Self-Esteem and Symptom Severity in General Anxiety Disorder and Major Depressive Disorder: A Serial Mediation Model of Experiential Avoidance and Psychological Resilience.

Experiential avoidance (EA) is a transdiagnostic construct that may underlie the high comorbidity between major depressive disorder (MDD) and generalized anxiety disorder (GAD). This analysis used data from a longitudinal study (conducted September 2010-April 2016) to examine whether adolescent EA varies by MDD and GAD symptomatology trajectory and predicts said trajectories. Longitudinal associations between EA, anxiety, and depression symptoms were also examined. Adolescents aged 15 to 20 years (N = 183) were followed for 2 years using a comprehensive assessment battery. Symptom trajectory modeling, using weekly symptom ratings, identified 4 MDD and 4 GAD trajectories that were collapsed to form combined MDD/GAD trajectory groups: Persistent (n = 81), High-Decreasing (n = 44), Normal-Increasing (n = 37), and Minimal (n = 21). Group-based trajectory modeling, analyses of covariance, structural equation modeling, and linear regression analyses were performed. DSM-IV-TR criteria were used for MDD and GAD diagnoses. The Persistent adolescents had higher EA than other groups (P values ≤ .001), with greater EA stability versus High-Decreasing adolescents (P = .008). EA predicted anxiety and depressive symptoms alike (P values ≤ .005), which in turn did not predict EA (P values ≥ .188). EA, at both time points, predicted combined MDD/GAD trajectories after adjustment for depressive and anxiety symptoms and other confounders (P values < .001). EA appears to be an important predictor of MDD and GAD symptomatology in older adolescents, potentially serving as a treatment target. Findings suggest a possible trait-like nature for EA, perhaps increasing risk for the emergence and persistence of MDD and/or GAD. ClinicalTrials.gov identifier: NCT02147184​.

Severity of anxiety– but not depression– is associated with oxidative stress in Major Depressive Disorder

Introduction: Somatic symptoms often occur as a manifestation of depression and anxiety. The subgenual anterior cingulate cortex (sgACC) has been shown to be closely related to both depression and anxiety and plays an important role in somatic symptoms. However, little is known regarding whether the abnormal function of the sgACC contributes to the common somatic symptoms of depression and anxiety. Methods: Resting-state functional connectivity (RSFC) analysis based on the seed of the sgACC was investigated in 23 major depressive disorder (MDD) patients with somatic symptoms, 20 generalized anxiety disorder (GAD) patients with somatic symptoms, and 22 demographically matched healthy controls (HCs). The severity of depression, anxiety, and somatic symptoms was assessed using the Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), and the 15-item somatic symptom severity scale from the Patient Health Questionnaire (PHQ-15), respectively. An analysis of covariance analysis (ANCOVA) was conducted to determine RSFC alterations among GAD, MDD, and HC groups with age, gender, and head motion as covariates. Correlation analyses were conducted between the RSFC of the sgACC and PHQ-15. Results: The significantly different RSFC of right sgACC among the three groups was found in right STG, left cerebellum, and right postcentral. Post hoc analysis indicated that both MDD and GAD patients showed a decreased RSFC between the right sgACC and right STG than HCs, and both were negatively correlated with the PHQ-15 scores. Conclusion: The abnormally decreased RSFC of the sgACC and STG may be the underlying common mechanisms of depression and anxiety combined with somatic symptoms.

A subset of patients with comorbid major depressive disorder and generalized anxiety disorder (GAD) was examined from a double-blind. placebo-controlled study comparing the efficacy and safety of venlafaxine extended release (XR) and fluoxetine. From a total of 368 patients, 92 patients meeting DSM-IV criteria for major depressive disorder who also had comorbid GAD were identified. The comparison group comprised 276 evaluable noncomorbid patients. Patients received venlafaxine XR (75-225 mg/day), fluoxetine (20-60 mg/day), or placebo for 12 weeks. Efficacy evaluations included Hamilton Rating Scale for Depression (HAM-D), Hamilton Rating Scale for Anxiety (HAM-A), and Clinical Global Impressions (CGI) scale. By the final assessment at week 12, comorbid patients in the venlafaxine XR group, but not in the fluoxetine group, showed a significantly greater decrease than those in the placebo group in the primary efficacy variables of mean HAM-D and HAM-A total scores (p < .05, pairwise comparison). In comorbid patients, significant pairwise differences were noted between venlafaxine XR and placebo at week 12 for the secondary variables of HAM-D anxiety-somatization and retardation factors, HAM-D depressed mood item. HAM-A psychic anxiety factor, the Hospital Anxiety and Depression scale (HAD) anxiety subscale score, and the Covi Anxiety Scale score. Fluoxetine was significantly different from placebo only on the HAD depression subscale score. Response, defined as > or = 50% decrease in symptoms score, was achieved in 66% and 59% of the comorbid patients for HAM-D and HAM-A, respectively, in the venlafaxine XR group at week 12. This response was higher than that seen with fluoxetine (52% and 45%) or placebo (36% and 24%). Onset of efficacy appeared to be slower in comorbid than in noncomorbid patients. This is the first evidence from a controlled study of the effectiveness of pharmacotherapy in patients with comorbid major depressive disorder and GAD. The delayed improvement in comorbid patients compared with noncomorbid patients suggests that a longer treatment period may be necessary in comorbid patients.

fNIRS in differential diagnosis and cognitive correlates of generalized anxiety disorder vs major depressive disorder and comorbidity.

Objective To investigate the relationship between executive function and depressive symptoms in patients with major depressive disorder(MDD) under the Tower of London Test (TOL). Methods Thirty depression patients and thirty age-, gender-, education-matched normal controls participated in the study. All subjects received the Tower of London Test. The severity of depressive and anxiety symptoms were assessed by Hamilton Rating Scale for Depression (HAMD), Hamilton Anxiety Rating Scale(HAMA) and Beck Depression Rating Scale(BDI). Results (1)The numbers of correct response and total response of the TOL in MDD(9.1±5.1, 12.1±5.3) were significantly lower than those of the control group(13.8±5.0, 17.3±3.9)(P<0.05). The response time of the TOL test in patients with MDD((10.4±2.8)s) was significantly longer than that of the control group((8.5±2.2)s)(P<0.05). (2)The scores of HAMD , BDI and HAMA were negatively correlated with numbers of total response(r=-0.403, -0.544, -0.495, ) in patients with MDD (all P<0.05). Conclusion The executive function of patients with MDD is impaired and negatively correlated with depressive and anxiety symptoms under the Tower of London Test. Key words: Depression; Tower of London test; Executive function

Why physically active people report lower anxiety than those who are inactive is not well understood. This study examined whether physical self-concept and self-esteem would mediate associations of self-reported physical activity with anxiety disorder symptoms in young women, a population with elevated risk for developing an anxiety disorder. College women (N = 1036, mean ± SD = 19.7 ± 2.9 yr) completed a physical activity recall, the Psychiatric Diagnostic Screening Questionnaire, and the Physical Self-Description Questionnaire. Structural equation modeling was used to test hypotheses. Physical activity had inverse, indirect associations with symptoms of social phobia, generalized anxiety disorder, and obsessive-compulsive disorder that were expressed through its positive association with specific and global physical self-concept and self-esteem. The results were independent of similar relations with symptoms of major depressive disorder as well as the estimates of body fatness and use of psychotropic medications. These correlational findings provide initial evidence to warrant experimental efficacy trials of whether physical activity will reduce the risk of anxiety disorders in young women by positive influences on physical self-concept and self-esteem.

These studies were designed to evaluate the efficacy and tolerability of the first nonpeptide vasopressin V(1b) receptor antagonist, SSR149415, in the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD). Studies were randomized 8-week, double-blind, placebo-controlled trials evaluating 100- and 250-mg twice daily doses of SSR149415, placebo, and escitalopram 10 mg/day or paroxetine 20 mg/day, conducted from August 2006 through February 2008. Participants met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for MDD or GAD. Baseline Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HDRS) total scores were ≥ 24 and 18, respectively, and in the GAD trial baseline Hamilton Anxiety Rating Scale (HARS) score was ≥ 22. Primary efficacy variables included changes from baseline in total score on HDRS or HARS and MADRS, and the secondary variable included changes in the Clinical Global Impressions-Severity of Illness score (CGI-S). A 4-week, double-blind, placebo-controlled study evaluating the effect of 100- and 250-mg twice daily doses of SSR149415 on the hypothalamic-pituitary-adrenal (HPA) axis in MDD patients was also conducted. In the GAD trial, SSR149415 did not separate from placebo on the primary (HARS-100 mg: P = .29; 250 mg: P = .21) and secondary (CGI-S-100 mg: P = .18; 250 mg: P = .24) outcome measures, while paroxetine demonstrated efficacy (HARS: P = .003; CGI-S: P = .01). In 2 MDD trials, SSR149415-treated patients did not show significant improvement from baseline on any outcome measure compared with placebo-treated patients (HDRS-100 mg: P = .21 and .48, respectively; 250 mg: P = .22 and P = .46, respectively; CGI-S-100 mg: P = .64 and P = .82, respectively; 250 mg: P = .33 and P = .08, respectively). In the third MDD study, SSR149415 250 mg (P = .04), but not escitalopram (P = .15), demonstrated significant improvement compared to placebo on the HDRS total score at week 8. SSR149415 had no deleterious effects on the HPA axis. These studies demonstrate that SSR149415 may not be useful for the treatment of GAD and that its antidepressant potential needs to be further evaluated. ClinicalTrials.gov identifiers: NCT00374166 (Sanofi ID number: DFI5880), NCT00361491 (Sanofi ID number: DFI5879), NCT00358631 (Sanofi ID number: DFI5878), NCT01606384 (Sanofi ID number: PDY5467).

Comorbidity of mood and anxiety disorders: the rule, not the exception?

The differences of event-related potential components in patients with comorbid depression and anxiety, depression, or anxiety alone

The authors investigated the theoretical and clinical role of depression among cocaine abusers in treatment. Eighty-nine cocaine-abusing patients underwent 2 weeks of substance abuse treatment. Posttreatment major depressive disorder, depressive symptoms before and after substance abuse treatment, and alcohol diagnoses were assessed and their relation to pretreatment substance use, cravings in high-risk situations, and 3-month follow-up status was examined. High rates of major depressive disorder were found but were unrelated to pretreatment substance use. The decrease in depressive symptoms during treatment was independent of major depressive disorder or alcohol diagnoses and predicted treatment attrition. Higher levels of depressive symptoms during treatment were associated with greater urge to use cocaine, alcohol, and other drugs in high-risk situations. Concurrent major depressive disorder and depressive symptoms did not predict cocaine use at follow-up. However, patients who had an alcohol relapse episode experienced more depressive symptoms during treatment than did those who abstained. The results highlight the relationship of depression to alcohol use among cocaine abusers and suggest a need for further studies of the association between depression and substance use disorders.

Major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and generalized anxiety disorder (GAD) are known to have significant impact on sexual functioning. They have been studied individually. Therefore, this study was planned to compare the sexual dysfunction between MDD, OCD, and GAD with healthy subjects as controls. Four groups (MDD, OCD, GAD, and healthy subjects), matched for age, gender, marital status, and education status were identified by using the Psychiatric Diagnostic Screening Questionnaire. Subjects in these groups were assessed for absence of any major physical and psychiatric disorders. MDD, OCD, and GAD were rated for severity of illness by using the Hamilton Rating Scale for Depression, Yale-Brown Obsessive Compulsive Scale, and Hamilton Rating Scale for Anxiety, respectively. Subjects were evaluated with the Arizona Sexual Experiences Scale for sexual dysfunction, which was defined as either a score of ≥ 5 on any item or a total score of ≥ 17. Suitable statistical analysis was used to interpret the results. The study was conducted from May 2006 through July 2007. Fifty patients in each group were selected. The rate of sexual dysfunction was 30% in healthy controls, 76% in MDD subjects, 50% in OCD subjects, and 64% in GAD subjects. Low desire was the most commonly reported dysfunction among all the categories (p < .001). No particular dysfunction was associated with the 4 categories under study. Severity of illness did not correlate with the severity of sexual dysfunction. Persons with MDD have more sexual dysfunction than those with OCD and GAD. These disorders had a pervasive affect on sexual functioning of the individuals.

Objective: Decreased heart rate variability (HRV) has been reported in persons with major depressive disorder (MDD), but the results obtained are inconsistent. Little is known about the impact of comorbid anxiety disorders on HRV in MDD patients. Both issues necessitate further investigation. Materials and Methods: Forty-nine unmedicated, physically healthy, MDD patients without comorbidity, 21 MDD patients with comorbid generalized anxiety disorder (GAD), 24 MDD patients with comorbid panic disorder (PD), and 81 matched controls were recruited. The Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale are employed to assess the severity of depression and anxiety, respectively. The cardiac autonomic function was evaluated by measuring the HRV parameters. The frequency-domain indices of HRV were obtained. Results: MDD patients without comorbidity had lower high-frequency (HF)-HRV (which reflected vagal control of HRV) than controls. Any comorbid anxiety disorder (GAD or PD) was associated with significantly faster heart rates, relative to the controls, and caused greater reductions in HF-HRV among MDD patients. MDD participants with comorbid GAD displayed the greatest reductions in HF-HRV, relative to controls. Correlation analyses revealed that the severity of both depression and anxiety were significantly associated with the mean R wave to R wave (R-R) intervals, variance, low-frequency (LF)-HRV, and HF-HRV. Conclusion: The present results show decreased HRV in MDD patients, suggesting that reduction in HRV is a psychophysiological marker of MDD. MDD patients with comorbid GAD had the greatest reductions in HRV. Further investigation of the links between MDD and comorbid GAD, HRV, and cardiovascular disease is warranted.

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&lt;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&lt;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&lt;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.

Anxiety in major depression is associated with increased morbidity. The antidepressant, agomelatine, which acts as an agonist at melatonin MT(1) and MT(2) receptors and as an antagonist at serotonin 5-HT(2C) receptors, has demonstrated efficacy and safety in both major depression and generalized anxiety disorder. Here, we investigated the efficacy of agomelatine in anxious depression. Data from three placebo-controlled short-term trials of agomelatine and three comparative studies of agomelatine versus fluoxetine, sertraline, and venlafaxine were pooled. Effects of agomelatine on anxiety symptoms were assessed with the Hamilton Anxiety Rating Scale in four studies (one vs placebo and three vs active comparator) and with the Hamilton Depression Rating Scale (HAMD) anxiety subscore in all six studies. Anxiolytic and antidepressant efficacies of agomelatine were assessed in patients with more severe anxiety symptoms at baseline (score ≥5 on HAMD anxiety subscore). Agomelatine had a significantly greater effect on anxiety symptoms than both placebo and a number of comparator antidepressants. In more anxious depressed patients, agomelatine had a significantly greater effect on anxiety and depressive symptoms than both placebo and comparator antidepressants. Once-a-day oral agomelatine is a new, efficacious alternative option for the treatment of anxiety in patients with major depression.