Anethole as a promising antidepressant for maternal separation stress in mice by modulating oxidative stress and nitrite imbalance.

The occurrence of major depressive disorder is widespread and can be observed in individuals belonging to all societies. It has been suggested that changes in the NO pathway and heightened oxidative stress may play a role in developing this condition. Anethole is a diterpene aromatic compound found in the Umbelliferae, Apiaceae, and Schisandraceae families. It has potential pharmacological effects like antioxidant, anxiolytic, analgesic, anti-inflammatory, antidiabetic, gastroprotective, anticancer, estrogenic, and antimicrobial activities. This study aimed to investigate the potential antidepressant properties of Anethole in a mouse model experiencing maternal separation stress while also examining its impact on oxidative stress and nitrite levels. The research involved the participation of 40 male NMRI mice, separated into five distinct groups to conduct the study. The control group was administered 1 ml/kg of normal saline, while the MS groups were given normal saline and Anethole at 10, 50, and 100 mg/kg doses. The study comprised various behavioural tests, including the open field test (OFT), forced swimming test (FST), and splash test, to assess the effects of Anethole on the mice. In addition to the behavioural tests, measurements were taken to evaluate the total antioxidant capacity (TAC), malondialdehyde (MDA), and nitrite levels in the hippocampus of the mice. According to the findings, maternal separation stress (MS) led to depressive-like conduct in mice, including a rise in immobility duration during the FST and a reduction in the duration of grooming behaviour in the splash test. Additionally, the results indicated that MS correlated with an increase in the levels of MDA and nitrite and a reduction in the TAC in the hippocampus. However, the administration of Anethole resulted in an increase in grooming activity time during the splash test and a decrease in immobility time during the FST. Anethole also exhibited antioxidant characteristics, as demonstrated by its ability to lower MDA and nitrite levels while increasing the TAC in the hippocampus. The results suggest that Anethole may have an antidepressant-like impact on mice separated from their mothers, likely partly due to its antioxidant properties in the hippocampus.

Interaction between HTR2A rs3125 and negative life events in suicide attempts among patients with major depressive disorder: a cross-sectional study.

BACKGROUND: Both genetic and environmental factors play crucial roles in the development of major depressive disorder (MDD) and suicide attempts (SA). However, the interaction between both items remains unknown. This study aims to explore the interactions between the genetic variants of the serotonin 2 A receptor (HTR2A) and the nitric oxide synthase 1 (NOS1) and environmental factors in patients who experience MDD and SA. METHODS: A total of 334 patients with MDD and a history of SA (MDD-SA) were recruited alongside 518 patients with MDD with no history of SA (MDD-NSA), and 716 healthy controls (HC). The demographic data and clinical characteristics were collected. Sequenom mass spectrometry was used to detect eight tag-single nucleotide polymorphisms (tagSNPs) in HTR2A (rs1328683, rs17068986, and rs3125) and NOS1 (rs1123425, rs2682826, rs3741476, rs527590, and rs7959232). Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene-environment interactions. RESULTS: Four tagSNPs (rs17068986, rs3125, rs527590, and rs7959232) exhibited significant differences between the three groups. However, these differences were not significant between the MDD-SA and MDD-NSA groups after Bonferroni correction. A logistic regression analysis revealed that negative life events (OR = 1.495, 95%CI: 1.071-2.087, P = 0.018), self-guilt (OR = 2.263, 95%CI: 1.515-3.379, P < 0.001), and negative cognition (OR = 2.252, 95%CI: 1.264-4.013, P = 0.006) were all independently associated with SA in patients with MDD. Furthermore, GMDR analysis indicated a significant interaction between HTR2A rs3125 and negative life events. Negative life events in conjunction with the HTR2A rs3125 CG + GG genotype were associated with a higher SA risk in patients with MDD when compared to the absence of negative life events in conjunction with the CC genotype (OR = 2.547, 95% CI: 1.264-5.131, P = 0.009). CONCLUSION: Several risk factors and a potential interaction between HTR2A rs3125 and negative life events were identified in patients with SA and MDD. The observed interaction likely modulates the risk of MDD and SA, shedding light on the pathogenesis of SA in patients with MDD.

Associations between breakfast skipping and outcomes in neuropsychiatric disorders, cognitive performance, and frailty: a Mendelian randomization study.

BACKGROUND: Prior studies have identified a correlation between breakfast skipping and a heightened risk of mental health issues. This investigation aimed to employ a Two-Sample Mendelian Randomization (MR) approach to explore the potential causal links between breakfast skipping and various psychiatric, neurological disorders, cognitive performance, and frailty. METHODS: Utilizing data from genome-wide association studies within European demographics, this research scrutinized the association between breakfast habits and several neuropsychiatric conditions and physical health outcomes, including Alzheimer's disease (AD), Attention Deficit Hyperactivity Disorder (ADHD), Bipolar Disorder (BD), Major Depressive Disorder (MDD), Narcolepsy, Insomnia, cognitive performance, and frailty. In this MR analysis, the Inverse Variance Weighted (IVW) method was primarily utilized for evaluation. Outcomes were reported as Odds Ratios (OR) and regression coefficients (ß), and underwent validation through False Discovery Rate (FDR) corrections, thereby offering a rigorous evaluation of the effects of breakfast habits on both mental and physical health dimensions. RESULTS: Findings demonstrate a significant causal link between skipping breakfast and an increased risk of ADHD (OR = 2.74, 95%CI: 1.54-4.88, PFDR = 0.003) and MDD (OR = 1.7, 95%CI: 1.22-2.37, PFDR = 0.005). Conversely, no substantial causal associations were identified between breakfast skipping and AD, BD, narcolepsy, or insomnia (PFDR > 0.05). Moreover, a notable causal relationship was established between skipping breakfast and a reduction in cognitive performance (ß = -0.16, 95%CI: -0.29-0.04, PFDR = 0.024) and an increase in frailty (ß = 0.29, 95%CI: 0.12-0.45, PFDR = 0.003). CONCLUSION: The MR analysis reveals that skipping breakfast is associated with an increased risk of ADHD, MDD, decreased cognitive performance, and greater frailty, while showing no associations were found with AD, BD, narcolepsy, or insomnia. These findings warrant further investigation into the underlying mechanisms and emphasize the importance of regular breakfast consumption for mental and physical well-being.

Do Patient's Interpersonal Problems Improve Following Metacognitive Therapy? A Systematic Review and Meta-Analysis.

Metacognitive therapy (MCT) aims to modify dysfunctional metacognitions that are thought to be universal determinants of emotional distress and psychological dysfunction more generally. MCT is an effective treatment for emotional distress symptoms, but less is known about its effect for other types of psychological problems. Interpersonal problems are common in psychological disorders and should be improved following psychotherapy. Therefore, we conducted a systematic review and meta-analysis of trials on the effects associated with MCT for interpersonal problems among adults with mental health disorders published until 15 November 2023 using PubMed, Cochrane Library and PsycNet. Trials with a minimum of 10 participants were included. A total of six studies based on five trials reported on the effectiveness of MCT for interpersonal problems and met our inclusion criteria. Two trials evaluated MCT for patients with major depressive disorders, two for patients with anxiety disorders and one for borderline personality disorder. Three of the trials were randomized controlled trials. Four of the trials reported follow-up data but varied in their time-points. The within-group effect size estimate from pretreatment to posttreatment across five trials was large (g = 0.865, 95% CI [0.512-1.218]). Our results indicate that MCT is an effective treatment for improving interpersonal problems in individuals with common mental disorders, even though the treatment is short and primarily concern improving mental regulation through modifying metacognitions. While this finding is in line with metacognitive theory, more trials evaluating personality and interpersonal functioning are needed to draw firm conclusions.

The Relationship Between CYP46A1 Polymorphism and Suicide Risk: A Preliminary Investigation.

Suicide is a global public health issue, with a particularly high incidence in individuals suffering from Major Depressive Disorder (MDD). The role of cholesterol in suicide risk remains controversial, prompting investigations into genetic markers that may be implicated. This study examines the association between CYP46A1 polymorphisms, specifically SNPs rs754203 and rs4900442, and suicide risk in a Mexican MDD patient cohort. Our study involved 188 unrelated suicide death victims, 126 MDD patients, and 144 non-suicidal controls. Genotypic and allelic frequencies were assessed using the Real Time-polymerase chain reaction method, and associations with suicide risk were evaluated using chi-square tests. The study revealed significant differences in allelic and genotypic frequencies in rs754203 SNP between suicide death and controls. The CYP46A1 rs754203 genotype G/G was significantly linked with suicide, and the G allele was associated with a higher risk of suicide (OR = 1.370, 95% CI = 1.002-1.873). However, we did not observe any significant differences in genotype distribution or allele frequencies of CYP46A1 rs4900442. Our study suggests that carriers of the CYP46A1 rs754203 G allele (A/G + G/G) may play a role in suicidal behavior, especially in males. Our findings support that the CYP46A1 gene may be involved in susceptibility to suicide, which has not been investigated previously. These results underscore the importance of further research in different populations to elucidate the genetic underpinnings of the role of CYP46A1 in suicide risk and to develop targeted interventions for at-risk populations.

Evolution of Depressive Symptoms Among Depression Subtypes of Clinical and Functional Variables in Primary Care in Chile.

OBJECTIVE: To compare the evolution of depressive symptoms among depressive subtypes based on clinical and functional variables in a sample of primary care in Chile. METHODS: A longitudinal study was conducted in the Maule Region of Chile, focusing on 8 primary care from February 2014 to September 2015. Clinical and functional variables, including Mini International Neuro-psychiatric Interview, Outcome Questionnaire interpersonal and social sub-scales, were applied in a latent class analysis. This analysis categorized 210 patients into 3 subtypes: complex depression (N = 100), recurrent depression (n = 96), and unique depression (n = 14). Complex depression, exhibited a higher probability of suicide attempts, interpersonal and social dysfunction, and association with adverse childhood experiences according the Brief Physical and Sexual Abuse Questionnaire. Patients were monitored over 1 year with the Hamilton scale. The Kruskal-Wallis, non-parametric test, followed by paired Mann-Whitney test evaluated difference in the severity of depressive symptoms between the groups. Additionally, data on mental health interventions were collected. RESULTS: Out of the 210 patients, 89% were women, with a median age of 50 (range 37-58), and 40.1% with only primary education. Sociodemographic characteristics not differ between groups. Significant differences in depressive symptom severity between the groups were found (X2 90.06, P < .001, Kruskal-Wallis test, η2 = 0.084). Post hoc analyses indicated higher depressive symptoms in complex depression compared to recurrent (Z = -9.501, P < .001) and unique (Z = -2.877, P = .004) depression, with no significant difference between recurrent and unique depression (Z = -1.58, P = .113). There were no differences in the number of medical and psychological controls between the groups. The patients with complex depression required greater modifications in the pharmacological prescriptions than those belonging to the other groups. CONCLUSION: These results provide additional evidence of a complex depression subtype in primary care in Chile associated with adverse childhood experiences, that had worse resolution of depressive symptoms. Contrary to expectations, patients belonging to this group did not receive further medical and psychological interventions, probably due to a lack of specific clinical recommendations.

Olfactory genes affect major depression in highly educated, emotionally stable, lean women: a bridge between animal models and precision medicine.

Most current approaches to establish subgroups of depressed patients for precision medicine aim to rely on biomarkers that require highly specialized assessment. Our present aim was to stratify participants of the UK Biobank cohort based on three readily measurable common independent risk factors, and to investigate depression genomics in each group to discover common and separate biological etiology. Two-step cluster analysis was run separately in males (n = 149,879) and females (n = 174,572), with neuroticism (a tendency to experience negative emotions), body fat percentage, and years spent in education as input variables. Genome-wide association analyses were implemented within each of the resulting clusters, for the lifetime occurrence of either a depressive episode or recurrent depressive disorder as the outcome. Variant-based, gene-based, gene set-based, and tissue-specific gene expression test were applied. Phenotypically distinct clusters with high genetic intercorrelations in depression genomics were found. A two-cluster solution was the best model in each sex with some differences including the less important role of neuroticism in males. In females, in case of a protective pattern of low neuroticism, low body fat percentage, and high level of education, depression was associated with pathways related to olfactory function. While also in females but in a risk pattern of high neuroticism, high body fat percentage, and less years spent in education, depression showed association with complement system genes. Our results, on one hand, indicate that alteration of olfactory pathways, that can be paralleled to the well-known rodent depression models of olfactory bulbectomy, might be a novel target towards precision psychiatry in females with less other risk factors for depression. On the other hand, our results in multi-risk females may provide a special case of immunometabolic depression.

Impact of COVID-19 first wave on the mental health of healthcare workers in a Front-Line Spanish Tertiary Hospital: lessons learned.

Healthcare workers (HCWs) were at high risk of experiencing psychological distress during COVID-19 pandemic. The objective of this study was to evaluate the impact on HCWs' mental health in a Spanish hospital. Cross-sectional study of HCW, active between May and June 2020. A web-based survey assessed probable current mental disorders (major depressive disorder [PHQ-8 ≥ 10], generalized anxiety disorder [GAD-7 ≥ 10], panic attacks, post-traumatic stress disorder [PTSD; PLC-5 ≥ 7], or substance use disorder [CAGE-AID ≥ 2]). The Sheehan Disability Scale (SDS) was used to assess severe impairment and items taken from the modified self-report version of the Columbia Suicide Severity Rating Scale (C-SSRS) assessed suicidal thoughts and behaviors. A total of 870 HCWs completed the survey. Most frequent probable mental disorders were major depressive disorder (33.6%), generalized anxiety disorder (25.5%), panic attacks (26.9%), PTSD (27.2%), and substance use disorder (5.0%). Being female, having aged 18-29 years, being an auxiliary nurse, direct exposure to COVID-19-infected patients, and pre-pandemic lifetime mental disorders were positively associated with mental issues. Hospital HCWs presented a high prevalence of symptoms of mental disorders, especially depression, PTSD, panic attacks, and anxiety. Younger individuals and those with lifetime mental disorders have been more vulnerable to experiencing them.

Gender Differences in the Prevalence and Clinical Correlates of Metabolic Syndrome in First-Episode and Drug-Naïve Patients With Major Depressive Disorder.

OBJECTIVE: Major depressive disorder (MDD) is a severe psychiatric symptom worldwide, and the coexistence of MDD with metabolic syndrome (MetS) is common in clinical practice. However, gender differences in comorbid MetS in first-episode and drug-naïve (FEDN) MDD patients have not been reported. Here, we explored potential gender differences in the prevalence and clinical correlates of comorbid MetS in FEDN MDD patients. METHODS: A cross-sectional study of 1718 FEDN MDD patients was conducted. Demographic and clinical data were collected. The Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale, and Positive and Negative Syndrome Scale positive subscale were used to evaluate depression, anxiety, and psychotic symptoms, respectively. RESULTS: The prevalence of MetS was 1.645-fold higher in female MDD patients (38.50%) than in male patients (26.53%). Patients with MetS had higher HAMD score, Hamilton Anxiety Scale score, and Positive and Negative Syndrome Scale positive subscale score than patients without MetS (p values < .001). Furthermore, suicide attempts (male: odds ratio [OR] = 1.706, p = .034; female: OR = 1.639, p = .004) and HAMD score (male: OR = 1.251, p < .001; female: OR = 1.148, p < .001) were independently associated with MetS in male and female patients, whereas age of onset was independently associated with MetS only in female patients (OR = 1.744, p = .047). CONCLUSIONS: Our findings suggest significant gender differences in the prevalence and clinical correlates of comorbid MetS in FEDN MDD patients. Clinical variables (suicide attempts and HAMD scores) may be independently associated with MetS in MDD patients.

Association of major depression, schizophrenia and bipolar disorder with thyroid cancer: a bidirectional two-sample mendelian randomized study.

BACKGROUND: Major depressive disease (MDD), schizophrenia (SCZ), and bipolar disorder (BD) are common psychiatric disorders, and their relationship with thyroid cancer has been of great interest. This study aimed to investigate the potential causal effects of MDD, SCZ, BD, and thyroid cancer. METHODS: We used publicly available summary statistics from large-scale genome-wide association studies to select genetic variant loci associated with MDD, SCZ, BD, and thyroid cancer as instrumental variables (IVs), which were quality controlled and clustered. Additionally, we used three Mendelian randomization (MR) methods, inverse variance weighted (IVW), MR-Egger regression and weighted median estimator (WME) methods, to estimate the bidirectional causal relationship between psychiatric disorders and thyroid cancer. In addition, we performed heterogeneity and multivariate tests to verify the validity of the IVs. RESULTS: We used two-sample bidirectional MR analysis to determine whether there was a positive causal association between MDD and thyroid cancer risk. The results of the IVW analysis (OR = 3.956 95% CI = 1.177-13.299; P = 0.026) and the WME method (OR = 5.563 95% CI = 0.998-31.008; P = 0.050) confirmed that MDD may increase the risk of thyroid cancer. Additionally, our study revealed a correlation between genetic susceptibility to SCZ and thyroid cancer (OR = 1.532 95% CI = 1.123-2.088; P = 0.007). The results of the WME method analysis based on the median estimate (OR = 1.599 95% CI = 1.014-2.521; P = 0.043) also suggested that SCZ may increase the risk of thyroid cancer. Furthermore, our study did not find a causal relationship between BD and thyroid cancer incidence. In addition, the results of reverse MR analysis showed no significant causal relationships between thyroid cancer and MDD, SCZ, or BD (P > 0.05), ruling out the possibility of reverse causality. CONCLUSIONS: This MR method analysis provides new evidence that MDD and SCZ may be positively associated with thyroid cancer risk while also revealing a correlation between BD and thyroid cancer. These results may have important implications for public health policy and clinical practice. Future studies will help elucidate the biological mechanisms of these associations and potential confounders.

Real-world evidence from a retrospective study on suicide during depression: clinical characteristics, treatment patterns and disease burden.

BACKGROUND: Suicide stands as both a primary symptom and the direst outcome of major depressive disorder (MDD). The scarcity of effective treatment strategies makes managing MDD patients with suicide especially challenging. Hence, it is crucial to investigate disease characteristics and efficacious therapeutic strategies for these patients, drawing insights from disease databases and real-world data. METHODS: In this retrospective study, MDD patients hospitalized between January 2013 and December 2020 were investigated using Electronic Health Records (EHR) data from Beijing Anding Hospital. The study enrolled 4138 MDD patients with suicidal ideation or behavior (MDS) and 3848 without (MDNS). Demographic data, clinical attributes, treatment approaches, disease burden, and re-hospitalization within one year of discharge were extracted and compared. RESULTS: Patients in the MDS group were predominantly younger and female, exhibiting a higher prevalence of alcohol consumption, experiencing frequent life stress events, and having an earlier onset age. Re-hospitalizations within six months post-discharge in the MDS group were significantly higher than in the MDNS group (11.36% vs. 8.91%, p < 0.001). Moreover, a more considerable fraction of MDS patients underwent combined electroconvulsive therapy treatment (56.72% vs. 43.71%, p < 0.001). Approximately 38% of patients in both groups were prescribed two or more therapeutic regimes, and over 90% used antidepressants, either alone or combined. Selective serotonin reuptake inhibitors (SSRIs) were the predominant choice in both groups. Furthermore, antidepressants were often prescribed with antipsychotics or mood stabilizers. When medication alterations were necessary, the favoured options involved combination with antipsychotics or transitioning to alternative antidepressants. Yet, in the MDS group, following these initial modifications, the addition of mood stabilizers tended to be the more prioritized alternative. CONCLUSIONS: MDD patients with suicidal ideation or behaviour displayed distinctive demographic and clinical features. They exhibited intricate treatment patterns, a pronounced burden of illness, and an increased likelihood of relapse.

Study on exosomes for identifying bipolar disorder in early stage: A cross-sectional and validation study protocol.

BACKGROUND: The difficulty is remained to accurately distinguish bipolar disorder (BD) from major depressive disorder (MDD) in early stage, with a delayed diagnosis for 5-10 years. BD patients are often treated with antidepressants systematically due to being diagnosed with MDD, affecting the disease course and clinical outcomes. The current study aims to explore the role of plasma exosomes as biomarker to distinguish BD from MDD in early stage. METHODS: Two stages are included. The first stage is a cross-sectional study, comparing the concentrations of plasma exosome microRNA and related proteins among BD group, MDD group, and healthy controls (HC) group (n = 40 respectively), to identify target biomarkers preliminarily. The "Latent Class Analysis" and "Receiver Operating Characteristic" analysis will be performed to determine the optimal concentration range for each biomarker. The second stage is to validate target markers in subjects, coming from an ongoing study focusing on patients with a first depressive episode. All target biomarkers will be test in plasma samples reserved at the initial stage to detect whether the diagnosis indicated by biomarker level is consistent with the diagnosis by DSM-5. Furthermore, the correlation between specific biomarkers and the manic episode, suicidal ideation, and adverse reactions will also be observed. DISCUSSION: Exosome-derived microRNA and related proteins have potential in serving as a good medium for exploring mental disorders because it can pass through the blood-brain barrier bidirectionally and convey a large amount of information stably. Improving the early diagnosis of BD would help implement appropriate intervention strategy as early as possible and significantly reduce the burden of disease.

Childhood neglect, the neglected trauma. A systematic review and meta-analysis of its prevalence in psychiatric disorders.

Traumatic events increase risk of mental illnesses, but childhood neglect prevalence in psychiatric disorders is understudied. This systematic review and meta-analysis assessed neglect prevalence, including emotional neglect (EN) and physical neglect (PN), among adults with psychiatric disorders. We conducted a systematic search and meta-analysis in 122 studies assessing different psychiatric disorders. Prevalence was 46.6% (95%CI[34.5-59.0]) for unspecified neglect (Ne), 43.1% (95%CI[39.0-47.4]) for EN, and 34.8% (95%CI[30.6-39.2]) for PN. Although a moderating effect of the psychiatric diagnostic category was not confirmed, some clinical diagnoses had significantly lower prevalence rates than others. Patients with bipolar disorder and major depressive disorder showed lower prevalence rates of EN and PN, whereas lower prevalence was found in psychotic disorders and eating disorders for PN only. Neglect assessment was a significant moderator for Ne and PN. No moderating effect of age and sex on neglect prevalence was found. Heterogeneity levels within and between psychiatric diagnostic categories remained high. This is the first meta-analysis examining diverse types of neglect prevalence considering different psychiatric diagnoses. Our results explore the prevalence of childhood neglect and its subtypes among adults with psychiatric disorders, contributing to understanding the nuanced interplay between neglect and specific psychiatric conditions, and guiding interventions for affected individuals.

Characterizing Major Depressive Disorder (MDD) using alpha-band activity in resting-state electroencephalogram (EEG) combined with MATRICS Consensus Cognitive Battery (MCCB).

BACKGROUND: The diagnosis of major depressive disorder (MDD) is commonly based on the subjective evaluation by experienced psychiatrists using clinical scales. Hence, it is particularly important to find more objective biomarkers to aid in diagnosis and further treatment. Alpha-band activity (7-13 Hz) is the most prominent component in resting electroencephalogram (EEG), which is also thought to be a potential biomarker. Recent studies have shown the existence of multiple sub-oscillations within the alpha band, with distinct neural underpinnings. However, the specific contribution of these alpha sub-oscillations to the diagnosis and treatment of MDD remains unclear. METHODS: In this study, we recorded the resting-state EEG from MDD and HC populations in both open and closed-eye state conditions. We also assessed cognitive processing using the MATRICS Consensus Cognitive Battery (MCCB). RESULTS: We found that the MDD group showed significantly higher power in the high alpha range (10.5-11.5 Hz) and lower power in the low alpha range (7-8.5 Hz) compared to the HC group. Notably, high alpha power in the MDD group is negatively correlated with working memory performance in MCCB, whereas no such correlation was found in the HC group. Furthermore, using five established classification algorithms, we discovered that combining alpha oscillations with MCCB scores as features yielded the highest classification accuracy compared to using EEG or MCCB scores alone. CONCLUSIONS: Our results demonstrate the potential of sub-oscillations within the alpha frequency band as a potential distinct biomarker. When combined with psychological scales, they may provide guidance relevant for the diagnosis and treatment of MDD.

Spectral signatures of psilocybin, lysergic acid diethylamide (LSD) and ketamine in healthy volunteers and persons with major depressive disorder and treatment-resistant depression: A systematic review.

BACKGROUND: Electrophysiologic measures provide an opportunity to inform mechanistic models and possibly biomarker prediction of response. Serotonergic psychedelics (SPs) (i.e., psilocybin, lysergic acid diethylamide (LSD)) and ketamine represent new investigational and established treatments in mood disorders respectively. There is a need to better characterize the mechanism of action of these agents. METHODS: We conducted a systematic review investigating the spectral signatures of psilocybin, LSD, and ketamine in persons with major depressive disorder (MDD), treatment-resistant depression (TRD), and healthy controls. RESULTS: Ketamine and SPs are associated with increased theta power in persons with depression. Ketamine and SPs are also associated with decreased spectral power in the alpha, beta and delta bands in healthy controls and persons with depression. When administered with SPs, theta power was increased in persons with MDD when administered with SPs. Ketamine is associated with increased gamma band power in both healthy controls and persons with MDD. LIMITATIONS: The studies included in our review were heterogeneous in their patient population, exposure, dosing of treatment and devices used to evaluate EEG and MEG signatures. Our results were extracted entirely from persons who were either healthy volunteers or persons with MDD or TRD. CONCLUSIONS: Extant literature evaluating EEG and MEG spectral signatures indicate that ketamine and SPs have reproducible effects in keeping with disease models of network connectivity. Future research vistas should evaluate whether observed spectral signatures can guide further discovery of therapeutics within the psychedelic and dissociative classes of agents, and its prediction capability in persons treated for depression.

Sleep rebound leads to marked recovery of prolonged sleep deprivation-induced adversities in the stress response and hippocampal neuroplasticity of male rats.

BACKGROUND: Sleep disturbances are not only frequent symptoms, but also risk factors for major depressive disorder. We previously reported that depressed patients who experienced "Hypersomnia" showed a higher and more rapid response rate under paroxetine treatment, but the underlying mechanism remains unclear. The present study was conducted to clarify the beneficial effects of sleep rebound through an experimental "Hypersomnia" rat model on glucocorticoid and hippocampal neuroplasticity associated with antidepressive potency. METHODS: Thirty-four male Sprague-Dawley rats were subjected to sham treatment, 72-h sleep deprivation, or sleep deprivation and subsequent follow-up for one week. Approximately half of the animals were sacrificed to evaluate adrenal weight, plasma corticosterone level, hippocampal content of mRNA isoforms, and protein of the brain-derived neurotrophic factor (Bdnf) gene. In the other half of the rats, Ki-67- and doublecortin (DCX)-positive cells in the hippocampus were counted via immunostaining to quantify adult neurogenesis. RESULTS: Prolonged sleep deprivation led to adrenal hypertrophy and an increase in the plasma corticosterone level, which had returned to normal after one week follow-up. Of note, sleep deprivation-induced decreases in hippocampal Bdnf transcripts containing exons II, IV, VI, and IX and BDNF protein levels, Ki-67-(+)-proliferating cells, and DCX-(+)-newly-born neurons were not merely reversed, but overshot their normal levels with sleep rebound. LIMITATIONS: The present study did not record electroencephalogram or assess behavioral changes of the sleep-deprived rats. CONCLUSIONS: The present study demonstrated that prolonged sleep deprivation-induced adversities are reversed or recovered by sleep rebound, which supports "Hypersomnia" in depressed patients as having a beneficial pharmacological effect.

Digital mental health interventions as stand-alone vs. augmented treatment as usual.

BACKGROUND: Smartphone-based digital mental health interventions (DMHI) have been described as a purported solution to meet growing healthcare demands and lack of providers, but studies often don't account for whether patients are concurrently in another treatment modality. METHODS: This preregistered quasi-experimental intent-to-treat study with 354 patients enrolled in a therapist-supported DMHI examined the treatment effectiveness of the Meru Health Program (MHP) as a stand-alone treatment as compared to the MHP in combination with any other form of treatment, including (1) in-person therapy, (2) psychotropic medication use, and (3) in-person therapy and psychotropic medication use. RESULTS: Patients with higher baseline depressive and anxiety symptoms were more likely to self-select into multiple forms of treatment, an effect driven by patients in the MHP as adjunctive treatment to in-person therapy and psychotropic medication. Patients in combined treatments had significantly higher depressive and anxiety symptoms across treatment, but all treatment groups had similar decreasing depressive and anxiety symptom trajectories. Exploratory analyses revealed differential treatment outcomes across treatment combinations. Patients in the MHP in combination with another treatment had higher rates of major depressive episodes, psychiatric hospitalization, and attempted death by suicide at baseline. CONCLUSIONS: Patients with higher depressive and anxiety symptoms tend to self-select into using DMHI in addition to more traditional types of treatment, rather than as a stand-alone intervention, and have more severe clinical characteristics. The use the MHP alone was associated with improvement at a similar rate to those with higher baseline symptoms who are in traditional treatments and use MHP adjunctively.

The Formation and Function of the VTA Dopamine System.

The midbrain dopamine system is a sophisticated hub that integrates diverse inputs to control multiple physiological functions, including locomotion, motivation, cognition, reward, as well as maternal and reproductive behaviors. Dopamine is a neurotransmitter that binds to G-protein-coupled receptors. Dopamine also works together with other neurotransmitters and various neuropeptides to maintain the balance of synaptic functions. The dysfunction of the dopamine system leads to several conditions, including Parkinson's disease, Huntington's disease, major depression, schizophrenia, and drug addiction. The ventral tegmental area (VTA) has been identified as an important relay nucleus that modulates homeostatic plasticity in the midbrain dopamine system. Due to the complexity of synaptic transmissions and input-output connections in the VTA, the structure and function of this crucial brain region are still not fully understood. In this review article, we mainly focus on the cell types, neurotransmitters, neuropeptides, ion channels, receptors, and neural circuits of the VTA dopamine system, with the hope of obtaining new insight into the formation and function of this vital brain region.

Individuals vary in their overt attention preference for positive images consistently across time and stimulus types.

What humans look at strongly determines what they see. We show that individual differences in the tendency to look at positive stimuli are stable across time and across contents, establishing gaze positivity preference as a perceptual trait that determines the amount of positively valence stimuli individuals select for visual processing. Furthermore, we show that patients with major depressive disorder exhibit consistently low positivity preference before treatment. In a subset of patients, we also assessed the positivity preference after two months of treatment in which positivity gaze preference increased to levels similar to healthy individuals. We discuss the possible practical diagnostic applications of these findings, as well as how this general gaze-related trait may influence other behavioral and psychological aspects.

The relationship between serum resolvin D1, NLRP3, cytokine levels, and adolescents with first-episode medication-naïve major depressive disorder.

BACKGROUND: Inflammation has become a critical pathological mechanism of Major Depressive Disorder (MDD). NLRP3 is a critical inflammatory pathway to maintain the immune balance. Recently, preclinical evidence showed that Resolvin D1 might potentially offer a new option for antidepressant treatment due to its protective effects through the inhibition of neuroinflammation. However, whether they have clinical value in the diagnosis and treatment evaluation of adolescent depression was unclear. METHODS: Forty-eight untreated first-episode adolescent patients with moderate to severe major depressive disorder, as well as 30 healthy adolescents (HCs, age and gender-matched), were enrolled for this study. Their ages ranged from 13 to 18 (15.75 ± 1.36) years. The patients were treated with fluoxetine for 6-8 weeks. HDRS-17 was used to evaluate the severity of depressive symptoms. Venous blood samples were collected at baseline for the two groups and at the time-point of post-antidepressant treatment for the patients. Serum concentrations of RvD1, NLRP3, IL-1ß, IL-18, and IL-4 were measured by enzyme-linked immunosorbent assays (ELISA) pre- and post-fluoxetine treatment. RESULTS: Serum levels of RvD1 and anti-inflammatory cytokine IL-4 were significantly elevated in adolescents with MDD compared to healthy adolescents, but no significant difference in NLRP3, IL-1ß, and IL-18 between the two groups. Meanwhile, RvD1 (positively) and IL-4 (negatively) were correlated with the severity of symptoms (HDRS-17 scores) after adjusting age, gender, and BMI. Interestingly, fluoxetine treatment significantly reduced the serum levels of RvD1, NLRP3, IL-1ß, and IL-18 in MDD adolescents but increased the levels of IL-4 relative to baseline. Furthermore, we observed that serum levels of RvD1 might be an excellent distinguishing indicator for depression and healthy adolescents. CONCLUSIONS: Our study is the first to compare RvD1 and NLRP3 between adolescent MDD and HCs. Our findings of reactive increase of RvD1 in adolescent MDD comprised a novel and critical contribution. Our results showed the presence of inflammation resolution unbalanced in adolescents with MDD and indicated that RvD1 might be an ideal biomarker for diagnosing and treating adolescent MDD.