Consequences Of Major Depressive Disorder Research Articles

Causes and consequences of major depressive disorder: An encompassing Mendelian randomization study.

Major depressive disorder (MDD) is a prevalent and debilitating disorder that has been associated with a range of risk factors and outcomes. Causal pathways between MDD and other traits can be studied using genetic variants as instrumental variables. A literature review was conducted to identify 201 MDD-associated traits. For 115 traits, there were well-powered genome-wide association study (GWAS) results available that could be used to assess the genetic correlation with MDD. Of these, there were 89 meeting criteria for investigating causal associations in both directions using two-sample Mendelian randomization (TSMR). Of the traits that were not captured by GWAS, 43 could be included as outcomes of MDD using one-sample MR (OSMR). A range of methods and sensitivity tests was applied to gauge robustness of results, together with statistical power analyses to aid interpretation. Moderate to strong genetic overlap was found between MDD and most traits. Support for causal effects of MDD liability were found for circadian, cognitive, diet, medical disease, endocrine, functional, inflammatory, metabolic, mortality, physical activity, reproduction, risk behavior, social, socioeconomic, and suicide outcomes. Most associations were bidirectional, although there was less evidence for diet, disease, and endocrine traits causing MDD risk. Results were robust across sensitivity analyses. This study provides a systematic overview of traits putatively causally related to MDD, confirming previous findings as well as identifying new associations. Our results highlight the importance of MDD as a risk factor cross-cutting across medical, functional, and psychosocial domains and emphasize the need for concerted efforts at reducing this highly prevalent disorder.

Investigation of peripheral inflammatory biomarkers in association with suicide risk in major depression

IntroductionSuicide is the most severe consequence of major depressive disorder (MDD). The most novel researches assume the role of immunological dysregulation in the background – several studies have reported alterations of inflammatory cells related to both MDD and suicidal behaviour (SB).ObjectivesChanges in the number of certain immune cells and their ratios have been proposed as potential biomarkers of suicide risk (SR). The aim of our research was to investigate alterations of these values related not only to MDD as an assumed inflammatory state, but also to an increased risk of SB.Methods In our restrospective cohort study carried out between January 2015 and January 2020, we investigated laboratory parameters of psychiatric patients diagnosed with MDD (n=101). Individuals with recent (≤48 hours prior) suicide attempt (SA) (n=22) and with past SA (>48 hours prior) (n=19) represented the high SR group. MDD patients with no history of SA (n=60) composed the intermediate SR group. We compared the number of neutrophil granulocytes, monocytes, lymphocytes, platelets, leukocytes, neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), platelet-to-lymphocyte ratio (PLR), red blood cell distribution width (RDW) and erythrocyte sedimentation rate (ESR). Furthermore, we evaluated alterations of these parameters related to antidepressant (AD) treatment, which has been proved to have anti-inflammatory effects. Statistical analyses were carried out using GraphPad 9.5.0 and MedCalc 16.8 programmes.Results We found a significant increase in neutrophil granulocyte count (p=0.016), NLR (p=0.031, Fig. 1), monocyte count (p≤0.0001), MLR (p=0.005, Fig. 2), leukocyte count (p=0.048) and ESR (p=0.037) in patients with recent SA compared to patients with no history of SA. Moreover, there was a significant elevation in monocyte count (p≤0.0001), MLR (p=0.020, Fig. 3), ESR (p=0.041) and RDW (p=0.037) in patients with high SR compared to patients with intermediate SR. AD treatment resulted in a significant decrease in neutrophil granulocyte count (p=0.0163) and NLR (p=0.016), however, it did not affect the rest of the parameters.Image:Image 2:Image 3:ConclusionsAssuming immunological mechanisms in the background of MDD and SB, our findings support the role of NLR as a biomarker of acute SR, though its alterations may be masked by AD therapy in the long term. However, MLR – remaining unaffected by AD treatment – may be a possible indicator of both acute and long term suicidal vulnerability. In order to further specify the diagnostic value of these parameters, future prospective research is needed.The study was supported by the FIKP-IV and the TNIL projects.Disclosure of InterestNone Declared

A network study to differentiate suicide attempt risk profiles in male and female patients with major depressive disorder.

Suicide attempts are a possible consequence of Major Depressive Disorder (MDD), although their prevalence varies across different epidemiological studies. Suicide attempt is a significant predictor of death by suicide, highlighting its importance in understanding and preventing tragic outcomes. Researchers are increasingly recognizing the need to study the differences between males and females, as several distinctions emerge in terms of the characteristics, types and motivations of suicide attempts. These differences emphasize the importance of considering gender-specific factors in the study of suicide attempts and developing tailored prevention strategies. We conducted a network analysis to represent and investigate which among multiple neurocognitive, psychosocial, demographic and affective variables may prove to be a reliable predictor for identifying the 'suicide attempt risk' (SAR) in a sample of 81 adults who met DSM-5 criteria for MDD. Network analysis resulted in differences between males and females regarding the variables that were going to interact and predict the SAR; in particular, for males, there is a stronger link toward psychosocial aspects, while for females, the neurocognitive domain is more relevant in its mnestic subcomponents. Network analysis allowed us to describe otherwise less obvious differences in the risk profiles of males and females that attempted to take their own lives. Different neurocognitive and psychosocial variables and different interactions between them predict the probability of suicide attempt unique to male and female patients.

Bidirectional Associations of Temporomandibular Joint Disorders with Major Depressive and Anxiety Disorders.

Mounting evidence indicates the associations of temporomandibular disorders (TMD) with depression and anxiety symptoms. However, the temporal and casual relationships between TMD and depression and between TMD and anxiety must be further clarified. This study is a retrospective cohort analysis that employed data from the Taiwan National Health Insurance Database and comprised the following sub analyses: temporomandibular joint disorders (TMJD) as the cause of subsequent major depressive disorder (MDD) or anxiety disorders (AnxDs) and TMJD as the consequence of MDD or AnxDs. Patients with antecedent TMJD (N = 12,152 for the MDD study and 11,023 for the AnxD study), MDD (N = 28,743), or AnxDs (N = 21,071) and their respective control cohorts were identified between January 1, 1998 and December 31, 2011. The control cohorts (1:10) were matched by age, sex, income, residential location, and comorbidities. Individuals with subsequent new-onset TMJD, MDD, or AnxDs were identified from January 1, 1998 to December 31, 2013. The risk of the outcome disorders of the individuals with antecedent TMJD, MDD, or AnxD were estimated using Cox regression models. Patients with TMJD had an approximately 3-fold higher risk (hazard ratio [HR]: 3.98, 95% confidence interval [CI]: 3.28-4.84) of subsequent MDD development and a 7-fold higher risk (HR: 7.26, 95% CI: 5.90-8.94) of AnxD development than those without TMJD. Antecedent MDD and AnxDs were predictive of 5.80-fold (95% CI: 4.81-6.98) and 8.29-fold (95% CI: 6.67-10.30), respectively, increases in the risk of subsequent TMJD development. Our results demonstrate that precedent TMJD and MDD/AnxDs are associated with elevated risks of subsequent MDD/AnxDs and TMJD developments and indicate temporal associations of TMJD with MDD and AnxDs are bidirectional.

Altered gray matter volumes and plasma IL-6 level in major depressive disorder patients with suicidal ideation

BackgroundsSuicidal ideation (SI) is one of the most serious consequences of major depressive disorder (MDD). Understanding the unique mechanism of MDD with SI (MDD + S) is crucial for treatment development. While abundant research has studied MDD, past studies have not reached a consensus on the mechanism of MDD + S. The study aimed to investigate the abnormalities of the gray matter volumes (GMVs) and plasma IL-6 level in MDD + S to further reveal the mechanism of MDD + S. MethodsWe tested the plasma IL-6 level using Luminex multifactor assays and collected the Structural Magnetic Resonance Imaging (SMRI) data from 34 healthy controls (HCs), 36 MDD patients without SI (MDD − S) and 34 MDD + S patients. We performed a partial correlation between the GMVs of the brain regions with significant differences and plasma IL-6 level with age, sex, medication, scores of HAMD-17 and HAMA as the covariates. ResultsCompared with HCs and MDD − S, MDD + S had significantly decreased GMVs in the left cerebellum Crus I/II and significantly increased plasma IL-6 level; compared with HCs, both the MDD + S and MDD − S had significantly decreased GMVs in right precentral and postcentral gyri. No significant correlation was found between the GMVs and the plasma IL-6 level in the MDD + S and MDD − S, respectively. While the GMVs of the right precentral and postcentral gyri negatively correlated with the level of IL-6 in the whole MDD (r = −0.28, P = 0.03). The GMVs of the left cerebellum Crus I/II (r = −0.47, P = 0.02), and the right precentral and postcentral gyri (r = −0.42, P = 0.04) negatively correlated with the level of IL-6 in HCs. ConclusionThe altered GMVs and the plasma IL-6 level may provide a scientific basis to understand the pathophysiological mechanisms of MDD + S.

Psychometric validity of the Montgomery and Åsberg Depression Rating Scale for Youths (MADRS-Y)

Background Because of all the serious consequences of major depressive disorder (MDD), it is important to screen for MDD in adolescents. The aim of this study was to test the psychometric properties of the newly developed self-report depression scale MADRS-Y for adolescents in a normative Swedish sample. Methods The study included 620 adolescents in the age range of 12–20 years old. The normative sample was randomly split into two equal parts, to perform principal component analysis (PCA) on sample one and confirmatory factor analysis (CFA) on sample two. We investigated the psychometrics. Results The result from the PCA suggested that all 12 potential items should be used, and the items loaded on the same construct of depression. The CFA supported the one-factor structure with good fit indices. Measurement invariance was confirmed, allowing interpretation regardless of gender or age differences. Reliability was good, α .89, for both samples separately. Test-retest reliability was good to excellent (intraclass correlation coefficients = .87 and .91). Evidence of convergent and discriminant validity was shown. Conclusions The results in the current study suggest that the MADRS-Y is a brief, reliable, and valid self-report questionnaire of depressive symptoms for adolescents in the general population.

Psychological Assessment with Objective and Projective Techniques along with Self-Report: A Case Study of Young Widow with Major Depressive Disorder

The study investigated the psychological concerns of a young widow, who lost her husband just at the age of 21 and examined how psychotherapeutic techniques helped her overcome them in the present case study. Using a structured clinical interview and a complete report, we documented the impact of this significant loss on both temperament and emotional wellbeing. Including the Beck Depression Inventory (BDI), The Standard Progressive Matrices (SPM), Thematic Apperception Test (TAT), Rotter’s Incomplete Sentence Blank (RISB), Bender Gestalt Test (BGT), and Human Figure Drawing Test (HFD). These studies were crucial in assessing a diagnosis as well as a treatment strategy. The girl had a significant depressive episode and met all the diagnostic criteria. In similar circumstances, this mixture of psychological testing could help establish an accurate diagnosis and comprehend the behavioral and psychological consequences of Major Depressive Disorder (MDD). The study also indicated that Cognitive Behavior Therapy (CBT) is an effective treatment option for people suffering from Major Depressive Disorder. Keywords: objective and projective techniques, cognitive behavior therapy, major depressive disorder

Prefrontal cortex and depression.

The prefrontal cortex (PFC) has emerged as one of the regions most consistently impaired in major depressive disorder (MDD). Although functional and structural PFC abnormalities have been reported in both individuals with current MDD as well as those at increased vulnerability to MDD, this information has not translated into better treatment and prevention strategies. Here, we argue that dissecting depressive phenotypes into biologically more tractable dimensions - negative processing biases, anhedonia, despair-like behavior (learned helplessness) - affords unique opportunities for integrating clinical findings with mechanistic evidence emerging from preclinical models relevant to depression, and thereby promises to improve our understanding of MDD. To this end, we review and integrate clinical and preclinical literature pertinent to these core phenotypes, while emphasizing a systems-level approach, treatment effects, and whether specific PFC abnormalities are causes or consequences of MDD. In addition, we discuss several key issues linked to cross-species translation, including functional brain homology across species, the importance of dissecting neural pathways underlying specific functional domains that can be fruitfully probed across species, and the experimental approaches that best ensure translatability. Future directions and clinical implications of this burgeoning literature are discussed.

Molecular mechanisms of physical exercise on depression in the elderly: a systematic review

Depressive disorders are common among the elderly. Major depressive disorder will be one of the highest healthcare costs in middle and higher income countries by 2030. It is known that physical inactivity leads to negative effects on mental health in the elderly.The purpose of this review was to explore investigate the consequences of physical exercise (aerobic and resistance exercise) on major depressive disorder among elderly, and presenting its potential biological mechanisms. This study was designed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Clinical trials or randomized clinical trials or cohort studies participated of the study design. Ten studies were evaluated and the main outcomes of each were reported. Aerobic and resistance training revealed to be effective in fighting the symptoms of depression. The most common physical exercise protocol adopted to reduce the consequences of major depressive disorder in humans was the prescription of aerobic exercise at moderate-intensity lasting 60min per session, 3 times per week, for 24weeks. Physical exercise enhances IGF-I and activates PGC-1α/FNDC5/Irisin pathway. Physical exercise also increases expression of BDNF and its receptor, TrkB, in the hippocampus and prefrontal cortex leading to upstream of ERK and inhibiting depressive-like behavior. Physical exercise brings mental health benefits and plays a crucial role in avoiding the development of major depressive disorder.

Single and dual diagnoses of major depressive disorder and posttraumatic stress disorder predicted by triple comorbid trajectories of tobacco, alcohol, and marijuana use among urban adults

Background: The adverse consequences of major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) affect a significant portion of the US population every year (i.e., 15 million for MDD; 8 million for PTSD) and are of public health concern. The current study examines tobacco, alcohol, and marijuana use as possible longitudinal predictors of MDD and/or PTSD. Methods: A community sample of 674 participants (53% African Americans and 47% Puerto Ricans; 405 females and 269 males) were recruited from the Harlem Longitudinal Development Study. We used Mplus software to obtain the triple trajectories of tobacco, alcohol, and marijuana use from mean age 14 to 36. Logistic regression analyses were then conducted to examine the associations between those triple trajectory groups and a single diagnosis of MDD or PTSD as well as a dual diagnosis of MDD with PTSD at age 36. Results: The observed percentages of MDD, PTSD, and the comorbidity of MDD and PTSD were 17%, 8%, and 5%, respectively. The heavy use of all 3 substances group was associated with an increased likelihood of having MDD (adjusted odds ratio [AOR] = 3.14, P < .01), PTSD (AOR = 3.91, P < .05), and MDD with PTSD (AOR = 6.64, P < .01), as compared with the tobacco and alcohol use group. Conclusions: Treatment programs to quit or reduce the use of tobacco, alcohol, and marijuana may help decrease the prevalence of MDD and PTSD. This could lead to improvements in individualized treatments for patients who use tobacco, alcohol, and marijuana and who have both MDD and PTSD.

Cognitive Performance in First-Degree Relatives of Individuals With vs Without Major Depressive Disorder

Findings of cognitive impairment in major depressive disorder (MDD), including remitted MDD, raise the question whether impaired cognition is part of preexisting vulnerability rather than a consequence of MDD or its treatment. To our knowledge, no meta-analyses have been published on cognitive impairment in first-degree relatives of individuals with MDD. To compare cognitive performance between individuals with and without family history of MDD. Medline/PubMed, PsycINFO, and Embase using combinations of search terms for depression, first-degree relatives, and cognition from January 1, 1980, to July 15, 2018. Original articles that reported data on cognition in first-degree relatives of individuals with MDD compared with controls with no family history of major mental illness. Means and SDs were extracted, and standardized mean differences (SMD) between relatives and controls were calculated for each measure of cognitive performance. The relative-control differences in overall cognition and in specific cognitive domains were synthesized in random-effects meta-analyses with robust variance estimation that allows including multiple correlated measures of cognition within each study. Heterogeneity was quantified with τ2. Publication bias was assessed with funnel plots and Egger intercept. Performance on cognitive tests. Across 284 measures of cognition in 54 nonoverlapping samples including 3246 relatives of people with MDD (mean age 15.38 years, 57.68% females) and 5222 controls (mean age 14.70 years, 55.93% females), relatives of people with MDD performed worse than controls across all measures of cognition (SMD = -0.19; 95% CI, -0.27 to -0.11; P < .001). Domain-specific meta-analyses showed similar size of relative-control difference in most domains of cognition, including Full-Scale IQ (SMD = -0.19), verbal intelligence (SMD = -0.29), perceptual intelligence (SMD = -0.23), memory (SMD = -0.20), academic performance (SMD = -0.40), and language (SMD = -0.29). Study characteristics were not significantly associated with observed between-group differences. There was no evidence of publication bias. A general impairment in cognition is a feature of familial disposition for MDD. Cognition may contribute to early identification of risk for depression and may be examined as potential target for early intervention.

A comparison of the B-spline group-based trajectory model with the polynomial group-based trajectory model for identifying trajectories of depressive symptoms around old-age retirement

Objectives: The life event of retirement may be associated with changes in levels of depressive symptoms. The use of polynomial group-based trajectory modelling allows any changes to vary between different groups in a sample. A new approach, estimating these models using B-splines rather than polynomials, may improve modelling of complex changes in depressive symptoms at retirement.Methods: The sample contained 1497 participants from the Swedish Longitudinal Occupational Survey of Health (SLOSH). Polynomial and B-spline approaches to estimating group-based trajectory models were compared.Results: Polynomial group-based trajectory models produced unexpected changes in direction of trajectories unsupported by the data. In contrast, B-splines provided improved insights into trajectory shapes and more homogeneous groups. While retirement was associated with reductions in depressive symptoms in the sample as a whole, the nature of changes at retirement varied between groups.Conclusions: Depressive symptoms trajectories around old age retirement changed in complex ways that were modelled more accurately by the use of B-splines. We recommend estimation of group-based trajectory models with B-splines, particularly where abrupt changes might occur. Improved trajectory modelling may support research into risk factors and consequences of major depressive disorder, ultimately assisting with identification of groups which may benefit from treatment.

Is low cognitive functioning a predictor or consequence of major depressive disorder? A test in two longitudinal birth cohorts.

Cognitive impairment has been identified as an important aspect of major depressive disorder (MDD). We tested two theories regarding the association between MDD and cognitive functioning using data from longitudinal cohort studies. One theory, the cognitive reserve hypothesis, suggests that higher cognitive ability in childhood decreases risk of later MDD. The second, the scarring hypothesis, instead suggests that MDD leads to persistent cognitive deficits following disorder onset. We tested both theories in the Dunedin Study, a population-representative cohort followed from birth to midlife and assessed repeatedly for both cognitive functioning and psychopathology. We also used data from the Environmental Risk Longitudinal Twin Study to test whether childhood cognitive functioning predicts future MDD risk independent of family-wide and genetic risk using a discordant twin design. Contrary to both hypotheses, we found that childhood cognitive functioning did not predict future risk of MDD, nor did study members with a past history of MDD show evidence of greater cognitive decline unless MDD was accompanied by other comorbid psychiatric conditions. Our results thus suggest that low cognitive functioning is related to comorbidity, but is neither an antecedent nor an enduring consequence of MDD. Future research may benefit from considering cognitive deficits that occur during depressive episodes from a transdiagnostic perspective.

C.04.02 - Functional consequences of major depressive disorder

C.04.02 - Functional consequences of major depressive disorder

Study protocol: Hybrid Type I cost-effectiveness and implementation study of interpersonal psychotherapy (IPT) for men and women prisoners with major depression

PurposeThis article describes the protocol for a Hybrid Type I cost-effectiveness and implementation study of interpersonal psychotherapy (IPT) for men and women prisoners with major depressive disorder (MDD). The goal is to promote uptake of evidence-based treatments in criminal justice settings by conducting a randomized effectiveness study that collects implementation data, including a full cost-effectiveness analysis. BackgroundMore than 2.3million people are incarcerated in the United States on any given day. MDD is the most common severe mental illness among incarcerated individuals. Despite the prevalence and consequences of MDD among incarcerated populations, this study will be the first fully-powered randomized trial of any treatment for MDD in an incarcerated population. DesignGiven the politically charged nature of the justice system, advantageous health outcomes are often not enough to get an intervention implemented in prisons. To increase the policy impact of this trial, we sought advice from prison providers and administrators about outcomes that would be persuasive to policy-makers and defensible to the public. In this trial, effectiveness questions will be answered using a randomized clinical trial design comparing IPT plus prison treatment as usual (TAU) to TAU alone, with outcomes including depressive symptoms (primary), suicidality, and in prison functioning (enrollment and completion of correctional programs; disciplinary and incident reports; aggression/victimization; social support). Implementation outcomes will include cost-effectiveness; feasibility and acceptability of IPT to clients, providers, and administrators; prison provider intervention fidelity, attitudes, and competencies; and barriers and facilitators of implementation assessed through surveys, interviews, and process notes.

Muscle tenderness and psychiatric comorbidity: a vicious cycle in migraine chronicization.

Muscle tenderness and psychiatric comorbidity: a vicious cycle in migraine chronicization.

Hippocampal atrophy in major depression: a function of childhood maltreatment rather than diagnosis?

Reduced hippocampal volumes are probably the most frequently reported structural neuroimaging finding associated with major depressive disorder (MDD). However, it remains unclear whether altered hippocampal structure represents a risk factor for or a consequence of MDD. Reduced hippocampal volumes were consistently reported in subjects affected by childhood maltreatment. As the prevalence of childhood maltreatment is highly elevated in MDD populations, previous morphometric findings regarding hippocampal atrophy in MDD therefore might have been confounded by maltreatment experiences. The aim of this study was to differentiate the impact of childhood maltreatment from the influence of MDD diagnosis on hippocampal morphometry. Depressed patients (85) as well as 85 age- and sex-matched healthy controls underwent structural MRI. The Childhood Trauma Questionnaire was administered to estimate experiences of childhood maltreatment. Hippocampal volume and surface structure was examined by the use of two independent methods, automated segmentation (FSL-FIRST) and voxel-based morphometry (VBM8). In line with existing studies, MDD patients showed reduced hippocampal volumes, and childhood maltreatment was consistently associated with hippocampal volume loss in both, patients and healthy controls. However, no analysis revealed significant morphological differences between patients and controls if maltreatment experience was regressed out. Our results suggest that hippocampal alterations in MDD patients may at least partly be traced back to higher occurrence of early-life adverse experiences. Regarding the strong morphometric impact of childhood maltreatment and its distinctly elevated prevalence in MDD populations, this study provides an alternative explanation for frequently observed limbic structural abnormalities in depressed patients.

Genetic risk score analysis indicates migraine with and without comorbid depression are genetically different disorders.

Migraine and major depressive disorder (MDD) are comorbid, moderately heritable and to some extent influenced by the same genes. In a previous paper, we suggested the possibility of causality (one trait causing the other) underlying this comorbidity. We present a new application of polygenic (genetic risk) score analysis to investigate the mechanisms underlying the genetic overlap of migraine and MDD. Genetic risk scores were constructed based on data from two discovery samples in which genome-wide association analyses (GWA) were performed for migraine and MDD, respectively. The Australian Twin Migraine GWA study (N = 6,350) included 2,825 migraine cases and 3,525 controls, 805 of whom met the diagnostic criteria for MDD. The RADIANT GWA study (N = 3,230) included 1,636 MDD cases and 1,594 controls. Genetic risk scores for migraine and for MDD were used to predict pure and comorbid forms of migraine and MDD in an independent Dutch target sample (NTR-NESDA, N = 2,966), which included 1,476 MDD cases and 1,058 migraine cases (723 of these individuals had both disorders concurrently). The observed patterns of prediction suggest that the 'pure' forms of migraine and MDD are genetically distinct disorders. The subgroup of individuals with comorbid MDD and migraine were genetically most similar to MDD patients. These results indicate that in at least a subset of migraine patients with MDD, migraine may be a symptom or consequence of MDD.

Peripheral metabolic abnormalities of lipids and amino acids implicated in increased risk of suicidal behavior in major depressive disorder

Suicide is the most serious consequence of major depressive disorder (MDD), yet a vast majority of MDD patients never attempt nor commit suicide. This discrepancy suggests a predisposition to suicidal behavior independent of MDD. However, the molecular basis of this predisposition remains largely unknown, hampering development of specific and targeted treatment of MDD patients at risk for suicide. A proton nuclear magnetic resonance (1H NMR)-based metabonomic approach was used to capture metabolic perturbations related to suicide predisposition in the context of MDD. 1H NMR spectra of plasma sampled from drug-naive depressed suicide attempters (n = 21), non-attempters (n = 35), and healthy controls (n = 35) were recorded and analyzed through a multivariate statistical approach. Multivariate statistical analysis demonstrated that the depressed suicide attempter group was significantly distinguishable from the depressed non-attempter group and controls group. Several key metabolites, including lipids (low-density lipoprotein, very low-density lipoprotein, cholesterol and unsaturated lipid), lipid metabolism-related molecules (glucose, pyruvate and lactate) and amino acids (alanine, glycine and taurine) responsible for discriminating depressed suicide attempters from the nonattempters and controls were identified. This study is the first to indicate that peripheral perturbations in lipid and amino acid metabolism may be implicated in the predisposition to suicide in MDD patients.

Antidepressant Use in Children and Adolescents Diagnosed with Major Depressive Disorder: What Can We Learn from Published Data?

The consequences of major depression disorder (MDD) in youths are likely to be devastating for both the patient and his/her family. Thus, this review analyzes systematically the effectiveness of antidepressant drugs (ADDs) in managing such patients. Medical literature reporting primary data on use of ADDs in children and adolescents was identified through searches (1966-January 2010) of MEDLINE/PubMed, EMBASE, SCOPUS, and The Cochrane Library databases. Additional studies were manually identified from the reference lists of published articles. Search terms (variously combined) were: children, childhood, adolescents, adolescence, MDD, mood/affective disorders, depression, tricyclic antidepressants (TCAs) SSRIs, Serotonin-Norepinephrine Reuptake inhibitors (SNRIs), noradrenergic/specific serotoninergic antidepressants (NaSSA). A separate search was conducted to complete the profile of effectiveness of each single antidepressant agent. 43 peer-reviewed articles met the inclusion criteria. Reviewed information does not definitively support the use of antidepressants in children younger than 10 years old. In contrast, robust information suggests that fluoxetine should be considered as first-line agent in depressed adolescents whose clinical conditions require psychopharmacological approach. Depressed children should be primarily approached with non-pharmacological interventions that should include the evaluation of potential parental psychiatric disorders. In adolescents with MDD, the decision to use fluoxetine should be associated with specific social and health protocols focused to reinforce self-esteem, improve the quality of relationships with parents and peers, facilitate healthy life-style changes, and identify the potential onset/worsening of suicidality.