cognitive and functional impairment in individuals with the first episode of major depressive disorder (MDD) as compared to controls and individuals with recurrent MDD. Also to describe the functional and cognitive trajectory after the first episode of MDD. Methods A total of 52 studies were included in our systematic review. 32 studies compared the cognitive performance between first episode of depression (FED) and controls, 11 studies compared the cognitive performance between recurrent depression (RD) and FED, 10 compared global functioning between RD and FED, four studies assessed cognition in FED over time, and two studies assessed global functioning in FED over time. Results The majority of studies (n = 22/32, 68.8%) found that FED subjects performed significantly worse than controls on cognitive tests, with processing speed (n = 12) and executive/working memory (n = 11) being the most commonly impaired domains. Seven out of 11 studies (63.6%) found that RD performed significantly worse than FED, with verbal learning and memory being the most commonly impaired domain (n = 4). Most studies (n = 7/10, 70%) did not find a significant difference in global functioning between RD and FED. In three of four longitudinal studies assessing cognition, subgroup analyses were used instead of directly assessing cognition in FED over time while the remaining study found significant cognitive declines over time in FED when compared to controls. The two longitudinal studies assessing functional trajectory found that functioning significantly improved over time, possibly due to the improvement of depressive symptoms. Conclusion There is strong evidence that cognitive impairment is present during the first episode of depression, and individuals with multiple episodes display greater cognitive impairment than individuals with a single episode. Future studies aimed at identifying predictors of cognitive and functional impairment after the first episode of depression are needed to describe the functional and cognitive trajectory of individuals with the first episode of MDD over time.

OBJECTIVES Electroconvulsive therapy (ECT) is an effective treatment for depressive disorders and approved for use in adolescents and adults, but it is unclear whether efficacy or cognitive side effect burden differs with age or if effectiveness in usual clinical practice matches that in prospective studies. We examined the effects of ECT on depression and cognition in a large clinical cohort. METHODS A retrospective cohort study of patients ages 16 and older receiving ECT between 2011 and 2020 and who were evaluated with the Quick Inventory of Depressive Symptomatology (QIDS), the Behavior and Symptom Identification Scale-24 (BASIS-24), and the Montreal Cognitive Assessment (MoCA) at baseline and after treatment #10. RESULTS Among 1698 patients, ECT was associated with a decrease in depression symptoms (QIDS reduction from 17.1 ± 4.9 to 10.1 ± 5.2) and improvement in self-reported mental health (BASIS-24 scores improved from 1.92 ± 0.55 to 1.17 ± 0.60). There was a reduction in MoCA scores from 25.8 ± 3.1 to 25.4 ± 3.1. In multivariate models, age was not associated with a differential QIDS or BASIS-24 response, but older age was associated with a lesser reduction in MoCA. CONCLUSION Among 1698 patients aged 16 and older, ECT was associated with improvement in depression and overall self-reported mental health, with a slight decrease in cognition. Age was not associated with changes in efficacy, but older age was associated with a lesser cognitive change as measured by the MoCA. These results provide normative data of real-world effectiveness of ECT, and add further support to its utility in patients with severe psychiatric illness.

Objective Major depressive disorder (MDD) and anxiety disorders are both common and especially challenging during pregnancy. Considering possible risks of intrauterine drug exposure of the child, the role of psychopharmacological treatment is ambiguous and various negative obstetric outcomes were inconsistently associated with medication. Consequently, a critical examination of peri- and postnatal phenomena associated with intrauterine exposure to antidepressants based on serotonin-reuptake inhibition (SRI) and subsumed under the term "poor neonatal adaptation syndrome" (PNAS) is urgently called for. Methods A comprehensive literature search was conducted, revealing a total number of 33 relevant studies and 69 individual outcomes among 3025 screened studies. Seventeen outcomes allowed meta-analytic evaluation (random effects model). Measures for heterogeneity (I2 ) and contour-enhanced funnel plots were generated. Results Single studies showed increased risks for deficits in neurological functioning and autonomous adaptation in SRI exposed infants. Meta-analytical evaluation showed increased symptom occurrence or severity in exposed neonates for low APGAR scores, birth weight, size for gestational age, preterm delivery, neuromuscular and autonomous regulation, and higher rates of admission to specialized care. Mostly, increased risk after SRI exposure was supported by comparison to unexposed infants born to mothers diagnosed with depression. Conclusion Whereas statistically significant evidence for various effects of intrauterine exposure to SRI was found, the clinical relevance remains unresolved due to inherently low data quality in this research domain and insufficiently defined samples and outcomes. More systematic research under ethical considerations is required to improve multiprofessional counselling in the many women dealing with MDD during pregnancy and the peripartum.

Objective Depression has been associated with metabolomic alterations. Depressive and anxiety disorders are often comorbid diagnoses and are suggested to share etiology. We investigated whether differential metabolomic alterations are present between anxiety and depressive disorders and which clinical characteristics of these disorders are related to metabolomic alterations.Methods Data were from the Netherlands Study of Depression and Anxiety (NESDA), including individuals with current comorbid anxiety and depressive disorders (N = 531), only a current depression (N = 304), only a current anxiety disorder (N = 548), remitted depressive and/or anxiety disorders (N = 897), and healthy controls (N = 634). Forty metabolites from a proton nuclear magnetic resonance lipid-based metabolomics panel were analyzed. First, we examined differences in metabolites between disorder groups and healthy controls. Next, we assessed whether depression or anxiety clinical characteristics (severity and symptom duration) were associated with metabolites.Results As compared to healthy controls, seven metabolomic alterations were found in the group with only depression, reflecting an inflammatory (glycoprotein acetyls; Cohen's d = 0.12, p = 0.002) and atherogenic-lipoprotein-related (e.g., apolipoprotein B: Cohen's d = 0.08, p = 0.03, and VLDL cholesterol: Cohen's d = 0.08, p = 0.04) profile. The comorbid group showed an attenuated but similar pattern of deviations. No metabolomic alterations were found in the group with only anxiety disorders. The majority of metabolites associated with depression diagnosis were also associated with depression severity; no associations were found with anxiety severity or disease duration.Conclusion While substantial clinical overlap exists between depressive and anxiety disorders, this study suggests that altered inflammatory and atherogenic-lipoprotein-related metabolomic profiles are uniquely associated with depression rather than anxiety disorders.

OBJECTIVE Electroconvulsive therapy (ECT) is an effective acute treatment for severe and/or medication-resistant depression but maintaining remission following completion of a course remains a clinical challenge. METHODS EFFECT-Dep Trial (ISRCTN23577151) participants with a DSM-IV major depressive episode who met remission criteria after a randomly assigned course of twice-weekly brief-pulse bitemporal (1.5 × seizure threshold) or high-dose (6 × seizure threshold) right unilateral ECT were monitored for relapse for 12 months. In line with the pragmatic trial design, all patients received treatment-as-usual individualised pharmacotherapy during and after ECT; no remitter received continuation ECT. RESULTS Of 61 remitters, 24 (39.3%) relapsed, one (1.6%) withdrew from the study while in remission and the remaining 36 (59.0%) stayed well for a year. Most relapses occurred within the first six months, resulting in a cumulative six-month relapse rate of 31.1%. In a multivariable Cox proportional hazards regression model, older age (p = 0.039) and psychotic features at pre-ECT baseline (p = 0.037) were associated with a more favourable long-term prognosis while a greater number of previous depressive episodes (p = 0.028) and bipolar II (but not bipolar I) diagnosis (p = 0.030) were associated with a worse long-term outcome. Electrode placement and medication resistance prior to ECT had no effect on relapse. Adjusting for covariates, fewer patients treated with lithium relapsed in the overall group (p = 0.008) and in the unipolar depression subgroup (p = 0.027). CONCLUSION Long-term outcome following high-dose right unilateral ECT does not differ from bitemporal ECT. Prognosis is particularly favourable in older adults, psychotic depression and patients maintained on lithium.

Background The effect of relative age on the diagnoses of attention deficit hyperactivity disorder (ADHD), disruptive behavior disorder (DD), anxiety disorder, and depressive disorder and the prescription for ADHD and antidepressant medications remains unclear. Aim To clarify the impact of relative age in a school year with the diagnoses of ADHD, DD, anxiety disorder and depressive disorder and the prescription for ADHD and antidepressant medications. Methods The annual cutoff birthdate for entry to school in Taiwan is August 31. The Taiwan National Health Insurance Research Database was used to enroll 9,548,393 children and adolescents aged 3-17 years during the study period (September 1, 2001, to August 31, 2011). The poisson regression model was performed to examine the likelihood of receiving diagnoses of ADHD, DD, anxiety disorder, and depressive disorder, as well as the prescription of ADHD and antidepressant medications among children born in August (the youngest) and September (the oldest). Results Both boys and girls born in August had a higher risk of being diagnosed as having ADHD (odds ratio [OR] = boys: 1.65, girls: 1.80), DD (1.29, 1.45), anxiety disorder (1.49, 1.33), and depressive disorder (1.10, 1.10). Furthermore, children born in August were more likely to be prescribed ADHD medication (1.71, 1.72) and antidepressants (1.18, 1.09) compared with those born in September. Discussion Relative age, as an indicator of neurocognitive maturity, is a critical factor for the likelihood of being diagnosed as having ADHD, DD, anxiety disorder, and depressive disorder among children and adolescents.

Evidence of larger drug effects in highly standardized studies (efficacy) compared to clinical routine (effectiveness) is discussed as efficacy-effectiveness gap. This study aimed to quantify effect size differences of RCTs and non-RCTs in the treatment of depression with venlafaxine and duloxetine and to identify effect modifying predictors.A comprehensive systematic review and meta-analysis was conducted, including all prospective trials, which evaluated the treatment effects of duloxetine or venlafaxine in patients with depression. The primary outcome was the pre-post effect size after acute therapy, which were compared between RCTs and non-RCTs. Moreover, an exploratory analysis of predictors in a mixed meta-regression model within an information-theoretic approach was performed.171 RCTs and 74 non-RCTs were included. The pre-post effect size differed significantly between RCTs and non-RCTs (-3.04 vs. -2.62, Δ = 0.41, p = 0.012, high heterogeneity). Study characteristics were very similar between RCTs and non-RCTs. Most important variables to predict effect sizes were 'depression severity', 'dose' and 'number of participants'.Despite differences in effect sizes between RCTs and non-RCTs, study design is not clearly an important predictor for the effect sizes. Our results question the common assumption that non-RCTs are generally better suited to describe a drug's effectiveness in clinical practice than RCTs. Future studies and their reporting should put more emphasis on the description of external validity, in order to allow better assessments of clinical relevance.

Objective Electroconvulsive therapy (ECT) is a rapidly effective treatment for severe depression. Treatment with right unilateral (RUL) or bitemporal (BT) ECT may explain individual differences in speed of ECT effectiveness. There is limited evidence for demographic and clinical factors that predict speed of response and remission with ECT. We aimed to investigate differences in speed of improvement as well as achieving response and remission between twice-weekly brief-pulse high-dose (6 × seizure threshold) RUL ECT and moderate-dose (1.5 × seizure threshold) BT ECT. We also explored demographic and clinical characteristics that predict speed of response and remission. Methods Weekly 24-item Hamilton Depression Rating Scale scores were assessed among patients with severe depression who participated in the EFFECT-Dep trial (ISRCTN23577151). Speed of improvement in patients randomised to RUL ECT (n = 69) or BT ECT (n = 69) was compared using independent sample t tests. Pearson's chi-square and Fisher's exact tests compared proportions of responders and remitters at each weekly assessment. Predictors of speed of response and remission were explored using Cox regression analyses. Results There were no significant differences between RUL and BT ECT in speed of improvement, response or remission. Exploratory analyses indicated that speed of response and remission were not predicted by a wide variety of demographic and clinical characteristics. Conclusion ECT electrode placement did not have predictive value when determining speed of improvement, response and remission with ECT. Other clinical factors, such as cognitive side-effects, may be more relevant when making the clinical choice between RUL and BT ECT.

ObjectiveDepressed patients rate social support as important for prognosis, but evidence for a prognostic effect is lacking. We aimed to test the association between social support and prognosis independent of treatment type, and the severity of depression, and other clinical features indicating a more severe illness.MethodsIndividual patient data were collated from all six eligible RCTs (n = 2858) of adults seeking treatment for depression in primary care. Participants were randomized to any treatment and completed the same baseline assessment of social support and clinical severity factors. Two‐stage random effects meta‐analyses were conducted.ResultsSocial support was associated with prognosis independent of randomized treatment but effects were smaller when adjusting for depressive symptoms and durations of depression and anxiety, history of antidepressant treatment, and comorbid panic disorder: percentage decrease in depressive symptoms at 3–4 months per z‐score increase in social support = −4.14(95%CI: −6.91 to −1.29). Those with a severe lack of social support had considerably worse prognoses than those with no lack of social support: increase in depressive symptoms at 3–4 months = 14.64%(4.25% to 26.06%).ConclusionsOverall, large differences in social support pre‐treatment were associated with differences in prognostic outcomes. Adding the Social Support scale to clinical assessments may be informative, but after adjusting for routinely assessed clinical prognostic factors the differences in prognosis are unlikely to be of a clinically important magnitude. Future studies might investigate more intensive treatments and more regular clinical reviews to mitigate risks of poor prognosis for those reporting a severe lack of social support.

Objective To systematically review evidence for the association between trauma experienced in childhood or adolescence, and the subsequent experience of affective or psychotic mental disorders in adulthood. Methods Electronic databases (Scopus, Medline (for Ovid), EMBASE and PsychINFO) were searched for peer-reviewed, longitudinal cohort studies in the English language examining child or adolescent exposure to trauma, and adult-diagnosed depression, anxiety, psychotic disorder or bipolar disorder. A total of 23 manuscripts were retained. Results Results revealed a significant association between the following childhood exposures and adult mental disorder: bullying (victimhood, perpetration and frequency); emotional abuse; physical neglect; parental loss; and general maltreatment (unspecified and/or multiple trauma exposure). There was some evidence of a dose-response relationship with those exposed to multiple forms of maltreatment having more than three times the odds of developing a mental disorder (Odds ratio = 3.11, 95% CI = 1.36-7.14). There was no significant association found between physical or sexual abuse and adult mental disorder; however, this is likely an artefact of how these adversities were assessed. Conclusion There is strong evidence of an association between childhood trauma and later mental illness. This association is particularly evident for exposure to bullying, emotional abuse, maltreatment and parental loss. The evidence suggests that childhood and adolescence are an important time for risk for later mental illness, and an important period in which to focus intervention strategies.

Objective: Despite the proven efficacy and safety of ECT, there is still concern about the possible cognitive side effects of ECT in older patients. In this study, we aimed to characterize the long-term cognitive effects of ECT in patients with late-life depression (LLD) from before the start until 4 years after the index ECT course. Methods: Fourty one patients aged 55 years and older with a unipolar depression, referred for ECT, were included. The neuropsychological test battery was assessed prior to ECT, 6 months, 1 year, 2 years, 3 years, and 4 years after the last ECT session. Results: We did not find any statistically significant cognitive changes from before the start to 4 years after ending the ECT course. Although we could not detect cognitive changes at group level, we found clinically important differences on an individual level. Conclusion: Cognitive performance in patients with LLD runs a stable course from before the start of ECT until 4 years after the index course. At an individual level, however, both cognitive decline and improvement can be witnessed. Older patients can tolerate ECT and most of them will not experience long-term cognitive side effects.

OBJECTIVE Seasonal pattern (SP) is a bipolar disorder (BD) specifier that indicates a tendency towards affective relapses during specific moments of the year. SP affects 15%-25% of BD patients. In the past, SP was applied only to depressive relapses while, in DSM-5, SP may be applied to both depressive and (hypo)manic episodes. We examined the association between different clinical correlates of BD and SP according to its current definition in a cohort of patients with BD type I (BDI) and II (BDII). METHODS Patients were recruited from a specialized unit and assessed according to the season of relapse and type of episode per season. SP and non-SP patients were compared looking into sociodemographic and clinical correlates. Significant variables at univariate comparisons were included in multivariate logistic regression with SP as the dependent variable. RESULTS 708 patients were enrolled (503 BDI, 205 BDII), and 117 (16.5%) fulfilled DSM-5 criteria for SP. The mean age was 45.3 years (SD = 14.18), and 389 were female (54.9%). The logistic regression model included a significant contribution of BDII (OR = 2.23, CI 1.4-3.55), family history of mood disorder (OR = 1.97, CI 1.29-3.01), undetermined predominant polarity (OR = 0.44, CI 0.28-0.70), and aggressive behavior (OR = 0.42, CI 0.23-0.75). CONCLUSION Our results outline a novel positive association of SP with undetermined predominant polarity, BDII, family history of mood disorder, and with fewer aggressiveness-related symptoms. Seasonality is associated with a biphasic pattern with similar dominance of (hypo)mania and depression and is more frequent in BDII as compared to BDI. Seasonal episodes may be easier to predict, but difficult to prevent.

Objectives Predictors for unfavorable treatment outcome in major depressive disorder (MDD) applicable for treatment selection are still lacking. The database of a longitudinal multicenter study on 1079 acutely depressed patients, performed by the German research network on depression (GRND), allows supervised and unsupervised learning to further elucidate the interplay of clinical and psycho‐sociodemographic variables and their predictive impact on treatment outcome phenotypes. Experimental Procedures Treatment response was defined by a change of HAM‐D 17‐item baseline score ≥50% and remission by the established threshold of ≤7, respectively, after up to eight weeks of inpatient treatment. After hierarchical symptom clustering and stratification by treatment subtypes (serotonin reuptake inhibitors, tricyclic antidepressants, antipsychotic, and lithium augmentation), prediction models for different outcome phenotypes were computed with random forest in a cross‐center validation design. In total, 88 predictors were implemented. Results Clustering revealed four distinct HAM‐D subscores related to emotional, anxious, sleep, and appetite symptoms, respectively. After feature selection, classification models reached moderate to high accuracies up to 0.85. Highest accuracies were observed for the SSRI and TCA subgroups and for sleep and appetite symptoms, while anxious symptoms showed poor predictability. Conclusion Our results support a decisive role for machine learning in the management of antidepressant treatment. Treatment‐ and symptom‐specific algorithms may increase accuracies by reducing heterogeneity. Especially, predictors related to duration of illness, baseline depression severity, anxiety and somatic symptoms, and personality traits moderate treatment success. However, prospectives application of machine learning models will be necessary to prove their value for the clinic.

To evaluate morbidity during long-term follow-up with clinical treatment of affective and schizoaffective disorder subjects followed from hospitalization for first major psychotic episodes.We followed adult subjects systematically at regular intervals from hospitalization for first-lifetime episodes of major affective and schizoaffective disorders with initial psychotic features. We compiled % of days with morbidity types from detailed records and life charts, reviewed earliest antecedent morbidities, compared both with final diagnoses and initial presenting illness types, and evaluated morbidity risk factors with regression modeling.With final diagnoses of bipolar-I (BD-I, n = 216), schizoaffective (SzAffD, 71), and major depressive (MDD, 42) disorders, 329 subjects were followed for 4.47 [CI: 4.20-4.47] years. Initial episodes were mania (41.6%), mixed states (24.3%), depression (19.5%), or apparent nonaffective psychosis (14.6%). Antecedent morbidity presented 12.7 years before first episodes (ages: SzAffD ≤ BD-I MDD). Long-term % of days ill ranked SzAffD (83.0%), MDD (57.8%), BD-I (45.0%). Morbidity differed by diagnosis and first-episode types, and was predicted by first episodes and suggested by antecedent illnesses. Long-term wellness was greater with BD-I diagnosis, first episode not mixed or psychotic nonaffective, rapid onset, and being older at first antecedents, but not follow-up duration.Initially, psychotic BD-I, SzAffD, or MDD subjects followed for 4.47 years from first hospitalization experienced much illness, especially depressive or dysthymic, despite ongoing clinical treatment. Antecedent symptoms arose years before index first episodes; antecedents and first episode types predicted types and amounts of long-term morbidity, which ranked: SzAffD MDDBD-I.

Objective To perform a network meta‐analysis (NMA) to compare the long‐term effectiveness of mindfulness‐based cognitive therapy (MBCT) with available strategies for prevention and time to depressive relapse. Methods Seven electronic databases were searched up to June 2019. Studies evaluated MBCT for the management of depression‐related outcomes and follow‐up assessments occurred at 12 months or longer. Results Twenty‐three publications were included, 17 of which were randomised controlled trials (RCTs). Data from 14 RCTs including 2077 participants contributed to meta‐analysis (MA) and NMA to assess relapse of depression and 13 RCTs with 2017 participants contributed to MA and NMA for time to relapse of depression. NMAs showed statistically significant advantages for MBCT over treatment as usual (TAU) for relapse of depression (RR = 0.73, 95% CI 0.54 to 0.98) and for MBCT over TAU and placebo for time to relapse of depression (MBCT vs TAU: HR = 0.57, 95% CI 0.37 to 0.88; MBCT vs placebo: HR = 0.23, 95% CI 0.08 to 0.67). Subgroup meta‐analysis of relapse of depression by previous number of depressive episodes showed similar results between subgroups. Subgroup meta‐analysis by the use or not of booster sessions suggests these may lead to improved effectiveness. Conclusions MBCT is more effective than TAU in the long‐term in preventing relapse of depression and has statistically significant advantages over TAU and placebo for time to relapse of depression. No statistically significant differences were observed between MBCT and active treatment strategies for rate of relapse or time to relapse of depression.

Objective Meditation techniques are widely used as therapy and wellbeing practices, but there are growing concerns about its potential for harm. The aim of the present study is to systematically review meditation adverse events (MAEs), investigating its major clinical categories and its prevalence. Method We searched PubMed, PsycINFO, Scopus, Embase and AMED up to October 2019. Eligible studies included original reports of meditation practices (excluding related physical practices such as Yoga postures) with adult samples across experimental, observational and case studies. We identified a total of 6742 citations, 83 of which met the inclusion criteria for MAEs with a total of 6703 participants who undertook meditation practice. Results Of the 83 studies analysed, 55 (65%) included reports of at least one type of MAE. The total prevalence of adverse events was 8.3% (95% CI 0.05-0.12), though this varied considerably across types of studies - 3.7% (95% CI 0.02-0.05) for experimental and 33.2% (95% CI 0.25-0.41) for observational studies. The most common AEs were anxiety (33%, 18), depression (27%, 15) and cognitive anomalies (25%, 14); gastrointestinal problems and suicidal behaviours (both 11%, 6) were the least frequent. Conclusion We found that the occurrence of AEs during or after meditation practices is not uncommon, and may occur in individuals with no previous history of mental health problems. These results are relevant both for practitioners and clinicians, and contribute to a balanced perspective of meditation as a practice that may lead to both positive and negative outcomes.

Objective Ketamine's effects on different dimensions of depressive symptomatology, including typical/melancholic and atypical depression, remain largely unknown. This study examined the effects of a single intravenous dose of ketamine on general depressive symptoms (measured using the Montgomery-Asberg Depression Rating Scale (MADRS), typical/melancholic symptoms (measured using the MADRS5), and atypical symptoms (measured using the Scale for Atypical Symptoms (SAS)). Methods Data from 68 participants with treatment-resistant major depressive disorder (MDD) or bipolar depression were pooled from three separate, double-blind, placebo-controlled, crossover studies investigating ketamine's efficacy in depression. MDD participants were unmedicated; bipolar participants received therapeutic-dose lithium or valproate. Clinical symptoms were collected preinfusion and up to 14 days postinfusion. Effect sizes were calculated for days 1 and 3 postinfusion. The primary measures of interest for this exploratory analysis were total MADRS, MADRS5, and SAS scores. Individual symptoms were also analyzed in an exploratory manner. Results Scores improved significantly at Day 1 postinfusion (MADRS: Cohen's d = 0.64; MADRS5: Cohen's d = 0.61; SAS: Cohen's d = 0.41) and continued to be significantly improved over placebo at Day 3 (MADRS: Cohen's d = 0.49; MADRS5: Cohen's d = 0.43; SAS: Cohen's d = 0.39). Effect sizes were greater for typical/melancholic than atypical symptoms at Day 1 postinfusion. Conclusion Ketamine appears to effectively treat both the typical/melancholic and atypical symptoms of depression, but may have early preferential effects for the former.

Background Lithium is an old proven medication, but it is infrequently used in current practice. This review examines evidence for its benefits and risks and provides clinical guidance to its use. Method Narrative review. Results Besides its benefit in bipolar illness, lithium has important underappreciated proven benefits in prevention of unipolar depression and suicide. Emerging data support neurobiological benefits for cognition and possible dementia prevention. Likely benefits also exist in low doses for mood temperaments (cyclothymia and hyperthymia). High doses (over 1.0 mmol/L) should be avoided since they increase side effects, complications associated with long-term use, and risk of toxicity. Conversely, low dosing can be legitimate, especially for suicide and dementia prevention. Nuisance side effects of lithium may affect adherence, and medically serious side-effects can occur. Managing strategies are available for side effects. Conclusion Lithium is the most effective medication in psychiatry, because it has disease-modifying, not just symptomatic, effects. It is effective not only for bipolar illness but also for prevention of suicide, episodes of unipolar depression, mood temperaments, and possibly dementia. Its many benefits need better appreciation, while lowered dosing can reduce risks.

Contains fulltext : 220915.pdf (Publisher’s version ) (Open Access) OBJECTIVE: Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acid (PUFA) alterations in patients with major depressive disorder (MDD) have been shown to persist after remission. Whether these alterations are risk factors for MDD recurrence remains unknown. Here, we examined whether fatty acids predict time until MDD recurrence in remitted MDD patients. METHODS: Data were used from remitted MDD patients of the Netherlands Study of Depression and Anxiety (n = 356) and the Depression Evaluation Longitudinal Therapy Assessment studies (n = 118). Associations of FAs with time until MDD recurrence up to 8-year follow-up were analyzed using Cox regression analyses. Study-specific estimates were pooled using mega- and meta-analysis techniques. RESULTS: 27.5% (NESDA) and 56.8% (DELTA) participants had an MDD recurrence. Pooled results showed that no FA was significantly associated with time until MDD recurrence (n-3 PUFAs: hazard ratio (HR) = 1.17, 95% confidence interval (CI) = 0.98-1.41, P = 0.082; n-6 PUFAs: HR = 1.08, 95% CI = 0.84-1.38, P = 0.55). CONCLUSION: In remitted MDD patients, circulating PUFAs were not associated with prospective risk of MDD recurrence. Consequently, circulating PUFAs are unlikely to reflect a vulnerability marker for recurrence, so correcting n-3 PUFA 'deficits' through supplementation does not seem a promising option to prevent MDD recurrence.

Objective The aim of this study is to systematically review published studies, reporting outcomes to offspring following in utero exposure to antidepressant medications, which used an untreated depressed comparison group. Methods OVID, Scopus, EBSCO Collections, the Cochrane Library and Web of Science databases were searched for relevant publications published between January 1950 and May 2018 and a total of 188 potentially eligible studies were identified. Results Following review, 16 primary studies were eligible for inclusion. Antidepressant exposure was associated with an increased risk of lower gestational age, preterm birth, but not low birthweight or being small for gestational age compared to untreated depression. There is some evidence that congenital defects are associated with antidepressant use, particularly between cardiac defects and paroxetine use. There is conflicting evidence regarding neurodevelopment in offspring, with some reports of increased incidence of autistic spectrum disorders and depression, but also reports of no problems when measuring emotional symptoms, peer problems, conduct problems and hyperactivity-inattention scores. Conclusion When compared with an untreated depressed group, antidepressant exposure was associated with adverse outcomes at birth, while there is insufficient data to determine whether the association between antidepressants and congenital defects or developmental disorders is a true association. However, although we compared treated vs. untreated depression there still may be residual confounding as an untreated depressed group is likely to have less severe depression.

Objective About half or more of treatment-resistant depressed patients do not respond to ketamine, and few clinical predictors to gauge the most likely antidepressant response have been proposed. We explored whether depression subtypes are associated with response to ketamine. Method Ninety-seven participants with depression were administered six repeated-dose intravenous ketamine and assessed for depression (Montgomery-Asberg Depression Rating Scale, MADRS), anxiety (Hamilton Anxiety Rating Scale, HAMA), and suicidal ideation (Beck Scale for Suicidal Ideation, SSI) at baseline, 24 h after each infusion, and 2 weeks after the whole treatment. Participants were classified by melancholic/anxious subtype. Individuals who met criteria for neither or both subtypes were classified separately, resulting in four mutually exclusive groups. Results Patients with melancholic or melancholic-anxious features were less likely to respond (e.g., day 13, melancholic-anxious vs. anxious, OR 0.138, 95% CI 0.032-0.584, P = 0.007) or remit (e.g., day 26, melancholic vs. no subtype, OR 0.182, 95% CI 0.035-0.960, P = 0.045) and took longer to achieve response/remission than those with anxious or no subtype features. Faster HAMA score reductions were observed in patients with anxious or melancholic-anxious features, and faster SSI score reductions were observed among those with melancholic-anxious features. Conclusion Our study shows promising results for ketamine as a novel antidepressant preferentially for the treatment of non-melancholic or anxious depression.

Introduction Continuation electroconvulsive therapy (c‐ECT) is highly effective for the prevention of depressive symptom relapse. There is a lack of understanding, about how c‐ECT works in humans, particularly with regard to its effects on brain derived neurotrophic factor (BDNF) concentrations. Here, we aimed to close a gap in the literature by evaluating BDNF levels in patients receiving c‐ECT. Methods We included 13 patients with either unipolar or bipolar depression (mean age ± SD: 55.5 ± 17.1; f/m: 10/3; unipolar/bipolar: 10/3) who received between one and four c‐ECT (average per patient: 2.8). Serum BDNF (sBDNF) levels were assessed before and after each c‐ECT sessions. Clinical assessments were also administered both before and after treatment. Results Our analysis revealed a significant increase in sBDNF after each treatment (c‐ECT 1‐3: P

Objective Several studies have found an increase in hippocampal volume following electroconvulsive therapy (ECT), but the effect on cortical thickness has been less investigated. We aimed to examine the effects of ECT on cortical thickness and their associations with clinical outcome. Method Using 3 Tesla MRI scanner, we obtained T1-weighted brain images of 18 severely depressed patients at three time points: before, right after and 6 months after a series of ECT. The thickness of 68 cortical regions was extracted using Free Surfer, and Linear Mixed Model was used to analyze the longitudinal changes. Results We found significant increases in cortical thickness of 26 regions right after a series of ECT, mainly within the frontal, temporal and insular cortex. The thickness returned to the baseline values at 6-month follow-up. We detected no significant decreases in cortical thickness. The increase in the thickness of the right lateral orbitofrontal cortex was associated with a greater antidepressant effect, r = 0.75, P = 0.0005. None of the cortical regions showed any associations with cognitive side effects. Conclusion The increases in cortical thickness induced by ECT are transient. Further multimodal MRI studies should examine the neural correlates of these increases and their relationship with the antidepressant effect.

Background and aims The interrelationship between alcohol consumption and depression is complex, and the direction of the association is unclear. We investigated whether alcohol consumption influences the risk of depression while accounting for this potential bidirectionality. Methods A total of 10 441 individuals participated in the PART study in 1998-2000, 8622 in 2001-2003, and 5228 in 2010. Participants answered questions on their alcohol consumption, symptoms of depression, childhood adversity, and sociodemographic, socioeconomic, psychosocial, and lifestyle factors. A total of 5087 participants provided repeated information on alcohol consumption. We used marginal structural models to analyze the association between alcohol consumption and depression while controlling for previous alcohol consumption and depressive symptoms and other time-varying confounders. Results Non-drinkers had a higher depression risk than light drinkers (≤7 drinks/week) (risk ratio: 1.7; 95% confidence interval 1.3-2.1). Consumers of seven-fourteen drinks/week had a depression risk similar to that of light drinkers. Hazardous drinking was associated with a higher risk of depression than non-hazardous alcohol consumption (risk ratio: 1.8, 95% confidence interval: 1.4-2.4). Conclusion Light and moderate alcohol consumption and non-hazardous drinking were associated with the lowest risk of subsequent depression after accounting for potential bidirectional effects. Hazardous drinking increased the risk of depression.

Background: No study has gathered evidence from all randomized clinical trials (RCTs) with anti-inflammatory drugs measuring antidepressant effects including a detailed assessment of side-effects and bias. Methods: We performed a systematic review identifying RCTs published prior to January 1, 2018, studying antidepressant treatment effects and side-effects of pharmacological anti-inflammatory intervention in adults with major depressive disorder (MDD) or depressive symptoms. Outcomes were depression scores after treatment, remission, response, and side-effects. Pooled standard mean differences (SMD) and risk ratios (RR) including 95% confidence intervals (95%-CI) were calculated. Results: We identified 36 RCTs, whereof 13 investigated NSAIDs (N = 4214), 9 cytokine inhibitors (N = 3345), seven statins (N = 1576), 3 minocycline (N = 151), 2 pioglitazone (N = 77), and 2 glucocorticoids (N = 59). Anti-inflammatory agents improved depressive symptoms compared to placebo as add-on in patients with MDD (SMD = −0.64; 95%-CI = −0.88, −0.40; I 2 = 51%; N = 597) and as monotherapy (SMD = −0.41; 95%-CI = −0.60, −0.22; I 2 = 93%, N = 8825). Anti-inflammatory add-on improved response (RR = 1.76; 95%-CI = 1.44–2.16; I 2 = 16%; N = 341) and remission (RR = 2.14; 95%-CI = 1.03–4.48; I 2 = 57%; N = 270). We found a trend toward an increased risk for infections, and all studies showed high risk of bias. Conclusion: Anti-inflammatory agents improved antidepressant treatment effects. Future RCTs need to include longer follow-up, identify optimal doses and subgroups of patients that can benefit from anti-inflammatory intervention.

Objective: Associations between suicidality and lipid dysregulation are documented in mental illness, but the potential role of leptin remains unclear. We examined the association between leptin and suicidal behaviour in schizophrenia, together with the influence of other clinical and biological indices. Method: We recruited a sample of 270 participants with schizophrenia spectrum diagnoses. Blood samples were analysed for leptin, while symptom severity was assessed by Positive and Negative Syndrome Scale (PANSS ) and Inventory of Depressive Symptomatology (IDS ‐C). Patients' history of suicidal behaviour was categorized into three subgroups based on IDS ‐C suicide subscale: No suicidal behaviour, mild/moderate suicidal behaviour and severe suicidal behaviour with/without attempts. Results: Mild/moderate suicidal behaviour was present in 17.4% and severe suicidal behaviour in 34.8%. Both groups were significantly associated with female gender (OR = 6.0, P = 0.004; OR = 5.9, P = 0.001), lower leptin levels (OR = 0.4, P = 0.008; OR = 0.5, P = 0.008) and more severe depression (OR = 1.2, P < 0.001; OR = 1.1, P < 0.001) respectively. Smoking (OR = 2.6, P = 0.004), younger age of onset (OR = 0.9, P = 0.003) and less use of leptin‐increasing medications (OR = 0.5, P = 0.031) were associated with severe/attempts group, while higher C‐reactive protein CRP (OR = 1.3, P = 0.008) was associated with mild/moderate group. Conclusion: Lower leptin levels were associated with higher severity of suicidal behaviour in schizophrenia. publishedVersion

OBJECTIVES We evaluated birth-cohort differences in depressive symptom burden, prevalence of depression diagnoses, and neuroticism, among Swedish 70-year-olds examined between 1976 and 2016. METHODS We used a repeated cross-sectional design examining four representative population samples of Swedish 70-year-olds (total n = 2279) with identical methods in 1976-77 (n = 392), 1992-93 (n = 226), 2000-02 (n = 487), and 2014-16 (n = 1166). Depressive symptom burden was rated with the Montgomery Asberg Depression Rating Scale. Major depression was diagnosed according to DSM-5, and minor depression according to DSM-IV-TR research criteria. Neuroticism was rated with the Eysenck Personality Inventory. RESULTS For women in 2014-16, MADRS score (4.4 vs. 6.1 vs. 5.8; P

OBJECTIVE This meta-analysis investigates the efficacy of inpatient psychotherapy in major depressive disorders compared to control conditions. METHODS In total, 14 studies were entered into the meta-analysis with a total of 1.080 patients. Primary outcome was the standardized mean differences in self-rated depression outcomes. A priori planned subgroup analyses included the influence of different control conditions: (a) no psychiatric inpatient treatment (e.g., waitlist control), (b) treatment as usual (TAU; e.g., non-manualized clinical management), (c) TAU determined by study design (manualized/'placebo' control condition), as well as number of sessions and influence of self- vs. clinician ratings. RESULTS The meta-analysis of 19 available comparisons resulted in a moderate pooled effect size showing a small and statistically significant benefit of the psychotherapeutic intervention over control conditions (g = 0.24, P

Objective: To investigate whether early improvement, measured after two electroconvulsive therapy (ECT) sessions, is a good predictor of eventual remission in severely depressed in-patients receiving ECT. Method: A prospective cohort study was performed that included 89 major depressive disorder in-patients treated with bilateral ECT. Sensitivity, specificity, and predictive values were computed for various definitions of early improvement (15%, 20%, 25%, and 30% reduction on the Montgomery Asberg depression rating scale (MADRS) score) after 1 week (i.e. two sessions) of ECT regarding prediction of remission (final MADRS score ≤ 9). Results: A 15% reduction in MADRS score appeared to be the best definition of early improvement, with modest sensitivity (51%) and relatively good specificity (79%). Kaplan–Meier analysis showed a more than 2-week shorter time to remission in patients with early improvement compared with patients lacking early improvement. Conclusion: Early improvement during an ECT course may be assessed after two ECT sessions. Such improvement, defined as a 15% reduction in the MADRS score, is a moderately sensitive predictor for eventual remission in an in-patient population with severe major depression.

Objectives To determine whether past history of depression is associated with increased rates of gestational diabetes, and whether history of gestational diabetes is associated with increased rates of postpartum depression. Research design Data for this case-control study consisted of de-identified chart records for 1439 women who received pregnancy care at a large university hospital between 1998 and 2017. Results A history of depression prior to pregnancy was associated with gestational diabetes requiring insulin, although not with subtler degrees of gestational hyperglycemia. Diabetes in pregnancy was not associated with an increased risk of postpartum depression. Trauma history was associated with both impaired glucose tolerance in pregnancy and postpartum depression. Conclusions Past episodes of depression increase risk for the most severe form of gestational diabetes; however, gestational diabetes does not contribute significantly to risk for postpartum depression. This suggests a unidirectional association, unlike the bidirectional association of diabetes with depression among the general population. History of trauma increases risk for both gestational hyperglycemia and postpartum depression, suggesting important health effects of trauma that may differ measurably from those associated with depression.

© 2021 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.Objective: Meta-analyses of psychotherapies usually report effects sizes, while clinicians and patients need to know the proportion of patients who benefit from therapy. We conducted a meta-analysis of therapies for depression reporting the rates of response (50% symptom reduction), remission (HAM-D

Objective To use the Clinical Global Impression‐Severity (CGI‐S) scale to estimate clinically meaningful and clinically substantial changes as measured using the Montgomery‐Åsberg Depression Rating Scale (MADRS), the Sheehan Disability Scale (SDS), and the Patient Health Questionnaire‐9 (PHQ‐9) in patients with treatment‐resistant depression (TRD). Methods Pooled data were derived from two 4‐week, randomized, active‐controlled studies evaluating esketamine nasal spray (ESK) plus oral antidepressant (OAD) or OAD plus placebo nasal spray (PBO) in adults with TRD (N = 565). CGI‐S, MADRS, SDS, and PHQ‐9 scores were obtained at baseline and over 4 weeks of treatment. In this post hoc analysis, change scores on the MADRS, SDS, and PHQ‐9 that corresponded to a clinically meaningful (1‐point) or clinically substantial (2‐point) change on the CGI‐S scale were identified. Results Clinically meaningful changes in CGI‐S scores after 28 days corresponded to 6‐, 4‐, and 3‐point changes from baseline on the MADRS, SDS, and PHQ‐9, respectively. Similarly, a 2‐point CGI‐S score change (clinically substantial change) corresponded to a 12‐, 8‐, and 6‐point change on the MADRS, SDS, and PHQ‐9, respectively. The proportion of patients showing substantial clinical improvement in the ESK plus OAD group versus the OAD plus PBO group after 28 days of treatment favored ESK plus OAD: 69.0% vs 55.3% (MADRS), 64.5% vs 48.9% (SDS), and 77.1% vs 64.7% (PHQ‐9). Conclusion We provide a basis for identifying clinically meaningful and clinically substantial changes as assessed with commonly used outcome measures for depression to facilitate the translation of clinical trial results into clinical practice.

OBJECTIVE: Inflammation is associated with major depressive disorder (MDD) and suicidal behavior. According to the 'leaky gut hypothesis', increased intestinal permeability may contribute to this relationship via bacterial translocation across enterocytes. We measured plasma levels of gut permeability markers, in patients with a recent suicide attempt (rSA), MDD subjects with no history of a suicide attempt (nsMDD), and healthy controls (HC), and related these markers to symptom severity and inflammation. METHOD: We enrolled rSA (n = 54), nsMDD (n = 13), and HC (n = 17). Zonulin, intestinal fatty acid binding protein (I-FABP), soluble CD14, and interleukin-6 (IL-6) were quantified in plasma. Montgomery-Asberg Depression Rating Scale (MADRS) and Suicide Assessment Scale (SUAS) were used for symptom assessments. RESULTS: The rSA group displayed higher I-FABP and lower zonulin levels compared with both the nsMDD and the HC groups (all P < 0.001). IL-6 correlated positively with I-FABP (r = 0.24, P < 0.05) and negatively with zonulin (r = -0.25, P < 0.05). In all subjects, I-FABP levels correlated positively with MADRS (r = 0.25, P < 0.05) and SUAS scores (r = 0.38, P < 0.001), and the latter correlation was significant also in the nsMDD group (r = 0.60, P < 0.05). CONCLUSION: The 'leaky gut hypothesis' may improve our understanding of the link between inflammation and suicidal behavior. These findings should be considered preliminary until replicated in larger cohorts.

Objectives: Clinical variables were investigated in the ‘treatment resistant depression (TRD)- III’ sample to replicate earlier findings by the European research consortium ‘Group for the Study of Resistant Depression’ (GSRD) and enable cross-sample prediction of treatment outcome in TRD. Experimental procedures: TRD was defined by a Montgomery and Åsberg Depression Rating Scale (MADRS) score ≥22 after at least two antidepressive trials. Response was defined by a decline in MADRS score by ≥50% and below a threshold of 22. Logistic regression was applied to replicate predictors for TRD among 16 clinical variables in 916 patients. Elastic net regression was applied for prediction of treatment outcome. Results: Symptom severity (odds ratio (OR) = 3.31), psychotic symptoms (OR = 2.52), suicidal risk (OR = 1.74), generalized anxiety disorder (OR = 1.68), inpatient status (OR = 1.65), higher number of antidepressants administered previously (OR = 1.23), and lifetime depressive episodes (OR = 1.15) as well as longer duration of the current episode (OR = 1.022) increased the risk of TRD. Prediction of TRD reached an accuracy of 0.86 in the independent validation set, TRD-I. Conclusion: Symptom severity, suicidal risk, higher number of lifetime depressive episodes, and comorbid anxiety disorder were replicated as the most prominent risk factors for TRD. Significant predictors in TRD-III enabled robust prediction of treatment outcome in TRD-I., SCOPUS: ar.j, info:eu-repo/semantics/published

OBJECTIVES Depression is a frequent but potentially treatable clinical dimension in patients with schizophrenia spectrum disorders (PWS). However, there is a lack of consensual recommendations regarding the optimal strategy to manage depression in PWS. In this study, we aimed to compare the various proposed strategies to define a core set of valid care recommendations for depression management in PWS. METHODS After a systematic search of the literature, the methodological quality of 10 international guidelines from four continents was compared using a validated guideline appraisal instrument (AGREE II). Key recommendations for the management of depression in PWS were subsequently reviewed and discussed. RESULTS The methodological quality of the guidelines was heterogeneous. Although all guidelines proposed pharmacotherapy, psychosocial interventions were a minor concern. Waiting for antipsychotic effects mostly was recommended during the acute phase of schizophrenia. During the postpsychotic phase of the illness, a switch to a second-generation antipsychotic and/or the adjunction of an antidepressant were the primary recommendations. Cognitive behavioural therapy and other medications were considered with strong variations. CONCLUSIONS Further studies are needed to strengthen the level of evidence for antidepressive approaches in PWS. The inclusion of PWS as stakeholders is also considered to be a major issue for future guideline development.

Objective Bipolar disorder is a severe mental disorder for which currently no reliable biomarkers exist. It has been shown that patients with schizophrenia but not with unipolar depression have a reduced density of fast sleep spindles during N2 sleep. The aim of this study was to assess fast sleep spindle density in euthymic patients with bipolar disorder. Methods Patients with bipolar disorder (n = 24) and healthy control subjects (n = 25) were assessed using all-night polysomnography. Sleep spindles within stage N2 sleep were identified by visual inspection and subdivided into fast (>13 Hz) and slow (≤13 Hz) spindles. All spindles were subsequently characterised by density, frequency, amplitude, duration and coherence. Results Euthymic patients with bipolar disorder were found to have a reduced density and a lower mean frequency of fast spindles. Slow spindle density and frequency did not differ between groups. There were no differences regarding amplitude, duration or coherence. Conclusions A reduction in fast spindle density during N2 sleep points towards thalamic dysfunction as a potential neurobiological mechanism of relevance in bipolar disorder. In addition, a reduced sleep spindle density could be interpreted as a common endophenotype shared with schizophrenia but not unipolar depression and may - if replicated - be of utility in early recognition and risk stratification.

Objective We conducted a 12-week double-blind study of stabilization pharmacotherapy in patients with remitted psychotic depression (PD). Methods Seventy-one persons aged 18 years or older who had achieved remission of PD when randomized to either olanzapine plus sertraline or olanzapine plus placebo were continued on the double-blind treatment associated with remission. Symptoms of depression and psychosis, and weight, were measured once every 4 weeks. Cholesterol, triglycerides, and glucose were measured at stabilization phase baseline and Week 12/termination. Results The effect of treatment did not significantly change with time for depression, weight, or metabolic measures in the stabilization phase. Eight of the 71 participants (11.3%; 95% CI: 5.8, 20.7) experienced a relapse of major depression, psychosis, or both. Treatment groups did not differ in the frequency of relapse. In the entire study group, the adjusted estimate for change in weight was an increase of 1.66 kg (95% CI: 0.83, 2.48) and the adjusted estimate for change in total cholesterol was a decrease of 14.8 mg/dL (95% CI: 3.5, 26.1) during the 12-week stabilization phase; the remaining metabolic measures did not significantly change. Conclusion Continuation of acute treatment was associated with stability of remission.

Objective To assess differences between subjects with vs. without mixed features in major affective disorders. Methods In 3099 out-patient subjects with DSM-5 major depressive disorder (MDD, n = 1921) or bipolar disorders (BD, n = 1178), we compared those with (Mx) vs. without (Non-Mx) mixed features (agitated-irritable depression or dysphoric [hypo]mania) in an index episode. Results Prevalence of Mx averaged 21.9% [CI: 20.5-23.4] overall, ranking: BD-II > BD-I > MDD, and in BD depression ≥ [hypo]mania > MDD. Mx subjects were significantly more likely than Non-Mx cases to (i) have other mixed episodes, (ii) have higher irritable and agitated ratings, (iii) have more substance abuse, (iv) switch into mixed episodes, (v) have more suicide attempts and higher suicidal ratings, (vi) change diagnosis from depression to BD, (vii) have higher hypomania scores when depressed or depression scores when [hypo]manic, (viii) be unmarried or separated with fewer children and siblings, (ix) be diagnosed more with BD than MDD, (x) be unemployed, (xi) have BD, suicide and divorce among first-degree relatives, (xii) be female, (xiii) be younger at illness-onset. Both BD and MDD Mx subjects also received antidepressants less, but antipsychotics and mood-stabilizers more, alone and in combination with antidepressants. Conclusions Mood disorder subjects with agitated-irritable depression or dysphoric [hypo]mania differed from those without such mixed features, including having a less favorable clinical course and repeated mixed episodes. They may represent a distinct and prevalent, syndromal clinical subtype with prognostic and therapeutic significance.

Objective The role of baseline severity as effect modifier in various psychiatric disorders is a topic of controversy and of clinical import. This study aims to examine whether baseline severity modifies the efficacy of various antidepressants for major depression through individual participant data (IPD) meta‐analysis. Method We identified all placebo‐controlled, double‐blind randomised trials of new generation antidepressants in the acute phase treatment of major depression conducted in Japan and requested their IPD through the public–private partnerships (PPPs) between the relevant academic societies and the pharmaceutical companies. The effect modification by baseline depression severity was examined through six increasingly complex competing mixed‐effects models for repeated measures. Results We identified eleven eligible trials and obtained IPD from six, which compared duloxetine, escitalopram, mirtazapine, paroxetine or bupropion against placebo (total n = 2464). The best‐fitting model revealed that the interaction between baseline severity and treatment was not statistically significant (coefficient = −0.04, 95% confidence interval: −0.16 to 0.08, P = 0.49). Several sensitivity analyses confirmed the robustness of the findings. Conclusion We may expect as much benefit from antidepressant treatments for mild, moderate or severe major depression. Clinical practice guidelines will need to take these findings into consideration.

Objective To determine the level of agreement across a set of evidence-based guidelines for management of the unipolar depressive disorders and with a focus on physical treatments. Method A literature search was undertaken using the terms 'depression', 'depressive' and 'guidelines', using PubMed, Cochrane Database of Systematic Reviews and the National Guideline Clearinghouse. Twelve national psychiatric or professional guideline-producing organizations were identified from the period 2007-2017, with guidelines qualitatively reviewed by two assessors. Results For major depressive disorder (MDD), there was general consensus to use an antidepressant (AD) in cases of greater severity, although disagreement on AD use in mild to moderate depression. There was some agreement on choice of AD class in first-line treatment recommendations, though great variability in second- and third-line management particularly in recommended augmentation and combined AD strategies. Electroconvulsive therapy was considered in all but one guideline, with other neurostimulation treatments being less consistently covered and with variable recommendations. Finally, there was low consistency in the management of dysthymia, persistent depressive disorder and treatment resistant depression. Conclusion Our review identifies varying levels of consistency in guideline recommendations. Strategies to improve reliability in guideline formulation should also improve their validity.

Depression is associated with accelerated aging and age-related diseases. However, mechanisms underlying this relationship remain unclear. The aim of this study was to longitudinally assess the link between depressive symptoms, brain atrophy, and cortisol levels.Participants from the Betula prospective cohort study (mean age = 59 years, SD = 13.4 years) underwent clinical, neuropsychological and brain 3T MRI assessments at baseline and a 4-year follow-up. Cortisol levels were measured at baseline in four saliva samples. Cortical and hippocampal atrophy rates were estimated and compared between participants with and without depressive symptoms (n = 81) and correlated with cortisol levels (n = 49).Atrophy in the left superior frontal gyrus and right lingual gyrus developed in parallel with depressive symptoms, and in the left temporal pole, superior temporal cortex, and supramarginal cortex after the onset of depressive symptom. Depression-related atrophy was significantly associated with elevated cortisol levels. Elevated cortisol levels were also associated with widespread prefrontal, parietal, lateral, and medial temporal atrophy.Depressive symptoms and elevated cortisol levels are associated with atrophy of the prefrontal and limbic areas of the brain.

Objective Method To investigate the potential role of the Maudsley Staging Method (MSM) in the prediction of electroconvulsive therapy (ECT) outcome in severely depressed adults. Between August 2015 and August 2017, 73 consecutive patients with a major depressive episode (DSM-IV-TR) scheduled for ECT were recruited. Prior to their first ECT session, the MSM was completed to assess the level of therapy resistance. To determine the reduction in depression severity and response and remission rates, symptom severity was assessed at baseline and within one week after the last ECT session using the 17-item Hamilton Depression Rating Scale (HDRS17). Results Conclusion The percentage of symptom reduction following ECT was best predicted by the MSM episode duration and depression severity factors (R-2 completer sample 0.24). Episode duration alone was the best predictor of remission (area under the ROC curve for completers: 0.72). Adding age to the models increased their predictive capacity. An adapted version of the MSM gauging shorter episode duration, more severe depressive symptoms and older age is significantly associated with ECT effectiveness in adults with severe recurrent depression and is thus highly suitable for use in clinical practice, promoting the shared treatment decision-making process.

Objective: There is ongoing concern about the possible negative impact of ECT on neurocognitive functioning in older patients. In this study, we aimed to characterize the long-term cognitive effects of ECT in patients with late-life depression, using an extensive neuropsychological battery. Methods: A total of 110 patients aged 55 years and older with unipolar depression, referred for ECT were included. The neuropsychological test battery was assessed prior to ECT and 6 months after the last ECT session. Results: There were no statistically significant group-level changes from baseline to 6 months post-ECT in any of the neuropsychological measurements. Individual differences in cognitive performance were detected using the Reliable Change Index. Conclusion: Patients with late-life depression do not show deleterious cognitive effects 6 months following an ECT index course, although there are considerable differences at an individual level. Clinicians should not hesitate to prescribe ECT in older patients, as most of these patients will tolerate the treatment course and a small group will even experience a cognitive enhancement. However, clinicians should be aware that a small group of patients can experience cognitive side-effects. Further study is needed to predict which patients have a higher risk of developing cognitive side-effects.

Objective It still remains unclear whether psychotic features increase the risk of suicidal attempts in major depressive disorder. Thus, we attempted, through a systematic review coupled with a meta-analysis, to elucidate further whether unipolar psychotic depression (PMD) compared to non-PMD presents higher levels of suicidal attempts. Method A systematic search was conducted in PubMed, EMBASE, PsycINFO as well as in various databases of the so-called gray literature for all studies providing data on suicidal attempts in PMD compared to non-PMD, and the results were then subjected to meta-analysis. Results Twenty studies met our inclusion criteria, including in total 1,275 PMD patients and 5,761 non-PMD patients. An elevated risk for suicide attempt for PMD compared to non-PMD patients was found: The total (lifetime) fixed-effects pooled OR was 2.11 (95% CI: 1.81-2.47), and the fixed-effects pooled OR of the five studies of the acute phase of the disorder was 1.93 (95% CI: 1.33-2.80). This elevated risk of suicidal attempt for PMD patients remained stable across all age groups of adult patients. Conclusion Despite data inconsistency and clinical heterogeneity, this systematic review and meta-analysis showed that patients with PMD are at a two-fold higher risk, both during lifetime and in acute phase, of committing a suicidal attempt than patients with non-PMD.

Objective In the last decade, several studies have suggested that depression is accompanied by increased oxidative stress and decreased antioxidant defenses. We tested the hypothesis that high levels of the antioxidant uric acid are associated with lower risk of hospitalization with depression and use of prescription antidepressant medication. Method We examined plasma levels of the antioxidant uric acid in 96 989 individuals from two independent cohort studies. Logistic regression and Cox proportional hazards regression models were multivariable adjusted for age, gender, alcohol, smoking, income, body mass index, C-reactive protein, hemoglobin, triglycerides, cardiovascular disease, diabetes, and intake of meat and vegetables. Results were performed separately in each study and combined in a meta-analysis. Results In both studies, high uric acid was associated with lower risk of hospitalization as in-patient or out-patient with depression and antidepressant medication use. A doubling in uric acid was associated with an effect estimate of 0.57 (95% CI 0.49–0.65) and 0.77 (0.73–0.81) for hospitalization with depression and antidepressant medication use. The association was consistent across strata of all covariates. Results were attenuated in Cox regression analyses with less statistical power. Conclusion High plasma levels of uric acid were associated with low risk of depression hospitalization and antidepressant medication use.

Objective Depression in bipolar disorder (BipD) requires a therapeutic approach that is from treating unipolar major depressive disorder (UniD), but to date, no reliable methods could separate these two disorders. The aim of this study was to establish the clinical validity and utility of a non-invasive functional MRI-based method to classify BipD from UniD. Method The degree of connectivity (degree centrality or DC) of every small unit (voxel) with every other unit of the brain was estimated in 22 patients with BipD and 22 age, gender, and depressive severity-matched patients with UniD and 22 healthy controls. Pattern classification analysis was carried out using a support-vector machine (SVM) approach. Results Degree centrality pattern from 8-min resting fMRI discriminated BipD from UniD with an accuracy of 86% and diagnostic odds ratio of 9.6. DC was reduced in the left insula and increased in bilateral precuneus in BipD when compared to UniD. In this sample with a high degree of uncertainty (50% prior probability), positive predictive value of the DC test was 79%. Conclusion Degree centrality maps are potential candidate measures to separate bipolar depression from unipolar depression. Test performance reported here requires further pragmatic evaluation in regular clinical practice.

Objective To systematically review the published clinical trials, case series, and case reports on left unilateral (LUL) electrode placement for clinical electroconvulsive therapy (ECT). Method PubMed, Ovid Medline, and the Cochrane Library were searched for articles concerning LUL ECT. Number of patients, efficacy, and cognitive outcomes were extracted from the papers that met our inclusion criteria. Results A total of 52 articles were included in this review, consisting of 33 clinical trials, seven case series, and 12 case reports. Conclusion Overall, the efficacy of LUL electrode placement for the treatment of depression and psychosis is similar to that of right unilateral (RUL) and bilateral (BL) electrode placements. Patients receiving LUL ECT tend to experience more verbal memory impairment than patients receiving RUL ECT, but less verbal impairment than patients receiving BL ECT. In contrast, patients receiving LUL ECT tended to experience the least visual and nonverbal memory impairment, compared to patients receiving RUL or BL ECT.