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

OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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.

Healthcare Utilization and Its Correlates in Comorbid Type 2 Diabetes Mellitus and Generalized Anxiety Disorder.

This study investigated the healthcare utilization and medical expenditure of type 2 diabetes mellitus (T2DM) patients with generalized anxiety disorder (GAD) and identified the associated factors. The healthcare utilization and expenditure of T2DM patients with (case group) and without (control group) GAD between 2002 and 2013 were examined using the population-based Taiwan National Health Insurance Research Database. Healthcare utilization included outpatient visits and hospitalization; health expenditure included outpatient, inpatient, and total medical expenditure. Moreover, nonpsychiatric healthcare utilization and medical expenditure were distinguished from total healthcare utilization and medical expenditure. The average healthcare utilization, including outpatient visits and hospitalization, was significantly higher for the case group than for the control group (total and nonpsychiatric). The results regarding differences in average outpatient expenditure (total and nonpsychiatric), inpatient expenditure (total and nonpsychiatric), and total expenditure (total and nonpsychiatric) between the case and control groups are inconsistent. Sex, age, income, comorbidities/complications, and the diabetes mellitus complication severity index were significantly associated with outpatient visits, medical expenditure, and hospitalization in the case group (total and nonpsychiatric). Greater knowledge of factors affecting healthcare utilization and expenditure in comorbid individuals may help healthcare providers intervene to improve patient management and possibly reduce the healthcare burden in the future.

Savoring changes novel positive mindset targets of GAD treatment: Optimism, prioritizing positivity, kill-joy thinking, and worry mediation.

This study analyzed effects of savoring on unstudied positive mindset targets of generalized anxiety disorder (GAD) treatment (ClinicalTrials.gov: NCT05040061). 85 students with GAD were randomly assigned to one of two ecological momentary interventions (EMIs) on smartphone for seven days. The SkillJoy EMI promoted practices for savoring positive emotions. An active control EMI mirrored SkillJoy, yet did not include savoring or positive emotion. Optimism, worry, kill-joy thinking (lessening positive emotion with cognition), and prioritization of positive emotion activities and goals were assessed at pre-trial, eighth-day, post-trial, and 30th-day follow-up. Savoring was assessed pre-trial and fifth-day mid-trial. Longitudinal linear mixed models and simple slope analyses examined change between and within conditions. Bias-corrected bootstrapping path analysis examined mediation of worry change by increased savoring. SkillJoy led to significantly greater increases in both optimism and prioritizing positivity than the control from pre-trial to post-trial and pre-trial to follow-up. Both interventions significantly reduced kill-joy thinking at both timepoints with Skilljoy leading to marginally greater change at post-trial. Pre- to mid-trial increases in savoring mediated the relationships between treatment condition and reductions in worry at both post-trial and follow-up.

Meta-analysis of the comparative efficacy of benzodiazepines and antidepressants for psychic versus somatic symptoms of generalized anxiety disorder.

BACKGROUND: Benzodiazepines and antidepressants are effective agents for the treatment of generalized anxiety disorder (GAD), with the HAM-A frequently used as a primary outcome measure. The GAD literature is inconsistent regarding which medications are more effective for somatic versus psychic symptoms of GAD, and treatment guidelines do not advocate for prescribing based on subtype. This meta-analysis aimed to determine whether benzodiazepines and antidepressants have a differential impact on the somatic versus psychic subscales of the HAM-A in GAD. METHODS: An electronic search was undertaken for randomized controlled trials of either benzodiazepines or antidepressants for GAD that reported treatment response using the HAM-A subscales. Data were extracted by independent reviewers. A random effects assessment of weighted mean difference with 95% confidence intervals and subgroup difference was applied. All analysis was done on SPSS 26. An assessment of bias, and of quality of evidence was performed. RESULTS: 24 randomized controlled trials met the inclusion criteria: 18 antidepressant trials, 5 benzodiazepine trials and 1 of both. 14 studies were assessed as having between some and high risk of bias, while 10 were assessed as having low risk of bias. Benzodiazepines (WMD of 1.81 [CI 1.03, 2.58]) were significantly more effective than antidepressants (WMD of 0.83 [CI 0.64, 1.02]) for reducing somatic symptoms of GAD (Chi2 = 5.81, p = 0.02), and were also more effective (WMD of 2.46 [CI 1.83, 3.09]) in reducing psychic symptoms than antidepressants (WMD of 1.83 [CI 1.55, 2.10]), although this comparison did not reach statistical significance (Chi2 = 3.31, p = 0.07). CONCLUSION: The finding that benzodiazepines were significantly more effective than antidepressants for somatic symptoms needs to be weighed up against potential benefits of antidepressants over benzodiazepines. It may be useful for future treatment guidelines for GAD to explicitly consider symptom subtype.

Exploring volumetric abnormalities in subcortical L-HPA axis structures in pediatric generalized anxiety disorder.

BACKGROUND: Pediatric generalized anxiety disorder (GAD) is debilitating and increasingly prevalent, yet its etiology remains unclear. Some believe the disorder to be propagated by chronic dysregulation of the limbic-hypothalamic-pituitary-adrenal (L-HPA) axis, but morphometric studies of implicated subcortical areas have been largely inconclusive. Recognizing that certain subcortical subdivisions are more directly involved in L-HPA axis functioning, this study aims to detect specific abnormalities in these critical areas. METHODS: Thirty-eight MRI scans of preschool children with (n = 15) and without (n = 23) GAD underwent segmentation and between-group volumetric comparisons of the basolateral amygdala (BLA), ventral hippocampal subiculum (vSC), and mediodorsal medial magnocellular (MDm) area of the thalamus. RESULTS: Children with GAD displayed significantly larger vSC compared to healthy peers, F(1, 31) = 6.50, pFDR = .048. On average, children with GAD presented with larger BLA and MDm, Fs(1, 31) ≥ 4.86, psFDR ≤ .054. Exploratory analyses revealed right-hemispheric lateralization of all measures, most notably the MDm, F(1, 31) = 8.13, pFDR = .024, the size of which scaled with symptom severity, r = .83, pFDR = .033. CONCLUSION: The BLA, vSC, and MDm are believed to be involved in the regulation of anxiety and stress, both individually and collectively through the excitation and inhibition of the L-HPA axis. All were found to be enlarged in children with GAD, perhaps reflecting hypertrophy related to hyperexcitability, or early neuronal overgrowth. Longitudinal studies should investigate the relationship between these early morphological differences and the long-term subcortical atrophy previously observed.

Prevalence and Correlates of Eating Disorder Symptoms in Adolescents with Bipolar I Disorder.

Objective: To investigate the prevalence and correlates of eating disorder symptoms in adolescents with bipolar I disorder (BP I). Methods: We retrospectively collected a DSM-IV-TR-based diagnostic assessment of 179 adolescents with BP I and evaluated clinical variables in those with and without eating disorder symptoms. For comparison, we retrospectively evaluated eating disorder symptoms in adolescents with generalized anxiety disorder (GAD). Results: Thirty-six percent of adolescents with BP I experienced lifetime eating disorder symptoms; among comorbid adolescents, 74% reported eating disorder cognitions and 40% reported symptoms related to bingeing, 25% purging, and 17% restricting. BP I adolescents with (vs. without) eating disorder symptoms had higher Children's Depression Rating Scale-Revised scores (40.5 vs. 34.5; p < 0.001; effect size = 0.59) and were more likely to be female (75% vs. 45%; p < 0.001; odds ratio = 3.8). There were no differences in Young Mania Rating Scale scores (p = 0.70); lifetime presence of attention-deficit/hyperactivity disorder (p = 0.86) and alcohol (p = 0.59) or substance (p = 0.89) abuse/dependence symptoms; age of BP I onset (p = 0.14); inpatient hospitalization status at baseline (p = 0.53); presence of lifetime inpatient hospitalization (p = 0.64) or suicide attempt (p = 0.35); seriousness of suicidality (p = 0.86); body mass index (p = 0.48); and second-generation antipsychotic (SGA; p = 0.32) or non-SGA mood stabilizer (p = 0.09) use. Eating disorder cognitions (rather than behaviors) were higher in the GAD group (58%) compared with the BP I group (27%; p = 0.004). Limitations: A retrospective study is subject to recall bias and limits our understanding of the temporal relationship between eating disorder and mood symptoms. Conclusions: Eating disorder symptoms are frequently comorbid in adolescents with BP I. The comorbidity is associated with more severe depression but does not confer a more severe illness course.

The Role of Artificial Intelligence in Identifying Depression and Anxiety: A Comprehensive Literature Review.

This narrative literature review undertakes a comprehensive examination of the burgeoning field, tracing the development of artificial intelligence (AI)-powered tools for depression and anxiety detection from the level of intricate algorithms to practical applications. Delivering essential mental health care services is now a significant public health priority. In recent years, AI has become a game-changer in the early identification and intervention of these pervasive mental health disorders. AI tools can potentially empower behavioral healthcare services by helping psychiatrists collect objective data on patients' progress and tasks. This study emphasizes the current understanding of AI, the different types of AI, its current use in multiple mental health disorders, advantages, disadvantages, and future potentials. As technology develops and the digitalization of the modern era increases, there will be a rise in the application of artificial intelligence in psychiatry; therefore, a comprehensive understanding will be needed. We searched PubMed, Google Scholar, and Science Direct using keywords for this. In a recent review of studies using electronic health records (EHR) with AI and machine learning techniques for diagnosing all clinical conditions, roughly 99 publications have been found. Out of these, 35 studies were identified for mental health disorders in all age groups, and among them, six studies utilized EHR data sources. By critically analyzing prominent scholarly works, we aim to illuminate the current state of this technology, exploring its successes, limitations, and future directions. In doing so, we hope to contribute to a nuanced understanding of AI's potential to revolutionize mental health diagnostics and pave the way for further research and development in this critically important domain.

[Treatment resistance in anxiety disorders-Definition and treatment options]. / Therapieresistenz bei Angsterkrankungen ­ Definition und Behandlungsoptionen.

Treatment resistance in anxiety disorders represents a clinical challenge, contributes to the chronicity of the diseases as well as sequential comorbidities, and is associated with a significant individual and socioeconomic burden. This narrative review presents the operational definition of treatment resistance in anxiety disorders according to international consensus criteria (< 50% reduction in the Hamilton Anxiety Scale, HAM­A, score or < 50% reduction in the Beck Anxiety Inventory, BAI, score or a clinical global impression-improvement, CGI­I, score > 2). At least two unsuccessful guideline-based treatment attempts with pharmacological monotherapy or at least one unsuccessful treatment attempt with adequately delivered cognitive behavioral therapy are required. Pharmacotherapeutically, after excluding pseudo-resistance, switching the medication within one class or to another class and augmentation strategies with other antidepressants (mirtazapine, agomelatine), antipsychotics (quetiapine) or anticonvulsants (valproate) are recommended. Psychotherapeutically, third-wave therapies, psychodynamic therapy, systemic therapy and physical exercise can be considered for therapy resistance. In cases of no response to psychotherapy or pharmacotherapy, the respective other form of therapy or a combination of both should be offered. Compounds targeting the glutamatergic and endocannabinoid systems as well as neuropeptides are being tested as potential innovative pharmaceuticals for treatment-resistant anxiety disorders. There is an urgent need for further research to identify predictive markers and mechanisms as well as to develop innovative pharmacological and psychotherapeutic interventions for treatment-resistant anxiety disorders.

An investigation into the abnormal dynamic connection mechanism of generalized anxiety disorders based on non-homogeneous Markov models.

BACKGROUND: The dynamic and hierarchical nature of the functional brain network. The neural dynamical systems tend to converge to multiple attractors (stable fixed points or dynamical states) in long run. Little is known about how the changes in this brain dynamic "long-term" behavior of the connectivity flow of brain network in generalized anxiety disorder (GAD). METHODS: This study recruited 92 patients with GAD and 77 healthy controls (HC). We applied a reachable probability approach combining a Non-homogeneous Markov model with transition probability to quantify all possible connectivity flows and the hierarchical structure of brain functional systems at the dynamic level and the stationary probability vector (10-step transition probabilities) to describe the steady state of the system in the long run. A random forest algorithm was conducted to predict the severity of anxiety. RESULTS: The dynamic functional patterns in distributed brain networks had larger possibility to converge in bilateral thalamus, posterior cingulate cortex (PCC), right superior occipital gyrus (SOG) and smaller possibility to converge in bilateral superior temporal gyrus (STG) and right parahippocampal gyrus (PHG) in patients with GAD compared to HC. The abnormal transition probability pattern could predict anxiety severity in patients with GAD. LIMITATIONS: Small samples and subjects taking medications may have influenced our results. Future studies are expected to rule out the potential confounding effects. CONCLUSION: Our results have revealed abnormal dynamic neural communication and integration in emotion regulation in patients with GAD, which give new insights to understand the dynamics of brain function of patients with GAD.

Fecal microbiota transplant on Escherichia-Shigella gut composition and its potential role in the treatment of generalized anxiety disorder: A systematic review.

BACKGROUND: The gut-brain-axis has a role in mental health disorders. In people with generalized anxiety disorder, GAD,1 normal flora Escherichia-Shigella, are significantly elevated. Fecal microbiota transplant, FMT,2 has been used to alter the gut composition in unhealthy individuals. There may be a role for FMT in the treatment of GAD to improve the gut-brain-axis. METHODS: A systematic review of literature was conducted on articles published in PubMed, CINAHL Plus, Scopus, Cochrane Library, and Wed of Science from 2000 to 2022 that analyzed FMT as a modality to alter the gut microbiome in which Escherichia-Shigella levels were quantified and reported. RESULTS: Of 1916 studies identified, 14 fit criteria and were included. Recipients undergoing FMT procedures had at least one enteric diagnosis and increased percentages of Escherichia-Shigella pre-FMT. Five studies on recurrent Clostridioides difficile infection, three irritable bowel syndrome, two ulcerative colitis, one ulcerative colitis and recurrent Clostridioides difficile infection, one acute intestinal and chronic graft-vs-host disease, one pouchitis, and one slow transit constipation. 10 articles (71.4 %) showed decreased levels of Escherichia-Shigella post-FMT compared to pre-FMT. Four studies claimed the results were significant (40 %). LIMITATIONS: Limitations include potential bias in study selection, study methods of analysis, and generalization of results. CONCLUSIONS: The gut-brain-axis has a role in GAD. Those with GAD have significantly higher Escherichia-Shigella compared to those without GAD. FMT has the potential to decrease Escherichia-Shigella in patients with GAD to positively alter the gut-brain-axis as a potential for future GAD treatment.

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.

The Impact of the Successive Outbreaks of COVID-19, Vaccination, and Physical Activity on Mental Health in the Argentine Population: A Repeated Cross-Sectional Study.

Background and objectives A controversy regarding the duration of generalized anxiety disorders (GAD) and depressive symptoms during the COVID-19 pandemic arose, stating that these symptoms last a short time, perhaps a few months, or that they are more persistent over time. After more than three years of the pandemic, this is still a question that requires an answer. The main goal of this work was to record the levels of self-perceived GAD and depression in the Argentine population at several time points during the pandemic to characterize whether they were transient or persisted over the successive waves of contagion. Furthermore, we studied the association between anti-COVID-19 vaccination and the high frequency of physical activity with GAD and depression levels to evaluate a possible protective role of these factors on mental health. Methods We used a descriptive and correlational research design. We carried out a repeated cross-sectional study performing seven online surveys (collection period: four to 15 days) at different time points in October 2020, May, August, October, and December 2021, and February and April 2022. The participants (24,308) were recruited through Instagram campaigns performed by renowned local scientific communicators and responded to the survey through Google Forms (Google, Mountain View, CA). Generalized anxiety was assessed using the Generalized Anxiety Disorder-7 (GAD-7). Depression was assessed using the Patient Health Questionnaire (PHQ-9). The respondents reported their symptoms using a four-point Likert scale, which led us to calculate the scores and also the prevalence (% of the population with moderate to severe symptoms) for GAD and depression and the frequency they performed physical activity per week. Data were statistically analyzed using the unpaired Mann-Whitney U-test, chi-squared, Spearman correlation, or Tukey's post hoc test after two-way ANOVA. Results Our results show that the highest prevalence for GAD and depression correspond to those of the second wave of infections (May 2021: 57.3% and 54.19%, respectively) and that the lower levels were reported by the end of the third wave (April 2022: 43.21% and 43.65%, respectively). Such levels were even lower than those reported during the first wave at the beginning of our study (October 2020: 45.94% and 48.92%, respectively). In other words, even though the third wave tripled the number of people infected with respect to the second one, its effects on mental health were attenuated. The increment in the vaccine doses inoculated between the last two waves of contagion was associated with a decrease in the GAD score (mean ± SEM: 10.75 ± 0.06 vs. 8.88 ± 0.13) and the depressive symptoms (mean ± SEM: 10.76 ± 0.07 vs. 9.23 ± 0.14). Throughout the entire study period, the fraction of the population that practiced physical activity three or more times per week was self-perceived with lower levels of GAD and depression than those who exercised less frequently. Conclusions Of the three waves of contagion that the Argentine population suffered, the highest rates of GAD and depression were recorded in the second wave, and these symptoms decreased over the months, even during the third wave, which presented the highest number of infections. Our results also suggest that the progress of the vaccination campaign and the practice of physical exercises with high frequency could play a protective role in the mental health of the population during COVID-19.

Temporal network of experience sampling methodology identifies sleep disturbance as a central symptom in generalized anxiety disorder.

BACKGROUND: A temporal network of generalized anxiety disorder (GAD) symptoms could provide valuable understanding of the occurrence and maintenance of GAD. We aim to obtain an exploratory conceptualization of temporal GAD network and identify the central symptom. METHODS: A sample of participants (n = 115) with elevated GAD-7 scores (Generalized Anxiety Disorder 7-Item Questionnaire [GAD-7] ≥ 10) participated in an online daily diary study in which they reported their GAD symptoms based on DSM-5 diagnostic criteria (eight symptoms in total) for 50 consecutive days. We used a multilevel VAR model to obtain the temporal network. RESULTS: In temporal network, a lot of lagged relationships exist among GAD symptoms and these lagged relationships are all positive. All symptoms have autocorrelations and there are also some interesting feedback loops in temporal network. Sleep disturbance has the highest Out-strength centrality. CONCLUSIONS: This study indicates how GAD symptoms interact with each other and strengthen themselves over time, and particularly highlights the relationships between sleep disturbance and other GAD symptoms. Sleep disturbance may play an important role in the dynamic development and maintenance process of GAD. The present study may develop the knowledge of the theoretical model, diagnosis, prevention and intervention of GAD from a temporal symptoms network perspective.

Assessing anxiety symptom severity in Rwandese adolescents: cross-gender measurement invariance of GAD-7.

Background: Anxiety disorders are among the most common mental health problems experienced by adolescents worldwide because of their evident significant impact on their quality of life and functioning. The generalized anxiety disorder item (GAD-7) was manufactured to identify the severity of self-reported anxiety symptoms. Efforts to address and screen for mental health problems in Rwanda have been limited, and the importance of screening for anxiety disorders is high. The primary aim of this study was to analyze the psychometric properties of the Kinyarwanda version of the Generalized Anxiety Disorder GAD-7, and then test the measurement invariance of the GAD-7 by gender. Methods: We used the Rwandese version of GAD-7 among secondary school students in Kigali city (n=1813). Measurement invariance of the GAD-7 across gender and report on anxiety symptom severity prevalence. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to examine measurement invariance. Results: Our findings demonstrated that in the sample of 1813 adolescents aged between 12 and 17 years, generalized anxiety symptoms prevalence rates were higher in females (46.4%) than males (n= 29.8%) GAD-7 demonstrated good reliability and validity coefficients with a Cronbach's α of .077 and KMO and Bartlett test of Sphericity = 0.835. In addition to these psychometric properties, the GAD-7 screening scale had equivalence for configural and metric invariance across groups with excellent fit indices, and we confirmed partial scalar invariance across groups. Conclusion: The GAD-7 can be used in cross-group comparison of generalized anxiety disorder prevalence, and we acknowledge that full scalar invariance is generally difficult to confirm, especially due to gender differences. We recommend that future studies further investigate populations living in rural areas and conduct trials that will focus on anxiety-specific treatment in Rwandan Clinical health care centers to determine the diagnostic accuracy of this screening tool.

Effect of cranial electrotherapy stimulation as an add-on therapy on late-life generalized anxiety disorder: An open-label study.

INTRODUCTION: Cranial electrotherapy stimulation (CES) is beneficial in reducing anxiety in psychiatric patients. However, no studies have reported on elderly patients with generalized anxiety disorders (GAD). This study aimed to determine the efficacy and safety of a 6-week CES intervention for late-life GAD. MATERIALS AND METHODS: This single-arm pilot study assessed 6-week CES treatment (Alpha-Stim AID) for late-life GAD and 4-week follow-up post intervention. The Hamilton Rating Scale for Anxiety (HAMA) and Beck Anxiety Inventory (BAI) were used as baseline and outcome measures at weeks 4, 6, and 10, respectively. Treatment response was defined as 50 % or more reduction of the HAMA score and remission was defined as a of score ≤7 on the HAMA. Other measures included depression, sleep quality, and quality of life assessment. RESULTS: We included participants (n = 27) aged 68.0 ± 5.0 years, 81.5 % of whom were female. Fifteen (55.6 %), 18 (66.7 %), and 15 (55.6 %) patients were concurrently treated with antidepressants, BZDs, and antipsychotics, respectively. Intention-to-treat (ITT) analysis revealed a significant decrease in HAMA scores from baseline (20.96 ± 3.30) to week 6 (12.26 ± 7.09) and one-month (12.85 ± 7.08) follow-up at W10 (all p < 0.001). The response and remission rates were 33.3 %, 40.7 %, and 48.1 % and 25.9 %, 29.6 %, and 25.9 % at W4, W6, and W10, respectively. The CES improved depression and sleep conditions as measured by the Beck Depression Inventory-II and Pittsburgh Sleep Quality Index. CONCLUSIONS: CES clinically reduces symptoms of anxiety and depression and may improve sleep quality in late-life GAD. Future randomized controlled study is needed.

When rare meets common: Treatable genetic diseases are enriched in the general psychiatric population.

Mental illnesses are one of the biggest contributors to the global disease burden. Despite the increased recognition, diagnosis and ongoing research of mental health disorders, the etiology and underlying molecular mechanisms of these disorders are yet to be fully elucidated. Moreover, despite many treatment options available, a large subset of the psychiatric patient population is nonresponsive to standard medications and therapies. There has not been a comprehensive study to date examining the burden and impact of treatable genetic disorders (TGDs) that can present with neuropsychiatric features in psychiatric patient populations. In this study, we test the hypothesis that TGDs that present with psychiatric symptoms are more prevalent within psychiatric patient populations compared to the general population by performing targeted next-generation sequencing of 129 genes associated with 108 TGDs in a cohort of 2301 psychiatric patients. In total, 48 putative affected and 180 putative carriers for TGDs were identified, with known or likely pathogenic variants in 79 genes. Despite screening for only 108 genetic disorders, this study showed a two-fold (2.09%) enrichment for genetic disorders within the psychiatric population relative to the estimated 1% cumulative prevalence of all single gene disorders globally. This strongly suggests that the prevalence of these, and most likely all, genetic diseases is greatly underestimated in psychiatric populations. Increasing awareness and ensuring accurate diagnosis of TGDs will open new avenues to targeted treatment for a subset of psychiatric patients.

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.

Development of an optimal short form of the GAD-7 scale with cross-cultural generalizability based on Riskslim.

Despite the relatively small number of items in the GAD-7, fewer items are increasingly sought to shorten testing time in large-scale mental health screenings. As a result, short forms based on the GAD-7, the GAD-2, and GAD-mini, have become popular. However, the GAD-2 and GAD-mini have reported lower diagnostic accuracy in some cultural contexts, implying that a validated short-form version of the GAD-7 may be lacking in large-scale cross-cultural anxiety screening. Based on this, to develop an optimal short form of the GAD-7 with cross-cultural stability, we utilized seven GAD-7 datasets from six different countries, totaling 47,484 participants. Five 2 to 6 item short forms of the GAD were constructed using the Riskslim machine learning algorithm. We evaluated the diagnostic accuracy of the GAD-7 short forms in the training and test sets based on the coefficient of determination(R2) and area under the curve(AUC) metrics, and the results showed that GAD-R2 performed poorly in some cultures, and all of the 3 to 6 item short forms of the GAD performed good in cross-cultural diagnostic rates, with the GAD-R6 showing the highest diagnostic accuracy in all cultures; GAD-R3 outperformed GAD-R2, GAD-2, and GAD-mini in all cultures; GAD-R3 had higher generalizability across cultures and special populations; Given that the GAD-R3 was shorter and nearly as accurate as the GAD-R6, we recommend the use of the GAD-R3 in clinical studies and epidemiologic investigations. And we recommend the optimal actual cutoff value of 15 for GAD-R3. Overall, we recommend GAD-R3 as the short-form version of GAD-7 in cross-cultural studies. However, the 2-item GAD scale is also optimal for the short-form version in clinical practice.

Self-guided imagery rescripting for worry images: A preliminary experimental investigation.

BACKGROUND: Mental images of feared events are overactive and intrusive in generalized anxiety disorder (GAD). Imagery rescripting involves integration of positive or neutral imagery and corrective information into images to facilitate emotional processing, reduce imagery intrusions, and re-structure underlying schema. Yet only one known study has applied the technique to treatment of worry. The present study aimed first to examine the relationship between trait worry and properties of future-oriented worry images, and second to examine the efficacy of a self-guided imagery rescripting intervention in improving individuals' response to their worries. METHODS: Participants recruited through Amazon Mechanical Turk (N = 365) identified their major worry and wrote the script of a worst-case scenario mental image. Participants were randomized to three conditions: re-writing the same worry image script (exposure), or writing scripts of either one or three positive alternative future-oriented images (rescripting conditions). RESULTS: In preliminary analyses, trait worry negatively predicted participants' ratings of worry images, including valence and ability to cope, and positively predicted distress, anticipated cost, and belief in their negative meaning. In experimental analyses, linear mixed-effects models revealed anxious response and cognitive appraisal of the threat were significantly lower among participants allocated to rescripting relative to exposure. There was no effect of rescripting type. CONCLUSIONS: This investigation demonstrated the impact of a future-oriented imagery rescripting task on anxiety and cognitive biases associated with real worries in an unselected sample. Results may contribute to the development of imagery rescripting interventions for GAD.

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.