Generalized Anxiety Disorder Symptom Severity Research Articles

Effectiveness and predictors of group cognitive behaviour therapy outcome for generalised anxiety disorder in an out-patient hospital setting.

Cognitive behavioural therapy (CBT) is an empirically supported treatment for generalized anxiety disorder (GAD). Little is known about the effectiveness of CBT for GAD in real-world treatment settings. This study investigated the effectiveness of group CBT and predictors of treatment response in an out-patient hospital clinic. Participants (n = 386) with GAD participated in 12 sessions of group CBT at an out-patient clinic. Of those who provided at least partial data (n = 326), 84.5% completed treatment. Most questionnaires were completed at pre- and post-treatment; worry severity was assessed weekly. Group CBT led to improvements in chronic worry (d = -0.91, n = 118), depressive symptoms (d = -1.22, n = 172), GAD symptom severity (d = -0.65, n = 171), intolerance of uncertainty (IU; d = -0.46, n = 174) and level of functional impairment (d = -0.35, n = 169). Greater pre-treatment GAD symptom severity (d = -0.17, n = 293), chronic worry (d = -0.20, n = 185), functional impairment (d = -0.12, n = 292), and number of comorbid diagnoses (d = -0.13, n = 299) predicted greater improvement in past week worry over treatment. Biological sex, age, depression symptom severity, number of treatment sessions attended, and IU did not predict change in past week worry over time. These findings provide support for the effectiveness of group CBT for GAD and suggest the outcomes are robust and are either not impacted or are slightly positively impacted by several demographic and clinical factors.

Positive reappraisal coping mediates the relationship between parental abuse and lack of affection on adulthood generalized anxiety severity

Exposure to parental abuse and lack of parental affection during childhood are risk factors for adulthood psychopathology. Tendency to engage in positive reappraisal may be a plausible mechanism underlying this relationship. The current study examined if positive reappraisal coping mediated the relationship between maternal/paternal abuse/affection and adulthood generalized anxiety disorder (GAD) symptoms. Participant data (N = 3294) from the Midlife Development in the United States study was collected in three waves, spaced nine years apart. Longitudinal structural equation mediation modeling examined whether positive reappraisal coping at Time 2 mediated the relationship between maternal/paternal abuse/affection at Time 1 and GAD symptoms at Time 3, controlling for GAD symptoms at Time 1. Positive reappraisal coping mediated maternal/paternal childhood abuse – GAD symptom severity and maternal/paternal childhood affection – GAD severity relations. Maternal and paternal abuse was associated with lower positive reappraisal tendencies, predicting increased GAD symptom severity. Conversely, higher maternal/paternal affection was associated with increased positive reappraisal, predicting lower GAD severity. Incremental prediction revealed that childhood abuse to GAD severity via positive reappraisal path was significant for maternal but not paternal abuse, whereas affection from both parents remained significant. Positive reappraisal coping may be a possible mechanism linking childhood experiences to adulthood GAD severity.

Elevated depression and anxiety predict future patterns of individualistic and collectivistic cultural values: A cross-lagged longitudinal network analysis

BackgroundSpecific components of independent and interdependent self-construal have been associated with psychopathology. However, most studies on this topic have been cross-sectional, precluding causal inferences. We used contemporaneous and temporal cross-lagged network analysis to establish weak causal effects in understanding the association between self-construal and psychopathology components. MethodsMiddle-aged and older community-dwelling adults (n = 3294) participated in the Midlife Development in the United States study across two time-points, spaced nine years apart. Six self-construal (interdependence: connection to others, commitment to others, receptiveness to influence; independence: behavioral consistency, sense of difference from others, self-reliance) and three psychopathology nodes (major depressive disorder (MDD), generalized anxiety disorder (GAD), and panic disorder (PD) symptom severity) were examined. All network analyses controlled for age, sex, race, and number of chronic illnesses as covariates. ResultsContemporaneous and temporal networks yielded relations between elevated MDD and PD and increased receptiveness to influence. Heightened GAD symptom severity was associated with future increased difference from others and decreased connection to others, commitment to others, and receptiveness to influence. Higher MDD, GAD, and PD severity were associated with future lower self-reliance. Network comparison tests revealed no consistent network differences across sex and race. LimitationsDSM-III-R measures of MDD, GAD, and PD were used. Results may not generalize to culturally diverse racial groups. ConclusionsChanges in self-construal may result from increased MDD, GAD, and PD severity. Findings suggest the importance of targeting common mental health symptoms to positively influence how individuals view the self and others in various social contexts.

P158: Efficacy of a self-help cognitive-behavioral therapy (GSH-CBT) guided by lay providers for generalized anxiety disorder (GAD) in older adults: preliminary results

Background:Only a small proportion of older adults with generalized anxiety disorder (GAD) seek professional help. One reason is the lack of access to mental health professionals licensed to provide psychotherapy. One way to improve access to psychotherapy is through guided self- help (GSH). GSH based on the principles of cognitive-behavior therapy (GSH-CBT) can be guided by trained lay providers (LPs). The purpose of this poster is to report preliminary results from a multisite randomized controlled trial testing the efficacy of a GSH-CBT guided by LPs for GAD in older adults.Methods:The sample included 150 participants (≥ 60 years old) with a diagnosis of threshold or subthreshold GAD randomly assigned to: 1) GSH-CBT guided by LPs (n = 75) or 2) waiting list (n = 75). The GSH-CBT lasted 15 weeks. Participants used a manual presenting weekly reading and at-home exercises. They also received weekly support calls (30 minutes maximum) by LPs (undergraduate psychology students) supervised by psychologists. Repeated-measures regression models were used to compare changes in the groups before and after 15 weeks on three outcomes: severity of GAD symptoms (Generalized Anxiety Disorder 7-item; GAD-7), tendency to worry (Penn State Worry Questionnaire; PSWQ), and level of anxiety (Geriatric Anxiety Inventory; GAI).Results:At the first assessment, both groups were similar in terms of age, sex, level of education, marital status, occupation, and did not differ significantly on outcomes. The GSH- CBT group decreased significantly on all three outcomes (GAD-7: -4.8, 95% CI [-5.7, -3.8], PSWQ: -11.7; 95% CI [-13.6, -9.9], GAI: -5.3 95% CI [-6.5, -4.1]) while the waiting list group remained stable over 15 weeks (GAD-7: -0.3, 95% CI [-1.2, 0.6], PSWQ: 0.7; 95% CI [-1.2, 2.5], GAI: -0.7 95% CI [-1.9, -0.5]).Conclusions:GSH-CBT guided by LPs appears to be an effective intervention for reducing severity of GAD symptoms, tendency to worry, and level of anxiety in older people with GAD. Further analyses will be conducted to test whether the intervention differs in efficacy between participants with a threshold vs. subthreshold GAD. The maintenance of long-term gains (6 and 12 months after the intervention) will also be tested.

Psychotherapies for Generalized Anxiety Disorder in Adults

Generalized anxiety disorder (GAD) is one of the most common mental disorders in adults. Psychotherapies are among the most recommended treatments for GAD, but which should be considered as first-line treatment needs to be clarified. To use a network meta-analysis to examine the short- and long-term associations of different psychotherapies with outcomes of effectiveness and acceptability in adults with GAD. MEDLINE, Embase, PsycINFO, and the Cochrane Register of Controlled Trials were searched from database inception to January 1, 2023, to identify randomized clinical trials (RCTs) of psychotherapies for adults with GAD. RCTs comparing any type of psychotherapy against another or with a control condition for the treatment of adults (≥18 years, both sexes) with a primary diagnosis of GAD were eligible for inclusion. This study followed Cochrane standards for extracting data and assessing data quality and used the PRISMA guideline for reporting. Risk of bias of individual studies was assessed using the second version of the Cochrane risk of bias tool, and the Confidence in Network Meta-Analysis was used to rate the certainty of evidence for meta-analytical results. Eight psychotherapies were compared against one another and with 2 control conditions. Primary outcomes were severity of GAD symptoms and acceptability of the psychotherapies. Random-effects model pairwise and network meta-analyses were conducted. For effectiveness, standardized mean differences (SMDs) were pooled, and for acceptability, relative risks with 95% CIs were calculated. Data from 65 RCTs were included. Effect size estimates on data from 5048 participants (mean [SD], 70.9% [11.9%] women; mean [SD] age, 42.2 [12.5] years) suggested that third-wave cognitive behavior therapies (CBTs) (SMD, -0.76 [95% CI, -1.15 to -0.36]; certainty, moderate), CBT (SMD, -0.74 [95% CI, -1.09 to -0.38]; certainty, moderate), and relaxation therapy (SMD, -0.59 [95% CI, -1.07 to -0.11]; certainty, low) were associated with reduced GAD symptoms vs treatment as usual. Relative risks for all-cause discontinuation (indication of acceptability) signaled no differences compared with treatment as usual for all psychotherapies (eg, relative risk, 1.04 [95% CI, 0.64-1.67] for CBT vs treatment as usual). When excluding studies at high risk of bias, relaxation therapy lost its superiority over treatment as usual (SMD, -0.47; 95% CI, -1.18 to 0.23). When considering anxiety severity at 3 to 12 months after completion of the intervention, only CBT remained significantly associated with greater effectiveness than treatment as usual (SMD, -0.60; 95% CI, -0.99 to -0.21). Given the evidence in this systematic review and network meta-analysis for its associations with both acute and long-term effectiveness, CBT may represent the first-line therapy of GAD. Third-wave CBTs and relaxation therapy were associated with short-term effectiveness and may also be offered.

Trait anxiety mediates the association between hippocampal–insula functional connectivity and anxiety symptom severity in adults with and without generalized anxiety disorder

BackgroundTrait anxiety is a vulnerability factor for the development of generalized anxiety disorder (GAD). The hippocampus has been implicated in trait anxiety in normal and GAD populations. However, the exact neural mechanism of hippocampal functional connectivity (FC) and its association with clinical symptoms and trait anxiety in GAD patients remains unknown. MethodsWe recruited 68 participants (37 drug-naïve non-comorbidity GAD patients and 31 matched healthy controls (HC)), assessed their trait and state anxiety, scanned them with structural and resting-state functional magnetic resonance imaging (fMRI), and compared their hippocampal FC and volumes. We explored the relationships between hippocampal FC, clinical symptoms, and trait anxiety using partial correlation analyses; we also investigated the mediating effects of trait anxiety on the association between hippocampal FC and GAD symptom severity. ResultsThe GAD group showed increased right hippocampal FC with left insula, which was positively correlated with the Self-Rating Anxiety Scale (SAS), State Anxiety Inventory (SAI), and Trait Anxiety Inventory (TAI). Trait anxiety mediated the relationship between hippocampal FC and anxiety levels. We found no significant difference in hippocampal volumes between GAD and HC. LimitationsThe sample size was moderate. The exclusion of comorbidity may reduce the generalizability of our results in normal clinical settings. ConclusionsThe GAD patients showed no structural change but had functional alterations in the hippocampus. More importantly, future psychotherapy for this disorder should consider that trait anxiety might play a crucial role in the altered hippocampal FC in GAD.

Correlates of Dampening and Savoring in Generalized Anxiety Disorder.

Chronic worry and generalized anxiety disorder (GAD) symptoms are associated with infrequent savoring, and high dampening, of positive emotions. The goal of the present study was to investigate the indirect role of GAD-relevant processes, including intolerance of uncertainty (IU), fear of negative emotional contrasts, and negative beliefs about positive emotion and its regulation, in the relationship between GAD symptom severity and the tendency to engage in dampening and not savor positive emotions. Community participants (N = 233) completed questionnaires online.In separate models, IU, fear of negative emotional contrasts, and negative beliefs about positive emotion and its regulation fully mediated the relationships between GAD symptom severity and greater dampening and lower savoring. However, controlling for depression, only IU remained a significant mediator. A post hoc latent analysis of the mediators provided support for an underlying construct that may reflect intolerance of uncomfortable states. Intolerance of uncomfortable states was found to significantly mediate the relationship between GAD symptoms and greater dampening and lower savoring. Difficulty withstanding uncertainty may be particularly relevant in understanding why people with elevated GAD symptoms engage in efforts to avoid experiencing positive emotions. Further, the findings suggest that there may be a common factor underlying a variety of GAD-associated constructs reflecting a broad intolerance of uncomfortable inner states. Theoretical and clinical implications are discussed.Supplementary InformationThe online version contains supplementary material available at 10.1007/s41811-022-00145-x.

Longitudinal changes in intolerance of uncertainty and worry severity during CBT for generalized anxiety disorder

Intolerance of uncertainty (IU) is a key construct in generalized anxiety disorder (GAD), but little is known about the concurrent and temporal patterns of associations between IU and GAD symptom severity during treatment. In addition, most of the extant literature focuses on IU as a unidimensional construct, whereas some researchers conceptualize IU as being comprised of two dimensions, inhibitory and prospective IU. Ninety individuals with GAD completed measures of IU and worry severity at pre-treatment, session 4, session 8, and end of treatment (session 12), during group-based cognitive behavior therapy (CBT) for GAD. Longitudinal multilevel modeling showed that IU predicted worry severity concurrently, but not prospectively over time; this pattern of associations was found with the total IUS score and the inhibitory (but not prospective) subscale score. Further, the relationship between IU total scores and worry severity became stronger over time. The relationship between inhibitory (but not prospective) IU and worry also became stronger over time. When the order of the variables in the model was reversed, worry severity also predicted concurrent but not future IU. Therefore, change in IU is associated with change in worry throughout the course of CBT, particularly as treatment progresses, though its directional association as a cause and/or effect remains unclear.

A randomized controlled feasibility trial of internet-delivered guided self-help for generalized anxiety disorder (GAD) among university students in India.

Online guided self-help may be an effective and scalable intervention for symptoms of generalized anxiety disorder (GAD) among university students in India. Based on an online screen for GAD administered at 4 Indian universities, 222 students classified as having clinical (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria) or subthreshold (Generalized Anxiety Disorder Questionnaire, Fourth Edition, score ≥ 5.7) GAD were randomly assigned to receive either 3 months of guided self-help cognitive-behavioral therapy (n = 117) or a waitlist control condition (n = 105). Guided self-help participants recorded high program usage on average across all participants enrolled (M = 9.99 hr on the platform; SD = 20.87). Intent-to-treat analyses indicated that participants in the guided self-help condition experienced significantly greater reductions than participants in the waitlist condition on GAD symptom severity (d = -.40), worry (d = -.43), and depressive symptoms (d = -.53). No usage variables predicted symptom change in the guided self-help condition. Participants on average reported that the program was moderately helpful, and a majority (82.1%) said they would recommend the program to a friend. Guided self-help appears to be a feasible and efficacious intervention for university students in India who meet clinical or subthreshold GAD criteria. The trial is registered with ClinicalTrials.gov (NCT02410265). (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Interpersonal dysfunction in individuals high in chronic worry: relations with interpersonal problem-solving.

Interpersonal dysfunction has been proposed as an important maintenance factor in chronic worry and generalized anxiety disorder (GAD). Perceptions of problems and the problem-solving process as threatening, and unhelpful (e.g. avoidant, impulsive) problem-solving styles are implicated in worry and have also been suggested to be associated with dysfunctional interpersonal styles. The present study assessed the relationships between interpersonal dysfunction and problem-solving orientation, approach, and effectiveness in a sample of individuals high in chronic worry and investigated the indirect effect of interpersonal dysfunction on GAD symptom severity through negative problem-solving beliefs and approaches. Fifty-nine community participants completed questionnaires and an interpersonal problem-solving task. Greater interpersonal dysfunction was significantly associated with greater negative problem-solving orientation and greater habitual avoidant and impulsive/careless problem-solving styles. Greater interpersonal dysfunction was associated with poorer effectiveness of solutions when the task problem involved conflict with a romantic partner. Negative problem-solving orientation fully mediated the relationship between interpersonal dysfunction and GAD symptoms. These findings support that problem-solving processes are implicated in interpersonal dysfunction and that negative beliefs about problem-solving account for the relationship between interpersonal dysfunction and GAD symptoms. Theoretical implications are discussed.

Evaluation of depression and anxiety control in greek patients with major depressive disorder with/without generalized anxiety disorder and cardiovascular disease–pronoi study

IntroductionPatients with depression are likely to eventually develop Cardiovascular disease(CVD) and have a higher mortality rate than general population. In addition, anxiety disorders, especially Generalized Anxiety Disorder (GAD), may be associated with mortality and other adverse cardiac outcomes.ObjectivesEvaluation of depression and anxiety control in Greek patients with Major Depressive Disorder (MDD) with/without GAD and CVD, under 6 months of treatment with citalopram, and/or quetiapine, and/or pregabalin.Methods565 patients with MDD with/without GAD, enrolled in this observational, study (NCT03317262). The subgroup of 133(24%) patients had CVD. Severity of MDD and GAD symptoms was evaluated using the HAM-D and HAM-A Scores at baseline (V1) and after 6 months (V3) respectively.ResultsMean HAM-D score in patients with CVD without GAD, at V1 and V3 was 23.94±7.51 and 8.14±4.65 respectively (p<0.0001). Similar results were observed in patients without CVD without GAD (HAM-D score 26.67±8.79 at V1 and 7.44±4.40 at V3). Mean HAM-A score in patients with CVD and GAD at V1 and V3 was 25.64±6.38 and 8.98±3.93, respectively (p<0.0001). Same magnitude reduction in HAM-A score was observed in patients without CVD and GAD, 26.27±8.16 at V1 and 9.28±6.48 at V3 (p<0.0001). Patients’ depression symptoms with/without CVD and GAD showed also a significant reduction between V1 and V3.ConclusionsMDD patients with CVD without GAD, had a marginally lower baseline HAM-D score versus patients with GAD. After 6 months of treatment with citalopram, and/or quetiapine, and/or pregabalin the improvement of depressive and anxiety symptoms was almost equal between MDD patients with/without GAD regardless of the presence of coexisting CVD.DisclosureEmployee of ELPEN Pharmaceutical Co. Inc.

Functional Brain Networks of Trait and State Anxiety in Late-Life Depression

<h3>Introduction</h3> Late-life depression (LLD) is associated with psychiatric comorbidities that may worsen mood outcomes in older adults, yet the neural mechanisms that underlie these comorbid conditions remain understudied. Anxiety and neuroticism have been independently associated with LLD, and its mood and cognitive outcomes. In a preliminary behavioral data analysis we found that anxiety measures correlated with depression measures in older adults. We also found that several baseline neuroticism and anxiety traits predicted depression scores over time. In this study, we analyzed neuroimaging data in the setting of anxiety and neuroticism measures in LLD and hypothesized that there would be differences in resting state activity patterns in the Salience network (SN), Default-Mode network (DMN) and Executive Control network (ECN) related to severity of: (1) generalized anxiety, (2) state and trait anxiety, and (3) neuroticism. <h3>Methods</h3> This was a cross-sectional secondary data analysis on clinical and MRI data collected from our NBOLD project. LLD patients without dementia were included. Generalized anxiety disorder (GAD) symptoms, state and trait anxiety, neuroticism and depression were assessed using a GAD questionnaire, State-Trait Anxiety Inventory (STAI), NEO Personality Inventory (NEO PI), and Montgomery-Asberg Depression Rating Scale (MADRS), respectively. A study psychiatrist confirmed or ruled out diagnosis of depression. There were 102 older adults with LLD, and among them, 87 subjects who had measures of STAI-trait, STAI-state anxiety, GAD symptoms and neuroticism as well as usable neuroimaging data were included into our final analyses. The neuroimaging data was collected from 3T Siemens Skyra scanner. The imaging parameters for T1-weighted images were: TR/TE=2200/2.8ms, flip angle=13^o, matrix = 256 × 256 × 169, Voxelsize=1×1×1mm³. The 7-min resting-state fMRI data was collected using EPI sequence with FOV=240mm, flip angle=90^o, TR/TE=2000/31ms, matrix=64×64×34, voxelsize = 3.8×3.8×3.75mm³. The fMRI data was preprocessed using the default protocol setting recommend by DPABI software. The Amplitude of Low-Frequency Fluctuations (ALFF) was calculated using DPABI. Multiple regression model was used to examine the association between ALFF and GAD, state and trait anxiety as well as neuroticism controlled for age, gender and depression severity (MADRS) using SPM12. Significance was set at p<0.05 with FDR correction for multiple comparisons. <h3>Results</h3> Data analyses revealed that trait anxiety was positively correlated with greater ALFF in the ECN (left dorsolateral prefrontal cortex - dlPFC, bilateral inferior parietal cortex - IPS, and precuneus) and lateral orbitofrontal cortex (OFC). Higher state anxiety was correlated with lower ALFF in bilateral OFC and frontal pole. GAD symptom severity was positively correlated with ALFF in the right superior temporal cortex (STG), Heschl's gyrus, and dorsomedial frontal cortex (dMFC). The GAD symptom severity was also negatively correlated with ALFF in the right hippocampus, parahippocampus and temporal pole (TP), whereas there was no significant clusters found between ALFF and neuroticism after regressing out the covariates. <h3>Conclusions</h3> This is one the few studies that examined resting state neural oscillation pattern (ALFF) specific to state and trait anxiety and GAD symptoms in LLD. Higher trait anxiety was associated with greater ALFF in the ECN and OFC, all of which are related to emotion regulation, whereas higher state anxiety was correlated with lower ALFF in regions related to emotion regulation. Higher GAD was specifically correlated with higher ALFF in brain regions related to sound and social information processing, but with lower ALFF in regions related to memory. No significant clusters were found related to neuroticism suggesting that neuroticism might be able explained by trait and state anxiety as well as GAD. These results suggests a distinct neural construct that may distinguish state and trait anxiety in LLD. Uncovering the brain connectivity changes related to state and trait anxiety would deepen our understanding in the neural mechanisms and mood outcomes of LLD. Future studies are needed to determine differences in these networks between depressed and non-depressed individuals. <h3>Funding</h3> The Leo and Anne Albert Charitable Trust, National Institute of Mental Health Grant R01 MH108578, The University of Connecticut Department of Psychiatry

Cognitive-Affective control training reduces worry and GAD symptoms: investigating training and transfer effect

Symptoms of Generalized Anxiety Disorder (GAD), have been considered as an index of cognitive control deficiency. The aim of this study was to investigate whether enhancing cognitive control over emotional stimuli can decrease worry intrusions and severity of GAD symptoms. Based on the results of structured clinical interview for the DSM-5 (SCID), 45 students of Ferdowsi University of Mashhad (FUM) were who had GAD, chosen to participate in this study. Then they were assigned equally and randomly to three conditions of intervention, control and active cotrol groups; then they completed PSWQ, GAD-7, emotional stroop task and Go/No Go task as pre-test. The intervention group received 16 sessions of cognitive-affective control training using emotional stroop with trial-based feedback, also the active control group received the same amount of training sessions of emotional stroop with no feedback, and finally the control group was on a waiting list. After post-test assessments, results of ANCOVA showed that training sessions was effective on stroop performance, reduction in worry intrusions and GAD symptoms, while training in cognitive inhibition did not transfer to behavioral inhibition. Findings revealed that not only cognitive control plays a major role in worry and GAD symptoms, but also cognitive control training might be a promising path to decrease the severity of anxiety disorders. Training with emotional stimuli can enhance performance and using trial-based feedback can pave the way to get better clinical results

Heart Rate Variability Moderates the Association Between Beliefs About Worry and Generalized Anxiety Disorder Symptoms.

Paradoxically, some individuals who experience pathological worry also have good capacity for top-down control over their thoughts. Why such individuals would nevertheless worry excessively remains unclear. One explanation is suggested by research showing that those experiencing pathological worry are set apart from healthy controls by their beliefs that worry has utility and that effective worrying requires them to consider all possibilities before terminating a worry bout. This suggests that worriers with good capacity for cognitive control may engage in prolonged worry because they believe it is adaptive to do so. In a sample of 109 college students, among whom individuals reporting pathological worry were overrepresented, we tested this hypothesis using an objective index of top-down control capacity (i.e., resting vagally mediated heart rate variability [vmHRV]) and self-report measures of beliefs about worry and generalized anxiety disorder (GAD) symptom severity/status. As predicted, GAD symptom severity and vmHRV interacted to predict beliefs about worry. Specifically, high GAD symptoms were most strongly associated with beliefs that worry has utility at higher levels of vmHRV. Furthermore, this pattern was mostly a function of the belief that worry serves to distract the worrier from more emotional things. Similarly, high GAD symptoms were most strongly associated with endorsement of an ‘as many as can’ (AMAC) problem-solving rule when vmHRV was high. From the opposite perspective, both worry utility beliefs and AMAC rule endorsement were associated with the highest GAD symptom severity at higher levels of vmHRV. This was also true for the belief that worry distracts from more emotional things predicting analog GAD status. These results suggest that worriers who have higher levels of top-down control capacity may initiate and persist in worry, at least initially, because they value it. However, why they nevertheless rate their worry as excessive and uncontrollable is an important question for future research.

Aberrant amplitude low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) in generalized anxiety disorder (GAD) and their roles in predicting treatment remission.

BackgroundGeneralized anxiety disorder (GAD) is a common affective disorder characterized by comprehensive anxiety with dysregulation of brain activity which can be reflected by functional magnetic resonance imaging (f-MRI). We aimed to examine abnormal aberrant amplitude low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) in GAD and evaluate their ability to predict treatment remission.MethodsUsing resting-state fMRI (Rs-fMRI), we examined ALFF and ReHo in 30 GAD patients and 30 healthy control (HC) participants. Using on DEPASF4.3 Advanced Edition, voxel-based two-sample t-test analysis was performed on the ALFF and ReHo maps to compare GAD to HC groups, and to compare remitters (n=9) and non-remitters (n=21). Pearson’s correlation analysis was used to explore the relationship between baseline Hamilton Anxiety Rating Scale (HAM-A) scores/illness duration and mean ALFF/ReHo values. The severity of GAD symptoms was rated with HAM-A. Remission was defined as HAM-A ≤7 by week 8.ResultsCompared to the HC group, GAD patients showed lower ALFF in the right postcentral and right precentral gyrus; lower ReHo in the right precentral, right postcentral, and left precentral gyrus; and higher ReHo in the left posterior cingulate cortex. ALFF values for left postcentral gyrus was negatively correlated with baseline HAM-A, while that of the middle frontal gyrus was positively correlated with baseline HAM-A scores. ReHo value of the left postcentral gyrus was negatively correlated with baseline HAM-A, while that of the right middle frontal gyrus was positively correlated with baseline HAM-A scores. ALFF of the right frontal_superior_orbital and right frontal-medial-orbital cortex was positively correlated with illness duration. ReHo of the left supplementary motor area cortex was negatively correlated with illness duration. Remitters showed higher ALFF in the left hippocampus and higher ReHo value in the right postcentral cortex compared to nonremitters.ConclusionsThese results suggest that altered regional brain activity and local synchronization may be related to the pathophysiology of GAD and have certain value in predicting remission in treatment.

Associations Between Physical Activity, Generalized Anxiety Disorder, And Social Physique Anxiety Among Young Adults

Social Physique Anxiety (SPA) has been associated with physical activity (PA) behaviors and anxiety disorder symptoms. However, little is known about the potential influence of SPA on associations between PA and Generalized Anxiety Disorder (GAD). PURPOSE: This study quantified associations between PA, GAD and SPA among young adults (N=470, 23.2±4.8y; 63.4% female) and explored SPA as a mediator of the association between PA and GAD. METHODS: Seven-day PA Recall determined estimated expenditure (kcal/wk) and classified inactive, moderately active, and highly active PA dose categories. The Psychiatric Diagnostic Screening Questionnaire GAD subscale assessed GAD symptom severity; a score of ≥6 indicated analogue GAD (AGAD) status. The Social Physique Anxiety Scale assessed SPA. Independent t-tests examined baseline differences based on gender and AGAD status. Cohen’s d quantified the magnitude of difference. Logistic regression quantified odds of AGAD based on PA dose, adjusting for age, gender, and smoking status. Simple mediation analyses examined mediation of the continuous PA-GAD symptom association by SPA. RESULTS: Females reported less PA (p≤0.002, d=0.31) and greater SPA (p≤0.001, d=-0.63) and GAD symptom severity (p≤0.001, d=-0.51). AGAD reported greater SPA (p≤0.001, d=0.92). Compared to inactive, odds of AGAD were 28.3% (OR=0.72, 95%CI: [0.43, 1.20], p≥0.21) and 42.5% (OR=0.58, [0.35, 0.94], p≤0.03) lower among moderately active and highly active, respectively. In adjusted models, compared to inactive, odds were 29.3% (OR= 0.71, [0.42, 1.20], p≥0.21) and 36.9% (OR=0.63, [0.38, 1.06], p≥0.08) lower among moderately active and highly active, respectively. Regression models of PA on GAD symptoms (β=-0.01, p≤0.04), SPA on PA (β=-0.02, p≤0.03), and SPA on GAD symptoms (β=0.14, p≤0.001) were significant. When regressed together, SPA was (β=0.14, p≤0.001), but PA was not (β=-0.003, p≤0.27), statistically significant, supporting mediation. CONCLUSION: PA may lower odds of GAD, but findings were not significant after adjusting for covariates. SPA, a modifiable factor that was higher among females and those with AGAD, mediated the association between PA and GAD. Future research should examine these relationships longitudinally and explore SPA experimentally.

Investigating the role of negative and positive emotional avoidance in the relation between generalized anxiety disorder and depression symptom severity

Generalized anxiety disorder (GAD), a chronic disorder characterized by excessive and difficult-to-control worry, has been shown to be associated with heightened risk for depression. However, despite the high rate of co-occurrence between GAD and depression, few studies have examined factors that might account for this comorbidity. Contemporary models of GAD suggest that the avoidance of positive- and negative-valenced emotions may be particularly worthwhile to investigate in this regard. Therefore, this study examined the extent with which positive and negative emotional avoidance explain the relationship between GAD and depression symptom severity. Participants were adults (N = 114) seeking treatment at an anxiety disorders clinic. Upon intake into the clinic, participants completed a variety of self-report measures assessing the constructs of interest in this study. Results revealed that GAD severity was associated with depression symptom severity through the avoidance of positive emotion, but not via negative emotional avoidance. Specifically, greater GAD severity was associated with greater positive emotional avoidance which, in turn, was associated with greater depression symptom severity. Consistent with the contrast avoidance model of GAD, findings suggest positive emotions may be avoided in an effort to maintain homeostasis and prevent negative emotional contrasts, which may increase the likelihood of depressive symptoms.

Within-person increase in pathological worry predicts future depletion of unique executive functioning domains.

Affective neuroscience and scar theories propose that increased excessive worry, the hallmark symptom of generalized anxiety disorder (GAD), predicts future declines in executive functioning (EF). However, the preponderance of cross-sectional designs used to examine between-person chronic worry-EF relationships has blocked progress on understanding their potentially causal within-person associations. Accordingly, this study used bivariate dual latent change score (LCS) models to test whether within-person increased GAD severity might relate to future reduced EF. Community-dwelling adults (N = 2581, 46 years on average, s.d. = 11.40, 54.71% female) were assessed for GAD symptom severity (Composite International Diagnostic Interview-Short Form) across three waves, spaced about 9 years apart. Three aspects of EF [inhibition, set-shifting, and mixing costs (MCs; a measure related to common EF)], were assessed with stop-and-go switch tasks. Participants responded to 20 normal and 20 reverse single-task block trials and 32 mixed-task switch block trials. EF tests were administered at time 2 (T2) and time 3 (T3), but not at time 1 (T1). After controlling for T1 depression, LCS models revealed that within-person increased T1 - T2 GAD severity substantially predicted future reduced T2 - T3 inhibition and set-shifting (both indexed by accuracy and latency), and MC (indexed by latency) with moderate-to-large effect sizes (|d| = 0.51-0.96). Results largely support scar theories by offering preliminary within-person, naturalistic evidence that heightened excessive worry can negatively predict future distinct aspects of cognitive flexibility. Effectively targeting pathological worry might prevent difficulties arising from executive dysfunction.

Dynamic changes of amplitude of low-frequency fluctuations in patients with generalized anxiety disorder.

Previous neuroimaging studies have mainly focused on alterations of static and dynamic functional connectivity in patients with generalized anxiety disorder (GAD). However, the characteristics of local brain activity over time in GAD are poorly understood. This study aimed to investigate the abnormal time‐varying local brain activity of GAD by using the amplitude of low‐frequency fluctuation (ALFF) method combined with sliding‐window approach. Group comparison results showed that compared with healthy controls (HCs), patients with GAD exhibited increased dynamic ALFF (dALFF) variability in widespread regions, including the bilateral dorsomedial prefrontal cortex, hippocampus, thalamus, striatum; and left orbital frontal gyrus, inferior parietal lobule, temporal pole, inferior temporal gyrus, and fusiform gyrus. The abnormal dALFF could be used to distinguish between patients with GAD and HCs. Increased dALFF variability values in the striatum were positively correlated with GAD symptom severity. These findings suggest that GAD patients are associated with abnormal temporal variability of local brain activity in regions implicated in executive, emotional, and social function. This study provides insight into the brain dysfunction of GAD from the perspective of dynamic local brain activity, highlighting the important role of dALFF variability in understanding neurophysiological mechanisms and potentially informing the diagnosis of GAD.

Newly diagnosed patients with advanced non-small cell lung cancer: A clinical description of those with moderate to severe depressive symptoms

ObjectivesThe aims of this observational study were to 1) accrue newly diagnosed patients with advanced-stage non-small cell lung cancer (NSCLC) awaiting the start of first-line treatment and identify those with moderate to severe depressive symptoms and, 2) provide a clinical description of the multiple, co-occurring psychological and behavioral difficulties and physical symptoms that potentially exacerbate and maintain depressive symptoms. Materials and methodsPatients with stage IV NSCLC (N = 186) were enrolled in an observational study (ClinicalTrials.gov Identifier: NCT03199651) and completed the American Society of Clinical Oncology-recommended screening measure for depression (Patient Health Questionnaire-9 [PHQ-9]). Individuals with none/mild (n = 119; 64 %), moderate (n = 52; 28 %), and severe (n = 15; 8 %) depressive symptoms were identified. Patients also completed measures of hopelessness, generalized anxiety disorder (GAD) symptoms, stress, illness perceptions, functional status, and symptoms. ResultsPatients with severe depressive symptoms reported concomitant feelings of hopelessness (elevating risk for suicidal behavior), anxiety symptoms suggestive of GAD, and traumatic, cancer-specific stress. They perceived lung cancer as consequential for their lives and not controllable with treatment. Pain and multiple severe symptoms were present along with substantial functional impairment. Patients with moderate depressive symptoms had generally lower levels of disturbance, though still substantial. The most salient differences were low GAD symptom severity and fewer functional impairments for those with moderate symptoms. ConclusionsDepressive symptoms of moderate to severe levels co-occur in a matrix of clinical levels of anxiety symptoms, traumatic stress, impaired functional status, and pain and other physical symptoms. All of the latter factors have been shown, individually and collectively, to contribute to the maintenance or exacerbation of depressive symptoms. As life-extending targeted and immunotherapy use expands, prompt identification of patients with moderate to severe depressive symptoms, referral for evaluation, and psychological/behavioral treatment are key to maximizing treatment outcomes and quality of life for individuals with advanced NSCLC.