INTRODUCTION:Adverse childhood experiences (ACE) and major depressive disorder (MDD) are associated with altered inflammatory processes, dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and an increased risk of developing metabolic diseases. Soluble Triggering Receptor Expressed on Myeloid Cells-1 and -2 (sTREM1, sTREM2) and Fractalkine (CX3CL1) are markers of the innate immune system regulating inflammatory response but are relatively underexplored in ACE and MDD. METHODS AND MATERIALS:In this exploratory study, we measured serum sTREM1, sTREM2 and CX3CL1 and pro-inflammatory cytokines in 23 women with ACE and MDD, 23 women with MDD without ACE, 22 healthy women with ACE with no current or lifetime MDD and 25 healthy women with neither ACE nor MDD. Additionally, explorative correlations between levels of sTREM1, sTREM2, CX3CL1 and cytokines, measures of trauma, depressive symptoms, anxiety, self-reported stress, metabolic parameters and cortisol release were calculated. RESULTS:The four groups did not differ in levels of sTREM1 and sTREM2. Healthy women without ACE had higher CX3CL1 concentrations than both depression groups. They also had lower IL-8 and IL-18 levels than each of the other three groups (ACE+/MDD+, ACE-/MDD+, and ACE+/MDD-). sTREM1 and CX3CL1 were related to pro-inflammatory activity, such as TNF-α and NGF, while sTREM2 was associated with an increased metabolic risk. Furthermore, CX3CL1 correlated with lower stress ratings and a higher cortisol release to psychosocial stress induction, while sTREM2 correlated positively with symptoms of depression and anxiety. DISCUSSION:Lower CX3CL1 and increased cytokines might be an unspecific correlate of mental disorders and early traumatic experiences. sTREM1, sTREM2 and CX3CL1 seem to be associated with somatic as well as mental health variables. Further studies are needed to investigate the specific role of sTREM1, sTREM2 and CX3CL1 in the interplay between physical and mental health.
INTRODUCTION:Anhedonia and reward processing deficits are core features of major depressive disorder (MDD). However, their persistence following remission remains unclear, hindering the differentiation between state versus trait characteristics. This study investigated clinically assessed anhedonia and reward-related learning in individuals with current MDD (MD), remitted MDD (RMD), and healthy controls (HCs). METHODS:We assessed 26 individuals with current MDD, 35 with RMD, and 37 HC. Anhedonia was measured using the Clinician-Administered Snaith-Hamilton Pleasure Scale (SHAPS-C-TR). Reward-related learning was evaluated using the probabilistic reward task (PRT). Depressive and anxiety symptoms were also assessed. RESULTS:The MD group exhibited significantly higher anhedonia and greater depressive and anxiety symptoms compared to both RMD and HC groups. Crucially, anhedonia scores did not differ between the RMD and HC groups. While a significant learning effect on the PRT was observed across the entire sample, there were no significant differences in task performance among the three groups, even after controlling for covariates. CONCLUSION:Clinically assessed anhedonia appears to be a state-dependent symptom that normalizes with remission. In contrast, reward-related learning, assessed via the PRT, was not significantly impaired in either current or remitted depression. These findings suggest a potential dissociation between the experience of clinically assessed anhedonia and reward learning deficits in MDD.
INTRODUCTION:Left-right brain asymmetry is an important feature of human neuroanatomy, with implications for cognition, behaviour, and vulnerability to mental disorders. Despite evidence for lateralized sensitivity to hormonal fluctuations, the cortical and subcortical asymmetry profile of individuals with premenstrual dysphoric disorder (PMDD), a hormone-related mood disorder associated with alterations in brain structure, remains unexplored. METHODS:In this study, a total of 68 females with PMDD and 51 healthy females underwent magnetic resonance imaging (MRI) during the luteal phase of the menstrual cycle. Structural asymmetry was assessed using voxel-wise whole-brain analysis and region of interest (ROI) approaches for grey matter volume (GMV), as well as ROI-based analysis of cortical thickness. Associations between asymmetry and symptom severity were also investigated. RESULTS:Whole-brain analyses revealed significantly greater leftward GMV asymmetry in PMDD participants in two clusters within the anterior fusiform gyrus and the anterior insula. ROI-based analyses did not show any asymmetry group differences in either GMV or cortical thickness. Within the PMDD group, greater leftward asymmetry in the amygdala GMV was moderately associated with higher irritability. CONCLUSION:These findings provide novel, region-specific evidence for structural asymmetry in PMDD and suggest that lateralized brain architecture may contribute to affective symptom expression in this disorder.
BACKGROUND:Autism spectrum disorder (ASD) lacks disease-modifying therapies. Gene therapy offers a promising avenue to target the underlying molecular causes of ASD, particularly in monogenic or syndromic forms where single-gene mutations play a central role. METHODS:A scoping review was conducted following the PRISMA-ScR framework. We searched PubMed, Scopus, Web of Science, PsycINFO, and the Cochrane Library (2000-July 2025), with the last search completed in July 2025. Eligible studies included preclinical or translational investigations involving gene-therapy modalities (e.g., AAV vectors, ASOs, CRISPR-based editing) targeting high-confidence ASD-linked genes; non-gene-therapy studies, unrelated conditions, reviews, and non-English papers were excluded. Data were charted using a standardized extraction form and synthesized descriptively across two evidence streams. Stream 1 evaluated preclinical studies of gene therapy, while Stream 2 examined translational advances and ethical considerations. RESULTS:Twenty-one preclinical studies were identified in Stream 1, focusing on genes such as UBE3A, MECP2, FMR1, SHANK3/2, SCN2A, and SYNGAP1. Most demonstrated molecular correction and improvements in synaptic, electrophysiological, and behavioral outcomes, with therapeutic effects observed from early developmental to adult timepoints. Stream 2 synthesized 12 studies highlighting translational challenges, including delivery innovations (e.g., engineered viral capsids, nanoparticles), safety concerns (immune responses, dose-dependent toxicities), and ethical considerations (pediatric consent, neurodiversity perspectives, equity in access). Limitations include heterogeneity across models, reliance on rodent studies, and absence of completed human clinical trials. CONCLUSIONS:Gene therapy for ASD shows considerable promise but faces significant translational and ethical hurdles. Standardized study designs, comprehensive safety evaluation, and transparent stakeholder engagement will be critical for developing responsible and effective clinical applications.
INTRODUCTION:Cancer-related cognitive impairment (CRCI) is a frequent adverse effect observed in patients, but the underlying mechanisms are still unclear. Cortisol has been proposed as a potential contributor to CRCI, so the aim of this review is to systematically evaluate the evidence on the role of cortisol in CRCI. METHODS:This review followed PRISMA guidelines and was registered in PROSPERO (CRD42024570561). The search was conducted in PubMed, Web of Science, SCOPUS, ProQuest, OSF PREPRINTS, OATD, NDLTD Global E-Theses and Dissertations, and EBSCO. Inclusion criteria were studies on adult cancer patients/survivors assessing cortisol and CRCI, published in English from inception to January 30, 2025. The risk of bias was analyzed with the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies, and a qualitative GRADE-like summary of the certainty of the evidence. RESULTS:Twelve articles were finally included and analyzed using content analysis methods. Overall, findings suggest that altered diurnal cortisol rhythm (i.e. blunted cortisol secretion pattern) might be involved in CRCI; although results are inconsistent and the exact mechanisms remain unknown. Stress response associated to diagnosis, surgery, and life changes, as well as certain treatments, of cancer patients may contribute to dysregulated cortisol secretion, which in turn has been linked to CRCI. Additionally, personality traits and sociodemographic factors may act as mediators between cortisol release and CRCI. CONCLUSION:Recent data suggest cortisol relates to CRCI; however, future research should standardize cognitive outcomes and cortisol assessment methods, and consider clinical, sociodemographic, and psychological factors that may modulate stress responses.
BACKGROUND:Women exhibit distinct stress-response patterns shaped by dynamic interactions between ovarian hormones, the autonomic nervous system (ANS), and cortical stress-processing circuits. Across the female lifespan, hormonal transitions, including the menstrual cycle, pregnancy, postpartum period, perimenopause, and menopause, are associated with heightened vulnerability to mood and anxiety disorders, underscoring the need for sex-specific physiological frameworks. This narrative review synthesizes current evidence on how hormonal fluctuations modulate stress physiology in women, with a particular focus on noninvasive biomarkers derived from heart rate variability (HRV), electrodermal activity (EDA), and electroencephalography (EEG). SUMMARY:HRV emerges as a key marker of female stress reactivity, reflecting shifts in sympathetic-parasympathetic balance that vary across hormonal states and life stages. Estrogen is generally associated with enhanced vagal modulation and higher HRV, whereas progesterone and estrogen withdrawal are linked to reduced vagal modulation and relatively greater sympathetic activation, patterns that are especially pronounced during the luteal phase, pregnancy progression, postpartum, and menopause. Complementary measures provide additional insight: EDA indexes sympathetic arousal and captures hormonally driven changes in emotional reactivity, while EEG reflects cortical dynamics underlying affective style, cognitive control, and stress sensitivity. Current evidence suggests that multimodal HRV-EDA-EEG assessment may provide a more comprehensive physiological characterization of stress-related autonomic and cortical regulation by integrating complementary signals across central and peripheral systems. However, its clinical and predictive utility remains to be established in longitudinal, hormone-informed studies. KEY MESSAGES:By consolidating findings across key female life stages, this review highlights how hormonal modulation of ANS-brain interactions contributes to sex-specific stress profiles and psychiatric risk. We conclude that multimodal physiological assessment represents a promising research framework for characterizing women's stress physiology, while its translation into personalized prevention or intervention strategies requires further validation through standardized, longitudinal, and hormone-informed studies.
INTRODUCTION:In patients with major depressive disorder (MDD), thyroid dysfunction is highly correlated with depression severity and psychotic symptoms such as hallucinations and delusions. However, the prevalence and clinical correlates of psychotic symptoms in older MDD patients with subclinical hypothyroidism are rarely reported in China. METHODS:We recruited 172 older patients with first-episode and untreated MDD (aged ≥50 years). We used the Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), Positive and Negative Syndrome Scale positive subscale, and Global Impression of Severity Scale to assess depression, anxiety, psychotic symptoms, and disease severity, with each symptom/dimension evaluated in turn. RESULTS:The prevalence of psychotic symptoms was 18.6% (95% confidence interval: 13.5%-25.1%) in older MDD patients with subclinical hypothyroidism. Thyroid-stimulating hormone (TSH) and HAMA scores were clinical correlates for psychotic symptoms in older MDD patients with subclinical hypothyroidism. CONCLUSIONS:Our results suggest that psychotic symptoms are common and higher TSH levels may indicate more psychotic symptoms in older MDD patients with subclinical hypothyroidism. Serum thyroid hormones screening is crucial in older MDD patients.
INTRODUCTION:Lithium remains a crucial treatment for bipolar disorder, with well-supported effectiveness in stabilizing mood and preventing suicide. A global decline in lithium prescriptions has been observed - often due to safety concerns, demand, and issues with clinician training. In Mexico, recent data on prescribing habits and barriers to lithium use are lacking. This study aimed to assess current trends, challenges, and clinical opinions about lithium among psychiatrists and psychiatry residents. METHODS:A 27-item Spanish questionnaire, adapted from the ISBD Lithium Task Force survey, was distributed electronically through national psychiatric associations and professional networks between April and June 2025. Descriptive and stratified analyses were performed based on practice setting and years of clinical experience, and a multivariable logistic regression identified predictors of frequent lithium avoidance. RESULTS:A total of 267 clinicians participated in the survey. Lithium was the preferred first-line option for maintenance therapy (46.1%), yet 52.5% of respondents reported avoiding it. During maintenance, 53.8% of clinicians aimed for serum lithium levels between 0.5 and 0.8 mEq/L. For manic episodes, higher targets were common: 65.0% aimed for 0.8-1.0 mEq/L, and 10.9% sought levels above 1.0 mEq/L. Early-career clinicians in public settings reported the greatest structural barriers, such as limited access to serum monitoring and medication shortages. Overall, nearly half faced availability challenges, with medication unavailability being the strongest predictor of lithium avoidance in multivariable models (OR = 3.4). The main barrier was medication unavailability (46.1%), and the most common adherence strategy was patient psychoeducation about lithium's long-term benefits (75.3%), followed by dose adjustments to reduce adverse effects (58.4%). CONCLUSION:Mexican clinicians generally support lithium as a key maintenance treatment for bipolar disorder. However, its use is limited by supply issues and infrastructure gaps, especially in the public sector and among early-career practitioners. Ensuring a steady supply of lithium, improving laboratory capacity, and providing practical training could help maintain lithium as an evidence-based, first-line option in Mexico's mental healthcare system.
INTRODUCTION:Enhanced game-related specific Pavlovian-to-instrumental transfer (SPIT) has been observed in Internet gaming disorder (IGD). However, it remains unclear whether this effect is malleable. This study examined whether short-term abstinence from gaming modulates game-related SPIT effect in this population. METHODS:Sixty young adults with IGD were recruited and assigned to two groups. The abstinence group (n = 29) refrained from gaming for 7 days, with compliance verified through daily mobile screenshots and self-reports; the control group (n = 31) maintained their usual gaming routines. Game-related SPIT was measured before (D0) and after (D7) the abstinence period, and social-reward general PIT (GPIT) was assessed as a comparison. During the Pavlovian phase, three abstract patterns (conditioned stimuli, CSs) were each paired with game-, social-, or shopping-related rewards. In the instrumental phase, 2 keys (G and F) were paired separately with game- and shopping-related rewards. Game and pleasure- and arousal-matched shopping and social-reward images were used as rewards in training. Finally, the influence of the CSs on instrumental responses (PIT effects) were tested in the transfer phase. Linear mixed models were applied to assess the change of SPIT and GPIT effects. RESULTS:(1) We observed a significant three-way CS × time × group interaction in the choice rate for game-related rewards; the abstinence group demonstrated a significant declined G-key choices from D0 to D7 (b = -1.413, z = -3.521, p < 0.001, OR = 0.243), whereas the control group remained stable, indicting a selective attenuation of SPIT effect following abstinence. (2) There was a significant time × group interaction for IGDS scores (F1, 58 = 8.008, p = 0.006, ηp2 = 0.121), where the abstinence group showed more reduction in IGDS scores over time than controls. (3) Within the abstinence group, the magnitude of the SPIT reduction was significantly correlated with the decrease in IGDS scores (r = 0.395, p = 0.046). (4) No significant changes of social-reward-related GPIT effect were observed in either group. CONCLUSIONS:Our findings demonstrate a declined game-related SPIT effect in young adults with IGD after a brief period of gaming abstinence. This points to a reversible incentive sensitization process in IGD, where heightened motivational salience attributed to gaming cues may diminish following abstinence, supporting the potential clinical value of integrating short-term, supervised abstinence within therapeutic interventions for IGD.
INTRODUCTION:Adolescent-onset major depressive disorder (MDD) is associated with high morbidity, recurrence, and suicide risk. However, few studies have prospectively examined its long-term course into emerging adulthood. METHODS:Ninety-four female adolescents (aged 15-17 years) diagnosed with MDD between January and August 2012 were enrolled. After 10 years, 54 participants were reassessed. Psychiatric diagnoses were established using the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) at baseline and the Structured Clinical Interview for DSM-5 Disorders (SCID-5) at follow-up. Global functioning was rated using the Global Assessment of Functioning (GAF). At both time points, participants completed the Beck Depression Inventory (BDI), Emotional Autonomy Scale (EAS), Parent Adolescent Relationship Questionnaire (PARQ), and Identity Development Assessment Tool (IDAT). RESULTS:Nearly, all participants (94.4%) experienced recurrent depressive episodes, and 79.6% met criteria for at least one current psychiatric disorder at the follow-up assessment. The most common current diagnoses were MDD and attention-deficit/hyperactivity disorder (each 35.2%). The mean GAF score at follow-up was 64.2 ± 8.1, indicating moderate functional impairment. Lifetime suicide attempts were reported by 32 participants (59.3%). Runaway behaviour was a significant risk factor for suicidal behaviour (odds ratio [OR] = 5.91, 95% confidence interval [CI]: [1.27-27.54], p = 0.024), while earlier psychiatric contact (OR = 0.40, 95% CI: [0.18-0.88], p = 0.027) served as a protective factor. Despite the ongoing need, one-fifth of individuals (n = 11) was receiving psychiatric care in emerging adulthood. CONCLUSION:Adolescent-onset major depressive disorder is highly recurrent and carries a significant long-term risk for further psychiatric issues and suicide. However, the rigid transition from child to adult services at age 18 appears to disrupt care continuity. Runaway behaviour should be considered a marker of suicide risk, whereas earlier psychiatric contact may be protective. Youth psychiatry programs are needed to bridge the child-adult service gap for adolescents with depression.
INTRODUCTION:The study aimed to investigate whether alterations in tryptophan (TRP) metabolites reflect dysregulation of the kynurenine (KYN) pathway, which has been implicated in bipolar disorder (BD), and to examine their relationship with cognitive functioning by assessing TRP metabolite levels alongside executive performance in non-affected offspring of individuals diagnosed with BD. METHODS:The study included 32 healthy offspring of parents with BD type I as the case group and 31 healthy offspring of parents without any psychiatric disorders as controls. Psychiatric screening was conducted using the Turkish adaptation of the Schedule for Affective Disorders and Schizophrenia for School Age Children - Present and Lifetime Version (K-SADS-PL-DSM-5). Executive functioning was examined using a neuropsychological battery that included the Stroop, Serial Digit Learning (SDLT), and Cancellation (CT) tests. Serum levels of TRP, KYN, kynurenic acid (KYNA), 3-hydroxy kynurenine (3-HK), and 3-hydroxyanthranilic acid, as well as metabolite ratios (KYN/TRP, KYNA/KYN, 3-HK/KYN, and KYNA/3-HK), were measured. Logistic regression analysis was applied as part of the statistical approach to evaluate whether these metabolites and ratios could distinguish the offspring of individuals with BD from healthy controls. RESULTS:Neurocognitive performance was significantly poorer in the case group than in the control group. Serum levels of TRP (t = 3.568, p = 0.001), KYN (t = 3.772, p = 0.001), KYNA (t = 2.797, p = 0.007), and the ratios of KYN/TRP (t = 2.550, p = 0.014) and KYNA/3-HK (z = -2.557, p = 0.011) were significantly decreased in cases, whereas KYNA/KYN (t = -2.562, p = 0.013) and 3-HK/KYN (z = -3.368, p = 0.001) ratios were significantly elevated. Correlation analyses showed significant associations between executive function deficits and TRP (r = 0.367, p = 0.039), KYN (r = 0.380, p = 0.032), KYNA (r = 0.488, p = 0.005), 3-HK (r = 0.492, p = 0.004), and the 3-HK/KYN ratio (r = 0.408, p = 0.020). Logistic regression analysis indicated that lower KYN levels distinguished cases from controls (OR = 0.986, 95% CI = 0.978-0.995, p = 0.002). CONCLUSIONS:The findings indicate that metabolism within the KYN pathway in the offspring of individuals with BD shows a shift toward its neurotoxic branch, reflected by increased 3-HK/KYN ratios and decreased KYNA-related indices, and this was associated with deficits in executive functioning. These findings indicate that alterations in TRP metabolism may play a role in altered cognitive processing among individuals with a familial predisposition to BD. Further research employing larger cohorts and dimensional analyses is needed to elucidate these relationships more precisely.
INTRODUCTION:Epilepsy is a chronic neurological disorder characterized by recurrent seizures, with variants in ion channel genes such as SCN1A, SCN1B, and CACNA2D2 implicated in neuronal excitability. This research aims to explore genetic polymorphisms in the SCN1A, SCN1B, and CACNA2D2 genes among Turkish epilepsy patients and assess their impact on responsiveness to anti-seizure medications (ASMs). METHODS:Targeted next-generation sequencing (tNGS) was applied to genomic DNA from 29 patients. RESULTS:Common 15 variants were analyzed in CACNA2D2 (rs2239801, rs56287038), SCN1A (rs2298771, rs3032638, rs11394960, rs67636132, rs566839, rs1461193, rs6432861, rs2020318), and SCN1B (rs72556351, rs2278995, rs557140301, rs67701503, rs55742440). A statistically significant difference in ASM response was observed in the recessive model of SCN1A rs2298771: C>T (TT vs. CC+CT) (p = 0.044), with the TT genotype associated with improved response. CACNA2D2 rs56287038:G>T showed significance in the allelic model (p = 0.012); the T allele was found only in resistant patients. SCN1A haplotype analysis revealed reduced C allele frequency in responders (p = 0.041). The CT (rs2298771+rs2020318), CG (rs2298771+rs1461193), and CC (rs2298771+rs6432861) haplotypes also showed considerable differences among groups (p = 0.041, p = 0.023, p = 0.041, respectively). Moreover, CTG (rs2298771+rs2020318+rs1461193), CCG (rs2298771+rs6432861+rs1461193), and CTCG (rs2298771+rs2020318+rs6432861+rs1461193) haplotypes were significantly associated with treatment response (p = 0.023, p = 0.023, p = 0.022). However, none of these associations remained statistically significant after false discovery rate correction, and all findings should therefore be interpreted as exploratory. CONCLUSION:CACNA2D2 rs56287038:G>T and SCN1A rs2298771:C>T may effect ASM response.
INTRODUCTION:One-third of patients with major depressive disorder (MDD) exhibit low-grade inflammation as reflected by C-reactive protein (CRP) concentrations >3 mg/L. We explored whether CRP changes from baseline to week one of antidepressant treatment (ΔCRP) can serve as a marker of treatment response. METHODS:CRP serum levels were measured at baseline and after the first week of treatment in 33 MDD patients and correlated with patients' Hamilton Depression Rating Scale (HAM-D), while adjusting for age, gender, and body mass index. We assessed antidepressant responses at weeks one and four of treatment as a >25% and >50% HAM-D score reduction (ΔHAM-D) compared to baseline, respectively. We compared baseline and week-one CRP levels with the paired t test within responders and nonresponders separately and ΔCRP between the groups with the ANCOVA. RESULTS:Higher ΔCRP correlated with lower week-four ΔHAM-D scores (r = -0.5, p = 0.006). Nonresponders showed higher ΔCRP - but not baseline and week-one CRP - than responders (p = 0.018, Cohen's d = 1.1). A ΔCRP increase was observed in 13/16 (81%) nonresponders and 7/17 (41%) responders (Fisher's exact test's p = 0.03). A ΔCRP increase combined with a week-one nonresponse was observed in 13/16 (81%) nonresponders and 1/17 (6%) responders (p < 0.0001). CONCLUSIONS:Rather ΔCRP at week one than baseline CRP might be indicative of treatment response at week four, especially if combined with week-one ΔHAM-D. In the future, ΔCRP could be introduced into psychiatric practice to guide treatment plans.
Introduction: In recent years, growing attention has been given to the role of sleep disturbances in mental health outcomes, assuming a potential link between sleep problems and suicidality. This study applies a network analysis to examine how sleep quality is interconnected with suicidal thoughts and behaviors, as well as with a range of psychopathological symptoms. Methods: A total sample of 1,674 participants (75.3% female, 24.7% male) from the general population were investigated and completed standardized assessments of sleep quality and psychopathological symptoms. A regularized cross-sectional partial correlation network between sleep quality (Pittsburgh Sleep Quality Index [PSQI]), suicidality (Scale for Suicidal Experience and Behavior [SSEV]), and psychopathological symptoms (Brief Symptom Inventory [BSI-18]) was estimated using the EBICglasso algorithm. Node centrality, predictability, and bridge centrality were evaluated, and bootstrap methods were employed to test the stability and significance of the network structure. Results: The network was found to be stable, supporting reliable interpretations. Active suicide thoughts, anxiety, and subjective sleep quality were found to be the most influential nodes within the investigated psychopathological network. Depression and daytime impairment due to poor sleep quality were observed as nodes with the highest bridge centrality. Conclusions: These findings highlight that depression and, importantly, daytime functioning related to poor sleep quality play a central role in linking suicidality and sleep quality. This emphasizes the need to address not only nighttime sleep problems but also daytime impairments as key clinical targets. Prioritizing interventions that improve sleep and restore daytime functioning may therefore be crucial in suicide prevention and clinical care.
Introduction: Severe depressive episodes with suicidal ideation present major therapeutic challenges and often require interventions beyond standard antidepressant therapy. Electroconvulsive therapy (ECT) remains a cornerstone treatment for refractory depression, while ketamine, an N-methyl-D-aspartate receptor antagonist, has emerged as a rapid-acting antidepressant with potential benefits in reducing suicidal ideation. This study compares the efficacy, onset of action, and tolerability of intravenous ketamine and ECT as adjunctive treatments in severe major depressive disorder with active suicidal ideation. METHODS:A randomised controlled trial was conducted at a tertiary care psychiatry department in India, enrolling 64 patients aged 18-60 years with severe depression (HAM-D ≥19, SSI ≥4). Participants were randomly assigned to receive either intravenous ketamine (n = 31) or ECT (n = 33), alongside ongoing oral antidepressants. Both groups underwent six treatment sessions over 2 weeks. Outcomes were assessed at baseline, post-treatment, and 4 weeks after completion. Primary endpoints included changes in depression severity (HAM-D) and suicidal ideation (SSI), while secondary outcomes included response and remission rates, as well as safety and tolerability profiles. RESULTS:Both ECT and ketamine significantly reduced depressive symptoms and suicidal ideation (p < 0.001). HAM-D scores declined from 27 to 1 in the ECT group and from 26 to 2 in the ketamine group by the 4-week follow-up. SSI scores showed parallel improvement, from 12.1 to 1.2 with ECT and 12.6 to 2.0 with ketamine. Ketamine demonstrated a faster onset of clinical improvement, while ECT showed slightly greater durability of response. Side effects were mild in both groups, though ECT was associated with transient cognitive impairment, whereas ketamine produced minor dissociative and urinary symptoms. CONCLUSION:Ketamine offers a faster reduction in suicidal ideation than ECT, making it a promising acute intervention. Both are effective, safe adjunctive therapies, with treatment choice guided by patient profile and tolerability. .
INTRODUCTION:Sensory processing sensitivity (SPS) describes innate temperament, which consists of three characteristics: ease of excitation (EOE), low sensory threshold (LST), and aesthetic sensitivity (AES). There has been no research on SPS in bipolar disorder (BD), nor the effect of treatment on these traits. Relations between temperament, personality, and the course of BD are complex and modify the effect of treatment. Long-term lithium treatment modifies course of the illness and excellent lithium responders are known from their unique clinical characteristic. The aim of the study was to examine the relation between pharmacological treatment and SPS in BD patients. METHODS:The study group comprised 35 patients (F/M = 26/9) with BD, where 20 patients were diagnosed with BD type I and 15 patients with BD type II. Twenty patients were treated with lithium (16 ± 13 years) and fifteen with other mood stabilizers (14 ± 4 years). The comparison between groups included parameters: BD type, clinical characteristics (family history, suicidal attempts, duration of illness, duration of treatment), type of treatment and gender in relation to sensory sensitivity traits. The highly sensitive person scale (HSPS) including 27 items and distinguishing three parameters: EOE, LST, and AES were used. To assess quality of lithium treatment, the Alda scale was implemented. RESULTS:Lithium-treated patients obtained significantly lower scores on HSPS total score (4.27 vs. 4.98, p = 0.009) and EOE (4.05 vs. 5.23, p = 0.002), compared to patients treated with other mood stabilizers. AES and LST remained on similar level in both groups (however, the results are limited by insufficient statistical power). Also, the negative correlation between LST score and Alda scale score was obtained (r = -0.484; p = 0.031). There was no difference according to clinical characteristics between BD I and BD II, as well as between males and females. CONCLUSIONS:Longitudinal treatment with lithium could reduce overall SPS traits, particularly "EOE". However, it is possible that low intensity of these traits is a factor in good response to lithium. Also, lithium treatment may not reduce aesthetic sensitivity, parameter related to creativity. "Low sensory threshold" can be considered as negative predictor of lithium treatment outcome.
INTRODUCTION:Exportin-6 (XPO6) regulates nuclear export of actin and related proteins, processes essential for cytoskeletal integrity and synaptic function. Given the importance of these mechanisms in mood regulation, XPO6 dysregulation may contribute to the pathophysiology of major depressive disorder (MDD), yet its role remains largely unknown. METHOD:XPO6 mRNA was measured in the peripheral blood of participants with MDD in an acute depressive episode (acute MDD group), MDD in remission, and healthy controls (screened using Chinese health questionnaire-12 and semi-structured interviews to exclude current or past psychiatric disorders) at baseline. XPO6 mRNA levels were measured after 4 weeks of antidepressant treatment in the acute MDD group. The 17-item Hamilton Depression Rating Scale was used to assess depression severity. XPO6 mRNA levels were quantified by quantitative reverse transcription polymerase chain reaction (RT-qPCR). RESULTS:We recruited 90 participants in the acute MDD group, 60 in the MDD in remission group, and 70 healthy controls. After adjusting for demographics, a significant difference in baseline XPO6 mRNA levels was found among the three groups (F = 4.34, p = 0.014). In the post hoc analysis, a stepwise pattern in XPO6 mRNA levels was observed (acute MDD group > MDD in remission group > healthy controls). After antidepressant treatment in the acute MDD group, XPO6 mRNA levels significantly decreased (2.23 ± 2.39 vs. 1.82 ± 1.96, p = 0.016). CONCLUSION:XPO6 mRNA levels could be a potential biomarker for MDD, which is also associated with depression disease state and treatment response to antidepressants. Larger sample sizes are needed to confirm these results in the future.
Introduction: Nutrition is an important determinant of health among people with mental disorders; however, barriers to dietary counselling exist. The Eating and Supplementation for Generalized Anxiety Disorder study ("EASe-GAD") was the first trial to assess the impact of these interventions on anxiety symptoms. The primary objective of the present companion qualitative study was to gather and analyze qualitative data about the acceptability, participant experience, impact, barriers and facilitators, strengths, and weaknesses of the EASe-GAD program while also identifying opportunities for improvement. Methods: Participants were eligible for this study if they participated in the EASe-GAD trial. Data were collected using focus groups which followed a semi-structured interview approach with a set of predetermined questions. The sessions were recorded and transcribed for data analysis. Data were analyzed by thematic analysis. Results: Three focus groups were completed, involving a total of 12 women. They reported a range of components that they found helpful, such as increased self-efficacy, as well as positive outcomes that they attributed to the intervention, such as improved mental and physical health. They reported components of the program that were less enjoyable, such as having their body weight measured, and also suggested opportunities for improvement. Many participants reported that cost implications of a diet intervention were an important consideration. Conclusion: This project provided valuable insight into the participant experience and impact of the pilot dietary counselling program. Participants reported benefits and opportunities for improvement for subsequent studies aimed at improving nutrition among people with anxiety disorders.
INTRODUCTION:Current predictors of electroconvulsive therapy (ECT) effects rely on static measures. The prognostic value of anxiety evolution during ECT remains unestablished, which impedes personalized treatment. This study aims to investigate the dynamic evolution of anxiety during ECT and its predictive role in treatment effects. METHODS:We collected 1,053 data points from 117 patients with depression who were undergoing ECT, measuring both the Hamilton Anxiety Rating Scale (HAMA) and the 17-item Hamilton Depression Rating Scale (HAMD-17) at baseline and at each of the first eight ECT sessions. K-means longitudinal clustering identified anxiety evolution patterns, while linear mixed-effects modeling (LMM) and survival analysis were used to assess associations with treatment outcomes. RESULTS:Three distinct anxiety trajectory phenotypes were identified: rapid anxiety remitters (cluster A: 47%), gradual anxiety improvers (cluster B: 41%), and anxiety non-remitters (cluster C: 12%). LMM analysis demonstrated significantly greater HAMD-17 reduction slopes in cluster A (β = -1.32, p = 0.003) and cluster B (β = -1.15, p = 0.007) compared to cluster C. Kaplan-Meier analysis revealed a hierarchical response advantage (cluster A > B > C; log-rank χ2 = 32.15, p < 0.001). Multivariable Cox regression confirmed the superior predictive value of trajectories over baseline HAMA: rapid anxiety remitters showed a 19.77-fold higher response likelihood than anxiety non-remitters (95% CI 8.21-47.63), compared to only a 4% increased probability per HAMA point (hazard ratios = 1.04). CONCLUSION:Dynamic anxiety trajectories are effective biomarkers for ECT response, offering enhanced predictive value over baseline HAMA scores and enabling personalized treatment strategies for depression.
INTRODUCTION:Throughout time, there has always been a trend connecting stress and tangible damage to one's physical well-being. However, there's a lack of research that elucidates the physical and molecular traits of this stress on organ integrity. Chronic stress disrupts homeostasis, causing oxidative stress, mitochondrial dysfunction, inflammatory markers, and histological damage. METHODS:In this study, a repeated forced-swim stress was used to induce stress in the C57BL/6 mice model, and its effects on the brain and liver were analyzed at behavioral, biochemical, histological, and genetic marker levels. RESULTS:Behavioral analysis showed reduced mobility duration in experimental mice. This was further supplemented by histopathological data, which revealed mild brain deterioration and moderate liver damage. Biochemical analysis revealed upregulated levels of aminotransferase and alkaline phosphatase (ALP) and decreased levels of mean corpuscular hemoglobin, pointing toward the existence of liver dysfunctionality due to stress. Moreover, we reported the gene expression analysis of stress biomarkers (Bdnf, Fkbp5, Npy, Comt, Ppm1f, Adra2b, and Slc6a4), with a particular focus on Fkbp5, which is associated with depression and cognitive impairment. Similarly, we also studied the expressions of Crp, Cyp2e1, and Irs-2 to gauge liver damage. Results revealed significantly upregulated expression of Npy, Fkbp5, and Ppm1f in stressed mice. CONCLUSION:Our study identifies that chronic stress shows physical and molecular realizations. Additionally, this offers further incentive to look closely at Fkbp5, Npy, and Ppm1f under similar conditions and highlights their possible roles as markers of stress-induced damage.
