Anxiety In Depressed Patients Research Articles

The Effects of Variation in the GABAA Receptor Gene on Anxious Depression are Mediated by the Functional Connectivity Between the Amygdala and Middle Frontal Gyrus.

γ-aminobutyric acid (GABA) and its main receptor, the GABAA receptor, are implicated in major depressive disorder (MDD). Anxious depression (AD) is deemed to be a primary subtype of MDD. The amygdala and the dorsolateral prefrontal cortex (DLPFC) are key brain regions involved in emotional regulation. These regions contain the most GABAA receptors. Although the GABAergic deficit hypothesis of MDD is generally accepted, few studies have demonstrated how GABAA receptor gene polymorphisms affect the functions of specific brain regions, in particular, the amygdala and the DLPFC. The sample comprised 83 patients with AD, 70 patients with non-anxious depression (NAD), and 62healthy controls (HC).All participants underwent genotyping for polymorphisms of GABAA receptor subunit genes, followed by a resting-state fMRI scan. The HAMD-17 was used to evaluate the severity of MDD. ANOVA was performed to obtain the difference in the imaging data, GABAA receptor multi-locus genetic profile scores (MGPS), and HAMD-17 scores among three groups, then the significant differences between AD and NAD groups were identified. Mediating effect analysis was used to explore the role of functional connectivity (FC) between the amygdala and DLPFC in the association between the GABAA receptor gene MGPS and AD clinical features. Compared with the NAD group, the AD group had a higher GABAA receptor MGPS. AD patients exhibited a negative correlation between the MGPS and FC of the right centromedial (CM) subregion, and the right middle frontal gyrus (MFG). A negative correlation was also observed between the MGPS and anxiety/somatic symptoms. More importantly, the right CM and right MFG connectivity mediated the association between the GABAA receptor MGPS and anxiety/somatic symptoms in patients with AD. The decreased FC between the right MFG and right CM subregion mediates the association between GABAA receptor MGPS and AD.

Sex differences and risk factors of self-reported suicide attempts in middle-aged Chinese Han patients with first-episode drug-naïve anxious depression: a large-scale cross-sectional study.

This study aims to investigate sex differences and risk factors for self-reported suicide attempts among Chinese Han middle-aged patients with first-episode drug-naïve (FEDN) anxious depression (AD). A total of 1796 patients with FEDN major depressive disorder were enrolled in this study, including 341 middle-aged patients with AD. We compared the prevalence, demographics, and clinical characteristics of suicide attempts between male and female patients with FEDN middle-aged AD. We also explored the risk factors for self-reported suicide attempts in this population using binary logistic regression analysis. The male/female ratio was 91/250 and the age of onset was 51.50 ± 4.13. Our results showed that there were no significant sex differences in the prevalence of self-reported suicide attempts in middle-aged patients with FEDN AD. However, we did find significant differences in several demographic and clinical characteristics between self-reported suicide attempters and non-suicide attempters. Moreover, severe anxiety, measured by the Hamilton Anxiety Rating Scale score, was identified as a risk factor for self-reported suicide attempts in female middle-aged AD patients. Additionally, elevated thyroid peroxidase antibody (TPOAb) levels were linked to self-reported suicide attempts in male AD patients. Our findings suggest that there are no significant sex differences in the prevalence of self-reported suicide attempts in this population, but there may be sex-specific risk factors for self-reported suicide attempts in middle-aged AD. Clinical psychiatrists need to pay attention to thyroid hormone levels in middle-aged anxious depression.

The Clinical Characteristics and Manifestation of Anxious Depression Among Patients With Major Depressive Disorders-Results From a Taiwan Multicenter Study.

Anxious depression is a prevalent characteristic observed in Asian psychiatric patients diagnosed with major depressive disorder (MDD). This study aims to investigate the prevalence and clinical presentation of anxious depression in Taiwanese individuals diagnosed with MDD. We recruited psychiatric outpatients aged over 18 who had been diagnosed with MDD through clinical interviews. This recruitment took place at five hospitals located in northern Taiwan. We gathered baseline clinical and demographic information from the participants. Anxious depression was identified using a threshold of an anxiety/somatization factor score ≥7 on the 21-item Hamilton Rating Scale for Depression (HAM-D). In our study of 399 patients (84.21% female), 64.16% met the criteria for anxious depression. They tended to be older, married, less educated, with more children, and an older age of onset. Anxious depression patients had higher HAM-D and Clinical Global Impression-Severity scale score, more panic disorder (without agoraphobia), and exhibited symptoms like agitation, irritability, concentration difficulties, psychological and somatic anxiety, somatic complaints, hypochondriasis, weight loss, and increased insight. Surprisingly, their suicide rates did not significantly differ from non-anxious depression patients. This highlights the importance of recognizing and addressing these unique characteristics. Our study findings unveiled that the prevalence of anxious depression among Taiwanese outpatients diagnosed with MDD was lower compared to inpatients but substantially higher than the reported rates in European countries and the United States. Furthermore, patients with anxious depression exhibited a greater occurrence of somatic symptoms.

The 5-HT1A receptor biased agonists, NLX-204 and NLX-101, like ketamine, elicit rapid-acting antidepressant activity in the rat chronic mild stress model via cortical mechanisms.

The highly selective 5-HT1A serotonin receptor "biased" agonists NLX-101 and NLX-204 display, like ketamine, potent and efficacious rapid-acting antidepressant (RAAD) activity in the rat chronic mild stress (CMS) model with systemic (i.p.) administration. They rapidly (within 1 day) reverse anhedonia (i.e., CMS-induced sucrose consumption deficit), attenuate working memory deficit (novel object recognition: NOR), and decrease anxiety behavior in the elevated-plus maze (EPM). Here, we sought to explore the contribution of prefrontal cortex (PFC) 5-HT1A receptor activation in the RAAD activity of NLX compounds. In male Wistar rats, unilateral PFC microinjections of NLX-204 and NLX-101 (16 µg), like ketamine (10 µg), reproduced the effects of their systemic administration: they reversed CMS-induced sucrose consumption deficit, attenuated anxiety (EPM), and reduced working memory deficits (NOR). In addition, unilateral PFC microinjections of the selective 5-HT1A antagonist, WAY-100,635 (2 µg), attenuated the beneficial effects of systemic NLX-204 and NLX-101 (0.16 mg/kg i.p.) in the sucrose intake and NOR models, indicating that these compounds exert their RAAD activity specifically through activation of PFC 5-HT1A receptors. These data indicate that 5-HT1A receptor biased agonists share with ketamine a common neuroanatomical site for RAAD activity, which can be obtained not only by targeting glutamatergic/NMDA neurotransmission (ketamine's primary mechanism of action) but also by activating 5-HT1A receptors, as is the case for the NLX compounds. The present observations also reinforce the notion that biased agonism at 5-HT1A receptors constitutes a promising strategy to achieve RAAD effects, with additional benefits against cognitive deficits and anxiety in depressed patients, without ketamine's troublesome side effects.

Heart rate variability, interoceptive accuracy and functional connectivity in middle-aged and older patients with depression

Background and objectiveMajor depressive disorder (MDD) is associated with increased cardiac morbidity. Reduced heart rate variability (HRV) as well as lower interoceptive accuracy (IAc) have been observed in MDD as possible sympathomimetic mechanisms related to insula activity. The salience network (SN) anchored by the insula has been posited as a crucial functional network for cardiac sensations and the default mode network (DMN) for MDD. This study aimed to investigate the relation between insula-centered and depression-related brain networks, IAc and HRV in patients with depression as a possible mechanism by which MDD increases cardiac morbidity. Methods30 depressed inpatients and 30 healthy subjects (derived from the population-based “Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression” cohort study, STAAB) all over 50 years were examined. HRV and IAc were assessed via electrocardiogram and a heartbeat perception task prior to a 3 T resting-state functional magnetic resonance imaging. Seed-to-voxel resting-state functional connectivity (FC) analysis was conducted with six seeds in the insula and two seeds in the DMN. ResultsDepressed patients on the one hand showed decreased FC between insula cortex and frontal as well occipital cortical brain regions compared to controls. Depressed patients on the other hand exhibited higher FC between the medial prefrontal cortex and the insula cortex compared to controls. However, depressed patients did not differ in HRV nor in IAc compared to controls. ConclusionThus, differences in insula-related brain networks in depression in our study were not mirrored by differences in HRV and IAc. Future research is needed to define the mechanism by which depression increases cardiac morbidity.

Effects of Anxious Depression on Antidepressant Treatment Response.

Anxious depression represents a subtype of major depressive disorder and is associated with increased suicidality, severity, chronicity and lower treatment response. Only a few studies have investigated the differences between anxious depressed (aMDD) and non-anxious depressed (naMDD) patients regarding treatment dosage, serum-concentration and drug-specific treatment response. In our naturalistic and prospective study, we investigated whether the effectiveness of therapy including antidepressants (SSRI, SNRI, NaSSA, tricyclics and combinations) in aMDD patients differs significantly from that in naMDD patients. In a sample of 346 patients, we calculated the anxiety somatization factor (ASF) and defined treatment response as a reduction (≥50%) in the Hamilton Depression Rating Scale (HDRS)-21 score after 7 weeks of pharmacological treatment. We did not observe an association between therapy response and the baseline ASF-scores, or differences in therapy outcomes between aMDD and naMDD patients. However, non-responders had higher ASF-scores, and at week 7 aMDD patients displayed a worse therapy outcome than naMDD patients. In subgroup analyses for different antidepressant drugs, venlafaxine-treated aMDD patients showed a significantly worse outcome at week 7. Future prospective, randomized-controlled studies should address the question of a worse therapy outcome in aMDD patients for different psychopharmaceuticals individually.

The 5-HT1A receptor biased agonists, NLX-204 and NLX-101, display ketamine-like RAAD and anti-TRD activities in rat CMS models.

NLX-101 and NLX-204 are highly selective serotonin 5-HT1A 'biased' agonists, displaying potent and efficacious antidepressant-likeactivity upon acute administration in models such as the forced swim test. we compared the effects of repeated administration of NLX-101, NLX-204 and ketamine in the chronic mild stress (CMS) model of depression, considered to have high translational potential, on sucrose consumption (anhedonia measure), novel object recognition (NOR; working memory measure) and elevated plus maze (EPM; anxiety measure) in male Wistar and Wistar-Kyoto rats (the latter being resistant to classical antidepressants). in Wistar rats, NLX-204 and NLX-101 (0.08-0.16mg/kg i.p.), like ketamine (10mg/kg i.p.) dose-dependently reversed CMS-induced sucrose intake deficit from treatment Day 1, with nearly full reversal observed at the higher dose at Days 8 and 15. These effects persisted for 3weeks following treatment cessation. In the NOR test, both doses of NLX-101/NLX-204, and ketamine, rescued the deficit in discrimination index caused by CMS on Days 3 and 17; all three compounds increased time spent in open arms (EPM) but only NLX-204 achieved statistical significance on Days 2 and 16. In Wistar-Kyoto rats, all 3 compounds were also active in the sucrose test and, to a lesser extent, in the NOR and EPM. In non-stressed rats (both strains), the three compounds produced no significanteffects in all tests. these observations further strengthen the hypothesis that biased agonism at 5-HT1A receptors constitutes a promising strategy to achieve rapid-acting/sustained antidepressant effects combined with activity against TRD, in addition to providing beneficial effects against memory deficit and anxiety in depressed patients.

Directed brain network analysis in anxious and non-anxious depression based on EEG source reconstruction and graph theory

Patients with anxious depression have more severe symptoms, more side effects, and higher resistance to treatment than patients with non-anxious depression; therefore, it is crucial to clarify the differences between these two types of patients. In this study, a 5-minute resting EEG was recorded in 15 patients with anxious depression and 9 patients with non-anxious depression under eyes open and closed conditions. Sixty-eight subcortical regions were extracted using exact low resolution brain electromagnetic tomography (eLORETA). The directed transfer function was then used to construct brain networks. Specific features based on graph theory including the strength of connectivity and betweenness centrality (BC) were calculated from the networks. Finally, significant features were selected using the Mann-Whitney U test, and patients were classified into anxious and non-anxious depressive groups using the Support Vector Machine (SVM). Results showed that features of outward connectivity strength led to the highest accuracy, F-score, and specificity with 91.66%, 87. 5%, and 100% in the eyes-closed state, respectively. Moreover, we found that the strength of connectivity in both directions increased for the anxious depressive group during the eyes-open state. In particular, higher outward connectivity was observed in the right hemisphere for the anxious depressive group. Further findings also revealed that features with the most significant difference were mainly associated with the beta band. In addition, significant increased inward and outward connectivity and decreased nodal centrality were observed in the posterior regions of the default mode network. These preliminary findings might provide new insights into the recognition of anxious depressed patients.

Functional connectivity differences in the amygdala are related to the antidepressant efficacy of ketamine in patients with anxious depression

BackgroundThe antidepressant effects of ketamine in patients with anxious depression (AD) remain unclear. Functional connectivity (FC) differences in the amygdala have been linked to depression improvement after ketamine treatment in depressed patients, but their role in AD patients is uncertain. We investigated the correlation between depression improvement after ketamine treatment and amygdala FC in AD patients. MethodsThirty-one AD patients and 18 non-anxious depression (NAD) patients received six intravenous ketamine infusions (0.5 mg/kg) over two weeks. AD patients were further divided into responders (defined as a ≥50% MADRS total score reduction on day 13) and non-responders. The FC of the amygdala subregions, including the laterobasal amygdala (LBA), centromedial amygdala (CMA), and superficial amygdala, were compared between the groups. Receiver operating characteristic curves were used to predict treatment response after ketamine infusions. ResultsThe baseline FC difference in the left LBA and the left precuneus between responders and non-responders among AD patients was found to be associated with depression improvement and was a significant predictor of treatment response to ketamine. A marked reduction in baseline LBA-precuneus FC after ketamine infusion was observed in responders. Unlike in patients with NAD, a lower right CMA-right middle temporal gyrus FC was found in AD patients. LimitationsThe sample size is rather small. ConclusionsOur findings may suggest that amygdala FC is a significant predictor of treatment response to ketamine infusions in patients with AD. Further studies exploring the potential antidepressant mechanisms of ketamine may aid in the treatment of AD patients.

Antianhedonic effects of serial intravenous subanaesthetic ketamine in anxious versus nonanxious depression

ObjectivesPatents with anxious depression have poor treatment outcomes compared to their nonanxious counterparts. Ketamine has a rapid and robust antianhedonic effect, independent of depressive symptoms. The difference in the antianhedonic effect of ketamine between patients with anxious versus nonanxious depression remains unknown. MethodsOne hundred thirty-five Chinese individuals with anxious depression (n = 92) and nonanxious depression (n = 43) received six intravenous infusions of ketamine (0.5 mg/kg). Post hoc analyses compared changes in anhedonic symptoms, as measured by the Montgomery–Åsberg Depression Rating Scale (MADRS), between patients with anxious depression (defined by a Hamilton Depression Rating Scale Anxiety-Somatization score ≥7) and nonanxious depression. ResultsIn this study, 68.1 % of patients were found to have anxious depression. Anxious depressed patients were associated with a relatively lower antianhedonic response (47.8 % versus 51.2 %, p > 0.05) and remission (17.4 % versus 27.9 %, p > 0.05) than their nonanxious counterparts. When compared to baseline, a significant reduction in anhedonic symptoms was observed from the first infusion to the last infusion and 2-week follow-up in both groups (all p < 0.05). A linear mixed model did not find a significant group main effect on the MADRS anhedonia subscale scores (F = 0.5, p = 0.46). ConclusionThis preliminary study shows that repeated intravenous infusions of ketamine rapidly ameliorate anhedonic symptoms in individuals experiencing anxious depression, but these individuals displayed a weaker antianhedonic response to ketamine than nonanxious depressed patients.

Effectiveness of aromatherapy with inhaled lavender essential oil and breathing exercises on ECT-related anxiety in depressed patients

Background and aims Electroconvulsive therapy (ECT) is considered a safe, effective, and significant treatment in patients suffering from a major depressive disorder. Anxiety caused by this invasive treatment may impose several side effects on patients. The purpose of this study was to evaluate the effectiveness of aromatherapy with inhaled lavender essential oil and breathing exercises on ECT-related anxiety in depressed patients.Methods In this randomized controlled clinical trial, 90 depressed patients were selected and divided into three groups: aromatherapy, breathing exercise, and routine care using a random allocation method. Before undergoing ECT, the aromatherapy group was exposed to the inhaled lavender essential oil (n = 30), the breathing exercise group performed the breathing exercises (n = 30), and the routine care group received routine care (n = 30). Before (20 min) and after the intervention (30 min later), patients' anxiety was assessed using Beck Anxiety Inventory.Results After the intervention, the results revealed that anxiety score changes were statistically significant among the three groups (p < 0.001). In addition, it was found that the patients’ mean anxiety scores significantly decreased in the aromatherapy and breathing exercise groups compared to with the pre-intervention scores (p < 0.001).Conclusion Aromatherapy with inhaled lavender essential oil and breathing exercises can be considered by clinical nurses as simple, applicable, and effective interventions to reduce ECT-related anxiety in depressed patients.

Obsessive–compulsive symptoms in anxiety and depressive disorders: Influence of recent and/or traumatic life events

IntroductionA high prevalence of obsessive–compulsive symptoms (OCSs) in anxiety-depressive disorders ranging from 30 to 67% has been described. ObjectiveThis study aims to assess the presence and persistence of OCSs in an outpatient sample of subjects with anxiety and depressive disorders, as well as its relationship with recent life events (RLEs) and/or traumatic experiences (TEs). MethodWe conducted a prospective, observational, analytical study of 200 subjects with DSM-5 diagnoses of anxiety and/or depression. Participants were included by consecutive sampling and were evaluated at baseline and after 6–12 months (mean 8.5 months) of follow-up. The severity of the symptoms was assessed through the Hamilton Anxiety Scale (HARS) and Hamilton Scale for the evaluation of depression (HRSD-17), and comorbidity was assessed through the International Neuropsychiatric Interview (MINI). The Revised Inventory of Obsessions and Compulsions (OCI-R), the Recent Vital Changes Questionnaire (CVSV), and the Diagnostic Scale for Post-Traumatic Stress (PDS) were also administered. Results54% of the sample presented OCSs, and 30.5% presented one or more TEs throughout life. At the baseline visit, the presence of OCSs was associated with the severity of depressive symptoms (p=0.028), the presence of TEs (p<0.01), symptoms of post-traumatic stress disorder (p<0.01) and the number of RLEs (p<0.01). Response rate at follow-up was 38%, and persistence of OCSs was found in 60.5% of patients, independent of depressive or anxious symptoms, but was associated with the number of RLEs (p<0.01). ConclusionThe presence of OCSs in patients with anxiety and depressive disorders is frequent and persistent. Anxious-depressive patients with a history of TEs and RLEs had higher OCS levels. These findings highlight the importance of early detection and the use of therapeutic strategies focused on resilience to stress and trauma.

Reminiscence therapy-based care program for reducing anxiety and depression in glioma survivors: A randomized controlled trial.

This study aimed to evaluate the effect of reminiscence therapy-based care (RTBC) program on anxiety, depression, patients satisfaction, and survival benefit in glioma patients after tumor resection.A total of 150 eligible glioma patients were randomized into the RTBC group (N = 75, receiving RTBC) and the control care (CC) group (N = 75, receiving CC). Interventions were performed twice a month for 12 months. Anxiety was evaluated by Hospital Anxiety and Depression Scale (HADS) for anxiety score and Zung self-rating anxiety scale (SAS) score; meanwhile, depression was evaluated by HADS for depression score and Zung self-rating depression scale (SDS) score; additionally, patients satisfaction was scored. A 36-month follow-up was performed, and accumulating overall survival (OS) were calculated.Both anxiety level and depression level were reduced in the RTBC group compared with the CC group at month 9 and month 12 (all P < .05); meanwhile, the proportion of anxious patients and depressed patients were decreased in the RTBC group compared with the CC group at month 12 (all P < .05). Moreover, patients satisfaction scores were increased in the RTBC group compared to the CC group at month 6, month 9, and month 12 (all P < .05). Additionally, accumulating OS showed an increasing tendency in the RTBC group compared to the CC group, but no statistical significance was observed (P = .186).RTBC program ameliorates anxiety, depression, and promotes patients satisfaction in glioma patients after tumor resection.

Obsessive-compulsive symptoms in anxiety and depressive disorders: Influence of recent and/or traumatic life events.

A high prevalence of obsessive-compulsive symptoms (OCSs) in anxiety-depressive disorders ranging from 30 to 67% has been described. This study aims to assess the presence and persistence of OCSs in an outpatient sample of subjects with anxiety and depressive disorders, as well as its relationship with recent life events (RLEs) and/or traumatic experiences (TEs). We conducted a prospective, observational, analytical study of 200 subjects with DSM-5 diagnoses of anxiety and/or depression. Participants were included by consecutive sampling and were evaluated at baseline and after 6-12 months (mean 8.5 months) of follow-up. The severity of the symptoms was assessed through the Hamilton Anxiety Scale (HARS) and Hamilton Scale for the evaluation of depression (HRSD-17), and comorbidity was assessed through the International Neuropsychiatric Interview (MINI). The Revised Inventory of Obsessions and Compulsions (OCI-R), the Recent Vital Changes Questionnaire (CVSV), and the Diagnostic Scale for Post-Traumatic Stress (PDS) were also administered. 54% of the sample presented OCSs, and 30.5% presented one or more TEs throughout life. At the baseline visit, the presence of OCSs was associated with the severity of depressive symptoms (p=0.028), the presence of TEs (p<0.01), symptoms of post-traumatic stress disorder (p<0.01) and the number of RLEs (p<0.01). Response rate at follow-up was 38%, and persistence of OCSs was found in 60.5% of patients, independent of depressive or anxious symptoms, but was associated with the number of RLEs (p<0.01). The presence of OCSs in patients with anxiety and depressive disorders is frequent and persistent. Anxious-depressive patients with a history of TEs and RLEs had higher OCS levels. These findings highlight the importance of early detection and the use of therapeutic strategies focused on resilience to stress and trauma.

Research on Cognitive Function in Anxious Depression Patients in China

Background: This study aimed to evaluate cognitive function in patients with anxious depression.Methods: This was a part of the “Objective Diagnostic Indicators and Individualized Drug Intervention of Major Depressive Disorder (MDD)” study. All participants, including patients with MDD and healthy controls (HCs), completed the 17-item Hamilton Depression Scale (HAMD17) and the Hamilton Anxiety Scale (HAMA). Anxious depression was defined as a HAMD17 anxiety/somatization factor score ≥7. Cognitive function was assessed at baseline and at the end of week 8. HC cognitive function was assessed at baseline.Results: A total of 1048 people were included in the analysis, including 328 patients in the anxious depression group (G1=328), 221 patients in the MDD without anxious depression group (G2=221), and 499 in the HC group (G3=499). There were significant differences in the HAMA at baseline (t=13.050, p<0.001), HAMD17 at baseline (t=16.722, p<0.001), and HAMA at weekend 8 (z=-3.477, p=0.001) between G1 and G2. Cognitive functioning on the Hopkins Verbal Learning Test-Revised (HVLT-R) (t=2.948, p=0.003) and the Brief Visual Memory Test-Revised (BVMT-R) (t=2.843, p=0.005) was better in G1 than in G2 at baseline. Cognitive functioning on the HVLT-R (OR=1.081, p=0.006) was better in G1 than in G2 at weekend 8. The Stroop-color-word test (SCWT) (OR=0.976, p=0.004) and the Continuous Performance Test (CPT) (OR=0.698, p=0.007) showed significant differences at baseline; however, after the acute treatment phase, there were no significant differences in executive function (assessed by SCWT) (p=0.148) or attention/vigilance (assessed by CPT) (p=0.416) between G1 and G3.Conclusions: Patients with anxious depression have more severe depressive symptoms but better cognitive function, especially for verbal learning, compared with nonanxious depression patients. After the acute treatment phase, executive function and attention/vigilance in anxious depression patients may be remitted.

Brain functional abnormalities in the amygdala subregions is associated with anxious depression

BackgroundFunctional neuroimaging studies have provided strong support for the critical role the amygdala plays in emotional processing. The amygdala is composed of three primary distinct nuclei that have different functions in emotional regulation. Anxious depression (AD) was considered as a common dimensional symptom of Major Depressive Disorder (MDD). However, the neuroimaging basis of this special MDD subtype remains largely unknown. Therefore, it is necessary to study the functional connectivity of the amygdala's subregions in AD patients. MethodsEighty-three patients with AD, 70 non-anxious depression (NAD) patients, and 62 healthy controls were collected. Age and gender were well-matched. The functional connectivity of three amygdala subregions, including centromedial (CM), laterobasal (LB), and superficial (SF), were compared among the AD, NAD, and HC groups. The correlation between functional connectivity in the amygdala subregions and the HAMD factor scores were further analyzed. ResultsPatients with AD showed decreased functional connectivity between the right CM/LB and the right middle frontal gyrus relative to the NAD group. The NAD patients showed decreased functional connectivity between the right precentral gyrus and the right CM/SF compared to the HC group. The functional connectivity between the right CM and the right middle frontal gyrus was negatively correlated with the anxiety/somatization factor. ConclusionThe functional connectivity between the right CM/LB and the right middle frontal gyrus might be the neurobiological mechanism of anxious depression. The FC between the right CM and the right middle frontal gyrus may help to explain the special clinical feature of the AD patients.

Blockade of NOP receptor modulates anxiety-related behaviors in mice exposed to inescapable stress.

Depression and anxiety frequently co-occur, and this has important clinical implications. Previous studies showed that activation of the nociceptin/orphanin FQ receptor (NOP) elicits anxiolytic effects, while its blockade promotes consistent antidepressant actions. NOP antagonists are effective in reversing footshock-induced depressive-like behaviors, but their effects on stress-induced anxiety are still unclear. This study aimed to investigate the effects of the NOP antagonist SB-612111 on footshock stress-induced anxiety behaviors. Male Swiss mice were exposed to inescapable electric footshock stress, and behavioral phenotype was screened based on the ability to escape from footshock (i.e., helpless or non-helpless). Animals were then treated with diazepam (1mg/kg) and SB-612111 (0.1-10mg/kg), and their behavior was assessed in the elevated plus-maze (EPM) and open field test. When compared with non-stressed mice, helpless, but not non-helpless, animals displayed significant reductions in the time spent in and entries into open arms in the EPM. Diazepam significantly increased open arms exploration in helpless, non-helpless, and non-stressed mice. However, treatment with the NOP antagonist SB-612111 was inactive in naive mice, while it reversed anxiogenic-related behaviors in helpless mice and increased anxiety states in non-helpless mice. No effects on locomotion were observed. Helpless mice displayed increased anxiety compared to non-stressed and non-helpless animals, thus supporting use of this approach as an animal model to investigate anxiety/depression comorbidity. Additionally, SB-612111 modulated anxiety-like behaviors in male mice depending on individual stress susceptibility. Ultimately, NOP antagonists could be useful for treating anxiety in depressed patients.

Reduced Resting State Neural Activity in the Right Orbital Part of Middle Frontal Gyrus in Anxious Depression.

BackgroundAnxious depression (AD), which is generally recognized as a common clinical subtype of major depressive disorder (MDD), holds distinctive features compared with unanxious depression (UAD). However, the neural mechanism of AD still remains unrevealed. To give insight to it, we compared resting-state functional magnetic resonance amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC) between AD and UAD patients.MethodThe data were collected from 60 AD patients, 38 UAD patients, and 60 matched healthy controls. The ALFF and seed-based FC were examined. Pearson correlations were computed between ALFF/FC and clinical measures.ResultsIn Comparison with the UAD group, the ALFF value of the right orbital part of middle frontal gyrus (RO-MFG) decreased in AD group. Specifically, the ALFF values of the RO-MFG were negatively correlated with retardation factor scores in AD group (r = -0.376, p = 0.003).ConclusionsAD patients exhibited disturbed intrinsic brain function compared with UAD patients. The decreased activity of the RO-MFG is indicative of the alterations involved in the neural basis of AD.

What is anxious depression? Overlap and agreement between different definitions

Anxiety is common in depressed patients. However, a problem with the research on the significance of anxiety in depressed patients is that anxiety has been characterized in different ways. Little research has examined the concordance and overlap between the various definitions of anxious depression. With research on the DSM-5 anxious distress specifier just beginning, it will be important to understand how defining anxious depression according to DSM-5 agrees with previously studied definitions. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project we examined the association between the DSM-5 anxious distress specifier and 6 other approaches towards defining anxious depression. Three hundred thirty-one patients with a principal diagnosis of major depressive disorder were evaluated with semi-structured diagnostic interviews. The mean number of anxious depression definitions met was 4.7 (SD = 2.1). Only 4.2% (n = 14) of the 331 patients did not meet any anxious depression definition, and 28.1% (n = 93) met all 7 definitions. The level of agreement between the definitions was significant, albeit modest (median kappa = .28). The modest association between the different definitions of anxious depression suggests that the results based on one approach towards subtyping may not generalize to the DSM-5 anxious distress specifier. It therefore cannot be assumed that the DSM-5 anxious distress specifier is valid just because other definitions of anxious depression have been shown to be valid.

Validity of the DSM-5 anxious distress specifier for major depressive disorder.

DSM-5 introduced the anxious distress specifier in recognition of the clinical significance of anxiety in depressed patients. Recent studies that supported the validity of the specifier did not use measures that were designed to assess the criteria of the specifier but instead approximated the DSM-5 criteria from scales that were part of an existing data base. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we examined the validity of the specifier diagnosed with a semistructured interview. Two hundred sixty patients with a principal diagnosis of major depressive disorder were evaluated with semistructured diagnostic interviews. The patients were rated on clinician rating scales of depression, anxiety and irritability, and completed self-report measures. Approximately three-quarters of the depressed patients met the criteria for the anxious distress specifier. Patients with anxious distress had a higher frequency of anxiety disorders, particularly panic disorder and generalized anxiety disorder, as well as higher scores on measures of anxiety, depression, and anger. The patients meeting the anxious distress subtype reported higher rates of drug use disorders, poorer functioning during the week before the evaluation, and poorer coping ability compared to the patients who did not meet the anxious distress specifier. Moreover, anxious distress was associated with poorer functioning and coping after controlling for the presence of an anxiety disorder. The results of the present study indicate that anxious distress is common in depressed patients and support the validity of the DSM-5 anxious distress specifier.