Generalized Anxiety Disorder Patients Research Articles

A comparative study on hair cortisol concentration among generalized anxiety disorder patients with and without alcohol dependence syndrome presenting to a tertiary care center: A pilot study

Background: Generalized anxiety disorder (GAD) affects up to 6% of the population, which if not detected early and adequately treated will continue as a hidden impairment resulting in disability. Aim: The primary objective of the study is to assess the hair cortisol levels (HairF) in persons with GAD with and without alcohol dependence syndrome (ADS), and the secondary objective is to assess whether HairF can be used as a biomarker for assessment of GAD. Materials and Methods: This comparative study was done on 94 subjects (68 persons with GAD with or without ADS and 26 healthy controls) who were divided into three groups. Hamilton Anxiety Rating Scale (HAM-A) and Patient Health Questionnaire-4 (PHQ4) were also used to assess severity of anxiety symptoms. These scores were compared with HairF. Diagnostic accuracy of the HairF analysis test was done. Statistical analysis was done using SPSS version 20. Results: The study found higher levels of HairF in persons with GAD (mean 189.4 ± 33.1) and GAD with ADS (164.2 ± 47.6) compared to healthy controls (mean 45.34 ± 40.7), which were statistically significant. Correlation of HAM-A and PHQ4 scores and HairF also showed positive correlation. The receiver operating characteristic curve suggested the best cutoff point at 88.4 pg/mg with a sensitivity of 98.5% and a specificity of 92.5%, clearly differentiating GAD from healthy controls. Conclusion: HairF were found to be higher in patients with GAD irrespective of ADS as comorbidity. The study supports the possibility of the HairF as a possible biomarker to detect GAD and play a complementary role in a multidimensional approach for management of chronic stress and anxiety.

Altered serum interleukin-17A and interleukin-23A levels may be associated with the pathophysiology and development of generalized anxiety disorder

In recent times, the pathogenesis of generalized anxiety disorder (GAD) and the influence of pro- and anti-inflammatory cytokines on it have garnered considerable interest. Cytokine research, especially Th-17 cytokine research on GAD patients, is limited. Here, we aim to assess the role of interleukin-17A (IL-17A) and interleukin-23A (IL-23A) in the pathophysiology and development of GAD. This investigation included 50 GAD patients and 38 age-sex-matched healthy controls (HCs). A psychiatrist diagnosed patients with GAD and assessed symptom severity using the DSM-5 and the GAD-7 scales. The serum concentrations of IL-17A and IL-23A were determined using commercially available ELISA kits. GAD patients exhibited elevated levels of IL-17A (77.14 ± 58.30 pg/ml) and IL-23A (644.90 ± 296.70 pg/ml) compared to HCs (43.50 ± 25.54 pg/ml and 334.40 ± 176.0 pg/ml). We observed a positive correlation between disease severity and cytokine changes (IL-23A: r = 0.359, p = 0.039; IL-17A: r = 0.397, p = 0.032). These findings indicate that IL-17A and IL-23A may be associated with the pathophysiology of GAD. ROC analysis revealed moderately higher AUC values (IL-23A: 0.824 and IL-17A: 0.710), demonstrating their potential to discriminate between patients and HCs. Also, the sensitivity values of both cytokines were relatively higher (IL-23A: 80.49% and IL-17A: 77.27%). According to the present findings, there may be an association between peripheral serum levels of IL-17A and IL-23A and the pathophysiology and development of GAD. These altered serum IL-17A and IL-23A levels may play a role in directing the early risk of developing GAD. We recommend further research to ascertain their exact role in the pathophysiology and their performance as risk assessment markers of GAD.

Prevalence of the generalized anxiety disorder in Tunisia: A study of 707 primary care outpatients.

This study examined the prevalence and correlates of generalized anxiety disorder (GAD) among primary care outpatients. A multicenter, cross-sectional study was conducted that included 707 primary care outpatients being seen at 20 primary healthcare centers in Tunis and Sfax, Tunisia. The Mini International Neuropsychiatric Interview was used to identify a diagnosis of GAD. The Beck Depression Inventory was used to assess depressive symptom severity, and the Sheehan Disability Scale (SDS) was used to measure functional impairment. The prevalence of GAD was 11%. GAD was positively correlated with female gender (P = .005), family history of psychiatric disorder (P < .001), personal history of suicide attempt (P = .019), and depressive symptoms (P < .001). Based on the SDS, severe to very severe functional limitations were reported at work, in social life, and family life (56.4%, 60.2%, and 73.1%, respectively) among GAD patients. This study indicated a relatively high prevalence of GAD among primary care patients in Tunisia. Risk factors were also determined that may help to identify these patients. This information may help primary care physicians recognize this diagnosis and provide timely referrals to mental health professionals to prevent complications and preserve quality of life.

Prevalence of Generalized Anxiety Disorder in Japan: A General Population Survey.

Generalized anxiety disorder (GAD) is among the most prevalent and highly disabling mental health conditions that negatively impacts patient's quality of life (QOL) and disrupts activities of daily living. However, the recognition of GAD is difficult due to substantial overlap with other mental disorders. The purpose of this study was to estimate the prevalence of GAD, assess QOL of probable GAD patients in Japan, and gain insights on the status of visiting medical institutions as well as their recognition/awareness of the disorder. We conducted a web-based cross-sectional survey of 20,009 participants using a questionnaire with approximately 30 single/multiple choice or open-ended questions in Japanese. Overall prevalence of GAD based on Generalized Anxiety Disorder 7-item (GAD-7) cutoff score of ≥10 and questionnaires developed with reference to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria was 7.6% (n=1530) and 6.0% (n=1197), respectively. The degree of coincidence between GAD diagnosis by DSM-5 criteria and GAD-7 scores was moderate (Cohen's Kappa=0.47, p<0.01). Younger people reported a substantially higher prevalence of GAD compared to older. QOL scores assessed using EuroQol 5 dimensions 5-level and EuroQol Visual Analog Scale were substantially lower in probable GAD patients than those with GAD-7<10. Anxiety/depression and pain/discomfort were the most prevalent issues and depression was the most reported comorbidity for the probable GAD patients. Probable GAD patients "currently visiting medical institutions" for anxiety or other mental issues were 27.6% (422/1530); a majority had seen specialists. Most of the probable GAD patients had never heard of the disease. We found higher prevalence of GAD and lower QOL of probable GAD patients in Japan. There is a need for creating awareness about GAD among the general population and developing clinical guidelines on GAD in Japan so that physicians can educate their patients.

Integrating EEG and Ensemble Learning for Accurate Grading and Quantification of Generalized Anxiety Disorder: A Novel Diagnostic Approach.

Current assessments for generalized anxiety disorder (GAD) are often subjective and do not rely on a standardized measure to evaluate the GAD across its severity levels. The lack of objective and multi-level quantitative diagnostic criteria poses as a significant challenge for individualized treatment strategies. To address this need, this study aims to establish a GAD grading and quantification diagnostic model by integrating an electroencephalogram (EEG) and ensemble learning. In this context, a total of 39 normal subjects and 80 GAD patients were recruited and divided into four groups: normal control, mild GAD, moderate GAD, and severe GAD. Ten minutes resting state EEG data were collected for every subject. Functional connectivity features were extracted from each EEG segment with different time windows. Then, ensemble learning was employed for GAD classification studies and brain mechanism analysis. Hence, the results showed that the Catboost model with a 10 s time window achieved an impressive 98.1% accuracy for four-level classification. Particularly, it was found that those functional connections situated between the frontal and temporal lobes were significantly more abundant than in other regions, with the beta rhythm being the most prominent. The analysis framework and findings of this study provide substantial evidence for the applications of artificial intelligence in the clinical diagnosis of GAD.

Effect of listening music (Rabindra Sangeet) on autonomic dysfunction in patients with generalized anxiety disorder: A power spectral analysis of heart rate variability

Background: Power spectral analysis of heart rate variability (HRV) is a complex method for assessing cardiac autonomic nerve function (CANF) in generalized anxiety disorder (GAD) patients which is a common mental disorder in the world. Recently, music therapy is used as an adjunct to pharmacotherapy in clinical psychiatry for GAD. Objective: To observe the effect of music therapy on CANF by power spectral analysis of HRV in GAD patients was designed. Methods: This prospective non randomized intervention study was done in 2019 on 60 newly diagnosed GAD patients aged 20- 40 years, both male and female. Among them 30 patients were under music therapy with listening of Raga Bhairabi based Rabindra sangeet for 3 months and 30 patients were without music therapy for three months. Age, sex and BMI matched healthy control were also enrolled. HRV of all GAD patients and control were recorded at baseline and after three months of follow up. HRV were recorded by Power Lab 8/35. For statistical analysis Bonferroni’s Post Hoc test and paired sample‘t’ test were done. Results: Total power, LF power, HF power, LF n.u, HF n.u and LF/HF and were significantly lower in all GAD patients compared to healthy control at baseline. After 3 months of music therapy, significant increment of Total power, HF power, HF n.u and significant decrement of LF n.u and LF/HF occurred whereas no change of these except HF n.u were noted in patients without music after 3 months. Moreover, after three months of music therapy, Total power, HF n.u, and LF/HF were almost same to control. Conclusion: So this study concluded that music therapy improve autonomic dysfunction in GAD patients and can be used as an adjunct to pharmacotherapy in clinical psychiatry for good cardiac health in GAD patients. J Bangladesh Soc Physiol 2022;17(2): 91-100

Inflammatory markers changes following acceptance-based behavioral psychotherapy in generalized anxiety disorder patients: Evidence from a randomized controlled trial

IntroductionGeneralized anxiety disorder (GAD) has been associated with elevated levels of C-reactive protein (CRP) and proinflammatory cytokines. Despite robust evidence as an effective treatment for GAD, research on the effects of cognitive-behavioral therapies (CBT) in the inflammatory profile of patients with clinical anxiety has presented mixed results. ObjectiveThe present study aimed to investigate the effect of an acceptance-based behavior therapy (ABBT) on inflammatory biomarkers and their association with anxiety levels in GAD patients in comparison to supportive therapy as an active control. MethodsPeripheral inflammatory biomarkers (CRP, IL-1β, IL-4, IL-6, IL-10, TNF-α) were measured in 77 GAD patients who participated in a 14-week 10-session randomized clinical trial of group ABBT (experimental, n = 37) or supportive group therapy (ST: active control group, n = 40). ResultsThe concentrations of IL-1β decreased in the control group and the concentrations of IL-6 increased in the experimental group from baseline to post-treatment, whereas no difference was identified in IL-4, IL-10, TNF, or CRP. Although anxiety and depression levels decreased in both treatment conditions, no correlation with inflammation markers was found for most clinical and biological variables. A negative correlation between changes in IL-6 and IL-10 and anxiety symptom score changes was identified. ConclusionsThe present study results found that a short trial of acceptance-based behavior therapy did not change the proinflammatory profile which may be associated with GAD. Additional research is needed to evaluate the influence of other inflammation-related variables, longer periods of follow-up as well as the effect of supportive therapy on peripheral inflammatory biomarkers in GAD patients.

Grey matter alterations in generalized anxiety disorder: A voxel-wise meta-analysis of voxel-based morphometry studies.

Grey matter, a crucial component of the brain, has been found altered in generalized anxiety disorder (GAD) of several voxel-based morphometry studies. The conclusive and consistent grey matter alterations in GAD have not been confirmed. Eleven voxel-based morphometry studies of GAD patients were included in the current systematic review and meta-analysis. The linear model of anxiety severity scores was applied to explore the relationship of grey matter alterations and anxiety severity. The subgroup analysis of adult GAD and adolescent GAD was also performed. Significantly modest grey matter alterations in the left superior temporal gyrus of patients with GAD were found. The anxiety severity score was significantly correlated with grey matter alterations in the right insula, lenticular nucleus, putamen and striatum. The subgroup analysis of adult GAD and adolescent GAD all failed to show significant grey matter alterations. However, in the adult GAD subgroup, anxiety severity score was significantly correlated with grey matter alterations in the right insula. GAD might have the modest grey matter alterations in the left superior temporal gyrus. Anxiety severity might be related to the grey matter alterations in the limbic regions, such as the right insula, lenticular nucleus, putamen and striatum. This kind of correlation might be related to the effects of adult GAD. Future studies with adequate sample sizes and sophisticated GAD categories will be needed.

Shared and distinct prefrontal cortex alterations of implicit emotion regulation in depression and anxiety: An fNIRS investigation

BackgroundEmotion regulation deficits, particularly in cognitive reappraisal, are crucial in depression and anxiety. However, research on the neural mechanisms of implicit emotion regulation is lacking, and it remains unclear whether these mechanisms are shared or distinct between the two disorders. MethodsWe investigated the neural mechanisms of implicit cognitive reappraisal in 28 individuals with major depressive disorder (MDD), 25 with generalized anxiety disorder (GAD), and 30 healthy controls (HC) using functional near-infrared spectroscopy (fNIRS). Participants completed an implicit cognitive reappraisal task and underwent neuropsychological and clinical assessments. ResultsWe found that MDD patients reported higher levels of rumination and lower utilization of cognitive reappraisal, while GAD patients reported reduced use of perspective-taking. Notably, both MDD and GAD patients exhibited decreased activation in the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) compared to HC participants during implicit cognitive reappraisal. Specifically, inadequate OFC activation was observed in MDD patients, while GAD patients demonstrated OFC deactivation during the task. Furthermore, DLPFC activation showed a negative correlation with depression severity in MDD patients, while OFC activation was positively correlated with perspective-taking in GAD patients. LimitationsfNIRS has limited depth and spatial resolution. ConclusionOur fNIRS study is the first to reveal shared and distinct neurobiological profiles of depression and anxiety in implicit emotion regulation. These findings underscore the significance of reduced DLPFC/OFC activation in emotion regulation impairment and highlight unique OFC activation patterns in these disorders. These insights have potential implications for developing cognitive-behavioral therapy and transcranial magnetic stimulation as treatment approaches.

Evaluation of systemic immune-inflammation index, systemic inflammatory response index and hematologic inflammatory parameters in generalized anxiety disorder: a controlled study

Aims: The current study aimed to examine the values of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), and systemic inflammatory response index (SIRI) in generalized anxiety disorder (GAD).&#x0D; Methods: In this retrospective study, 147 GAD patients who did not receive treatment and 154 healthy controls with similar characteristics to the patient group were included. NLR, PLR, MLR, SII, and SIRI values calculated from the complete blood count values of the GAD group were compared with age- and sex-matched healthy controls.&#x0D; Results: Neutrophil, lymphocyte, monocyte, platelet counts and NLR, MLR, SII, and SIRI values were significantly higher in the GAD group compared to healthy controls (p

Exploring Abnormal Brain Functional Connectivity in Healthy Adults, Depressive Disorder, and Generalized Anxiety Disorder through EEG Signals: A Machine Learning Approach for Triple Classification.

Depressive disorder (DD) and generalized anxiety disorder (GAD), two prominent mental health conditions, are commonly diagnosed using subjective methods such as scales and interviews. Previous research indicated that machine learning (ML) can enhance our understanding of their underlying mechanisms. This study seeks to investigate the mechanisms of DD, GAD, and healthy controls (HC) while constructing a diagnostic framework for triple classifications. Specifically, the experiment involved collecting electroencephalogram (EEG) signals from 42 DD patients, 45 GAD patients, and 38 HC adults. The Phase Lag Index (PLI) was employed to quantify brain functional connectivity and analyze differences in functional connectivity among three groups. This study also explored the impact of time window feature computations on classification performance, including the XGBoost, CatBoost, LightGBM, and ensemble models. In order to enhance classification performance, a feature optimization algorithm based on Autogluon-Tabular was proposed. The results indicate that a 12 s time window provides optimal classification performance for the three groups, achieving the highest accuracy of 97.33% with the ensemble model. The analysis further reveals a significant reorganization of the brain, with the most pronounced changes observed in the frontal lobe and beta rhythm. These findings support the hypothesis of abnormal brain functional connectivity in DD and GAD, contributing valuable insights into the neural mechanisms underlying DD and GAD.

Abnormal prefrontal cortical activation during the GO/NOGO and verbal fluency tasks in adult patients with comorbid generalized anxiety disorder and attention-deficit/hyperactivity disorder: An fNIRS study

Generalized anxiety disorder (GAD) and adult attention-deficit/hyperactivity disorder (ADHD) are commonly reported comorbidities. Adult GAD patients with comorbid ADHD are often underdiagnosed and undertreated. To explore the clinical value of functional near-infrared spectroscopy (fNIRS) data for assisting in the accurate diagnosis of ADHD in individuals with GAD, haemoglobin (HbO) concentration changes in the prefrontal cortex (PFC) were detected via fNIRS in 49 patients with both GAD and ADHD, 46 patients with GAD, and 34 healthy controls (HCs) during a verbal fluency task (VFT) and a GO/NOGO task. The correlations between PFC fNIRS data and the severity of inattention and hyperactivity symptoms assessed using the adult ADHD Self-Report Scale (ASRS) were analyzed. Our results showed that, during the GO/NOGO task, channels in the left dorsolateral PFC (channels 28 and 29) were hyperactivated, while channels in the medial PFC (channels 36, 37, and 47) were hypoactivated in participants with ADHD and GAD compared with those with GAD alone. During the VFT, compared with the HC group, both the ADHD + GAD group and the GAD group exhibited significantly decreased HbO activation in the medial PFC (channels 37, 38, and 48) and in the left ventrolateral PFC (channel 39); moreover, no difference was found between the ADHD + GAD group and the GAD group. Activation in the left dorsolateral PFC (channels 28 and 29) during the GO/NOGO task showed a significant positive correlation with ASRS-inattention scores. Our results indicated that fNIRS data collected during the GO/NOGO task may help to distinguish patients with comorbid GAD and ADHD from those with GAD alone.

Functional and Structural Abnormalities in the Pain Network of Generalized Anxiety Disorder Patients with Pain Symptoms

Pain symptoms significantly impact the well-being and work capacity of individuals with generalized anxiety disorder (GAD), and hinder treatment and recovery. Despite existing literature focusing on the neural substrate of pain and anxiety separately, further exploration is needed to understand the possible neuroimaging mechanisms of the pain symptoms in GAD patients. We recruited 73 GAD patients and 75 matched healthy controls (HC) for clinical assessments, as well as resting-state functional and structural magnetic resonance imaging scans. We defined a pain-related network through a published meta-analysis, including the insula, thalamus, periaqueductal gray, prefrontal cortex, anterior cingulate cortex, amygdala, and hippocampus. Subsequently, we conducted the regional homogeneity (ReHo) and the gray matter volume (GMV) within the pain-related network. Correlation analysis was then employed to explore associations between abnormal regions and self-reported outcomes, assessed using the Patient Health Questionnaire-15 (PHQ-15) and pain scores. We observed significantly increased ReHo in the bilateral insula but decreased GMV in the bilateral thalamus of GAD compared to HC. Further correlation analysis revealed a positive correlation between ReHo of the left anterior insula and pain scores in GAD patients, while a respective negative correlation between GMV of the bilateral thalamus and PHQ-15 scores. In summary, GAD patients exhibit structural and functional abnormalities in pain-related networks. The enhanced ReHo in the left anterior insula is correlated with pain symptoms, which might be a crucial brain region of pain symptoms in GAD.

Regulation of miRNA expression in the prefrontal cortex by fecal microbiota transplantation in anxiety-like mice.

The gut-brain axis and gut microbiota have emerged as key players in emotional disorders. Recent studies suggest that alterations in gut microbiota may impact psychiatric symptoms through brain miRNA along the gut-brain axis. However, direct evidence linking gut microbiota to the pathophysiology of generalized anxiety disorder (GAD) via brain miRNA is limited. In this study, we explored the effects of fecal microbiota transplantation (FMT) from GAD donors on gut microbiota and prefrontal cortex miRNA in recipient mice, aiming to understand the relationship between these two factors. Anxiety scores and gut microbiota composition were assessed in GAD patients, and their fecal samples were utilized for FMT in C57BL/6J mice. Anxiety-like behavior in mice was evaluated using open field and elevated plus maze tests. High-throughput sequencing of gut microbiota 16S rRNA and prefrontal cortex miRNA was performed. The fecal microbiota of GAD patients exhibited a distinct microbial structure compared to the healthy group, characterized by a significant decrease in Verrucomicrobia and Akkermansia, and a significant increase in Actinobacteria and Bacteroides. Subsequent FMT from GAD patients to mice induced anxiety-like behavior in recipients. Detailed analysis of gut microbiota composition revealed lower abundances of Verrucomicrobia, Akkermansia, Bifidobacterium, and Butyricimonas, and higher abundances of Deferribacteres, Allobaculum, Bacteroides, and Clostridium in mice that received FMT from GAD patients. MiRNA analysis identified five key miRNAs affecting GAD pathogenesis, including mmu-miR-10a-5p, mmu-miR-1224-5p, mmu-miR-218-5p, mmu-miR-10b-5p, and mmu-miR-488-3p. Notably, mmu-miR-488-3p showed a strong negative correlation with Verrucomicrobia and Akkermansia. This study demonstrates that anxiety-like behavior induced by human FMT can be transmitted through gut microbiota and is associated with miRNA expression in the prefrontal cortex. It is inferred that the reduction of Akkermansia caused by FMT from GAD patients leads to the upregulation of mmu-miR-488-3p expression, resulting in the downregulation of its downstream target gene Creb1 and interference with its related signaling pathway. These findings highlight the gut microbiota's crucial role in the GAD pathophysiology.

UK Medical Cannabis Registry: a case series analyzing clinical outcomes of medical cannabis therapy for generalized anxiety disorder patients.

This study aims to analyze changes in health-related quality of life (HRQoL) and safety in patients with generalized anxiety disorder (GAD) prescribed a homogenous selection of cannabis-based medicinal products (CBMPs). Patients prescribed Adven CBMPs (Curaleaf International, UK) for GAD were identified from the UK Medical Cannabis Registry. Primary outcomes were changes in patient-reported outcome measures (PROMs) from baseline up to 12 months, including GAD-7, Single-Item Sleep Quality Scale (SQS), and EQ-5D-5L. Adverse events were recorded using CTCAE version 4.0. A total of 120 patients were identified for inclusion, of which 38 (31.67%), 52 (43.33%), and 30 (25.00%) were prescribed oils, dried flower, and both formulations of CBMP. Associated improvements in GAD-7, SQS, and EQ-5D-5L at 1, 3, 6, and 12 months were observed compared to baseline (P < 0.010). There were 24 (20.00%) patients who reported 442 (368.33%) adverse events, most of which were mild (n = 184, 41.63%) and moderate (n = 197, 44.57%). This study reports an association between initiation of a homogeneous CBMP therapy and improvements in anxiety severity and HRQoL in individuals with GAD. Moreover, therapy was well-tolerated at 12 months follow-up. Further investigation through randomized controlled trials will ultimately be required to determine causation.

Polysomnographic features of insomnia occurring in major depressive disorder, generalized anxiety disorder and bipolar mania: Comparison with primary insomnia and association with metabolic indicators

BackgroundInsomnia is very common in psychiatric disorders, but the polysomnographic (PSG) characteristics of insomnia in various psychiatric disorders are still not agreed upon. This study aimed to investigate the characteristics of PSG and its relationship with metabolic indicators in insomnia patients with affective disorders and primary insomnia (PI) patients. MethodsA total of 38 patients with PI, 44 major depressive disorder patients with insomnia (DI), 49 generalized anxiety disorder patients with insomnia (GI), and 19 bipolar mania patients with insomnia (BI) were included. PSG was used to detect sleep problems in subjects, and biochemical indicators were also collected. ResultsThe results of this study found that subjects with BI were lower on REM sleep latency (RL), awakenings number (AN), number of microarousals (NM), and apnea–hypopnea index (AHI) than those with DI and GI, and lower on RL and AN than those with PI. Subjects with PI had lower NM and AHI than those with DI and GI. Patients with DI had a higher RL than those with GI. All results passed Bonferroni correction (p < 0.00078). No differences in biochemical indices were found among the four groups of subjects. Also, AHI was found to be positively correlated with free triiodothyronine (FT3) and fasting blood glucose in subjects. ConclusionThis study suggests that various psychiatric disorders may have their characteristics in terms of PSG parameters, which prompted us to focus on the PSG characteristics of these disorders when assessing them, as well as to focus on their biochemical indicators.

Psychodynamic profiles of major depressive disorder and generalized anxiety disorder in China.

Traditional clinical diagnoses relying on symptoms may overlook latent factors that illuminate mechanisms and potentially guide treatment. The Operationalized Psychodynamic Diagnosis (OPD) system may compensate for symptom-based diagnosis by measuring psychodynamic profiles underlying mental disorders through conflicts and structure axes. However, OPD has not been widely adopted in China, and it remains unclear whether OPD can be used as an effective approach to distinguish between depression and anxiety. The current study aims to adopt the OPD system to investigate the psychodynamic profiles of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in China, targeting patients with "pure" symptoms without comorbidity. We recruited 42 MDD patients, 32 GAD patients, and 31 healthy controls (HC), and assessed their self-report depression and anxiety symptoms, along with their underlying psychodynamic profiles through OPD interviews. Overall, both MDD and GAD patients showed more prominent conflict issues and lower levels of structure than HC. The MDD and GAD groups yielded different conflict profiles and conflict processing modes when processing their second conflicts. Importantly, the multi-dimensional psychodynamic profiles achieved machine learning classification of clinical groups with an accuracy of 0.84, supporting successful distinction of MDD and GAD patients. In conclusion, the OPD demonstrated sensitivity in revealing distinct psychodynamic profiles underlying "pure" depression and anxiety clinical populations in China. This work calls for future incorporation of OPD as a tool to investigate psychodynamic formulations underlying mental disorders, compensating for traditional symptom-based diagnostic approaches to guide precise individualized interventions.

Serum proteomics analysis of drug-naïve patients with generalised anxiety disorder: Tandem mass tags and multiple reaction monitoring

Objectives The prevalence of generalised anxiety disorder (GAD) is high. However, the underlying mechanisms remain elusive. Proteomics techniques can be employed to assess the pathological mechanisms involved in GAD. Methods Twenty-two drug-naive GAD patients were recruited, their serum samples were used for protein quantification and identified using Tandem Mass Tag and Multiple Reaction Monitoring (MRM). Machine learning models were employed to construct predictive models for disease occurrence by using clinical scores and target proteins as input variables. Results A total of 991 proteins were differentially expressed between GAD and healthy participants. Gene Ontology analysis revealed that these proteins were significantly associated with stress response and biological regulation, suggesting a significant implication in anxiety disorders. MRM validation revealed evident disparities in 12 specific proteins. The machine learning model found a set of five proteins accurately predicting the occurrence of the disease at a rate of 87.5%, such as alpha 1B-glycoprotein, complement component 4 A, transferrin, V3-3, and defensin alpha 1. These proteins had a functional association with immune inflammation. Conclusions The development of generalised anxiety disorder might be closely linked to the immune inflammatory stress response.

Causal role of immune cells in generalized anxiety disorder: Mendelian randomization study.

Generalized anxiety disorder (GAD) is a prevalent emotional disorder that has received relatively little attention regarding its immunological basis. Recent years have seen the widespread use of high-density genetic markers such as SNPs or CNVs for genotyping, as well as the advancement of genome-wide association studies (GWAS) technologies, which have facilitated the understanding of immunological mechanisms underlying several major psychiatric disorders. Despite these advancements, the immunological basis of GAD remains poorly understood. In light of this, we aimed to explore the causal relationship between immune cells and the disease through a Mendelian randomization study. The summary information for GAD (Ncase=4,666, Ncontrol=337,577) was obtained from the FinnGen dataset. Summary statistics for the characterization of 731 immune cells, including morphological parameters (MP=32), median fluorescence intensity (MFI=389), absolute cells (AC=118), and relative cells (RC=192), were derived from the GWAS catalog. The study involved both forward MR analysis, with immune cell traits as the exposure and GAD as the outcome, and reverse MR analysis, with GAD as the exposure and immune cell traits as the outcome. We performed extensive sensitivity analyses to confirm the robustness, heterogeneity, and potential multi-biological effects of the study results. Also, to control for false positive results during multiple hypothesis testing, we adopted a false discovery rate (FDR) to control for statistical bias due to multiple comparisons. After FDR correction, GAD had no statistically significant effect on immunophenotypes. Several phenotypes with unadjusted low P-values are worth mentioning, including decreased PB/PC levels on B cells(β=-0.289, 95%CI=0.044~0.194, P=0.002), reduced PB/PC AC in GAD patients (β=-0.270, 95% CI=0.77~0.92, P=0.000), and diminished PB/PC on lymphocytes (β=-0.315, 95% CI=0.77~0.93, P=0.001). GAD also exerted a causal effect on CD27 on IgD-CD38br (β=-0.155,95%CI=0.78~0.94,P=0.002), CD20-%B cell (β= -0.105,95% CI=0.77~0.94, P=0.002), IgD-CD38br%lymphocyte(β=-0.305, 95%CI=0.79~0.95, P=0.002), FSC-A level on granulocytes (β=0.200, 95%CI=0.75~0.91, P=8.35×10-5), and CD4RA on TD CD4+(β=-0.150, 95% CI=0.82~1.02, P=0.099). Furthermore, Two lymphocyte subsets were identified to be significantly associated with GAD risk: CD24+ CD27+ B cell (OR=1.066,95%CI=1.04~1.10,P=1.237×10-5),CD28+CD4+T cell (OR=0.927, 95%CI=0.89~0.96, P=8.085×10-5). The study has shown the close association between immune cells and GAD through genetic methods, thereby offering direction for future clinical research.

Prolonged Disease Course Leads to Impaired Brain Function in Anxiety Disorder: A Resting State EEG Study.

Anxiety disorder (AD) is a common disabling disease. The prolonged disease course may lead to impaired cognitive performance, brain function, and a bad prognosis. Few studies have examined the effect of disease course on brain function by electroencephalogram (EEG). Resting-state EEG analysis was performed in 34 AD patients. The 34 patients with AD were divided into two groups according to the duration of their illness: anxious state (AS) and generalized anxiety disorder (GAD). Then, EEG features, including univariate power spectral density (PSD), fuzzy entropy (FE), and multivariable functional connectivity (FC), were extracted and compared between AS and GAD. These features were evaluated by three previously validated machine learning methods to test the accuracy of classification in AS and GAD. Significant decreased PSD and FE in GAD were detected compared with AS, especially in the Alpha 2 band. In addition, FC analysis indicated that GAD patients' connection between the left and right hemispheres decreased. Based on machine learning, AS and GAD are classified on a six-month criterion with the highest classification accuracy of up to 0.99 ± 0.0015. The brain function of patients is more severely impaired in AD patients with longer illness duration. Resting-state EEG demonstrated to be a promising examination in the classification in GAD and AS using machine learning methods with better classification accuracy.