In contemporary neuroimaging studies, it has been observed that patients with major depressive disorder (MDD) exhibit aberrant spontaneous neural activity, commonly quantified through the amplitude of low-frequency fluctuations (ALFF). However, the substantial individual heterogeneity among patients poses a challenge to reaching a unified conclusion.

To address this variability, our study adopts a novel framework to parse individualized ALFF abnormalities. We hypothesize that individualized ALFF abnormalities can be portrayed as a unique linear combination of shared differential factors. Our study involved two large multi-center datasets, comprising 2424 patients with MDD and 2183 healthy controls. In patients, individualized ALFF abnormalities were derived through normative modeling and further deconstructed into differential factors using non-negative matrix factorization.

Two positive and two negative factors were identified. These factors were closely linked to clinical characteristics and explained group-level ALFF abnormalities in the two datasets. Moreover, these factors exhibited distinct associations with the distribution of neurotransmitter receptors/transporters, transcriptional profiles of inflammation-related genes, and connectome-informed epicenters, underscoring their neurobiological relevance. Additionally, factor compositions facilitated the identification of four distinct depressive subtypes, each characterized by unique abnormal ALFF patterns and clinical features. Importantly, these findings were successfully replicated in another dataset with different acquisition equipment, protocols, preprocessing strategies, and medication statuses, validating their robustness and generalizability.

This research identifies shared differential factors underlying individual spontaneous neural activity abnormalities in MDD and contributes novel insights into the heterogeneity of spontaneous neural activity abnormalities in MDD.

Diagnosing mental health challenges in bereavement is controversial; however, regardless of one’s position on this matter, assessments of bereaved individuals continue to occur in clinical and research contexts. It is critical for evaluations to account for contextual factors that are unique to bereavement. This paper summarizes considerations for diagnosing depression in bereaved individuals, focusing on use of the six-item Hamilton Depression Rating Scale (HAM-D6).

Following a literature review of the Hamilton Depression Rating Scale (HAM-D) and various versions, we summarized decision rules we used in scoring the HAM-D6 in a study of parents bereaved by cancer. We expanded on existing scoring guidelines for each of the HAM-D6 items, including depressed mood, work and activities, general somatic symptoms, guilt, psychic anxiety, and psychomotor retardation, and illustrated clinical distinctions and probes for assessors to consider through case examples from our research with bereaved parents.

Considerations for assessing depressive symptoms and behavior changes in the context of bereavement were summarized. Symptoms that may be diagnostic of depression in some populations may reflect other factors in the bereaved, such as a change in priorities, social expectations surrounding grief, or avoidance of grief activators. Nuanced factors are important for assessors to consider when administering the HAM-D6 to bereaved individuals.

Our sharing of these considerations is not intended to promote diagnosis of depression in bereavement but to highlight the unique contextual factors that distinguish symptoms of depression from common experiences of grievers when applying an assessment tool such as the HAM-D6. While validated measures can be constraining, they can have clinical utility; they may increase standardization in research, help clinicians communicate with each other, advance the field more generally to understand the varying struggles bereaved individuals experience, and systemically facilitate access to services via managed care.

Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) have emerged as important peripheral inflammatory biomarkers. Recent data suggest a possible role of the immune system in the pathophysiology of suicidal behavior (SB). The aim of this study is to evaluate the association among NLR, MLR, and PLR and SB in patients with major depressive disorder (MDD), and to test its validity as a biomarker for suicidality.

We evaluated 538 patients with MDD (mean age [standard deviation] = 43.87 [14.36] years; females: 68.8%). A logistic regression model was estimated to determine the independent factors associated with suicide risk in patients with and without a history of suicide attempt (SA).

Three hundred ninety-three patients (74.7%) had a personal history of SA. Patients with a previous SA were more frequently female (71.9% vs. 59.6%; p = 0.007), significantly younger (41.20 vs. 51.77 years; p < 0.001), had lower depression severity at enrolment (15.58 vs. 18.42; p < 0.000), and significantly higher mean NLR and PLR ratios (2.27 vs. 1.68, p = 0.001; 127.90 vs. 109.97, p = 0.007, respectively). In the final logistic regression model, after controlling for age, sex, and depression severity, NLR was significantly associated with SB (β = 0.489, p = 0.000; odds ratio [95% confidence intervals] = 1.631 [1.266–2.102]). We propose a cut-off value of NLR = 1.30 (sensitivity = 75% and specificity = 35%).

Our data suggest that NLR may be a valuable, reproducible, easily accessible, and cost-effective strategy to determine suicide risk in MDD.

Reports of changes in patients’ social behavior during deep brain stimulation (DBS) raised the question whether DBS induces changes in personality. This study explored if (1) DBS is associated with changes in personality in patients suffering from treatment-resistant depression (TRD), (2) how personality dimensions and depression are associated, and (3) if TRD patients’ self-ratings of personality are valid.

TRD patients were assessed before DBS (n = 30), 6 months (t2, n = 21), 2 (t3, n = 17) and 5 years (t4, n = 11) after the initiation of DBS of the supero-lateral branch of the medial forebrain bundle (slMFB-DBS). Personality was measured with the NEO-Five-Factor Inventory (NEO-FFI), depression severity with Hamilton (HDRS), and Montgomery–Åsberg Depression Rating Scale (MADRS).

Personality dimensions did not change with slMFB-DBS compared with baseline. Extraversion was negatively correlated with HDRS28 (r = −0.48, p < 0.05) and MADRS (r = −0.45, p < 0.05) at t2. Inter-rater reliability was high for the NEO-FFI at baseline (Cronbach's α = 0.74) and at t4 (α = 0.65). Extraversion [t(29) = −5.20; p < 0.001] and openness to experience [t(29) = −6.96; p < 0.001] differed statistically significant from the normative sample, and did not predict the antidepressant response.

slMFB-DBS was not associated with a change in personality. The severity of depression was associated with extraversion. Personality of TRD patients differed from the healthy population and did not change with response, indicating a possible scar effect. Self-ratings of personality seem valid to assess personality during TRD.

Oxidative stress is one of the suggested mechanisms in major depression.

To determine the oxidative and antioxidative status of plasma of patients with major depression and to investigate whether there is a relationship between the potency of oxidative stress and the severity of depression.

To determine the antioxidative status of plasma, total and individual antioxidant levels which are total antioxidant potential (TAOP), total protein, albumin, uric acid, vitamin C and total bilirubin were measured. To determine the oxidative status, total peroxide level of plasma was measured in patients with drug-free depressive patients and compared with those of controls. Per cent ratio of total peroxide to TAOP was evaluated as oxidative stress index (OSI).

Plasma TAOP and individual antioxidant levels were found to be lower in patients with depression than those of controls. On the contrary, the patients had high total plasma peroxide levels. OSI values of the patients were significantly higher than those of controls (P = 0.002), and a significant positive correlation between Hamilton Depression Rating Scale (HDRS) and OSI values was found (r = 0.54, P = 0.01).

The patients with major depression are exposed to oxidative stress, and OSI may be useful to reflect the severity of the disease.