Comprehensive Sex-Stratified Genetic Analysis of 28 Blood Biomarkers and Depression Reveals a Significant Association between Depression and Low Levels of Total Protein in Females.

Introduction: Major depression (MD) is more common amongst women than men, and MD episodes have been associated with fluctuations in reproductive hormones amongst women. To investigate biological underpinnings of heterogeneity in MD, the associations between depression, stratified by sex and including perinatal depression (PND), and blood biomarkers, using UK Biobank (UKB) data, were evaluated, and extended to include the association of depression with biomarker polygenic scores (PGS), generated as proxy for each biomarker. Method: Using female (N = 39,761) and male (N = 38,821) UKB participants, lifetime MD and PND were tested for association with 28 blood biomarkers. A GWAS was conducted for each biomarker and genetic correlations with depression subgroups were estimated. Using independent data from the Australian Genetics of Depression Study, PGS were constructed for each biomarker, and tested for association with depression status (n [female cases/controls] = 9,006/6,442; n [male cases/controls] = 3,106/6,222). Regions of significant local genetic correlation between depression subgroups and biomarkers highlighted by the PGS analysis were identified. Results: Depression in females was significantly associated with levels of twelve biomarkers, including total protein (OR = 0.90, CI = [0.86, 0.94], p = 3.9 × 10-6) and vitamin D (OR = 0.94, CI = [0.90, 0.97], p = 2.6 × 10-4), and PND with five biomarker levels, also including total protein (OR = 0.88, CI = [0.81, 0.96], p = 4.7 × 10-3). Depression in males was significantly associated with levels of eleven biomarkers. In the independent Australian Genetics of Depression Study, PGS analysis found significant associations for female depression and PND with total protein (female depression: OR = 0.93, CI = [0.88, 0.98], p = 3.6 × 10-3; PND: OR = 0.91, CI = [0.86, 0.96], p = 1.1 × 10-3), as well as with vitamin D (female depression: OR = 0.93, CI = [0.89, 0.97], p = 2.0 × 10-3; PND: OR = 0.92, CI = [0.87, 0.97], p = 1.4 × 10-3). The male depression sample did not report any significant results, and the point estimate of total protein (OR = 0.98, CI = [0.92-1.04], p = 4.7 × 10-1) did not indicate any association. Local genetic correlation analysis highlighted significant genetic correlation between PND and total protein, located in 5q13.3 (rG = 0.68, CI = [0.33, 1.0], p = 3.6 × 10-4). Discussion and Conclusion: Multiple lines of evidence from genetic analysis highlight an association between total serum protein levels and depression in females. Further research involving prospective measurement of total protein and depressive symptoms is warranted.

The impact of menopause on antidepressant response: an explorative analysis from a real-world study.

This study endeavors to deepen our understanding of the subject matter by exploring, within a real-world sample, the impact of menopausal status on the antidepressant treatments response. The whole sample included a total of 447 patients, 156 male and 291 female, 110 pre-menopause and 181 post-menopause. In our sample post-menopause women showed a worse response to antidepressants than pre-menopause women (p = 0.006), and this difference seems to be unrelated to age or brain aging.

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.

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.

Changes in the ability to correctly identify schizophrenia and depression: results from general population surveys in Germany over 30 years.

PURPOSE: This study aims to examine time trends in the ability to correctly identify schizophrenia and major depression within the German general population from 1990 to 2020, as an indicator of changing mental health literacy (MHL). Additionally, we investigated shifts in the use of stigmatizing language. METHODS: Our analysis is based on four waves of representative population surveys in Germany in 1990/1993 (West Germany: N = 2044, East Germany: N = 1563), 2001 (N = 5025), 2011 (N = 2455), and 2020 (N = 3042) using identical methodology. Respondents were presented with an unlabelled case vignette describing a person who exhibited symptoms of either schizophrenia or major depression. Participants were then asked to name the problem described in the vignette using an open-ended question. RESULTS: From 1990/1993 to 2020, correct identification of schizophrenia increased from 18% to 34% and from 27% to 46% for major depression. However, derogatory labels remained constant throughout all survey waves, particularly for schizophrenia (19% in 1990/1993 and 18% in 2020). For depression, more trivializing and potentially devaluing statements were recorded. CONCLUSION: Despite the increasing use of psychiatric terminology among the general population, the persistence of derogatory labels suggests that improved MHL, reflected in higher recognition rates, may not automatically translate into a reduction in stigmatizing language. With depression, a normalization and trivialization of a severe illness could pose new challenges to people with major depression. Dedicated efforts to combat the stigma of severe mental illness are still needed.

One size does not fit all: notable individual variation in brain activity correlates of antidepressant treatment response.

Introduction: To date, no robust electroencephalography (EEG) markers of antidepressant treatment response have been identified. Variable findings may arise from the use of group analyses, which neglect individual variation. Using a combination of group and single-participant analyses, we explored individual variability in EEG characteristics of treatment response. Methods: Resting-state EEG data and Montgomery-Åsberg Depression Rating Scale (MADRS) symptom scores were collected from 43 patients with depression before, at 1 and 12 weeks of pharmacotherapy. Partial least squares (PLS) was used to: 1) identify group differences in EEG connectivity (weighted phase lag index) and complexity (multiscale entropy) between eventual medication responders and non-responders, and 2) determine whether group patterns could be identified in individual patients. Results: Responders showed decreased alpha and increased beta connectivity, and early, widespread decreases in complexity over treatment. Non-responders showed an opposite connectivity pattern, and later, spatially confined decreases in complexity. Thus, as in previous studies, our group analyses identified significant differences between groups of patients with different treatment outcomes. These group-level EEG characteristics were only identified in ~40-60% of individual patients, as assessed quantitatively by correlating the spatiotemporal brain patterns between groups and individual results, and by independent raters through visualization. Discussion: Our single-participant analyses suggest that substantial individual variation exists, and needs to be considered when investigating characteristics of antidepressant treatment response for potential clinical applicability. Clinical trial registration: https://clinicaltrials.gov, identifier NCT00519428.

Computerized cognitive control training to reduce rumination in major depression: A randomized controlled trial.

OBJECTIVE: Rumination is a major risk factor for the onset and recurrence of depressive episodes and has been associated with deficits in updating working memory content. This randomized controlled trial examines whether training updating-specific cognitive control processes reduces daily ruminative thoughts in clinically depressed individuals. METHODS: Sixty-five individuals with a current major depressive episode were randomized to 10 sessions of either cognitive control training (N = 31) or placebo training (N = 34). The frequency and negativity of individuals' daily ruminative thoughts were assessed for seven days before training, after training, and at a 3-month follow-up using experience sampling methodology. Secondary outcomes were depressive symptoms, depressed mood, and level of disability. RESULTS: Cognitive control training led to stronger improvements in the trained task than placebo training. However, cognitive control training did not lead to greater reductions in the frequency or negativity of daily ruminative thoughts than placebo training. There were no training-specific effects on participants' depressive symptoms or level of disability. CONCLUSIONS: The robustness of the present null-findings, combined with the methodological strengths of the study, suggest that training currently depressed individuals to update emotional content in working memory does not affect the frequency or negativity of their daily ruminative thoughts.

Human olfactory neural progenitor cells reveal differences in IL-6, IL-8, thrombospondin-1, and MCP-1 in major depression disorder and borderline personality disorder.

Background: Discovering biological markers is essential for understanding and treating mental disorders. Despite the limitations of current non-invasive methods, neural progenitor cells from the olfactory epithelium (hNPCs-OE) have been emphasized as potential biomarker sources. This study measured soluble factors in these cells in Major Depressive Disorder (MDD), Borderline Personality Disorder (BPD), and healthy controls (HC). Methods: We assessed thirty-five participants divided into MDD (n=14), BPD (n=14), and HC (n=7). MDD was assessed using the Hamilton Depression Rating Scale. BPD was evaluated using the DSM-5 criteria and the Structured Clinical Interview for Personality Disorders. We isolated hNPCs-OE, collected intracellular proteins and conditioned medium, and quantified markers and soluble factors, including Interleukin-6, interleukin-8, and others. Analysis was conducted using one-way ANOVA or Kruskal-Wallis test and linear regression. Results: We found that hNPCs-OE of MDD and BPD decreased Sox2 and laminin receptor-67 kDa levels. MASH-1 decreased in BPD, while tubulin beta-III decreased in MDD compared to controls and BPD. Also, we found significant differences in IL-6, IL-8, MCP-1, and thrombospondin-1 levels between controls and MDD, or BPD, but not between MDD and BPD. Conclusions: Altered protein markers are evident in the nhNPCs-OE in MDD and BPD patients. These cells also secrete higher concentrations of inflammatory cytokines than HC cells. The results suggest the potential utility of hNPCs-OE as an in vitro model for researching biological protein markers in psychiatric disorders. However, more extensive validation studies are needed to confirm their effectiveness and specificity in neuropsychiatric disorders.

B cells and the stressed brain: emerging evidence of neuroimmune interactions in the context of psychosocial stress and major depression.

The immune system has emerged as a key regulator of central nervous system (CNS) function in health and in disease. Importantly, improved understanding of immune contributions to mood disorders has provided novel opportunities for the treatment of debilitating stress-related mental health conditions such as major depressive disorder (MDD). Yet, the impact to, and involvement of, B lymphocytes in the response to stress is not well-understood, leaving a fundamental gap in our knowledge underlying the immune theory of depression. Several emerging clinical and preclinical findings highlight pronounced consequences for B cells in stress and MDD and may indicate key roles for B cells in modulating mood. This review will describe the clinical and foundational observations implicating B cell-psychological stress interactions, discuss potential mechanisms by which B cells may impact brain function in the context of stress and mood disorders, describe research tools that support the investigation of their neurobiological impacts, and highlight remaining research questions. The goal here is for this discussion to illuminate both the scope and limitations of our current understanding regarding the role of B cells, stress, mood, and depression.

Vitamin D: An Overlooked Parameter in Studies of Depression Using Optic Coherence Tomography.

Introduction: The relationship between depression and inflammation and the resulting vascular/neuronal damage have been demonstrated in recent studies. In this study we aimed to investigate inflammation and the possible degeneration that can be caused by depression and accompanying vitamin D deficiency using a non-invasive imaging method of optical coherence tomography (OCT). Methods: Twenty-four healthy controls and 42 drug free major depressive patients matched for age, sex and eye measurements were compared in terms of vitamin D, C Reactive Protein (CRP) and OCT parameters. The Hamilton Depression Rating Scale (HAM-D), The Clinical Global Impressions Scale (CGI) and Global Assessment of Functioning Scale (GAF) were used to assess disease severity. Results: CRP level and choroidal thickness in the major depression group were significantly higher than the healthy controls. Vitamin D level and the ganglion cell layer (GCL) volume was significantly lower in the major depression group compared to healthy controls. Positive correlation was found between HAM-D and CRP in major depressive patients; a negative correlation was found between current attack duration and GCL volume. CGI was positively correlated with CRP and HAM-D. GAS was negatively correlated with CRP and HAM-D. Conclusion: It has been shown that major depression might be an inflammatory disorder with possible degenerative processes observed with OCT and CRP measurements. But longitudinal follow up studies are needed to demonstrate a cause and effect relationship.

Causal associations between severe mental illness and sepsis: a Mendelian randomization study.

Objective: SMI (severe mental illness) has been identified as a risk factor for sepsis in observational studies; however, the causal association between them has yet to be firmly established. We conducted MR (mendelian randomization) to unveil the causal relationship between SMI and sepsis as well as sepsis mortality. Methods: GWAS (Genome-wide association) data for major depression and schizophrenia were selected as exposure. GWAS data for sepsis and sepsis mortality were selected as outcome. Genetic variants significantly associated with the exposure (P value<1x10-6) were selected as instruments. We primarily employed the IVW (inverse-variance weighted) method for analysis. Furthermore, we employed Cochrane's Q test to assess heterogeneity and the MR-Egger intercept test to identify horizontal pleiotropy. Results: We selected 108 SNPs (single nucleotide polymorphism) used to predict major depression and 260 SNPs that predicted schizophrenia. Genetically predicted major depression was suggestively linked to a higher sepsis risk (OR=1.13, 95%CI 1.02-1.26, P=0.023). In contrast, MR analysis did not find an association between schizophrenia and sepsis risk (OR=1.00, 95%CI 0.97-1.04, P=0.811). Furthermore, no significant causal evidence was found for genetically predicted SMI in sepsis mortality. Moreover, no heterogeneity and horizontal pleiotropy were detected. Conclusion: Our research revealed a suggestive association between genetically predicted major depression and an elevated risk of sepsis in individuals of European ancestry. This finding can serve as a reminder for clinicians to consider the possibility of subsequent infection and sepsis in depressive patients, which may help reduce the incidence of sepsis in individuals with depression.

Fronto-striato network function is reduced in major depressive disorder.

Introduction: Major depressive disorder (MDD) is a major cause of poor quality of life and disability and is highly prevalent worldwide. Various pathological mechanisms are implicated in MDD, including the reward system. The human brain is equipped with a reward system that is involved in aspects such as motivation, pleasure, and learning. Several studies including a meta-analysis have been reported on the reward system network and MDD. However, to our knowledge, no studies have examined the relationship between the reward system network of drug-naïve, first-episode MDD patients and the detailed symptoms of MDD or age. The fronto-striato network (FSN) is closely related to the reward system network. The present study primarily aimed to elucidate this point. Methods: A total of 89 drug-naïve first-episode MDD patients and 82 healthy controls (HCs) patients were enrolled in the study. The correlation between the FSN and age and the interaction between age and illness in the FSN were investigated in 75 patients in the MDD group and 79 patients in the HC group with available information on the FSN and age. In addition, the association between the FSN and the total scores on the 17-item Hamilton Rating Scale for Depression (HAMD-17) and scores in each symptom item was analyzed in 76 MDD subjects with information on the FSN and HAMD-17. The significance of each result was evaluated according to a p-value of <0.05. Results: Age was inversely correlated with the FSN (p=2.14e-11) in the HC group but not in the MDD group (p=0.79). FSN varied with the presence of MDD and with age, particularly showing an interaction with MDD and age (p=1.04e-08). Specifically, age and the presence or absence of MDD each affected FSN, but the effect of age on FSN changed in the presence of depression. FSN did not correlate with total HAMD-17 scores or scores in each item. Discussion: The reward system may be dysfunctional in patients with MDD. In addition, the effect could be greater in younger patients. Meanwhile, there is no correlation between the function of the reward system and the severity of MDD or the severity of each symptom. Thus, the reward system network may be an important biological marker of MDD, although careful consideration should be given to age and its association with the severity of the disorder. Conclusion: The reward system function is decreased in MDD patients, and this decrease may be more pronounced in younger patients, although further research is still needed.

In major dysmood disorder, physiosomatic, chronic fatigue and fibromyalgia symptoms are driven by immune activation and increased immune-associated neurotoxicity.

Major depressive disorder (MDD) is accompanied by activated neuro-immune pathways, increased physiosomatic and chronic fatigue-fibromyalgia (FF) symptoms. The most severe MDD phenotype, namely major dysmood disorder (MDMD), is associated with adverse childhood experiences (ACEs) and negative life events (NLEs) which induce cytokines/chemokines/growth factors. To delineate the impact of ACE + NLEs on physiosomatic and FF symptoms in first episode (FE)-MDMD, and examine whether these effects are mediated by immune profiles. ACEs, NLEs, physiosomatic and FF symptoms, and 48 cytokines/chemokines/growth factors were measured in 64 FE-MDMD patients and 32 normal controls. Physiosomatic, FF and gastro-intestinal symptoms belong to the same factor as depression, anxiety, melancholia, and insomnia. The first factor extracted from these seven domains is labeled the physio-affective phenome of depression. A part (59.0%) of the variance in physiosomatic symptoms is explained by the independent effects of interleukin (IL)-16 and IL-8 (positively), CCL3 and IL-1 receptor antagonist (inversely correlated). A part (46.5%) of the variance in physiosomatic (59.0%) symptoms is explained by the independent effects of interleukin (IL)-16, TNF-related apoptosis-inducing ligand (TRAIL) (positively) and combined activities of negative immunoregulatory cytokines (inversely associated). Partial least squares analysis shows that ACE + NLEs exert a substantial influence on the physio-affective phenome which are partly mediated by an immune network composed of interleukin-16, CCL27, TRAIL, macrophage-colony stimulating factor, and stem cell growth factor. The physiosomatic and FF symptoms of FE-MDMD are partly caused by immune-associated neurotoxicity due to T helper (Th)-1 polarization and M1 macrophage activation and relative lowered compensatory immunoregulatory protection.

Global prevalence of major depressive disorder, generalized anxiety, stress, and depression among infertile women: a systematic review and meta-analysis.

BACKGROUND: In recent years, the global prevalence of infertility has increased among women (Talmor and Dunphy, Best Pract Res Clin Obstet Gynaecol 29(4):498-506, 2015) and is considered as a public health concern. One of the impacts of infertility is mental health problems in the patients, which can lead to complications such as stress, anxiety, and depression. The aim of this study is to investigate the global prevalence of major depressive disorder, general anxiety, stress, and depression in infertile women through a systematic review and meta-analysis. METHODS: To identify studies that have reported the prevalence of major depressive disorder, generalized anxiety, stress, and depression in infertile women, the PubMed, Scopus, Web of Science, Embase, ScienceDirect, and Google Scholar repositories were systematically searched. Articles published up until February 2023 were included, while no lower time limit was imposed in the search strategy. Heterogeneity of studies was examined using the I2 test and, thus, random-effects model was used to perform the analysis. Data analysis was conducted within the Comprehensive Meta-Analysis (v.2) software. RESULTS: In the review of 44 studies with a sample size of 53,300 infertile female patients, the overall prevalence of major depressive disorder (clinical depression), generalized anxiety, stress, and depression was found to be 22.9%, 13.3%, 78.8%, and 31.6% respectively. It was also found that mental health complications are more prevalent among infertile women in Asia (continent). CONCLUSION: Considering the prevalence of mental disorders among infertile women, health policymakers can use the results of the present meta-analysis to pay more attention to the mental health of infertile women and devise suitable interventions and programs to reduce and prevent the spread of psychological disorders among infertile women.

Adverse childhood experiences and recent negative events are associated with activated immune and growth factor pathways, the phenome of first episode major depression and suicidal behaviors.

This research assessed the effects of adverse childhood experiences (ACEs) and negative life events (NLEs) on forty-eight cytokines/chemokines/growth factors, in 71 FE-MDMD patients and forty heathy controls. ACEs are highly significantly associated with the classical M1 macrophage, T helper (Th)-1, Th-1 polarization, IRS, and neurotoxicity immune profiles, and not with the alternative M2, and Th-2 immune profiles. There are highly significant correlations between ACEs and NLEs and different cytokines/chemokines/growth factors, especially with interleukin (IL)-16, CCL27, stem cell growth factor, and platelet-derived growth factor. Partial Least Squares analysis showed that 62.3 % of the variance in the depression phenome (based on severity of depression, anxiety and suicidal behaviors) was explained by the regression on IL-4 (p = 0.001, inversely), the sum of ACEs + NLEs (p < 0.0001), and a vector extracted from 10 cytokines/chemokines/growth factors (p < 0.0001; both positively associated). The latter partially mediated (p < 0.0001) the effects of ACE + NLEs on the depression phenome. In conclusion, part of the effects of ACEs and NLEs on the depression phenome is mediated via activation of immune and growth factor networks. These pathways have a stronger impact in subjects with lowered activities of the compensatory immune-regulatory system.

The role of resilience in the development of depression, anxiety, and post-traumatic stress disorder after trauma in children and adolescents.

This investigation, conducted within the Texas Childhood Trauma Research Network, investigated the prospective relationships between resiliency and emergent internalizing symptoms among trauma-exposed youth. The cohort encompassed 1262 youth, aged 8-20, from twelve health-related institutions across Texas, who completed assessments at baseline and one- and six-month follow-ups for resiliency, symptoms of depression, generalized anxiety, posttraumatic stress disorder (PTSD), and other demographic and clinical characteristics. At baseline, greater resilience was positively associated with older age, male (vs female) sex assigned at birth, and history of mental health treatment. Unadjusted for covariates, higher baseline resilience was associated with greater prospective depression and PTSD symptoms but not anxiety symptoms. Upon adjusting for demographic and clinical factors, higher baseline resilience was no longer associated with depression, PTSD, or anxiety symptoms. Our analyses demonstrate that the predictive value of resilience on psychopathology is relatively small compared to more readily observable clinical and demographic factors. These data suggest a relatively minor prospective role of resilience in protecting against internalizing symptoms among trauma-exposed youth and highlight the importance of controlling for relevant youth characteristics when investigating a protective effect of resilience on internalizing symptoms.

Severe Refractory Obsessive Compulsive Disorder and Depression: Should We Consider Stereotactic Neurosurgery?

Functional neurosurgery involves modulation of activity within neural circuits that drive pathological activity. Neurologists and neurosurgeons have worked closely together, advancing the field for over a century, such that neurosurgical procedures for movement disorders are now accepted as "standard of care", benefiting hundreds of thousands of patients. As with movement disorders, some neuropsychiatric illnesses, including obsessive compulsive disorder and depression, can be framed as disorders of neural networks. Over the past two decades, evidence has accumulated that stereotactic neurosurgery can help some patients with mental disorders. Nevertheless, despite the availability of class I evidence for some interventions, there is a huge mismatch between the prevalence of severe refractory mental disorders and the number of referrals made to specialised functional neurosurgery services. This paper examines the historical trajectory of neurosurgery for movement and mental disorders. A review of neurosurgical techniques, including stereotactic radiofrequency ablation, gamma knife, deep brain stimulation, and magnetic resonance imaging guided focused ultrasound, explains the high degree of safety afforded by technological advances in the field. Evidence from clinical trials supporting functional neurosurgery for mental disorders, including obsessive compulsive disorder and depression, is presented. An improved understanding of modern functional neurosurgery should foster collaboration between psychiatry and neurosurgery, providing hope to patients whose symptoms are refractory to all other treatments.

Neuropathological characteristics of abnormal white matter functional signaling in adolescents with major depression.

BACKGROUND: Major depression disorder (MDD) constitutes a significant mental health concern. Epidemiological surveys indicate that the lifetime prevalence of depression in adolescents is much higher than that in adults, with a corresponding increased risk of suicide. In studying brain dysfunction associated with MDD in adole-scents, research on brain white matter (WM) is sparse. Some researchers even mistakenly regard the signals generated by the WM as noise points. In fact, studies have shown that WM exhibits similar blood oxygen level-dependent signal fluctuations. The alterations in WM signals and their relationship with disease severity in adolescents with MDD remain unclear. AIM: To explore potential abnormalities in WM functional signals in adolescents with MDD. METHODS: This study involved 48 adolescent patients with MDD and 31 healthy controls (HC). All participants were assessed using the Patient Health Questionnaire-9 Scale and the mini international neuropsychiatric interview (MINI) suicide inventory. In addition, a Siemens Skyra 3.0T magnetic resonance scanner was used to obtain the subjects' image data. The DPABI software was utilized to calculate the WM signal of the fractional amplitude of low frequency fluctuations (fALFF) and regional homogeneity, followed by a two-sample t-test between the MDD and HC groups. Independent component analysis (ICA) was also used to evaluate the WM functional signal. Pearson's correlation was performed to assess the relationship between statistical test results and clinical scales. RESULTS: Compared to HC, individuals with MDD demonstrated a decrease in the fALFF of WM in the corpus callosum body, left posterior limb of the internal capsule, right superior corona radiata, and bilateral posterior corona radiata [P < 0.001, family-wise error (FWE) voxel correction]. The regional homogeneity of WM increased in the right posterior limb of internal capsule and left superior corona radiata, and decreased in the left superior longitudinal fasciculus (P < 0.001, FWE voxel correction). The ICA results of WM overlapped with those of regional homo-geneity. The fALFF of WM signal in the left posterior limb of the internal capsule was negatively correlated with the MINI suicide scale (P = 0.026, r = -0.32), and the right posterior corona radiata was also negatively correlated with the MINI suicide scale (P = 0.047, r = -0.288). CONCLUSION: Adolescents with MDD involves changes in WM functional signals, and these differences in brain regions may increase the risk of suicide.

Impact of Patient-Reported Allergies on Post-operative Complications and Healthcare Utilization Following Carpal Tunnel Release.

INTRODUCTION: Open carpal tunnel release (O-CTR) is associated with high patient satisfaction and low complication rates. Risk factors for complications are well-established. Recent studies have found that patient-reported allergies (PRAs) and psychiatric comorbidities may be associated with increased complication rates. The impact of these factors after elective hand surgery has not been evaluated. This study sought to identify whether PRAs and psychiatric comorbidities are associated with complications after O-CTR and to evaluate their association with prolonged follow-up and the need for post-operative occupational therapy (OT). METHODS: Patient demographics, PRAs, Patient Health Questionnaire-2 score, Charlson Comorbidity Index, Carpal Tunnel Symptoms-6 score, postoperative complications, OT utilization, and time to final follow-up were recorded for patients who underwent elective O-CTR between 2014 and 2022. Multivariable binomial logistic regression analysis was used to determine pre-operative variables associated with increased risk for complication. RESULTS: About 250 patients met the inclusion criteria. Fifty-one (20.4%) patients developed minor complications, including scar tenderness (N=34, 13.6%), superficial wound dehiscence (N=9, 3.6%), and superficial infection (N=8, 3.2%). There were no major complications. Independent risk factors for complications included PRAs (OR 1.80, p<0.01) and PHQ-2 score (OR 1.39, p=0.04). Five or more PRAs and PHQ-2 score ≥3 are significant independent risk factors for increased post-operative complications. Increased PRAs and PHQ-2 scores were associated with longer follow-up (p=0.01 and p<0.01, respectively) but not increased OT utilization. CONCLUSION: An increased number of PRAs and higher PHQ-2 scores are significant, independent risk factors for minor complications following O-CTR. Risk adjustment and peri-operative counseling should incorporate and account for these variables.

Ketamine for depressive symptoms: A retrospective chart review of a private ketamine clinic.

Background: There is currently no published evidence demonstrating the effectiveness and safety of subanaesthetic doses of ketamine, when administered intravenously as an adjunct treatment for depressive symptoms, in a real world setting in South Africa. Aim: This retrospective chart review reports the clinical response (change in Patient Health Questionnaire - 7 score) to an initial infusion series of ketamine added to usual treatment, and the pattern of its subsequent maintenance use, for depressive symptoms. Setting: A private ketamine clinic in Hilton, KwaZulu-Natal. Methods: The medical records of all patients who attended a private ketamine clinic between August 2019 and 31 May 2021 were retrospectively analysed. Depression symptoms were evaluated using the Patient Health Questionaire-9 (PHQ-9) administered immediately before and 24 h after each treatment. Response was defined as a score decrease of more than 50%. Results: Among the 154 patients who received ketamine infusions for depression, 67 completed a six infusion initial series, with a response rate of 60.6% and remission rate of 32.4%. Of the 154, 50% no longer experienced any suicidal ideation after treatment and adverse events were uncommon, with 6.2% of infusions requiring intervention for adverse events, mostly nausea. In addition, 48.5% of those who completed the initial series continued to receive maintenance infusions, with no evidence of escalating use or abuse. Conclusion: Incorporating intravenous ketamine into the existing treatment regimens at a private clinic was associated with reduced acuteness of depression severity and suicidal ideation. This approach appeared safe and tolerable, showing no signs of abuse or dependence. Contribution: This is the first known naturalistic study reporting on ketamine use for depressive symptoms in South Africa.