Molecular Characteristics of Spontaneous Remission in Major Depressive Disorder: Changes in Serum Acetylcarnitine and Glycerophosphcholine Levels

AIM: Psychological resilience is closely related to recurrence of depression. There are few previous studies on the influencing factors of psychological resilience in patients diagnosed with major depressive disorder in remission (MDDR). Here, we investigated the current status of resilience in patients diagnosed with MDDR and its influencing factors. A descriptive cross-sectional study was conducted from June 2019 to April 2021. One hundred and forty-two patients diagnosed with MDDR were recruited from the Department of Psychiatry and Psychology of the General Hospital of Northern Theater Command. Demographic information, social support, well-being, self-efficacy and psychological resilience were collected using self-reported questionnaires. The psychological resilience of MDDR patients was lower than that of the healthy Chinese adults in China. Multiple logistic regression analysis showed that education, personal monthly income, social support, well-being and self-efficacy were associated with psychological resilience. Receiver operating characteristic (ROC) curve analysis further confirmed that social support, well-being and self-efficacy were associated with psychological resilience. The psychological resilience of MDDR patients was lower than that of the general population in China. The education levels, personal monthly income, social support, well-being and self-efficacy were influencing factors of psychological resilience. According to the factors affecting the psychological resilience of patients diagnosed with MDDR, targeted clinical nursing is helpful to prevent the recurrence of depression.

The pathophysiologic mechanism of major depressive disorder (MDD) has been consistently associated with altered catecholaminergic function, especially with decreased dopamine neurotransmission, by various sources of largely indirect evidence. An instructive paradigm for more directly investigating the relationship between catecholaminergic function and depression has involved the mood response to experimental catecholamine depletion (CD). To determine whether catecholaminergic dysfunction represents a trait abnormality in MDD and to identify brain circuitry abnormalities involved in the pathophysiologic mechanism of MDD. Randomized, double-blind, placebo-controlled, crossover, single-site experimental trial. Psychiatric outpatient clinic. Fifteen unmedicated subjects with MDD in full remission (hereinafter referred to as RMDD subjects) and 13 healthy controls. Induction of CD by oral administration of alpha-methylparatyrosine. Sham depletion used identical capsules containing hydrous lactose. Quantitative positron emission tomography of regional cerebral glucose utilization to study the neural effects of CD and sham depletion. Behavioral assessments included the Montgomery-Asberg Depression Rating Scale and the Snaith-Hamilton Pleasure Scale (anhedonia). Depressive and anhedonic symptoms increased during CD to a greater extent in RMDD subjects than in controls. In both groups, CD increased metabolism in the anteroventral striatum and decreased metabolism in the orbital gyri. In a limbic-cortical-striatal-pallidal-thalamic network previously implicated in MDD, composed of the ventromedial frontal polar cortex, midcingulate and subgenual anterior cingulate cortex, temporopolar cortex, ventral striatum, and thalamus, metabolism increased in RMDD subjects but decreased or remained unchanged in controls. Metabolic changes induced by CD in the left ventromedial frontal polar cortex correlated positively with depressive symptoms, whereas changes in the anteroventral striatum were correlated with anhedonic symptoms. This study provides direct evidence for catecholaminergic dysfunction as a trait abnormality in MDD. It demonstrates that depressive and anhedonic symptoms as a result of decreased catecholaminergic neurotransmission are related to elevated activity within the limbic-cortical-striatal-pallidal-thalamic circuitry.

Dysfunction in the monoamine systems of serotonin (5-HT), norepinephrine (NE) and dopamine (DA) may causally be related to major depressive disorder (MDD). Monoamine depletion studies investigate the direct effects of monoamines on mood. Acute tryptophan depletion (ATD) or para-chlorophenylalanine (PCPA) deplete 5-HT, acute phenylalanine/tyrosine depletion (APTD) or alpha-methyl-para-tyrosine (AMPT) deplete NE/DA. Available depletion studies found conflicting results in heterogeneous populations: healthy controls, patients with previous MDD in remission and patients suffering from MDD. The decrease in mood after 5-HT and NE/DA depletion in humans is reviewed and quantified. Systematic search of MEDLINE and EMBASE (1966-October 2006) and cross-references was carried out. Randomized studies applying ATD, PCPA, APTD or AMPT vs control depletion were included. Pooling of results by meta-analyses was stratified for studied population and design of the study (within or between subjects). Seventy-three ATD, 2 PCPA, 10 APTD and 8 AMPT studies were identified of which 45 ATD and 8 APTD studies could be meta-analyzed. 5-HT or NE/DA depletion did not decrease mood in healthy controls. 5-HT or NE/DA depletion slightly lowered mood in healthy controls with a family history of MDD. In drug-free patients with MDD in remission, a moderate mood decrease was found for ATD, without an effect of APTD. ATD induced relapse in patients with MDD in remission who used serotonergic antidepressants. In conclusion, monoamine depletion studies demonstrate decreased mood in subjects with a family history of MDD and in drug-free patients with MDD in remission, but do not decrease mood in healthy humans. Although depletion studies usefully investigate the etiological link of 5-HT and NE with MDD, they fail to demonstrate a causal relation. They presumably clarify a vulnerability trait to become depressed. Directions for further investigation of this vulnerability trait are proposed.

Elevated Neuroimmune Biomarkers in Sweat Patches and Plasma of Premenopausal Women with Major Depressive Disorder in Remission: The POWER Study

Cardiovascular risk factors (CVRFs) have been linked to both depression and cognitive decline but their role in neuropsychiatric symptoms (NPS) has yet to be clarified. Understanding the role of CVRFs in the etiology of NPS for prospective treatments and preventive strategies to minimize these symptoms. We examined the distribution of NPS using the Neuropsychiatric Inventory (NPI) scores in three cohorts from the Prevention of Alzheimer's Dementia with Cognitive Remediation Plus Transcranial Direct Current Stimulation in Mild Cognitive Impairment and Depression (PACt-MD) study: older patients with a lifetime history of major depressive disorder (MDD) in remission, patients with mild cognitive impairment (MCI), and patients with combined MCI and MDD. We also examined the link between individual NPS and CVRFs, Framingham risk score, and Hachinski ischemic score in a combined sample. Analyses were based on a sample of 140 subjects, 70 with MCI, 38 with MCI plus MDD, and 32 with MDD. There was no effect of age, gender, education, cognition, or CVRFs on the presence (NPI >1) or absence (NPI = 0) of NPS. Depression was the most prevalent affective NPS domain followed by night-time behaviors and appetite changes across all three diagnostic groups. Agitation and aggression correlated negatively while anxiety, disinhibition, night-time behaviors, and irritability correlated positively with CVRFs (all p-values <0.05). Other NPS domains showed no significant association with CVRFs. CVRFs are significantly associated with individual NPI sub-scores but not with total NPI scores, suggesting that different pathologies may contribute to different NPS domains.

Subtypes of Mild Cognitive Impairment Among the Elderly With Major Depressive Disorder in Remission

Major depressive disorder (MDD) has a higher prevalence in women with supraphysiologic androgen levels. Whether there is also an association between depression and androgen levels in the physiological range, is unknown. This study examined if women with current MDD have higher androgen levels compared to women who have never had MDD, and if androgen levels are associated with onset and remission of MDD. In 1659 women (513 current MDD, 754 remitted MDD, and 392 never MDD), baseline plasma levels of total testosterone, 5α-dihydrotestosterone, and androstenedione were determined with liquid chromatography-tandem mass spectrometry, and dehydroepiandrosterone-sulfate and sex hormone binding globulin (SHBG) with radioimmunoassays. Free testosterone was calculated. MDD status was assessed at baseline, and at 2 and 4 years follow-up. Women were aged between 18 and 65 years (mean age 41) with total testosterone levels in the physiological range (geometric mean 0.72 nmol/L [95% CI 0.27–1.93]). After adjusting for covariates and multiple testing, women with current MDD had a higher mean free testosterone than women who never had MDD (adjusted geometric mean 8.50 vs. 7.55 pmol/L, p = 0.0005), but this difference was not large enough to be considered clinically meaningful as it was consistent with statistical equivalence. Levels of other androgens and SHBG did not differ and were also statistically equivalent between the groups. None of the androgens or SHBG levels predicted onset or remission of MDD. Our findings support the idea that plasma androgens within the physiological range have no or only limited effects on depressive disorders in women.

BackgroundCognitive symptoms are one of the core symptoms of depressive disorders with a bearing effect on functional outcomes. Cognitive symptoms, including poor concentration and difficulty making decisions, are one of the DSM-IV diagnostic criteria for major depressive disorder. This study was designed to evaluate cognitive deficits in a sample of adult patients with major depressive disorder (MDD) in remission. A cross-sectional study was done on 60 patients fulfilling the diagnostic criteria of MDD in remission state. In addition, 60 normal subjects with matched age, sex, and educational level were compared with the patients group. Participants in both patients and control groups were subjected to clinical assessment using Mini-International Neuropsychiatric Interview plus (MINI-plus), assessment of cognitive functions using Wechsler Memory Scale-Revised (WMS-R) short form, and Wisconsin Card Sorting Test (WCST).ResultsThere were statistically significant differences between patients and control groups regarding cognitive function. The patients group scored less in visual memory, verbal memory, attention/concentration, and psychomotor speed. They also performed poorly regarding executive functions. But there was no statistically significant difference between the patients and control groups regarding sustained attention and visuospatial function. No significant correlations did exist between age at onset of MDD and the duration of illness with different domains of cognitive function except for figural memory of WMS-R and categories completed of Wisconsin card sorting test.ConclusionPatients with MDD in remission experienced deficits in several cognitive functions when compared to matched control subjects. The cognitive functions do not reach normal levels of performance, particularly in visual memory and executive functioning with remission of depressive symptoms.

Objective: This study investigated the interrelationships between chronotype, impulsivity, resilience, and affective symptomatology in individuals with Major Depressive Disorder (MDD) in remission. Specifically, it examined whether impulsivity and resilience mediate the association between eveningness and depressive and anxiety symptoms, and whether sleep quality moderates these pathways. Materials and Methods: This cross-sectional study was conducted between February and April 2025 at Istanbul Tuzla State Hospital, Türkiye, and included 203 patients diagnosed with MDD in remission. Participants were assessed using validated psychometric instruments, including the Morningness-Eveningness Questionnaire (MEQ), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Psychological Resilience Scale (PRS-33), Barratt Impulsiveness Scale (BIS-11), and the Pittsburgh Sleep Quality Index (PSQI). Analyses were conducted using SPSS 22.0, including correlations, multiple linear regression, and PROCESS-based mediation and moderation models. Results: Eveningness was significantly associated with increased severity of both depressive and anxiety symptoms. Non-planning and attentional impulsivity partially mediated the relationship between eveningness and depressive symptoms. Resilience also partially mediated the link between eveningness and depression, indicating a protective psychological buffer. Sleep quality moderated the chronotype–depression association, such that poor sleep exacerbated depressive symptoms in evening types, but it did not moderate the chronotype–anxiety link. Conclusion: Chronotype influences mental health outcomes through intricate cognitive-affective pathways. Evening-type individuals are more vulnerable to affective symptoms due to heightened impulsivity and reduced resilience. These findings emphasize the need for multidimensional interventions that address not only circadian misalignment but also impulsivity regulation and resilience enhancement to improve psychological outcomes in mood disorder populations.

Social phobia (SP) and major depressive disorder (MDD) are frequently concurrent, which negatively affects quality of life (QOL), functioning, and depressive symptom severity. We hypothesized individuals with comorbid SP and MDD (MDD + SP) would have worse treatment outcomes than those with MDD alone (MDDnoSP), but that both groups would have significant responses to treatment, and those who achieved MDD remission would have the best increases in QOL and functioning. We analyzed data for 2280 adults who received citalopram monotherapy in phase 1 of the NIH-funded Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Participants (82 MDD + SP and 2198 MDDnoSP) with complete entry and exit scores across QOL, functioning, and depressive symptom severity were examined. MDD remission status following treatment was determined. Patient-reported QOL and functioning scores were classified as within-normal or severely-impaired. No significant between-group differences were observed across all outcomes at entry or exit. Both groups experienced significant improvements in QOL and functioning (all p values .77). Although non-significant, the MDD + SP group was more likely to achieve within-normal scores and MDD remission post-treatment. Findings were interesting as we initially expected the MDD + SP participants to have worse outcomes, yet those with MDD alone had a more chronic course. Regardless, participants who were able to achieve MDD remission post-treatment had significantly better improvements in QOL and functioning. Accordingly, researchers and clinicians should utilize QOL and functioning measures when examining treatment effectiveness, while also considering the role of remission from major depressive disorder on quality of life.

QUESTION: How do anti-depressants and psychotherapy compare in generating full remission in major depressive disorder? DesignSystematic review with meta-analysis.

Optimally combining transcranial magnetic stimulation with antidepressants in major depressive disorder: A systematic review and Meta-analysis

The interplay between mental health and mental illness in the daily experience of persons with major depressive disorder in remission: A real-time sampling study.

Major depressive disorder (MDD) is one of the leading causes of disability worldwide, and its incidence is expected to increase. Despite tremendous efforts to understand its underlying biological mechanisms, MDD pathophysiology remains elusive and pharmacotherapy outcomes are still far from ideal. Low-grade chronic inflammation seems to play a key role in mediating the interface between psychological stress, depressive symptomatology, altered intestinal microbiology, and MDD onset. We review the available pre-clinical and clinical evidence of an involvement of pro-inflammatory pathways in the pathogenesis, treatment, and remission of MDD. We focus on caspase 1, inducible nitric oxide synthase, and interferon gamma, three inflammatory systems dysregulated in MDD. Treatment strategies aiming at targeting such pathways alone or in combination with classical therapies could prove valuable in MDD. Further studies are needed to assess the safety and efficacy of immune modulation in MDD and other psychiatric disorders with neuroinflammatory components.

Impulsivity is an important risk for suicidality, which is common in patients with major depressive disorder (MDD). The goal of this study was to examine multiple facets of impulsivity in depressed patients compared with healthy controls and to assess their relationship to suicidality. Outpatients diagnosed with MDD using the Structured Clinical Interview for DSM-IV were recruited. Two groups were constituted as "MDD in remission" (n=32) and "MDD" (n=71). The "healthy control" group (n=30) consisted of individuals who had never been diagnosed with any psychiatric disorder. Impulsivity was assessed with the Barratt Impulsivity Scale (BIS), a self-rating measure, and with the following behavioral tasks: Go/No-go Task, Iowa Gambling Task, and Balloon Analogue Risk Task. The scores of the 3 groups (n=133) were compared to evaluate the effect of MDD. The scores were also analyzed and compared in the patients in the 2 MDD groups (n=103) with respect to their current and lifetime suicidality. There was no difference in the 3 groups in task scores, but nonplanning BIS was correlated with the severity of depressive symptoms. Patients with suicidal ideation (SI) had higher BIS total and attention impulsivity scores and more commission errors on the Go/No-go Task, reflecting failure in response inhibition, compared with the patients without SI. Failure to show differences in impulsivity-related tasks suggests that there might be no relationship between the state of depression and impulsivity. However, these findings confirm that there is an association between SI and response inhibition and the attention facet of impulsivity in depression.