Subtypes Of Depression Research Articles

The role of circadian clock gene Arntl in the winter depression-like behavior in melatonin-proficient female CBA/N mice

Seasonal affective disorder (SAD), also known as winter depression, is a subtype of depression typically manifesting in winter. Typical symptoms of SAD, such as an increased need for sleep and carbohydrate cravings associated with increased appetite and weight, are distinct from those of major depression, and the underlying mechanisms of SAD remain unclear. Although laboratory mice are generally considered non-seasonal animals, we observed depression-like behaviors in melatonin-proficient female CBA/N mice maintained under winter-mimicking conditions. Transcriptome analysis of the brains of CBA/N mice maintained under winter- and summer-mimicking conditions revealed changes in the expression of circadian clock genes, including Arntl (also known as Bmal1). We generated Arntl-deficient, melatonin-proficient CBA/N mice using the speed congenic method to examine the role of Arntl in depressive behavior. The tail suspension test in these mice revealed a depressive phenotype. These results suggested that the circadian clock gene Arntl may be involved in winter depression-like behavior.

Distinct prefrontal cortex alterations in confirmed and suspected depression individuals with different perceived stress during an emotional autobiographical memory task: One fNIRS investigation

BackgroundPrevious research showed that perceived stress was strongly linked to depression, little is known about the underlying neurological mechanism of different depression subtypes with different perceived stress, and there is currently no classification of stress-based subtypes of depression. This study aimed at using fNIRS to uncover the neuromechanism of confirmed and suspected depression with different perceived stress, hence providing neurobiological evidence for the classification of stress-based depression subtypes. It is a significant target for effective depression treatment. MethodThe study included 551 young adults: 256 healthy control individuals, 62 confirmed depression patients, and 233 suspected depression participants. A 53-channel fNIRS imaging system was used to gather the average oxyhemoglobin level in the PFC during EAMT. ResultsCompared with HC, confirmed and suspected depression group show significant lower hemodynamic activation in right frontal lobe of frame under high loss of control. Confirmed depression with high sense of tension had higher activation than with high loss of control in right dlPFC, while for suspected depression, the activation with high sense of tension was lower than with high loss of control in left broca's area (BA) and front polar cortex (FPC). ConclusionAll perceived stresses were not equal in their impacts on different depression types. The confirmed and suspected depression were two different depression subtypes sharing distinct activation pattern under different perceived stress in PFC, which may be an important target for stress-linked psychopathology. Depression can be further classified precisely based on stress. fNIRS can provide neuroimaging evidence for classification of stress-based depression subtypes.

Exploring associations between eat-lancet diet adherence and depression subtypes

Exploring associations between eat-lancet diet adherence and depression subtypes

Major depression symptom severity associations with willingness to exert effort and patch foraging strategy.

Individuals with major depressive disorder (MDD) can experience reduced motivation and cognitive function, leading to challenges with goal-directed behavior. When selecting goals, people maximize 'expected value' by selecting actions that maximize potential reward while minimizing associated costs, including effort 'costs' and the opportunity cost of time. In MDD, differential weighing of costs and benefits are theorized mechanisms underlying changes in goal-directed cognition and may contribute to symptom heterogeneity. We used the Effort Foraging Task to quantify cognitive and physical effort costs, and patch leaving thresholds in low effort conditions (reflecting perceived opportunity cost of time) and investigated their shared versus distinct relationships to clinical features in participants with MDD (N=52, 43 in-episode) and comparisons (N=27). Contrary to our predictions, none of the decision-making measures differed with MDD diagnosis. However, each of the measures were related to symptom severity, over and above effects of ability (i.e., performance). Greater anxiety symptoms were selectively associated with lower cognitive effort cost (i.e. greater willingness to exert effort). Anhedonia and behavioral apathy were associated with increased physical effort costs. Finally, greater overall depression was related to decreased patch leaving thresholds. Markers of effort-based decision-making may inform understanding of MDD heterogeneity. Increased willingness to exert cognitive effort may contribute to anxiety symptoms such as worry. Decreased leaving thresholds associations with symptom severity is consistent with reward rate-based accounts of reduced vigor in MDD. Future research should address subtypes of depression with or without anxiety, which may relate differentially to cognitive effort decisions.

Types of depression in patients with coronary heart disease: Results from the THORESCI study

BackgroundBoth coronary heart diseases (CHD) and depression are highly prevalent and bidirectionally related. The precise nature of this relationship remains unclear. Defining depressive subtypes could help unravel this relationship. Therefore, the aim of this study was to explore depressive subtypes in patients with CHD. Methods1530 patients (21.3 % women, mean age: 64.7 years (SD = 10.1)) were included in latent class analysis with nine indicators derived from the PHQ-9 and BDI-II representing symptoms of depression as described in the DSM-5 criteria. The best-fitting latent class model was confirmed with double cross-validation. Classes were characterized using demographic, medical, psychiatric, and cardiovascular (risk) factors. ResultsA 3-class model demonstrated the best fit to the data, resulting in a depressed (5.4 %), fatigued (13.5 %), and non-depressed class (81.1 %). Having medical comorbidities, a history of psychiatric problems, negative affectivity, and anxiety symptoms increased the odds of belonging to the depressed group (OR 3.02, 95%CI 1.19–7.68, OR 3.61, 95%CI 1.44–9.02, OR 1.16, 95%CI 1.04–1.30, and OR 1.89, 95%CI 1.66–2.15, respectively). Belonging to the fatigued group was associated with increased odds of having an elective PCI (OR 2.12, 95%CI 1.27–3.55), insufficient physical activity (OR 2.19, 95%CI 1.20–3.99), comorbid medical conditions (OR 2.15, 95%CI 1.21–3.81), a history of psychiatric problems (OR 2.25, 95%CI 1.25–4.05), and anxiety symptoms (OR 1.48, 95%CI 1.34–1.63) compared with the non-depressed group. LimitationsFuture studies should include more people with depressive symptoms. ConclusionsPatients with CHD and medical or psychiatric risk factors should be offered support to decrease or prevent depressive or fatigue symptoms.

The longitudinal patterns of depression subtypes and stressors in depression severity in the Canadian longitudinal study on aging (CLSA).

The current study aims to characterize the longitudinal patterns of depression subtypes and investigate the associations among the stability of depression subtypes, COVID-19-related stressors, and depression severity. The study utilized data from the Canadian Longitudinal Study on Aging, which is a national, long-term study of Canadian adults aged 45 and older (n = 12,957). Latent profile analysis was used to identify latent depression subtypes. Latent transition analysis was then applied to assess the stability of these subtypes over time. Hierarchical multivariate linear regression was used to explore the relationships among these identified depression subtypes, COVID-19-related stressors, and depression severity among males and females, respectively. Distinct depression subtypes were identified. Except for atypical depression, other depression subtypes showed greater stability over time. We also found that melancholic depression (B = 9.432) and typical depression (B = 6.677) were strongly associated with depression severity during the pandemic. Health-related stressors (B = 0.840), conflict (B = 3.639), difficulties accessing resources (B = 0.927), separation from family (B = 0.840), and caregiving experience (B = 0.764), were significantly associated with increased depression severity. Sex-specific analyses also revealed differences in the associations between stressors and depression severity between males and females. This study contributes valuable insights into the latent clustering of depression subtypes and their stability. Stressors were associated with increased depression severity, with distinct associations observed among males and females. These findings have implications for targeted early interventions and integrated clinical management strategies by providing the evidence base for tailored mental health care during and after the pandemic.

Quercetin alleviates depressive-like behavior by modulating acetyl-H3K9 mediated ferroptosis pathway in hypothalamus of perimenopausal depression rat model

Perimenopausal depression is a subtype of depression and is prevalent among perimenopausal women, which has brought a heavy burden to family and society. The pathogenesis of perimenopausal depression is still unclear, which affects the prevention and treatment of perimenopausal depression to a certain extent. Quercetin is a flavonoid compound, and has estrogenic activity and pharmacological effects such as antioxidant, anti-inflammatory, and neuroprotective effects. This study investigated whether quercetin improved perimenopausal depression-like behaviors and potential mechanism. The results demonstrated that quercetin could alleviate the depression-like behaviors in perimenopausal depression rat model, inhibit astrocyte activation, improve ferroptosis-associated mitochondrial damage (such as mitochondrial pyknosis and mitochondrial cristae reduction) in hypothalamus, increase the expressions of histone 3 lysine 9 acetylation (acetyl-H3K9), ferroptosis-associated protein including glutathione peroxidase 4 (GPX4) and Xc- antiporter (SLC7A11), and reduce the expressions of endoplasmic reticulum stress-related proteins including inositol-requiring enzyme 1 (IRE1α), phosphorylated IRE1α (p-IRE1α), X-box binding protein 1 (XBP1) and glucose-regulated protein 78 (GRP78) in hypothalamus of perimenopausal depression rat model. Furtherly, in vitro study indicated that quercetin could restore histone acetylase (HAT)/histone deacetylase (HDAC) homeostasis through binding to estrogen receptors and increase the expression of acetyl-H3K9, inhibiting ferroptosis through IRE1α/XBP1 pathway in astrocytes of hypothalamus. Our findings demonstrated that acetyl-H3K9 is a crucial target in development of perimenopausal depression, and quercetin exhibited antidepressant effects through modulating acetyl-H3K9 mediated ferroptosis in perimenopausal depression. Quercetin might be the prevention and adjuvant treatment strategy of perimenopausal depression.

Markers of positive affect and brain state synchrony discriminate melancholic from non-melancholic depression using naturalistic stimuli.

Melancholia has been proposed as a qualitatively distinct depressive subtype associated with a characteristic symptom profile (psychomotor retardation, profound anhedonia) and a better response to biological therapies. Existing work has suggested that individuals with melancholia are blunted in their display of positive emotions and differ in their neural response to emotionally evocative stimuli. Here, we unify these brain and behavioural findings amongst a carefully phenotyped group of seventy depressed participants, drawn from an established Australian database (the Australian Genetics of Depression Study) and further enriched for melancholia (high ratings of psychomotor retardation and anhedonia). Melancholic (n = 30) or non-melancholic status (n = 40) was defined using a semi-structured interview (the Sydney Melancholia Prototype Index). Complex facial expressions were captured whilst participants watched a movie clip of a comedian and classified using a machine learning algorithm. Subsequently, the dynamics of sequential changes in brain activity were modelled during the viewing of an emotionally evocative movie in the MRI scanner. We found a quantitative reduction in positive facial expressivity amongst participants with melancholia, combined with differences in the synchronous expression of brain states during positive epochs of the movie. In non-melancholic depression, the display of positive affect was inversely related to the activity of cerebellar regions implicated in the processing of affect. However, this relationship was reduced in those with a melancholic phenotype. Our multimodal findings show differences in evaluative and motoric domains between melancholic and non-melancholic depression through engagement in ecologically valid tasks that evoke positive emotion. These findings provide new markers to stratify depression and an opportunity to support the development of targeted interventions.

Low-Grade Inflammation Associated with Major Depression Subtypes: A Cross-Sectional Study.

Major depressive disorder (MDD) is associated with inflammation and a high level of comorbidities. Atypical depression (AD) is a MDD subtype based on DSM criteria, that could have specific underlying biological mechanisms. AD is associated with elevated cardiovascular (CVD) comorbidities, higher risk of suicide attempts, hypersomnia, and anxiety disorder. In this study, we aim to investigate if AD and polysomnographic parameters could be associated with low-grade inflammation (LGI). LGI is defined by a range from 3 to 10 mg/L of C-reactive protein levels. We carried out a retrospective cohort study in which 765 individuals with MDD were split into two groups: with and without LGI. Our results exhibit differences between the groups for the polysomnographic parameters, with the LGI group showing parameters already associated with inflammation such as reduced rapid eye movement sleep and elevated hypoxemia markers (identified as CVD risk factor). We found that AD is associated with LGI (OR 1.48; p = 0.047) after adjustment. Likewise, we found an LGI prevalence in AD higher (34.8%) than in MDD without atypical features (26.8%). Overall, these results confirm the low-grade inflammation feature of AD and highlight polysomnographic parameters associated with LGI that could also act as risk factors in this context.

Disembodiment and Affective Resonances in Esketamine Treatment of Depersonalized Depression Subtype: Two Case Studies

Introduction: Dissociative experiences are considered undesirable ketamine’s adverse events. However, they might be crucial for ketamine’s antidepressant effects, at least in some depression subtypes. Current understandings of ketamine’s therapeutic potentials converge on the so-called “relaxed prior hypothesis,” suggesting that glutamatergic blockage up-weights bottom-up surprising somatosensory/affective states. As a result, ketamine improves short-term plasticity in depression by enhancing sensitivity to interoceptive signals. Methods: We selected 2 case studies for their paradigmatic description of “depersonalized depression” (Entfremdungsdepression) symptoms. Patients were included in a 6-month-long esketamine program for treatment resistant depression, during which we collected their spontaneous experience with esketamine. According to a neurophenomenological approach, we combined subjective reports from unstructured clinical interviews and the review of previous objective neuroimaging results and neurocomputational models to unveil the relation between esketamine antidepressant effects and interoceptive sensitivity. Results: According to our clinical observations, esketamine-induced dissociation might be particularly effective in the depersonalized depression subtype, in which interoceptive awareness and interaffectivity are particularly compromised. Ketamine and esketamine’s dissociative effects and particularly disembodiment might suspend previously acquired patterns of feeling, sensing, and behaving. Conclusions: Coherently with previous research, we suggest that esketamine-induced disembodiment allows for a transient window of psychological plasticity and enhanced sensitivity, where the body recovers its permeability to affective affordances.

Altered dynamic functional connectivity of nucleus accumbens subregions in major depressive disorder: the interactive effect of childhood trauma and diagnosis.

Major depressive disorder (MDD) with childhood trauma represents a heterogeneous clinical subtype of depression. Previous research has observed alterations in the reward circuitry centered around the nucleus accumbens (NAc) in MDD patients. However, limited investigations have focused on aberrant functional connectivity (FC) within NAc subregions among MDD with childhood trauma. Thus, this study adopts analyses of both static FC (sFC) and dynamic FC (dFC) to examine neurobiological changes in MDD with childhood trauma. The bilateral nucleus accumbens shell (NAc-shell) and nucleus accumbens core (NAc-core) were selected as the seeds. Four participant groups were included: MDD with childhood trauma (n = 48), MDD without childhood trauma (n = 30), healthy controls (HCs) with childhood trauma (n = 57), and HCs without childhood trauma (n = 46). Our findings revealed both abnormal sFC and dFC between NAc-shell and NAc-core and regions including the middle occipital gyrus (MOG), anterior cingulate cortex, and inferior frontal gyrus in MDD with childhood trauma. Furthermore, a significant correlation was identified between the dFC of the left NAc-shell and the right MOG in relation to childhood trauma. Additionally, abnormal dFC moderated the link between childhood abuse and depression severity. These outcomes shed light on the neurobiological underpinnings of MDD with childhood trauma.

Hierarchical Encoding and Fusion of Brain Functions for Depression Subtype Classification

Hierarchical Encoding and Fusion of Brain Functions for Depression Subtype Classification

Potential transition of depression of older adults affected by socioeconomic status show different styles: A longitudinal study of Chinese older adults

Socioeconomic status' (SES) impact on depressive symptoms has been extensively examined; however, previous studies have generally used variable-centered approaches and cross-sectional designs. Therefore, this study explored the subtypes of depression and examined the degree of association between SES and latent transition probabilities. We used latent profile and latent transition analyses with the 2015 and 2018 waves of data from the China Health and Retirement Longitudinal Study (N = 4904). Three subtypes of depression were identified based on symptoms: severe symptom (SS), low symptom (LS), and sub-health (MS). The SS subtype had the highest probability of staying within the original subtype. Individuals in the MS subtype were more likely to move to the SS subtype than those in the LS subtype. The heterogeneity analysis also showed that the effect of SES on latent transition probabilities is heterogeneous to the satisfaction with their relationship with their children, as well as the number of children. Additionally, decision tree analysis found SES and gender can predict transitioning. These findings add to literature on the effects of SES on the heterogeneity of depression and have implications for depression screening and identifying individuals in need of targeted interventions.

Depression Severity, Slow- versus Fast-Wave Neural Activity, and Symptoms of Melancholia.

Melancholia is a major and severe subtype of depression, with only limited data regarding its association with neurological phenomena. To extend the current understanding of how particular aspects of melancholia are correlated with brain activity, electroencephalographic data were collected from 100 adults (44 males and 56 females, all aged 18 y or more) and investigated for the association between symptoms of melancholia and the ratios of alpha/beta activity and theta/beta activity at parietal-occipital EEG sites PO1 and PO2. The results indicate differences in these associations according to the depressive status of participants and the particular symptom of melancholia. Depressed participants exhibited meaningfully direct correlations between alpha/beta and theta/beta activity and the feeling that "Others would be better off if I was dead" at PO1, whereas non-depressed participants had significant inverse correlations between theta/beta activity and "Feeling useless and not needed" and "I find it hard to make decisions" at PO1. The results are discussed in terms of the relative levels of fast-wave (beta) versus slow-wave (alpha, theta) activity exhibited by depressed and non-depressed participants in the parietal-occipital region and the cognitive activities that are relevant to that region.

Integrative Modeling of Accelerometry-Derived Sleep, Physical Activity, and Circadian Rhythm Domains With Current or Remitted Major Depression

Accelerometry has been increasingly used as an objective index of sleep, physical activity, and circadian rhythms in people with mood disorders. However, most prior research has focused on sleep or physical activity alone without consideration of the strong within- and cross-domain intercorrelations; and few studies have distinguished between trait and state profiles of accelerometry domains in major depressive disorder (MDD). To identify joint and individual components of the domains derived from accelerometry, including sleep, physical activity, and circadian rhythmicity using the Joint and Individual Variation Explained method (JIVE), a novel multimodal integrative dimension-reduction technique; and to examine associations between joint and individual components with current and remitted MDD. This cross-sectional study examined data from the second wave of a population cohort study from Lausanne, Switzerland. Participants included 2317 adults (1164 without MDD, 185 with current MDD, and 968 with remitted MDD) with accelerometry for at least 7 days. Statistical analysis was conducted from January 2021 to June 2023. Features derived from accelerometry for 14 days; current and remitted MDD. Logistic regression adjusted for age, sex, body mass index, and anxiety and substance use disorders. Among 2317 adults included in the study, 1261 (54.42%) were female, and mean (SD) age was 61.79 (9.97) years. JIVE reduced 28 accelerometry features to 3 joint and 6 individual components (1 sleep, 2 physical activity, 3 circadian rhythms). Joint components explained 58.5%, 79.5%, 54.5% of the total variation in sleep, physical activity, and circadian rhythm domains, respectively. Both current and remitted depression were associated with the first 2 joint components that were distinguished by the salience of high-intensity physical activity and amplitude of circadian rhythm and timing of both sleep and physical activity, respectively. MDD had significantly weaker circadian rhythmicity. Application of a novel multimodal dimension-reduction technique demonstrates the importance of joint influences of physical activity, circadian rhythms, and timing of both sleep and physical activity with MDD; dampened circadian rhythmicity may constitute a trait marker for MDD. This work illustrates the value of accelerometry as a potential biomarker for subtypes of depression and highlights the importance of consideration of the full 24-hour sleep-wake cycle in future studies.

Task-induced deactivation dysfunction during reward processing is associated with low self-esteem in a possible subtype of major depression.

Low self-esteem is a frequent symptom in major depressive disorder (MDD). This functional magnetic resonance imaging study investigated whether MDD patients with low self-esteem show a distinct neural pathophysiology. Previous studies linked low self-esteem to reduced task-induced deactivation of the pregenual anterior cingulate cortex (pgACC) as a part of the default mode network, and to reduced connectivity between pgACC and reward system. Goya-Maldonado etal. identified an MDD subtype with pgACC and ventral striatal overactivations during reward processing. We hypothesized that this subtype might be characterized by low self-esteem. Eighty-three MDD patients performed the desire-reason dilemma task and completed the Rosenberg Self-Esteem Scale (RSES). Brain activity during bottom-up reward processing was regressed upon the RSES scores, controlling for depression severity measured by the Montgomery-Åsberg Depression Rating Scale. To corroborate the findings, we compared self-esteem scores between patient subgroups with impaired task-induced deactivation (n=31) and with preserved task-induced deactivation (n=31) of the pgACC. Consistent with our a priori hypothesis, activity in a bilateral fronto-striatal network including pgACC and ventral striatum correlated negatively with RSES scores, also when controlling for depression severity. In the additional analysis, patients with impaired task-induced pgACC deactivation showed lower self-esteem (t (52.82)=-2.27; p=.027, d=0.58) compared to those with preserved task-induced pgACC deactivation. We conclude that low self-esteem in MDD patients is linked to a task-induced deactivation dysfunction of the pgACC. Our findings suggest that a previously described possible subtype of MDD with pgACC and ventral striatal overactivations during reward processing is clinically characterized by low self-esteem.

Neural correlates of stress-reactive rumination in depression – The role of childhood trauma and social anxiety

Recent work showed an association of prefrontal dysfunctions in patients with Major Depressive Disorder (MDD) and social stress induced rumination. However, up to date it is unclear which etiological features of MDD might cause prefrontal dysfunctions. In the study at hand, we aimed to replicate recent findings, that showed prefrontal activation alterations during the Trier Social Stress Test (TSST) and subsequently increased stress-reactive rumination in MDD compared to healthy controls. Moreover, we aimed to explore the role of adverse childhood experiences and other clinical variables in this relationship. N = 55 patients currently suffering from MDD and n = 42 healthy controls (HC) underwent the TSST, while cortical activity in areas of the Cognitive Control Network (CCN) was measured via functional near-infrared spectroscopy (fNIRS). The TSST successfully induced a stress reaction (physiologically, as well as indicated by subjective stress ratings) and state rumination in all subjects with moderate to large effect sizes. In comparison to HC, MDD patients showed elevated levels of state rumination with large effect sizes, as well as a typical pattern of reduced cortical oxygenation during stress in the CCN with moderate effect sizes. Self-reported emotional abuse and social anxiety were moderately positively associated with increased stress-reactive rumination. Within the MDD sample, emotional abuse was negatively and social anxiety positively associated with cortical oxygenation within the CCN with moderate to large effect sizes. In conclusion, our results replicate previous findings on MDD-associated prefrontal hypoactivity during stress and extends the research toward specific subtypes of depression.

Characterization of depression subtypes and their relationships to stressor profiles among middle-aged and older adults: An analysis of the canadian longitudinal study on aging (CLSA)

The current diagnostic criteria for depression do not sufficiently reflect its heterogeneous clinical presentations. Associations between adverse childhood experiences (ACEs), allostatic load (AL), and depression subtypes have not been extensively studied. Depression subtypes were determined based on clinical presentations, and their relationships to AL biomarkers and ACEs were elucidated in a sample of middle-aged and older adults. Participants from the Canadian Longitudinal Study on Aging who screened positive for depression were included (n = 3966). Depression subtypes, AL profiles and ACE profiles were determined with latent profile analyses, and associations between them were determined using multinomial logistic regression. Four depression subtypes were identified: positive affect, melancholic, typical, and atypical. Distinct associations between depression subtypes, stressor profiles and covariates were observed. Among the subtypes compared to positive affect, atypical subtype had the most numerous significant associations, and the subtypes had unique relationships to stressor profiles. Age, sex, smoking status, chronic conditions, marital status, and physical activity were significant covariates. The present study describes distinct associations between depression subtypes and measures of stress (objective and self-reported), as well as related factors that differentiate subtypes. The findings may inform more targeted and integrated clinical management strategies for depression in individuals exposed to multiple stressors.

Electrocortical Reactivity During Self-Referential Processing Predicts the Development of Depression Across Adolescence

BackgroundNegative attentional biases and self-schemas have been implicated in the development of depression. Research has indicated that a larger late positive potential (LPP) to negative self-referential words is associated with depression—as well as a maternal history of depression, an indicator of risk. However, it is unclear whether the LPP to self-referential words predicts the actual development of depression. In the current study, we examined whether electrocortical reactivity during self-referential processing predicted the development of depression across adolescence. MethodsThe sample consisted of 165 8- to 14-year-old girls with no lifetime history of a depressive disorder who completed the self-referential encoding task while electroencephalography was recorded at a baseline assessment. Participants and their parent completed the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children at the baseline and 2-, 4-, and 6-year follow-up assessments. ResultsResults indicated that a larger LPP to negative self-referential words at baseline predicted an increased likelihood of developing chronic-intermittent depression (i.e., persistent and/or recurrent), but not nonchronic, single-episode depression, across adolescence. In contrast, neither self-referential encoding task recall biases nor the LPP to positive self-referential words predicted the development of either type of depression. ConclusionsThe results of the current study suggest that electrocortical reactivity associated with a negative self-schema in late childhood predicts the development of a more pernicious subtype of depression across adolescence. Moreover, the current study highlights the importance of considering clinical course in the examination of biomarkers of risk for depression.

An Effect of Chronic Negative Stress on Hippocampal Structures and Functional Connectivity in Patients with Depressive Disorder.

Depressive disorder is a mental health disorder with complicated etiopathogenesis. Environmental stress and neurodevelopment combined with other factors contribute to the occurrence of depression. Especially for the depressive disorder with chronic negative stress, it has characteristics of recurrence and poor curative effect because of unclear mechanism. Here, we investigated the hippocampal structures and functional connectivity (FC) according to resting-state functional magnetic resonance imaging in patients with depression who underwent chronic negative stress. A total of 65 patients with depression (34 underwent chronic negative stress and 31 non-underwent chronic negative stress) and 30 healthy controls who did not undergo chronic negative stress were included in the study. The volumes of hippocampal subfields, seed-based FCs between hippocampus and the whole brain voxels, and ROI-wise-based FC between hippocampal subfields were compared among the three groups. In the patients with depression who underwent chronic negative stress, the volumes of right_GC-ML-DG-head, right_CA4-head and right_CA3-head increased, FCs between Temporal_Mid_R, Precuneus_R, Frontal_Sup_R, Temporal_Sup_R, Angular_L, Frontal_Inf_Tri_R, Supp_Motor_Area_R, Precentral_L and hippocampus increased, and FCs between parasubiculum and CA3, and presubiculum and CA1 decreased. When compared to the patients who did not undergo chronic negative stress, the patients who underwent chronic negative stress had larger volumes of right_GC-ML-DG-head and right_CA3-head, higher FCs between Frontal_Sup_R, Frontal_Inf_Tri_R and hippocampus, and lower FCs between presubiculum and CA1. The depression underwent chronic negative stress may experience disrupted hippocampal structures and functional connectivity. It may be one of potential depressive disorder subtypes.