Early-onset Depression Research Articles

P15: Esketamine in the elderly-is it efficient and safe?

Background:elderly patients are significantly impacted by MDD and are less responsive to treatment. ECT is used more often in older patients but has its drawbacks. There is a need for for novel antidepressants. Esketamine, is a FDA approved novel treatment to treatment resistant depression(TRD). Studies of esketamine nasal spray administered with a newly initiated oral antidepressant in TRD aged patients 18-64 years demonstrated rapid onset versus a newly initiated oral antidepressant plus placebo, with maintenance of the treatment effects following long term intermittent dosing. Side effects are dose related, psychotomimetic dissociative, elevation in HR+BP, cognitive impairment, hepatotoxicity and inflammation of bladder endothelium.Objective:to review the current data regarding esketimine treatment in elderly TRD patients.Results:beside several case reports only 2 RCTs checked efficiency and safety in elderly patients. A pilot RCT of titrated subcutaneous ketamine in older patients with TRD was conducted in 2017. 16 participants> 60 years with TRD who relapsed after remission or did not remit in the RCT were than administered an open label phase. Up to 5 doses of ketamine (0.1 to 0.5 mg\kg) were administered with midazolam as an active control, randomly inserted. 12 ketamine treatments were given in separate sessions at least 1 week apart. Remitters in each phase were followed up for 6 months with MADRS scale. Results provided evidence for the efficacy and safety of ketamine in treating elderly depressed. There was a significant improvement in all ketamine dosages apart from 0.1 mg/kg. 7 participants reached remission. 5/7 had relapse than entered open trial and remitted again. Ochs-Ross, et al 2020 study,138 patients with TRD> 65 years received flexibly dosed esketamine nasal spray and new antidepressant or new antidepressant with placebo. The groups did not achieve statistical significance in MADRS score change from baseline to day 28. Patients with earlier onset of depression and younger patients (65-74) showed greater response to treatment.Conclusion:Esketamine is safe in elderly TRD patients. There is not enough evidence to conclude if it is efficient. It seems that patients younger than 75 and with earlier onset of depression might benefit from esketamine.

STRUCTURAL BRAIN CHANGES IN LATE ONSET DEPRESSION

AbstractBackgroundStructural brain changes in grey matter in late‐life depression (LLD) remains an intriguing area of research. Furthermore, late‐onset depression (LOD) has been frequently associated with general medical comorbidities, cognitive deficits and structural abnormalities of the brain. This magnetic resonance imaging (MRI) study compares the grey matter volume of elderly people with and without major depression (DSM‐IV‐TR criteria), as well LOD, early onset depression (EOD) and controls.MethodThe sample consisted of elders with and without depression from community. Brain MRI scans were processed using statistical parametric mapping and voxel‐based morphometry.ResultSixty three elders with depression and 24 controls were enrolled. Demographic characteristics were analyzed and sex showed a statistically significant difference (p = 0.001) between the groups, with males representing 17.5% of the patient sample and 54.2% of the control sample. Furthermore, MMSE and CAMCOG showed a statistically significant difference between groups (p<0.0001 for both tests), with the control group performing better. Although we excluded cases of patients with below‐expected performance according to the neuropsychological assessment, it is likely that this cognitive impairment presented by the patient group is secondary to major depressive disorder. We did not find a significant volumetric difference between depressed and control group (CG). We used the age of onset of depression as another way of classifying the patient sample and compared it with the control group regarding key demographic and clinical characteristics. Gender was statistically significant different between groups, however there were only 2 male subjects in the EOD group, making it not possible to control the analysis by gender. Compared to the CG (n = 24), the LOD group (n = 32) showed a statistically significant volumetric reduction with correction for multiple comparisons in the right thalamus (464 voxels; peak xyz coordinates = 14 ‐10 16; Z = 4, 62; p‐FWEcorr = 0.052) when using the whole brain for multiple comparisons.ConclusionOur findings support the use of regional brain atrophy as a tool to better understand LOD.

To assess the knowledge and attitudes about depression in the general population in the Wardha District, India.

Background: Physical symptoms of depression, especially tiredness, pain, or disturbed sleep, are common. Some people may experience depression as a chronic condition, with more episodes increasing the risk of recurrence. Others may experience a single episode of depression in their lifetime. Given its great incidence and crippling consequences on development, early-onset depression is regarded as one of the most common mental illnesses in children and adolescents which can last into adulthood. The following categories can be used to classify the factors that affect depression susceptibility: genetics, familial environment, individual characteristics, and extreme stress. Gender, history of depression in the family, subclinical symptoms, poor cognitive style, and negative life events are also main risk factors. Methods: This protocol is for an observational study, which will take place over a four month period in the Wardha district. Participants will be recruited via the Acharya Vinoba Bhave Rural Hospital (AVBRH) as a medical center from the general population. A piloted questionnaire with a Likert scale will be completed by the participants enrolled in the study with assistance from interviewers. Frequency percentage, mean, and SD will be calculated to understand the relationship between various demographic variables and knowledge. Chi-square tests will also be used. Distribution: The data collection of this study is supposed to be completed August 2023 and the results will be communicated to the external funding body through formal report. In addition, the trial results will be communicated to the public through publishing as dataset and original research published in the relevant scientific journals.

Lesion location and serum levels of homocysteine are associated with early-onset post-stroke depression in acute ischemic stroke.

It is well known that post-stroke depression (PSD) is a psychiatric complication after stroke which leads to worse functional outcome and poorer quality of life. Some risk factors including gender, stroke severity, lesion location, homocysteine (HCY), and so on are associated with PSD. This study aims to further explore the possible relationship between serum levels of HCY and early-onset PSD and the predictive value of HCY combined with stroke characteristics for early-onset PSD. Two hundred forty-five patients with acute ischemic stroke who met the criteria were included in this study from March 2015 to March 2017. PSD was diagnosed at 2weeks after stroke. The severity of depressive symptoms was evaluated with the Hamilton depression scale 17 items (HAMD-17), and patients with HAMD scores ≥7 were included in the PSD group. The demographic data, clinical characteristics, serum levels of HCY, and detailed radiological variables (e.g., lesion location and quantity of the brain infarct) were also examined. In total, 97 (39.6%) patients of the 245 patients were diagnosed with depression. The univariate analyses suggested that patients in PSD group had a higher NIHSS score, modified Rankin Scale score, and HCY levels than patients in non-PSD group (p < .001). The patients with PSD had higher proportion of multiple-site acute infarcts and frontal lobe lesion (p < .05). In multivariate logistic regression analysis, NIHSS score at admission, serum levels of HCY, and multiple-site lesions were independently related to early-onset PSD. Based on receiver operating characteristic curves analysis, the combination of HCY, NIHSS scores, multiple-site lesions, and lesion location revealed a highest area under the curve of 0.807 (95% confidence interval [CI]: 0.748-0.865, p < .001). Furthermore, there was a significantly increased risk of early-onset PSD associated with serum levels of HCY ≥16.98μmol/L (odds ratio [OR]=10.976, 95% CI: 5.585-21.573, p < .001). Our study indicated that higher NIHSS score, elevated serum levels of HCY, and multiple-site lesions may be independent risk factors of early-onset PSD. The combination of HCY, NIHSS scores, multiple-site lesions, and lesion location may provide greater predictive value than HCY alone for early-onset PSD. Early intervention for elevated serum levels of HCY may be a potential target for the intervention and prevention of PSD.

Effectiveness of family-based therapy for depressive symptoms in children and adolescents: A systematic review and meta-analysis.

Early-onset depression contributes significantly to the global health burden and has long-term negative effects. This meta-analysis collates and examines the effectiveness of family-based interventions, where family members are involved in the treatment of depression in children and adolescents. A literature search was performed up to 8th March 2023. Randomised controlled trials of family-based interventions were included for participants aged 3-18 years with a diagnosis of major depressive disorder or dysthymia, according to the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5; American Psychiatric Association, 2013) or with a score above a cut-off on a standardised self-report depression measure. The overall effect size for treatment versus active control was g = 0.22 (95% confidence interval [CI]: -0.05-0.50) (nine studies; 659 participants), and for treatment versus non-active control it was g = 0.46 (95% CI: -0.09-1.01) (four studies; 385 participants). Effect sizes were not statistically significant, and heterogeneity was high, ranging between I2 = 64.3-81.1%. Subgroup analysis comparing attachment-based family therapy with family therapy using other theoretical frameworks did not yield a significant difference between the two. The effects of family-based therapies were larger than those in the comparison groups, but family-based therapy did not demonstrate a significant treatment benefit compared to the controls. More randomised controlled trials are warranted, considering that evidence for other psychotherapies for depression in children and adolescents, indicates modest effects. Family-based therapy may be an alternative for children and adolescents whose needs are not addressed by these treatments.

The Heart and Brain Connection

The relationship between depression and cardiovascular disease (CVD) is bidirectional. Depression is a risk factor for developing CVD, and this, together with vascular risk factors (VascRFs), increases vulnerability to precipitate some types of geriatric depression (vascular depression). The particular semiology of depression of vascular origin (polymorphic), the symptoms of the comorbidities (vascular disease and/or risk factors), and those symptoms of old age constitute a challenge for clinical medicine. Although the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth/Fifth Edition do not differentiate between early-onset (young adult) and late-onset depression (older adult), the clinical expression of patients with depression of vascular origin presents its own characteristics as well as a poor response to treatment. Thus, cerebrovascular disease could be considered the link between VascRFs and the clinical expression of mood disorders (vascular depression), creating a challenge not only in its diagnosis but also in its treatment.

CBT for difficult-to-treat depression: self-regulation model.

Cognitive behavioural therapy (CBT) is an effective treatment for depression but a significant minority of clients do not complete therapy, do not respond to it, or subsequently relapse. Non-responders, and those at risk of relapse, are more likely to have adverse childhood experiences, early-onset depression, co-morbidities, interpersonal problems and heightened risk. This is a heterogeneous group of clients who are currently difficult to treat. The aim was to develop a CBT model of depression that will be effective for difficult-to-treat clients who have not responded to standard CBT. The method was to unify theory, evidence and clinical strategies within the field of CBT to develop an integrated CBT model. Single case methods were used to develop the treatment components. A self-regulation model of depression has been developed. It proposes that depression is maintained by repeated interactions of self-identity disruption, impaired motivation, disengagement, rumination, intrusive memories and passive life goals. Depression is more difficult to treat when these processes become interlocked. Treatment based on the model builds self-regulation skills and restructures self-identity, rather than target negative beliefs. A bespoke therapy plan is formed out of ten treatment components, based on an individual case formulation. A self-regulation model of depression is proposed that integrates theory, evidence and practice within the field of CBT. It has been developed with difficult-to-treat cases as its primary purpose. A case example is described in a concurrent article (Barton et al., 2022) and further empirical tests are on-going.

Deficits in doors P300 amplitude during adolescence associated with preschool-onset depression.

The psychophysiological underpinnings of preschool-onset depression (PO-MDD) remain underexplored. Moreover, there is currently a limited understanding of the potential impact that PO-MDD might have on neurobiological functions later in development such as general cognitive domains and reward processing. Thus, the current study sought to examine potential neurophysiological differences, measured via electroencephalography (EEG), in adolescents with and without a history of PO-MDD. Participants and their caregivers (N = 138) from a large longitudinal study completed semi-structured clinical interviews at a baseline visit (ages 3-7) to determine PO-MDD status. At a follow-up visit approximately 11 years later, adolescents (ages 13-19) completed the doors gambling task while EEG was recorded to measure event-related potentials (ERPs) elicited by both the doors and feedback stimuli, to index cognitive and reward processing functions (i.e., doors-P300, gain/loss feedback-P300, and RewP). Adolescents with a history of PO-MDD exhibited significantly smaller doors-P300 compared with adolescents with no history of PO-MDD, whereas there were no group differences in gain/loss feedback-P300 or RewP. Additionally, reduced doors-P300 was independently associated with lower baseline income-to-needs ratio, older age, and female gender. The current study suggests that reduced doors-P300 amplitude during adolescence might reflect impaired neurophysiological development related to PO-MDD. Thus, the P300 derived from the doors stimuli might be a valuable neural measure to further our understanding of potential neurophysiological differences associated with early-onset childhood depression.

Neural Circuit Markers of Familial Risk for Depression Among Healthy Youths in the Adolescent Brain Cognitive Development Study

BackgroundFamily history of depression is a robust predictor of early-onset depression, which may confer risk through alterations in neural circuits that have been implicated in reward and emotional processing. These alterations may be evident in youths who are at familial risk for depression but who do not currently have depression. However, the identification of robust and replicable findings has been hindered by few studies and small sample sizes. In the current study, we sought to identify functional connectivity (FC) patterns associated with familial risk for depression. MethodsParticipants included healthy (i.e., no lifetime psychiatric diagnoses) youths at high familial risk for depression (HR) (n = 754; at least one parent with a history of depression) and healthy youths at low familial risk for psychiatric problems (LR) (n = 1745; no parental history of psychopathology) who were 9 to 10 years of age and from the Adolescent Brain Cognitive Development (ABCD) Study sample. We conducted whole-brain seed-to-voxel analyses to examine group differences in resting-state FC with the amygdala, caudate, nucleus accumbens, and putamen. We hypothesized that HR youths would exhibit global amygdala hyperconnectivity and striatal hypoconnectivity patterns primarily driven by maternal risk. ResultsHR youths exhibited weaker caudate–angular gyrus FC than LR youths (α = 0.04, Cohen’s d = 0.17). HR youths with a history of maternal depression specifically exhibited weaker caudate–angular gyrus FC (α = 0.03, Cohen’s d = 0.19) as well as weaker caudate–dorsolateral prefrontal cortex FC (α = 0.04, Cohen’s d = 0.21) than LR youths. ConclusionsWeaker striatal connectivity may be related to heightened familial risk for depression, primarily driven by maternal history. Identifying brain-based markers of depression risk in youths can inform approaches to improving early detection, diagnosis, and treatment.

Late-Onset Depression but not Early-Onset Depression may Increase the Risk of All-Cause Mortality in Older Age: 8-Year Follow-Up of the Salus in Apulia Study.

Individuals with late-life depression (LLD) may have shorter survival, but there is a lack of findings in population-based settings about health-related outcomes of LLD and its subtypes: early-onset depression (EOD) and late-onset depression (LOD). We aimed to evaluate the risk of all-cause mortality of individuals with LLD and its subtypes in an older population-based cohort. Moreover, we investigated whether inflammatory, cognitive, genetic features and multimorbidity could modify the effect of this association. Longitudinal population-based study with 8-year follow-up. We analyzed data on a sample of 1479 participants, all aged >65years, in the Salus in Apulia Study. LLD was diagnosed through DSM-IV-TR criteria and LOD and EOD according to the age of onset. Multimorbidity status was defined as the copresence of 2 or more chronic diseases. The overall prevalence of LLD in this older sample from Southern Italy was 10.2%, subdivided into 3.4% EOD and 6.8% LOD. In multivariable Cox models adjusted for age, gender, education, global cognition, apolipoprotein E ε4 allele, physical frailty, interleukin-6, and multimorbidity, LLD showed a greater risk of all-cause mortality. LOD differed from EOD regarding gender, education, cognitive dysfunctions, and diabetes mellitus. There was a significantly increased risk of all-cause mortality for participants with LOD (hazard ratio:1.99; 95% CI 1.33-2.97) in the time of observation between enrollment date and death date (7.31 ± 2.17months). In older age, individuals with LOD but not with EOD had a significantly decreased survival, probably related to increased inflammation, multimorbidity, and cognitive impairments.

Prevalence and natural history of depression after stroke: A systematic review and meta-analysis of observational studies.

Depression is the most frequent psychiatric condition after stroke and is associated with negative health outcomes. We aim to undertake a systematic review and meta-analysis of the prevalence and natural history of depression after stroke. Studies published up to 4 November 2022 on Medline, Embase, PsycINFO, and Web of Science Core Collection were searched. We included studies of adults with stroke, where depression was assessed at a prespecified time point. Studies excluding people with aphasia and history of depression are excluded. Critical Appraisal Skills Programme(CASP) cohort study tool was used to assess risk of bias. A total of 77 studies were included in the pooled estimates of the prevalence of poststroke depression (PSD). The overall prevalence of depression was 27% (95% CI 25 to 30). Prevalence of depression was 24% (95% CI 21 to 28) by clinical interview and 29% (95% CI 25 to 32) by rating scales. Twenty-four studies with more than one assessment time point reported the natural history of PSD. Among people who were depressed within 3 months of stroke, 53% (95% CI 47 to 59) experienced persistent depression, while 44% (95% CI 38 to 50) recovered. The incidence of later depression (3 to 12 months after stroke) was 9% (95% CI 7 to 12). The cumulative incidence during 1 year after stroke was 38% (95% CI 33 to 43), and the majority (71% (95% CI 65 to 76)) of depression had onset within 3 months after stroke. The main limitation of the present study is that excluding people in source studies with severe impairments may produce imprecise estimates of the prevalence of PSD. In this study, we observed that stroke survivors with early-onset depression (within 3 months after stroke) are at high risks for remaining depressed and make up two-thirds of the incident cases during 1 year after stroke. This highlights the need for ongoing clinical monitoring of patients depressed shortly after stroke. PROSPERO CRD42022314146.

Age or age of onset: which is the best criterion to classify late-life depression?

In late-life depression (LLD), several differences between patients whose first episode is reported after age 65 (late-onset depression, LOD) and those with early-onset depression (EOD) might reflect the effects of brain ageing. To test this hypothesis, we analysed the impact of current age and age at illness onset on a number of clinical and cognitive manifestations in 438 outpatients with major depressive disorder aged >60 years, treated with venlafaxine for 12 weeks. When compared to the EOD group, patients with LOD were older ( P < 0.00001) and associated with lower depression severity ( P = 0.0029), lower global cognitive functioning [Mini-Mental State Examination (MMSE): P = 0.0001; Repeatable Battery for the Assessment of Neuropsychological Status: immediate memory, P = 0.0009, and delayed memory, P < 0.00001; Delis-Kaplan Executive Function System measuring executive functions: Trail-Making Test (TMT) - P = 0.0004 and Colour-Word Interference Test, Inhibition - P = 0.0063], and more dyskinesias (Abnormal Involuntary Movement Scale: P = 0.0006). After controlling for its interactions with age of onset, current age was inversely correlated with Montgomery Åsberg Depression Rating Scale scores at baseline ( P < 0.00001) and week 12 ( P = 0.0066), MMSE ( P < 0.00001), delayed memory ( P < 0.00001), and TMT ( P = 0.0021). Age of onset predicted impairment in immediate ( P = 0.023) and delayed memory ( P = 0.0181), and dyskinesias ( P = 0.0006). Although most features of LLD are related to ageing rather than to late-onset, LOD is a possible separate diagnostic entity characterised by memory dysfunction and increased liability to movement disorders.

Differences in olfactory functional connectivity in early-onset depression and late-onset depression.

Late-onset depression (LOD) and early-onset depression (EOD) exhibit different pathological mechanisms and clinical phenotypes, including different extents of olfactory dysfunction. However, the brain abnormalities underlying the differences in olfactory dysfunction between EOD and LOD remain unclear. The aim of this study was to compare the functional connectivity (FC) patterns of olfactory regions between EOD patients and LOD patients and examine their relationship with cognitive function. One hundred and five patients with EOD, 101 patients with LOD and 160 normal controls (NCs) were recruited for the present study. Participants underwent clinical assessment, olfactory testing, cognitive assessments, and magnetic resonance imaging. Eight regions of the primary and secondary olfactory regions were selected to investigate olfactory FC. Patients with LOD exhibited decreased odor identification (OI) compared with patients with EOD and NCs. The LOD group exhibited decreased FC compared with the EOD and NC groups when primary and secondary olfactory regions were selected as the regions of interest (the piriform cortex, lateral entorhinal cortex, and orbital-frontal cortex). Additionally, these abnormal olfactory FCs were associated with decreased cognitive function scores and OI, and the FC between the left orbital-frontal cortex and left amygdala was a partial mediator of the relationship between global cognitive scores and OI. Overall, patients with LOD exhibited decreased FC in both the primary and secondary olfactory cortices compared with patients with EOD, and abnormal olfactory FC was associated with OI dysfunction and cognitive impairment. The FC between the orbital-frontal cortex and amygdala mediated the relationship between global cognitive function and OI.

Open-Label placebo for the treatment of unipolar depression: Results from a randomized controlled trial

IntroductionThe response to placebo is robust in studies of various antidepressant treatments. The strong placebo response, combined with the absence of side-effects, has prompted suggestions to use the ethically sound open-label placebo (OLP) as a treatment for depression.ObjectivesThe aim of the present study was to assess the efficacy of OLP in the setting of a randomized controlled trial for the treatment of unipolar depression.MethodsThirty-eight patients (28 females, 73.7%) were randomized to either an eight-week treatment with OLP (n=18) or four week of treatment as usual (TAU) followed by four weeks of OLP (n=20). Clinical and socio-demographic measures were assessed at baseline, after four weeks, and at the end of the trial. Response to treatment was determined using the Quick Inventory of Depressive Symptomatology (QIDS SR-16).ResultsThere was an overall decrease in depression levels over time, F(2,35) = 3.98, p = .028). A significant group x time interaction was found only among non-geriatric patients (&lt;65y) with an early onset of depression (&lt;50y), F(2,22) = 3.89, p = .036]. Post-hoc tests indicated a significant decrease during the first four weeks, but only in the OLP group, t(11) = 2.29, p = .043. Table 1:Demographic measures of OLP and TAU patients.MeasuresOLP (n = 18)TAU (n =20)Statistical analysesAge (years) [Mean ± SD]48.17 ± 16.8651.65 ± 17.68t(36) = -0.62, p = .539Education level (years) [Mean ± SD]15.61 ± 3.6614.22 ± 2.62t(34) = 1.31, p = .200Gender (male/female) [no.]4 / 146 / 14X2(1) = 0.30, p = .587Age of onset (years) [Mean ± SD]34.19 ± 15.8232.45 ± 17.72t(36) = 0.32, p= .752Number of depressive episodes (no.) [Mean ± SD]2.58 ± 2.616.64 ± 9.16t(21) = -1.47, p = .156Number of hospitalizations (no.) [Mean ± SD]0.12 ± 0.330.17 ± 0.38t(33)= -0.40, p = .689NotesOLP = Open label placebo; SD = Standard deviation; TAU = Treatment as usual.Image 3:ConclusionsOur findings support the possibility that OLP is an effective treatment for the relatively young population of patients suffering from depression. Additional studies are warranted in order to explore the use of open-label placebo in clinical work.Disclosure of InterestNone Declared

The role of indoleamine 2,3-dioxygenase 1 in early-onset post-stroke depression.

The immune-inflammatory response has been widely considered to be involved in the pathogenesis of post-stroke depression (PSD), but there is ambiguity about the mechanism underlying such association. According to Diagnostic and Statistical Manual of Mental Disorders (5th edition), depressive symptoms were assessed at 2 weeks after stroke onset. 15 single nucleotide polymorphisms (SNPs) in genes of indoleamine 2,3-dioxygenase (IDO, including IDO1 and IDO2) and its inducers (including pro-inflammatory cytokines interferon [IFN]-γ, tumor necrosis factor [TNF]-α, interleukin [IL]-1β, IL-2 and IL-6) were genotyped using SNPscan™ technology, and serum IDO1 levels were detected by double-antibody sandwich enzyme-linked immune-sorbent assay. Fifty-nine patients (31.72%) were diagnosed with depression at 2 weeks after stroke onset (early-onset PSD). The IDO1 rs9657182 T/T genotype was independently associated with early-onset PSD (adjusted odds ratio [OR] = 3.008, 95% confidence interval [CI] 1.157-7.822, p = 0.024) and the frequency of rs9657182 T allele was significantly higher in patients with PSD than that in patients with non-PSD (χ2 = 4.355, p = 0.037), but these results did not reach the Bonferroni significance threshold (p > 0.003). Serum IDO1 levels were also independently linked to early-onset PSD (adjusted OR = 1.071, 95% CI 1.002-1.145, p = 0.044) and patients with PSD had higher serum IDO1 levels than patients with non-PSD in the presence of the rs9657182 T allele but not homozygous C allele (t = -2.046, p = 0.043). Stroke patients with the TNF-α rs361525 G/G genotype had higher serum IDO1 levels compared to those with the G/A genotype (Z = -2.451, p = 0.014). Our findings provided evidence that IDO1 gene polymorphisms and protein levels were involved in the development of early-onset PSD and TNF-α polymorphism was associated with IDO1 levels, supporting that IDO1 which underlie strongly regulation by cytokines may be a specific pathway for the involvement of immune-inflammatory mechanism in the pathophysiology of PSD.

Risk factors for the intergenerational transmission of depression in women and girls: Understanding neural correlates of major depressive disorder and the role of early-onset maternal depression.

Deficits in neural reward processing have been implicated in the etiology of depression and have been observed in high-risk individuals. However, depression is a heterogeneous disorder,and not all depressed individuals exhibit blunted neural reward response, suggesting the need to examine more specific depression phenotypes. Early-onset depression, a well-defined phenotype, has been associated with greater intergenerational transmission of depression and appears more closely linked to neural reward processing deficits. The present study examined whether a maternal history of early-onset depression was associated with neural reward response among mothers and their daughters. Mothers with and without a history of depression, as well as their biological, adolescent daughters (N = 109 dyads), completed a monetary reward guessing task while electroencephalogram was collected. Analyses focused on the Reward Positivity (RewP), an event-related potential following reward receipt. Adjusting for current depressive symptoms, maternal early-onset depression was associated with a blunted RewP in the mothers and a numerically smaller RewP in their never-depressed, adolescent daughters. Maternal adult-onset depression was not statistically associated with a blunted RewP in mothers or daughters. Thus, a blunted RewP appears to be a trait-like vulnerability marker for depression that emerges before depression onset and relates to more specific depression phenotypes (e.g., early-onset depression). These findings have implications for early identification of individuals at risk of depression and for developing more targeted interventions.

Psychopathological network for early-onset post-stroke depression symptoms

BackgroundPost-stroke depression (PSD) can be conceptualized as a complex network where PSD symptoms (PSDS) interact with each other. The neural mechanism of PSD and interactions among PSDS remain to be elucidated. This study aimed to investigate the neuroanatomical substrates of, as well as the interactions between, individual PSDS to better understand the pathogenesis of early-onset PSD.MethodsA total of 861 first-ever stroke patients admitted within 7 days poststroke were consecutively recruited from three independent hospitals in China. Sociodemographic, clinical and neuroimaging data werecollected upon admission. PSDS assessment with Hamilton Depression Rating Scale was performed at 2 weeks after stroke. Thirteen PSDS were included to develop a psychopathological network in which central symptoms (i.e. symptoms most strongly correlated with other PSDS) were identified. Voxel-based lesion-symptom mapping (VLSM) was performed to uncover the lesion locations associated with overall PSDS severity and severities of individual PSDS, in order to test the hypothesis that strategic lesion locations for central symptoms could significantly contribute to higher overall PSDS severity.ResultsDepressed mood, Psychiatric anxiety and Loss of interest in work and activities were identified as central PSDS at the early stage of stroke in our relatively stable PSDS network. Lesions in bilateral (especially the right) basal ganglia and capsular regions were found significantly associated with higher overall PSDS severity. Most of the above regions were also correlated with higher severities of 3 central PSDS. The other 10 PSDS could not be mapped to any certain brain region.ConclusionsThere are stable interactions among early-onset PSDS with Depressed mood, Psychiatric anxiety and Loss of interest as central symptoms. The strategic lesion locations for central symptoms may indirectly induce other PSDS via the symptom network, resulting in higher overall PSDSseverity.Trial registrationURL: http://www.chictr.org.cn/enIndex.aspx; Unique identifier: ChiCTR-ROC-17013993.

GluCEST Imaging and Structural Alterations of the Bilateral Hippocampus in First-Episode and Early-Onset Major Depression Disorder.

Glutamate dysregulation is one of the key pathogenic mechanisms of major depressive disorder (MDD), and glutamate chemical exchange saturation transfer (GluCEST) has been used for glutamate measurement in some brain diseases but rarely in depression. To investigate the GluCEST changes in hippocampus in MDD and the relationship between glutamate and hippocampal subregional volumes. Cross-sectional. Thirty-two MDD patients (34% males; 22.03 ± 7.21 years) and 47 healthy controls (HCs) (43% males; 22.00 ± 3.28 years). 3.0 T; magnetization prepared rapid gradient echo (MPRAGE) for three-dimensional T1-weighted images, two-dimensional turbo spin echo GluCEST, and multivoxel chemical shift imaging (CSI) for proton magnetic resonance spectroscopy (1 H MRS). GluCEST data were quantified by magnetization transfer ratio asymmetry (MTRasym ) analysis and assessed by the relative concentration of 1 H MRS-measured glutamate. FreeSurfer was used for hippocampus segmentation. The independent sample t test, Mann-Whitney U test, Spearman's correlation, and partial correlation analysis were used. P < 0.05 was considered statistically significant. In the left hippocampus, GluCEST values were significantly decreased in MDD (2.00 ± 1.08 [MDD] vs. 2.62 ± 1.41 [HCs]) and showed a significantly positive correlation with Glx/Cr (r = 0.37). GluCEST values were significantly positively correlated with the volumes of CA1 (r = 0.40), subiculum (r = 0.40) in the left hippocampus and CA1 (r = 0.51), molecular_layer_HP (r = 0.50), GC-ML-DG (r = 0.42), CA3 (r = 0.44), CA4 (r = 0.44), hippocampus-amygdala-transition-area (r = 0.46), and the whole hippocampus (r = 0.47) in the right hippocampus. Hamilton Depression Rating Scale scores showed significantly negative correlations with the volumes of the left presubiculum (r = -0.40), left parasubiculum (r = -0.47), and right presubiculum (r = -0.41). GluCEST can be used to measure glutamate changes and help to understand the mechanism of hippocampal volume loss in MDD. Hippocampal volume changes are associated with disease severity. 2 TECHNICAL EFFICACY: Stage 1.

A Link between Parental Psychopathology and Preschool Depression: Take Care of Parents to Take Care of Children.

The first aim of this outcome research was to analyze the impact of parental support treatment in a sample of depressed preschool children divided into two groups of comparison (under-reactive and over-reactive) through evolution in the Clinical Global Impression (CGI). The second aim was to analyze the correlation between the presence of parental psychopathology and the severity of children's disorders. Our clinical sample consisted of 32 preschool-age children with a final diagnosis of MDD. The children's assessment included a psychiatric assessment to establish a diagnosis of MDD, confirmed by means of a semi-structured interview, which was administered again one month after the end of parental treatment. All the parents began a six-month parent training treatment conducted by experienced child psychiatrists, whereas children were not treated. During this period, the Clinical Global Impression Scale (CGI) was filled out monthly in order to observe the evolution of the children's disorders. Post-hoc tests showed a significant difference from before the treatment to after the treatment only in the over-reactive group (p = 0.00). Regarding parental psychiatric disorders, in the over-reactive group, only 3 children had no parents with psychopathology. In the under-reactive group, no child lacked a parent with psychopathology. Parent training treatment seems to be a valid intervention to improve preschool depression, especially in over-reactive groups, and to prevent dysfunctional parental styles connected to parental psychopathology.

A Standardized Protocol for Early-life Stress-induced Social Defeat in Mice.

Neuropsychiatric diseases, like depression, have a considerable and persistent impact on human health; however, little is known about their underlying pathogenesis. Social defeat is a model for stress-induced psychopathologies that could present with behaviors resembling those observed in humans with depression. However, previous animal models of social defeat mainly focus on adults. Here, we re-design the protocol of early-life stress-induced social defeat paradigm, which is based on a classic resident-intruder model. Briefly, each two-week-old experimental mouse of C57BL/6 strain is introduced into the home cage of an unfamiliar CD1 aggressor mouse for 30 min per day for 10 consecutive days. Later, all experimental mice are raised individually for another month. Finally, the mice are identified as defeated through social interaction and open field tests. This model has been shown to be etiological and predictive and provide high validity and could be a powerful tool to investigate the underlying pathogenesis of early onset depression. Graphical overview.