Early-onset Depression Research Articles

Differences in Odor Identification in Early-Onset and Late-Onset Depression.

(1) Background: Odor identification (OI) dysfunction is a potential predictor of developing dementia in late life depression (LLD). However, it is not clear whether patients with early onset depression (EOD) and late onset depression (LOD) may exhibit different OI dysfunctions. The aim of this study was to compare OI between EOD patients and LOD patients and its relationship with cognitive function. (2) Methods: A total of 179 patients with LLD and 189 normal controls were recruited. Participants underwent clinical assessment, olfactory testing, and comprehensive neuropsychological assessment. The OI scores of EOD patients and LOD patients were compared, and correlation analyses and mediation analyses were used to explore the relationship between OI and cognition. (3) Result: LOD patients exhibited lower OI scores than EOD patients and normal controls (NCs). Additionally, the LOD patients exhibited a higher percentage of OI dysfunction than the EOD patients. Moreover, OI scores were associated with global cognition, memory, language, and visuospatial ability in the EOD group (p < 0.05) but were not associated with any cognitive score in the LOD patients (p > 0.05). Finally, the scores of the Auditory Verbal Learning Test Immediate recall and Boston Naming Test exhibited a partially mediating effect on the difference in OI scores between the EOD and LOD patients. (4) Conclusions: LOD patients exhibited worse OI than EOD patients, and their difference in OI was mediated by their memory and language function.

The Association between Late Third-Trimester Oxytocin Level and Early-Onset Postpartum Depression Symptoms among Jordanian Mothers: A Cross-sectional Study.

Purpose Oxytocin has been suggested to play a vital role in modulating maternal behavior and stress-related disorders. However, the relationship between antenatal oxytocin and postpartum depression is not well established. We aim to investigate the association between serum oxytocin level in the late third-trimester and early-onset postpartum depression symptoms. Materials and Methods A total of 172 healthy pregnant women participated in this cross-sectional descriptive study. The serum oxytocin level was measured between 34 and 37 weeks. A validated Edinburgh Postnatal Depression Scale (EPDS) was used to assess symptoms of depression four to six weeks postpartum. Participants who scored more than 12 on the EPDS were considered having depressive symptoms. Independent sample t-test and Pearson r were used to examine differences in depression scores. The level of significance was set at α = 0.05. Results 30.8% of the participants experienced depressive symptoms. There was no association between EPDS scores and oxytocin level r(170) = 0.10, p = 0.23. The association also did not exist even among women with a lifetime history of depression r(43) = −0.13, p = 0.37. Participants with low education, low income, previous history of depression, positive family history of depression, positive family issues, and absent emotional family support have scored significantly higher on EPDS scores than their counterparts. The strongest association was with previous lifetime history of depression t(170) = −4.40, p < 0.001. Conclusions Postpartum depression is a major public health problem in Jordan. Late trimester serum oxytocin level has no association with early-onset postpartum depression.

Cognitive functions in late-life depression.

Cognitive disorders are frequently found during late-life depression (LLD). Many cognitive functions may be concerned and can be explained by frontostriatal brain circuits and hippocampus dysfunctions partly through abnormalities related to cerebrovascular diseases. It seems important to distinguish between early and late onset depression, the cognitive characterisation and aetiopathogenesis of which differ in some respects. Cognitive impairment may represent markers of depression, but it is still unclear whether potential biomarkers of disease should be considered as markers of condition, trait or risk factors. These disorders may precede depression and persist despite symptomatic remission. Moreover, the interest of specifying these disorders is multiple because they can have pejorative consequences, such as by modifying emotional content, encouraging suicidal acts, limiting the effectiveness of psychotherapy, being a risk factor for a poor response to antidepressants, or being a potential risk factor for progression to a minor or major neurocognitive disorder, especially Alzheimer disease.

CBT for difficult-to-treat depression: single complex case

Abstract Cognitive behavioural therapy (CBT) is an effective treatment for depression but a significant minority of clients are difficult to treat: they are more likely to have adverse childhood experiences, early-onset depression, co-morbidities, interpersonal problems and heightened risk, and are prone to drop out, non-response or relapse. CBT based on a self-regulation model (SR-CBT) has been developed for this client group which incorporates aspects of first, second and third wave therapies. The model and treatment components are described in a concurrent article (Barton et al., 2022). The aims of this study were: (1) to illustrate the application of high dose SR-CBT in a difficult-to-treat case, including treatment decisions, therapy process and outcomes, and (2) to highlight the similarities and differences between SR-CBT and standard CBT models. A single case quasi-experimental design was used with a depressed client who was an active participant in treatment decisions, data collection and interpretation. The client had highly recurrent depression with atypical features and had received several psychological therapies prior to receiving SR-CBT, including standard CBT. The client responded well to SR-CBT over a 10-month acute phase: compared with baseline, her moods were less severe and less reactive to setbacks and challenges. Over a 15-month maintenance phase, with approximately monthly booster sessions, the client maintained these gains and further stabilized her mood. High dose SR-CBT was effective in treating depression in a client who had not received lasting benefit from standard CBT and other therapies. An extended maintenance phase had a stabilizing effect and the client did not relapse. Further empirical studies are underway to replicate these results. Key learning aims (1) To find out similarities and differences between self-regulation CBT and other CBT models; (2) To discover how self-regulation CBT treatment components are delivered in a bespoke way, based on the needs of the individual case; (3) To consider the advantages of using single case methods in routine clinical practice, particularly with difficult-to-treat cases.

Thalamic abnormalities in older adults with remitted early-onset depression using structural magnetic resonance imaging

BackgroundThe thalamus is a key diencephalic structure involved in major depressive disorder (MDD). Studies have consistently revealed abnormalities in thalamic volumes in older adults with late-onset depression (LOD), however abnormalities in older adults with early-onset depression (EOD) have not yet been well-studied. MethodsFifty-nine euthymic participants with a history of EOD and fifty-nine matched comparison participants without a lifetime history of depression underwent neuroimaging, medical and neuropsychological assessments. Thalamic volumes were compared between groups. To investigate the previously-proposed right hemispheric (RH) dominance theory of MDD, we explored the bilateral, right and left hemispheric (LH) thalamic volumes. Multiple regression analyses were used to evaluate between-group and within-group effects. Correlational analyses examined associations between group and cognitive performance. ResultsRelative to the comparison group, those with EOD had significantly larger bilateral, LH and RH thalamic volumes. Those with EOD, those who were younger, and those who had fewer years of education demonstrated larger bilateral and LH thalamic volumes. For RH thalamic volumes, those with EOD and those who were younger demonstrated larger RH thalamic volumes. EOD within-group models were also run to assess associations between relevant depression variables. The results showed that only age was significant for bilateral and RH thalamic volumes. For the LH thalamic volumes, the model was not significant. No significant correlations were found between cognitive performance and EOD groups. ConclusionOlder adults with a history of EOD showed significantly larger bilateral, RH and LH thalamic volumes. Further research is needed to delineate potential underlying mechanisms of this change.

Cross-lagged Relationships Between Depressive Symptoms and Altered Default Mode Network Connectivity Over the Course of Adolescence

BackgroundAlthough the peak onset of depressive symptoms occurs during adolescence, very few studies have directly examined depression-related changes in resting-state (RS) default mode network activity during adolescence, controlling for potential neural markers of risk. MethodsThis study used data from a longitudinal adolescent cohort to investigate age-specific, persistent (i.e., lagged), and dynamic associations between RS functional connectivity within the default mode network and depressive symptoms during adolescence using a random intercept cross-lagged panel framework. The Neuroventure sample consisted of 151 adolescents ages 12–14 at study entry without any neurological illness who were assessed three times during a 5-year follow-up with 97% follow-up across the three assessments. Depressive symptoms were measured using the depression subscale of the Brief Symptoms Inventory. RS functional magnetic resonance imaging data were collected using a 3T Siemens Magnetom Trio scanner in a single 6-minute sequence. ResultsAfter controlling for relationships between random intercepts, future depression risk was predicted by RS couplings in the perigenual anterior cingulate cortex and anterior dorsomedial prefrontal cortex (β = −0.69, p = .014) and in the left inferior parietal lobule and anterior superior frontal gyrus (β = −0.43, p = .035). Increases in depressive symptoms at previous time points significantly predicted changes in functional connectivity between the posterior cingulate cortex and the precuneus and posterior middle temporal gyrus (β = 0.37, p = .039) and between the dorsal precuneus and posterior middle temporal gyrus (β = 0.47, p = .036). ConclusionsThis study was able to disassociate the RS brain markers of depression from those that appear to follow early-onset depression.

Thalamic abnormalities in older adults with early‐onset depression using structural magnetic resonance imaging

AbstractBackgroundThe thalamus is a key diencephalic structure involved in major depressive disorder (MDD). In particular, studies have consistently revealed abnormalities in thalamic volumes in older adults with late‐onset depression (LOD). However, similar abnormalities in older adults with early‐onset depression (EOD) have not been well studied.MethodFifty‐nine euthymic participants with a history of EOD and fifty‐nine matched comparison participants without a lifetime history of depression underwent neuroimaging, medical and neuropsychological assessments. Thalamic volumes were compared between groups. Due to the right hemispheric (RH) dominance theory of MDD, we explored both bilateral and right hemispheric thalamic volumes. Multiple regression analyses were used to evaluate between‐group and within‐group effects. A correlational analysis examined associations between group and cognitive performance.ResultRelative to the comparison group, those with EOD had significantly larger bilateral and RH thalamic volumes. Those with EOD, those who were younger, and those who had fewer years of education, demonstrated larger bilateral thalamic volumes. When split by group (EOD vs comparison group), only age remained significantly different for those with EOD. For RH volumes, those with EOD and those who were younger demonstrated larger RH thalamic volumes. When split by group, the results showed that age only was significant for both groups. No significant correlations were found between cognitive performance and EOD groups.ConclusionOlder adults with a history of EOD showed significantly larger bilateral and RH thalamic volumes. Further research is needed to further elucidate the underlying mechanism of this change.

Latent profile analysis of cognitive decline and depressive symptoms after intracerebral hemorrhage

BackgroundCognitive impairment and depressive symptoms are highly prevalent after Intracerebral Hemorrhage (ICH). We leveraged Latent Profile Analysis (LPA) to identify profiles for cognitive decline and depression onset after ICH. We also investigated differences in clinical, genetic and neuroimaging characteristics across patients’ profiles.MethodsWe analyzed data from the ICH study conducted at Massachusetts General Hospital between January 1998 and December 2019. We collected information from electronical health records, follow-up interviews, CT and MRI imaging, and APOE genotype. We conducted LPA and multinomial logistic regression analyses to: 1) identify distinct profiles for cognitive decline and depression onset after ICH; 2) identify clinical, neuroimaging and genetic factors predicting individuals’ likelihood to express a specific profile.ResultsWe followed 784 ICH survivors for a median of 45.8 months. We identified four distinct profiles in cognitive and depressive symptoms after ICH: low depression and dementia risk, early-onset depression and dementia, late-onset depression and dementia, high depression with low dementia risk. Cerebral small vessel disease severity and APOE genotype were specifically associated with the late-onset profile (both p < 0.05). Acute hematoma characteristics (size, intraventricular extension) and functional disability were specifically associated with the early-onset profile (all p < 0.05).ConclusionWe identified four distinct profiles for cognitive and depressive symptoms after ICH, each displaying specific associations with individual patients’ clinical, genetic and neuroimaging data. These associations reflect separate biological mechanisms influencing dementia and depression risk after ICH. Our findings support employing LPA in future ICH studies, and is likely applicable to stroke survivors at large.

Early-onset late-life depression: Association with body mass index, obesity, and treatment response

Early-onset (EOD) and late-onset (LOD) late-life depression might differ in etiology, clinical features, and treatment response. While EOD is more frequently associated with a family history of affective disorders and personality aspects, LOD is thought to be more strongly driven by acquired cerebrovascular risk factors associated with vascular pathology, executive dysfunction, and poor treatment response. However, in a systematic review, EOD and LOD only differed in the frequency of affective disorders in the family history. We compared EOD versus LOD using medical records. In this retrospective chart review, elderly depressed patients (N = 108; mean age: 69.0 ± 7.2 years) were characterized by sociodemographic, psychiatric, and somatic variables and divided according to age-at-onset (cut-off: 60 years): EOD (N = 67, mean age-at-onset: 40.2 ± 13.6 years) and LOD (N = 41, 67.5 ± 6.3 years). A family history of affective disorders was more common in EOD than LOD patients (49.2% vs. 19.5%). EOD patients had a higher body mass index (mean: 27.0 kg/m2 vs. 23.1 kg/m2) and were more often obese compared with LOD patients (20% vs. 0%). There were fewer treatment responders in the EOD group than in the LOD group on trend level significance (46.3% vs. 63.4%). Higher frequency of affective disorders in the family history is compatible with a greater genetic risk of EOD. The larger metabolic burden of EOD might stem from the longer duration of depressive illness.

Changes in Regional Homogeneity of Medication-Free Major Depressive Disorder Patients With Different Onset Ages.

Background: Neurobiological mechanisms underlying the development of major depressive disorder (MDD) may differ depending on onset ages. Our aim was to determine whether regional homogeneity (ReHo) changes in early-onset depression (EOD) and late-onset depression (LOD) are different, which could also delineate EOD and LOD.Methods: Ninety-one MDD patients and 115 healthy controls (HCs) were recruited, and resting-state functional magnetic resonance imaging data were collected. The ReHo comparison was conducted using analysis of variance.Results: Compared with HCs, MDD patients showed decreased ReHo in the left precentral gyrus and the left middle cingulum area, and increased ReHo in the left middle orbital frontal gyrus and superior temporal gyrus. Compared with LOD patients, young HC separately, EOD patients had significantly increased ReHo in the right inferior frontal triangular gyrus and the left postcentral gyrus. However, compared with young HC, EOD patients showed decreased ReHo in the right superior frontal gyrus/supplementary motor area and the right medial frontal gyrus. ReHo in the right inferior frontal triangular gyrus was negatively correlated with the severity of cognitive disturbance in LOD patients (r = −0.47, p = 0.002), but not in EOD patients (r = 0.21, p = 0.178).Conclusion: MDD patients with different onset ages may have different pathophysiological mechanisms; the EOD patients had more abnormal ReHo than LOD patients in the prefrontal lobe, especially the right inferior frontal triangular gyrus.

Family depression profiles among adolescents and their parents: A group-based multitrajectory modeling.

Early onset of depression predicts unfavorable psychosocial and health outcomes, and depression often co-occurs for children and their parents, yet family profiles of depression trajectories are not fully examined. This population-based longitudinal prospective cohort study included 2,111 families drawn from the Chinese Family Panel Study (CFPS) with biannual assessments from 2010 to 2018. Group-based multitrajectory modeling was used to identify depression trajectories of children, fathers, and mothers. Six distinct profiles of depression symptoms were identified. Based upon multitrajectory findings of family depression profiles, when adolescents are at risk for depression, there is likely at least one parent concurrently at risk for depression, but not vice versa. Families with social disadvantages and children of delayed developmental milestones are at elevated risk for depression. Even when children are at low risk for depression, depression in parents can spill over to impact other psychosocial and health outcomes. These findings suggest examining depression and its associating psychosocial factors could help identify trajectories of varying onset and continuity, which can inform early prevention and intervention from a family system perspective. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Biomarkers in Child and Adolescent Depression

Despite the significant prevalence of Major Depressive Disorder in the pediatric population, the pathophysiology of this condition remains unclear, and the treatment outcomes poor. Investigating tools that might aid in diagnosing and treating early-onset depression seems essential in improving the prognosis of the future disease course. Recent studies have focused on searching for biomarkers that constitute biochemical indicators of MDD susceptibility, diagnosis, or treatment outcome. In comparison to increasing evidence of possible biomarkers in adult depression, the studies investigating this subject in the youth population are lacking. This narrative review aims to summarize research on molecular and biochemical biomarkers in child and adolescent depression in order to advocate future directions in the research on this subject. More studies on depression involving the youth population seem vital to comprehend the natural course of the disease and identify features that may underlie commonly observed differences in treatment outcomes between adults and children.

ADHD in adults with recurrent depression

BackgroundDepression is highly heterogeneous in its clinical presentation. Those with attention deficit/hyperactivity disorder (ADHD) may be at risk of a more chronic and impairing depression compared to those with depression alone according to studies of young people. However, no studies to date have examined ADHD in recurrently depressed adults in mid-life. MethodIn a sample of women in mid-life (n=148) taken from a UK based prospective cohort of adults with a history of recurrent depression, we investigated the prevalence of ADHD and the association of ADHD with clinical features of depression. Results12.8% of the recurrently depressed women had elevated ADHD symptoms and 3.4% met DSM-5 diagnostic criteria for ADHD. None of the women reported having a diagnosis of ADHD from a medical professional. ADHD symptoms were associated with earlier age of depression onset, higher depression associated impairment, a greater recurrence of depressive episodes and increased persistence of subthreshold depression symptoms over the study period, higher levels of irritability and increased risk of self-harm or suicide attempt. ADHD symptoms were associated with increased risk of hospitalisation and receiving non-first-line antidepressant medication. LimitationsADHD was measured using a questionnaire measure. We focussed on mothers in a longitudinal study of recurrent depression, so the findings may not apply to males or other groups. ConclusionsHigher ADHD symptoms appear to index a worse clinical presentation for depression. Clinical implications include that in women with early onset, impairing and recurrent depression, the possibility of underlying ADHD masked by depression needs to be considered.

Metabolic syndrome among young adults at high and low familial risk for depression.

Our study examined whether the early-onset depression phenotype among young adults (probands) is associated with the metabolic syndrome (MetS) and its components, and if MetS characterizes unaffected but high-risk siblings of probands. We studied three groups of young adults (Mage = 25 years, s.d. = 3.84 years): probands with histories of childhood onset depression - i.e. early-onset phenotype - (n = 293), their unaffected siblings (high-risk siblings, n = 273), and healthy controls (n = 171). Participants completed a full psychiatric interview, physical and laboratory assessments, and self-rating scales. MetS was defined using the criteria of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (). Early-onset depression phenotype and being a high-risk sibling were associated with higher MetS composite scores relative to that of controls, but did not differ from one another. With regard to MetS components: Probands and siblings had similarly larger waist circumference and lower HDL than did controls, while siblings and controls had lower triglyceride levels than did probands but did not differ from one another. Groups did not differ on glucose levels and SBP. Our study extends the literature on the association between MetS and depression and underscores the importance of depression phenotypes: failure to account for the clinical heterogeneity of depression may partly underlie the inconsistent findings regarding its relation to MetS. The results also suggest that, in depression-prone populations, MetS may predate and possibly function as a risk factor for eventual depression.

Early Childhood Socioeconomic Status and Cognitive and Adaptive Outcomes at the Transition to Adulthood: The Mediating Role of Gray Matter Development Across Five Scan Waves

BackgroundEarly low socioeconomic status (SES) is associated with poor outcomes in childhood, many of which endure into adulthood. It is critical to determine how early low SES relates to trajectories of brain development and whether these mediate relationships to poor outcomes. We use data from a unique 17-year longitudinal study with five waves of structural brain imaging to prospectively examine relationships between preschool SES and cognitive, social, academic, and psychiatric outcomes in early adulthood. MethodsChildren (n = 216, 50% female, 47.2% non-White) were recruited from a study of early onset depression and followed approximately annually. Family income-to-needs ratios (SES) were assessed when children were ages 3 to 5 years. Volumes of cortical gray and white matter and subcortical gray matter collected across five scan waves were processed using the FreeSurfer Longitudinal pipeline. When youth were ages 16+ years, cognitive function was assessed using the NIH Toolbox, and psychiatric diagnoses, high-risk behaviors, educational function, and social function were assessed using clinician administered and parent/youth report measures. ResultsLower preschool SES related to worse cognitive, high-risk, educational, and social outcomes (|standardized B| = 0.20–0.31, p values < .003). Lower SES was associated with overall lower cortical (standardized B = 0.12, p < .0001) and subcortical gray matter (standardized B = 0.17, p < .0001) volumes, as well as a shallower slope of subcortical gray matter growth over time (standardized B = 0.04, p = .012). Subcortical gray matter mediated the relationship of preschool SES to cognition and high-risk behaviors. ConclusionsThese novel longitudinal data underscore the key role of brain development in understanding the long-lasting relations of early low SES to outcomes in children.

Early-Onset Depression in Stroke Patients: Effects on Unfavorable Outcome 5 Years Post-stroke.

Background: Post-stroke depression (PSD) constitutes an essential complication of stroke and is associated with high-risk unfavorable outcome after stroke. The main objective of this prospective study was to determine the relationship between early-onset PSD (1 month after stroke) and functional outcomes 5 years after baseline enrollment.Methods: Four hundred thirty-six patients who met the criteria were included in this study from October 2013 to February 2015. The follow-up time for each patient was ~5 years, with follow-up every 3 months. Patients received questionnaires including the 17-item Hamilton Depression Scale (HAMD), the Mini-Mental State Examination (MMSE), the National Institutes of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), and the Barthel Index (BI).Results: Of the 436 patients, 154 (35.3%) patients with the prevalence of PSD status at baseline, 26 (7.2%) patients with the prevalence of PSD status, and 73 (20.1%) had an unfavorable outcome 5 years after stroke. The odds ratio (OR) for unfavorable outcome at 5 years in the PSD group was ~2.2 relative to the non-PSD group after adjusting for potential risk factors [OR = 2.217, 95% confidence interval (CI) = 1.179–4.421, P = 0.015]. In the early-onset PSD group, HAMD scores were independently associated with 5-year unfavorable outcome rates (OR = 1.168, 95% CI = 1.015–1.345, P = 0.031).Conclusions: Our findings indicate that early-onset PSD status in Chinese patients is an independent risk factor for unfavorable outcome 5 years after stroke, and that the severity of PSD is also related to unfavorable outcome.

Adolescent depression and adult labor market marginalization: a longitudinal cohort study

Adolescent depression is linked to adult ill-health and functional impairment, but recent research suggests that individual/contextual factors might account for this association. This study aimed to test whether the clinical heterogeneity of adolescent depression is related to marginalization from the labor market across early to middle adulthood. Data were drawn from the Uppsala Longitudinal Adolescent Depression Study, a community-based cohort initially assessed with structured clinical interviews at age 16–17. The cohort (n = 321 depressed; n = 218 nondepressed) was followed up after 2+ decades through linkage to nationwide population-based registries. Outcomes included consecutive annual data on unemployment, work disability, social welfare recipiency, and a composite marginalization measure, spanning from age 21 to 40. Longitudinal associations were examined using logistic regression analysis in a generalized estimating equations modeling framework. Subsequent depressive episodes and educational attainment in early adulthood were explored as potential pathways. The results showed that adolescent depression was associated with adult marginalization outcomes, but the strength of association varied across depressed subgroups. Adolescents with persistent depressive disorder had higher odds of all outcomes, including the composite marginalization measure (adjusted OR = 2.0, 95% CI = 1.4–2.7, p < 0.001), and this was partially (31%) mediated by subsequent depressive episodes in early adulthood. Exploratory moderation analysis revealed that entry into tertiary education mitigated the association with later marginalization, but only for adolescents with episodic major depression. In conclusion, the risk for future labor market marginalization is elevated among depressed adolescents, particularly those presenting with persistent depressive disorder. Targeted interventions seem crucial to mitigate the long-lasting impact of early-onset depression.

Cognitive functions in late life depression

Cognitive disorders are frequently found during late-life depression. Many cognitive functions may be concerned and can be explained by fronto-striatal brain circuits and hippocampus dysfunctions partly through abnormalities related to cerebrovascular diseases. It seems important to distinguish between early and late onset depression whose cognitive characterisation and etiopathogenia differ in some aspects. Cognitive impairment may represent markers of depression but it is still unclear whether one should consider potential biomarkers of disease state or trait or risk factor. These disorders may precede depression and persist despite symptomatic remission. Moreover, the interest of specifying these disorders is multiple because they can have pejorative consequences such as the modification of emotional content, promote suicidal act, limit the effectiveness of psychotherapy, be a risk factor for poor response to antidepressants. or be a potential risk factor for progression to a minor or major neurocognitive disorder, especially Alzheimer's disease.

Early onset of depression and treatment outcome in patients with major depressive disorder

Major depressive disorder (MDD) is a highly heterogeneous disorder, which may partly explain why treatment outcome using antidepressants is unsatisfactory. We investigated the onset of depression as a possible clinical marker for therapy response prediction in the context of somatic biomarkers blood pressure and plasma electrolyte concentration. 889 MDD patients were divided into early (EO, n = 226), intermediate (IO, n = 493), and late onset (LO, n = 169) patients and were analyzed for differences in socio-demographic and clinical parameters, comorbidities and treatment outcome as well as systolic blood pressure and electrolytes. EO patients more often suffered from a recurrent depression, had more previous depressive episodes, a higher rate of comorbid axis I and II disorders, and more often reported of suicidality (p < 0.001) compared to IO and LO patients. Treatment outcome was not different from IO and LO patients, although LO patients responded faster. EO patients who showed an early non-improvement of depression after 2 weeks of therapy (<20% improvement) had a 4.3-fold higher likelihood to become non-remitter as compared to LO patients with an early improvement. EO patients had significantly lower systolic blood pressure than patients with IO or LO and electrolytes in EO patients were significantly correlated with depression severity. Our results confirm other studies showing an association of an early onset of depression with a slower treatment response. The worse treatment outcome in patients with an additional early non-improvement to antidepressant therapy opens perspectives to develop and test individualized treatment approaches for EO and LO patients in the future, which may be based on differences in autonomic regulation.

Morphometry of the Hippocampus Across the Adult Life-Span in Patients with Depressive Disorders: Association with Neuroticism.

Neuroticism is one of the main endophenotypes of major depressive disorder (MDD) and is closely related to the negative effect systems of Research Domain Criteria (RDoC) domains. The relationship between neuroticism and aging is dynamic and complex. Moreover, reduced hippocampal volumes are probably the most frequently reported structural neuroimaging finding associated with MDD. However, it remains unclear to what extent hippocampal abnormalities are linked with age and neuroticism changes in people with depression through the adult life span. This study aimed to examine the interplay between aging and neuroticism on hippocampal morphometric across the adult life-span in a relative large sample of patients with depressive disorders (114 patients, 73 females, age range: 18-74 years) and healthy control (HC) subjects (112 healthy controls, 72 females, age range: 19-72 years). MDD patients showed reduced bilateral hippocampal volumes. The effect of aging on the left hippocampal showed linear and the right hippocampal volume non-linear trajectories throughout the adult life span in healthy groups and MDD groups respectively. The hippocampal atrophy was dynamically impacted by depression at the early stages of adult life. Furthermore, we observed that right hippocampal volume reduction was associated with higher neuroticism in depressive patients younger than 30.65 years old. Our results suggest that the age-related atrophy in the right hippocampal volume was more affected by individual differences in neuroticism among younger depressive patients. Hippocampal volume reduction as a vulnerability factor for early-onset and major geriatric depression may have a distinct endophenotype.