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Dysregulation of fear processing through altered sensitivity to threat is thought to contribute to the development of anxiety disorders and major depressive disorder (MDD). However, fewer studies have examined fear processing in MDD than in anxiety disorders. The current study used propensity matching to examine the hypothesis that comorbid MDD and anxiety (AnxMDD) shows greater neural correlates of fear processing than MDD, suggesting that the co-occurrence of AnxMDD is exemplified by exaggerated defense related processes. 195 individuals with MDD (N = 65) or AnxMDD (N = 130) were recruited from the community and completed multi-level assessments, including a Pavlovian fear learning task during functional imaging. Visual images paired with threat (conditioned stimuli: CS+) were compared to stimuli not paired with threat (CS-). MDD and AnxMDD showed significantly different patterns of activation for CS+ vs CS- in the dorsal anterior insula/inferior frontal gyrus (partial eta squared; ηp2 = 0.02), dorsolateral prefrontal cortex (ηp2 = 0.01) and dorsal anterior/mid cingulate cortex (ηp2 = 0.01). These differences were driven by greater activation to the CS+ in AnxMDD versus MDD. Limitations include the cross-sectional design, a scream US rather than shock and half the number of MDD as AnxMDD participants. AnxMDD showed a pattern of increased activation in regions identified with fear processing. Effects were consistently driven by threat, further suggesting fear signaling as the emergent target process. Differences emerged in regions associated with salience processing, attentional orienting/conflict, self-relevant processing and executive functioning in comorbid anxiety and depression, thereby highlighting potential treatment targets for this prevalent and treatment resistant group. • Few studies examine differences between anxious- and non-anxious depression. • Neural responses during fear conditioning were recorded in these groups. • Groups showed differential activation in insular, cingulate, and prefrontal regions. • Differences were driven by greater reactivity to the CS+ in anxious depression. [ABSTRACT FROM AUTHOR]

Anxious depression is a prevalent subtype of depression associated with adverse outcomes such as higher depression severity and higher rates of suicidality. This study leveraged a state-wide research registry of depressed and/or suicidal youth to compare the prevalence, clinical correlates, and symptom patterns of those with versus without anxious depression. We included baseline data from 797 participants (ages 8–20) with a diagnosis of a depressive disorder. A score on the Generalized Anxiety Disorder Scale (GAD-7) ≥ 10 was used to define individuals with and without anxious depression. A structured battery was used to capture psychiatric diagnostic status, depression/anxiety severity, suicide risk, history of trauma, functioning, and resilience. The prevalence of anxious depression among youth with depressive disorders was 59.5 % (n = 474). Youth with anxious depression had greater depression severity and anxiety symptoms, higher suicidality, and a higher prevalence of comorbid anxiety disorders than those without. Youth with anxious depression had greater impairment in functioning defined as worse pain interference, pain severity, fatigue, and social relationships compared to those without anxious depression. Youth with anxious depression also reported higher rates of depressive symptoms such as irritable mood, feelings of guilt, and psychomotor agitation compared to those without anxious depression. Anxious depression is associated with worse depression severity, higher suicidality, and lower functioning. Longitudinal work is needed to examine long-term courses of anxious depression to explore its stability as a diagnostic subcategory. • Anxious depression is a prevalent depression subtype primarily explored in adults. • In our sample of depressed youth (n = 747), 59.5 % had Anxious Depression. • It is associated with worse depression severity, suicidality, and functioning. • Longitudinal work is needed on the time-course and outcomes for Anxious Depression. [ABSTRACT FROM AUTHOR]

Using functional near-infrared spectroscopy (fNIRS) previous studies have found that activation differences in the dorsolateral prefrontal cortex (DLPFC) during an autobiographical memory task (AMT) under the condition of different emotional valences may be neurophysiological markers of depression and different depression subtypes. Additionally, compared with non-anxious depression, anxious depression presents abnormal hemodynamic activation in the DLPFC. This study aimed to use fNIRS to investigate hemodynamic activation in the DLPFC of depression patients with and without anxiety during AMT triggered by different emotional valence stimuli. We recruited 194 patients with depression (91 with non-anxious depression, 103 with anxious depression) and 110 healthy controls from Chinese college students. A 53-channel fNIRS was used to detect cerebral hemodynamic differences in the three groups during AMT. The results showed that: (1) the activation of oxy-Hb in the left DLPFC was significantly higher under positive emotional valence than under negative emotional valence for healthy controls and patients with non-anxious depression, while there was no significant difference between positive and negative emotional valence observed in response to anxious depression; and (2) Oxy-Hb activation under negative emotional valence was significantly higher in the anxious depression group than in the non-anxious depression group. This study revealed that the hemodynamic hyperactivation of negative emotional valence in the left DLPFC may be due to the neurophysiological differences between anxious and non-anxious patients with depression. • Activation in the left DLPFC may be the neurophysiological differences between anxious and non-anxious depression. • Activation in the left DLPFC was significantly higher under positive than negative valence for healthy controls and non-anxious depression. • No significant activation difference in the left DLPFC between positive and negative valence was observed in response to anxious depression. [ABSTRACT FROM AUTHOR]

Yali Zhu,1,* Weijia Yin,2,* Jun Ma,1 Lin Zhang1 1Department of Psychiatry, Wuhan Mental Health Center, Wuhan, People’s Republic of China; 2Department of Psychiatry, Suzhou Guangji Hospital, Suzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lin Zhang, Department of Psychiatry, Wuhan Mental Health Center, No.89, Gongnongbing Road, Wuhan, Hubei, People’s Republic of China, Email linzhang16@qq.comBackground: Anxious depression (AUD) is a common subtype of major depressive disorder (MDD) and has a significant negative impact on disease progression and patient prognosis. Our study aimed to determine the frequency of AUD in Chinese patients with MDD during their first hospitalization and to identify factors that may influence the emergence and intensity of these AUD.Methods: This study enrolled 981 Chinese MDD patients on their inaugural hospital admission. Data on demographic details, clinical profiles, and psychological symptoms-such as depression, anxiety, psychosis, and illness severity scores-were gathered and examined.Results: The study found that 10.30% of the target population exhibited AUD. Compared with the non-AUD group, the AUD group had higher scores on Hamilton Depression Scale (HAMD), Positive symptom subscale of the Positive and Negative Symptom Scale (PSS), and Clinical Global Impression Scale - Severity of Illness (CGI-SI) and higher levels of fasting blood glucose (FBG), total cholesterol (TC), body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressure (DBP). In addition, higher scores of HAMD, PSS and CGI-SI were risk factors for increasing the severity of anxiety, higher TC level was contrary.Conclusion: This study reveals the prevalence of AUD in hospitalized patients with MDD and identifies clinical factors that contribute to the onset and progression of AUD. Reporting these clinical features may help establish potential markers for early recognition and intervention.Keywords: major depressive disorder, anxious depression, metabolic parameter, clinical characteristic

Juan Qiao,1,2 Shiwan Tao,2 Yurong Sun,3,4 Jiabo Shi,2,5 Yu Chen,2,5 Shui Tian,3,4 Zhijian Yao,2,5 Qing Lu3,4 1Department of Psychology, Xuzhou East Hospital Affiliated to Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Department of Psychiatry, Brain Hospital Affiliated to Nanjing Medical University, Nanjing, People’s Republic of China; 3School of Biological Sciences and Medical Engineering, Southeast University, Nanjing, People’s Republic of China; 4Key Laboratory of Child Development and Learning Science, Ministry of Education, Nanjing, People’s Republic of China; 5Nanjing Brain Hospital, School of Medicine, Nanjing University, Nanjing, People’s Republic of ChinaCorrespondence: Zhijian Yao, Department of Psychiatry, Brain Hospital Affiliated to Nanjing Medical University, Nanjing, 210029, People’s Republic of China, Email zjyao@njmu.edu.cn Qing Lu, Email luq@seu.edu.cnBackground: 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.Methods: The sample comprised 83 patients with AD, 70 patients with non-anxious depression (NAD), and 62 healthy 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.Results: 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.Conclusion: The decreased FC between the right MFG and right CM subregion mediates the association between GABAA receptor MGPS and AD.Keywords: anxious depression, GABAA receptor, multi-locus genetic profile scores, dorsolateral prefrontal cortex, amygdala subregion

Abstract Background Anxious depression (AD) is a common subtype of major depressive disorder (MDD). Neuroimaging studies of AD have revealed inconsistent and heterogeneous brain alterations with the use of single-model methods. Therefore, it is necessary to explore the pathogenesis of AD using multi-model imaging analyses to obtain more homogeneous and robust results. Methods One hundred and eighty-two patients with MDD and 64 matched healthy controls (HCs) were recruited. Voxel-based morphometry (VBM) was used to estimate the gray matter volume (GMV) of all subjects. The GMV differences between the AD and non-anxious depression (NAD) participants were used as regions of interest (ROIs) for subsequent resting state functional connectivity (rs-FC) analyses. Correlation analysis was used to evaluate the associations between clinical symptoms and abnormal function in specific brain areas. Results Decreased GMV in the medial frontal gyrus (MFG) and the superior frontal gyrus (SFG) was observed in the AD group compared to the NAD group. Taking the MFG and SFG as ROIs, the rs-FC analysis revealed decreased FC between the left SFG and left temporal pole and between the left SFG and right MFG in the AD group compared to the NAD group. Finally, the FC between the left SFG and left temporal pole was negatively correlated with HAMD-17 scores in the AD group. Conclusion By combining the GMV and rs-FC models, this study revealed that structural and functional disruption of the affective network may be an important pathophysiology underlying AD. The structural impairment may serve as the foundation of the functional impairment.

Background: 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. Methods: The sample comprised 83 patients with AD, 70 patients with non-anxious depression (NAD), and 62 healthy 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. Results: 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. Conclusion: The decreased FC between the right MFG and right CM subregion mediates the association between GABAA receptor MGPS and AD. [ABSTRACT FROM AUTHOR]

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. Highlights: This study explores sex differences in self-reported suicide attempts among Chinese Han middle-aged patients with first-episode drug-naïve (FEDN) major depressive disorder (MDD) and anxious depression (AD). 1. No significant sex differences in the prevalence of self-reported suicide attempts were observed; however, important demographic and clinical differences between suicide attempters and non-suicide attempters were identified. 2. Middle-aged depression is associated with increased self-reported suicide attempts risk during ages 45–60 due to mood swings and hormonal changes. 3. Psychotic symptoms in MDD patients are linked to higher suicide risk, and severe anxiety, measured by the HAMA score, is a risk factor for self-reported suicide attempts in female middle-aged AD patients. 4. Elevated TPOAb levels are associated with self-reported suicide attempts in male AD patients. These findings emphasize the need for further research on sex-specific risk factors in middle-aged anxious depression to enhance suicide prevention strategies. [ABSTRACT FROM AUTHOR]

Background: Anxious depression (AD) is a common subtype of major depressive disorder (MDD). Neuroimaging studies of AD have revealed inconsistent and heterogeneous brain alterations with the use of single-model methods. Therefore, it is necessary to explore the pathogenesis of AD using multi-model imaging analyses to obtain more homogeneous and robust results. Methods: One hundred and eighty-two patients with MDD and 64 matched healthy controls (HCs) were recruited. Voxel-based morphometry (VBM) was used to estimate the gray matter volume (GMV) of all subjects. The GMV differences between the AD and non-anxious depression (NAD) participants were used as regions of interest (ROIs) for subsequent resting state functional connectivity (rs-FC) analyses. Correlation analysis was used to evaluate the associations between clinical symptoms and abnormal function in specific brain areas. Results: Decreased GMV in the medial frontal gyrus (MFG) and the superior frontal gyrus (SFG) was observed in the AD group compared to the NAD group. Taking the MFG and SFG as ROIs, the rs-FC analysis revealed decreased FC between the left SFG and left temporal pole and between the left SFG and right MFG in the AD group compared to the NAD group. Finally, the FC between the left SFG and left temporal pole was negatively correlated with HAMD-17 scores in the AD group. Conclusion: By combining the GMV and rs-FC models, this study revealed that structural and functional disruption of the affective network may be an important pathophysiology underlying AD. The structural impairment may serve as the foundation of the functional impairment. [ABSTRACT FROM AUTHOR]

Bingcong Zhao,1,2 Zhigang Li,3 Chuan Shi,4 Yan Liu,5 Yang Sun,3 Bin Li,1,2 Jie Zhang,6 Zhizhong Gong,7 Yuanzheng Wang,8 Xuehong Ma,9 Xinjing Yang,10 Huili Jiang,3 Yuanbo Fu,1,2 Xin Wang,1,2 Yang Li,6 Hengchia Liu,6 Tuya Bao,3 Yutong Fei11– 13 1Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing, People’s Republic of China; 3School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Psychological Assessment Center, Peking University Sixth Hospital, Beijing, People’s Republic of China; 5Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 6Department of Psychosomatic Medicine, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 7Division of Medical Affairs, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 8Department of Integrative TCM and Western Medicine, Peking University First Hospital, Beijing, People’s Republic of China; 9Department of Acupuncture & Moxibustion, Dongfang Hospital, the Second Clinical Medical College of Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 10Department of Traditional Chinese Medicine, South China Hospital of Shenzhen University, Shenzhen, People’s Republic of China; 11Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 12Institute of Excellence in Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 13Beijing GRADE Centre, Beijing, People’s Republic of ChinaCorrespondence: Tuya Bao, School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, No. 11, Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, People’s Republic of China, Email tuyab@263.net Yutong Fei, Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, No. 11, Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, People’s Republic of China, Email feiyt@bucm.edu.cnPurpose: Anxious depression (AD) is a common, distinct depression subtype. This exploratory subgroup analysis aimed to explore the effects of acupuncture as an add-on therapy of selective serotonin reuptake inhibitors (SSRIs) for patients with AD or non-anxious depression (NAD).Patients and Methods: Four hundred and sixty-five patients with moderate-to-severe depression from the AcuSDep pragmatic trial were included in analysis. Patients were randomly assigned to receive MA+SSRIs, EA+SSRIs, or SSRIs alone (1:1:1) for six weeks. AD was defined by using dimensional criteria. The measurement instruments included 17-items Hamilton Depression Scale (HAMD-17), Self-Rating Depression Scale (SDS), Clinical Global Impression (CGI), Rating Scale for Side Effects (SERS), and WHO Quality of Life-BREF (WHOQOL-BREF). Comparison between AD and NAD subgroups and comparisons between groups within either AD or NAD subgroups were conducted.Results: Eighty percent of the patients met the criteria for AD. The AD subgroup had poorer clinical manifestations and treatment outcomes compared to those of the NAD subgroup. For AD patients, the HAMD response rate, remission rate, early onset rate, and the score changes on each scale at most measurement points on the two acupuncture groups were significantly better than the SSRIs group. For NAD patients, the HAMD early onset rates of the two acupuncture groups were significantly better than the SSRIs group.Conclusion: For AD subtype patients, either MA or EA add-on SSRIs showed comprehensive improvements, with small-to-medium effect sizes. For NAD subtype patients, both the add-on acupuncture could accelerate the response to SSRIs treatment. The study contributed to the existing literature by providing insights into the potential benefits of acupuncture in combination with SSRIs, especially for patients with AD subtypes. Due to its limited nature as a post hoc subgroup analysis, prospectively designed, high-quality trials are warranted.Clinical Trials Registration: ChiCTR-TRC-08000297.Keywords: anxious depression, non-anxious depression, acupuncture, SSRIs, subgroup analysis

Psychotic symptoms (PS) frequently occur in young adults with anxious depression (AD), yet the mediators of the associations between depression and PS remain unclear. This study aimed to investigate the prevalence and risk factors of PS in first-episode and drug-naïve (FEDN) young adults with AD and attempted to elucidate the relationship between thyroid-stimulating hormone (TSH) levels, anxiety, depression, and PS, as well as to identify potential mediating roles. 369 FEDN young adults with AD were recruited. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale's positive subscale, the Hamilton Depression Rating Scale (HAMD), and the Hamilton Anxiety Rating Scale (HAMA). Fasting glucose, lipids, and thyroid function were also collected. The prevalence of PS in young adults with AD (21.68 %) was 12.24 times higher than in non-AD patients. The HAMD scores (P = 0.005, OR = 1.23), HAMA scores (P < 0.001, OR = 1.62), and TSH levels (P = 0.025, OR = 1.20) were significant predictors of PS. The combined area under the curve value for distinguishing young adults with AD with and without PS was 0.86. We also identified serial multiple mediating effects of TSH levels and anxiety on the association of depression with PS. These findings emphasize the role of anxiety and TSH levels as serial mediators of the association between depression and PS. Therefore, when treating PS in young adults with AD, it is important to focus not only on depression, but also on TSH levels and anxiety to maximize benefit. • Psychotic symptoms (PS) are common in young adults with anxious depression (AD). • The prevalence of PS in young adults with AD is significantly higher than in patients with non-AD. • Depression, anxiety, and thyroid-stimulating hormone (TSH) levels are predictors of PS in young patients with AD. • TSH levels and anxiety act as mediators in the association between depression and PS. • Treating PS in young adults with AD should address not only depression but also TSH levels and anxiety. [ABSTRACT FROM AUTHOR]

Background: The microbiota–gut–brain axis plays a critical role in neuropsychiatric disorders, particularly anxious depression, and attracts more attention gradually. Zhi Zi Chi decoction (ZZCD) consisting of Gardenia jasminoides J. Ellis and Glycine max (L.) Merr, is a classic formula in clinic and widely applied in anxiety and depression treatment. However, the underlying mechanisms of regulating microbiota–gut–brain axis in the treatment of anxious depression by oral administration of ZZCD remain elusive. Materials and Methods: In this project, we clarified the origin and preparation methods of the Gardenia jasminoides J. Ellis and Glycine max (L.) Merr and examined the chemical ingredients of ZZCD by liquid chromatograph mass spectrometer. Then, corticosterone combined with chronic restraint stress was applied to establish an anxious depression model. After treated with ZZCD standard decoction, based on enzyme‐linked immunosorbent assay (ELISA), 16S rRNA technology, high‐throughput sequencing, quantitative RT‐PCR and fecal microbiota transplantation (FMT), the multiple associations between nucleus accumbens and intestinal flora in anxious depression mice were determined to clarify the mechanism of ZZCD in the treatment of anxiety and depression disorder. Results: We found various substances with antidepressant and antianxiety properties in ZZCD such as rosiridin and oleanolic acid. ZZCD could alleviate depressive and anxiety behaviors in anxious depression mice via regulating the disturbance of gut microbiota. Meanwhile, the bioactive compounds of ZZCD might directly active on neurodevelopment and neuroimmune‐related genes. Furthermore, the secretion of prolactin and estrogen, and interfering with mitogen‐activated protein kinase (MAPK) and tumor necrosis factor (TNF) signaling pathways were mainly involved in the multi‐target therapeutic effects of ZZCD against anxiety and depression. Conclusions: These findings suggested that ZZCD exerts antidepressant effects pleiotropically through modulating the microbiota‐gut‐brain. [ABSTRACT FROM AUTHOR]

There have been many studies on the benefits of repeated ketamine infusions on patients' depression but few on the impact of ketamine on patients' long-term quality of life (QoL). This study investigated long-term QoL in individuals with depression, both anxious and nonanxious. A total of 107 individuals with a diagnosis of depression were included in the study. The patients were evaluated on Days 0, 13 and 26 and Months 6 and 9, and they received six ketamine infusions over the course of two weeks. The World Health Organization Quality of Life-BREF (WHOQOL-BREF) Scale and the Patient Health Questionnaire-9 (PHQ-9) Scale were used to measure depressive symptoms and QoL. Linear mixed models were used to evaluate depressive symptoms and QoL during ketamine treatment. A total of 67.2 % of patients were diagnosed with anxious depression. In the long term, there were no significant differences in the time-by-group interactions for general QoL (F = 0.510; P = 0.676), physical QoL (F = 2.092; P = 0.102), psychological QoL (F = 0.102; P = 0.959), social QoL (F = 2.180; P = 0.091), or environmental QoL (F = 1.849; P = 0.139) between the two groups. The main limitation of this study is its open-label design. The improvement in depression symptoms and QoL following ketamine treatment was not impacted by the presence or absence of anxiety in patients who were depressed prior to treatment. Only occasionally did depressed individuals with anxiety experience a worsening of their quality of life compared to those without anxiety. • we aimed to explore the long-term quality of life in anxious and non-anxious depression patients that was ignored in past years. • We included 107 patients with anxious and non-anxious depression who were given repeated ketamine infusions to evaluate the patients' outcomes and long-term quality. • Repeated ketamine infusions improved long-term QoL similarly between anxious and non-anxious depression patients. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a heterogeneous mental disorder, and accompanying anxiety symptoms, known as anxious depression (AD), are the most common subtype. However, the pathophysiology of AD may be distinct in depressed patients without anxiety (NAD) and remains unknown. This study aimed to investigate the relationship between functional connectivity and peripheral transcriptional profiles in patients with AD and NAD. Functional imaging data were collected to identify differences in functional networks among patients with AD (n = 66), patients with NAD (n = 115), and healthy controls (HC, n = 200). The peripheral transcriptional data were clustered as co-expression modules, and their associations with AD, AND, and HC were analyzed. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses of the genes in the significant module were performed. Correlation analysis was performed to identify functional network-associated gene co-expression modules. A network was identified which consisted of 23 nodes and 28 edges that were significantly different among three sample groups. The regions of the network were located in temporal and occipital lobe. Two gene co-expression modules were shown to be associated with NAD, and one of which was correlated with the disrupted network in the AD group. The biological function of this module was enriched in immune regulation pathways. The results suggested that immune-related mechanisms were associated with functional networks in AD. • The anxious depression is the most common subtype of depresison, and the pathophysiology of anxious depression may be distinct in non-anxious depression. • An FC network consisting of 23 nodes and 28 edges, mainly located in temporal and occipital regions, was associated with anxious depresion. • Peripheral transcriptional profiles showed that immune-related pathway might play important roles in MDD. • The immune-related biological processes were associated with disrupted functional connectivity in a widely distributed connectome centralized in paralimbic regions and the occipital lobe in patients with anxious depression. [ABSTRACT FROM AUTHOR]

Abstract—The study was aimed at investigating the peculiarities of the conformational changes in serum albumin in patients with anxious and melancholic depression. Albumin conformation was measured by the method of the subnanosecond laser time resolved fluorescence spectroscopy. Anxious depression was accompanied by a significant decrease in the values of the three amplitudes of the serum albumin in comparison with controls. In the melancholic depression, the values of all three amplitudes of serum albumin molecules were significantly elevated in comparison with controls. These results clearly indicate that anxious and melancholic depression are accompanied by oppositely directed changes in serum albumin conformation. [ABSTRACT FROM AUTHOR]

Abstract Background Anxious depression, which is a common subtype of major depressive disorder, has distinct clinical features from nonanxious depression. However, little is known about the neurobiological characteristics of anxious depression. In this study, we explored resting-state regional brain activity changes between anxious depression and nonanxious depression. Method Resting-state functional magnetic resonance (rs-fMRI) imaging data were collected from 60 patients with anxious depression, 38 patients with nonanxious depression, and 60 matched healthy controls (HCs). One-way analysis of variance was performed to compare the whole-brain fractional amplitude of low-frequency fluctuation (fALFF) in the three groups. The correlation between the fALFF values and the clinical measures was examined. Results Compared with those of HCs, the fALFF values in the left superior temporal gyrus (STG) in patients with anxious depression were significantly increased, while the fALFF values in the left middle temporal gyrus (MTG), left STG, and right STG in patients with nonanxious depression were significantly increased. Patients with anxious depression showed reduced fALFF values in the right STG compared with patients with nonanxious depression (p

Anxious depression is a common subtype of major depressive disorder (MDD) associated with adverse outcomes and severely impaired social function. It is important to clarify the underlying neurobiology of anxious depression to refine the diagnosis and stratify patients for therapy. Here we explored associations between anxiety and brain structure/function in MDD patients. A total of 260 MDD patients and 127 healthy controls underwent three-dimensional T1-weighted structural scanning and resting-state functional magnetic resonance imaging. Demographic data were collected from all participants. Differences in gray matter volume (GMV), (fractional) amplitude of low-frequency fluctuation ((f)ALFF), regional homogeneity (ReHo), and seed point-based functional connectivity were compared between anxious MDD patients, non-anxious MDD patients, and healthy controls. A random forest model was used to predict anxiety in MDD patients using neuroimaging features. Anxious MDD patients showed significant differences in GMV in the left middle temporal gyrus and ReHo in the right superior parietal gyrus and the left precuneus than HCs. Compared with non-anxious MDD patients, patients with anxious MDD showed significantly different GMV in the left inferior temporal gyrus, left superior temporal gyrus, left superior frontal gyrus (orbital part), and left dorsolateral superior frontal gyrus; fALFF in the left middle temporal gyrus; ReHo in the inferior temporal gyrus and the superior frontal gyrus (orbital part); and functional connectivity between the left superior temporal gyrus(temporal pole) and left medial superior frontal gyrus. A diagnostic predictive random forest model built using imaging features and validated by 10-fold cross-validation distinguished anxious from non-anxious MDD with an AUC of 0.802. Patients with anxious depression exhibit dysregulation of brain regions associated with emotion regulation, cognition, and decision-making, and our diagnostic model paves the way for more accurate, objective clinical diagnosis of anxious depression.

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. [ABSTRACT FROM AUTHOR]

Background: Anxious depression, which is a common subtype of major depressive disorder, has distinct clinical features from nonanxious depression. However, little is known about the neurobiological characteristics of anxious depression. In this study, we explored resting-state regional brain activity changes between anxious depression and nonanxious depression. Method: Resting-state functional magnetic resonance (rs-fMRI) imaging data were collected from 60 patients with anxious depression, 38 patients with nonanxious depression, and 60 matched healthy controls (HCs). One-way analysis of variance was performed to compare the whole-brain fractional amplitude of low-frequency fluctuation (fALFF) in the three groups. The correlation between the fALFF values and the clinical measures was examined. Results: Compared with those of HCs, the fALFF values in the left superior temporal gyrus (STG) in patients with anxious depression were significantly increased, while the fALFF values in the left middle temporal gyrus (MTG), left STG, and right STG in patients with nonanxious depression were significantly increased. Patients with anxious depression showed reduced fALFF values in the right STG compared with patients with nonanxious depression (p < 0.001, corrected). Within the anxious depression group, fALFF value in the right STG was positively correlated with the cognitive disturbance score (r = 0.36, p = 0.005 corrected). Conclusion: The bilateral STG and left MTG, which are related to the default mode network, appear to be key brain regions in nonanxious depression, while the right STG plays an essential role in the neuropathological mechanism of anxious depression. [ABSTRACT FROM AUTHOR]

Abstract Patients with depression require thorough clinical assessment, which should include symptom profile, severity and staging, personality factors, antecedent and concurrent psychiatric comorbidity, physical comorbidity, neurocognitive function, exposure to stressors in early life (e.g. trauma) or recently (e.g. bereavement), and protective factors. The presence of anxiety symptoms in a depressed patient is associated with more severe depression, increased suicidality and worse outcomes compared with non-anxious depression. A network meta-analysis of antidepressant treatments found that agomelatine, citalopram, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine and vortioxetine were all significantly more effective than other antidepressants for the treatment of depression, and that agomelatine, citalopram, escitalopram, fluoxetine, sertraline and vortioxetine were better tolerated than other antidepressants. Agomelatine has been shown to have two major effects—relieving depressive symptoms, and supporting symptomatic and functional recovery—and these benefits have been demonstrated in patients with depression as well as in patients with generalised anxiety disorder, including those with more severe symptoms. Agomelatine has also been shown to be efficacious and well tolerated in patients with depression plus concomitant anxiety symptoms. A pooled analysis of data from six agomelatine studies of depression (three placebo-controlled and three with active comparators—fluoxetine, sertraline and venlafaxine) found that agomelatine was significantly more effective than placebo at relieving the anxiety subscore on the Hamilton Depression Rating Scale, and that the difference between agomelatine and placebo was even more marked in the subgroup of patients with severe anxiety symptoms at baseline. Irrespective of the pharmacotherapy used in patients with depression, the likelihoods of response and remission are increased when pharmacotherapy is combined with psychotherapy, with this approach being more effective than either pharmacotherapy or psychotherapy alone. Persistence with treatment is important, and clinicians should therefore encourage patients to keep trying to obtain relief.

Patients with depression require thorough clinical assessment, which should include symptom profile, severity and staging, personality factors, antecedent and concurrent psychiatric comorbidity, physical comorbidity, neurocognitive function, exposure to stressors in early life (e.g. trauma) or recently (e.g. bereavement), and protective factors. The presence of anxiety symptoms in a depressed patient is associated with more severe depression, increased suicidality and worse outcomes compared with non-anxious depression. A network meta-analysis of antidepressant treatments found that agomelatine, citalopram, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine and vortioxetine were all significantly more effective than other antidepressants for the treatment of depression, and that agomelatine, citalopram, escitalopram, fluoxetine, sertraline and vortioxetine were better tolerated than other antidepressants. Agomelatine has been shown to have two major effects—relieving depressive symptoms, and supporting symptomatic and functional recovery—and these benefits have been demonstrated in patients with depression as well as in patients with generalised anxiety disorder, including those with more severe symptoms. Agomelatine has also been shown to be efficacious and well tolerated in patients with depression plus concomitant anxiety symptoms. A pooled analysis of data from six agomelatine studies of depression (three placebo-controlled and three with active comparators—fluoxetine, sertraline and venlafaxine) found that agomelatine was significantly more effective than placebo at relieving the anxiety subscore on the Hamilton Depression Rating Scale, and that the difference between agomelatine and placebo was even more marked in the subgroup of patients with severe anxiety symptoms at baseline. Irrespective of the pharmacotherapy used in patients with depression, the likelihoods of response and remission are increased when pharmacotherapy is combined with psychotherapy, with this approach being more effective than either pharmacotherapy or psychotherapy alone. Persistence with treatment is important, and clinicians should therefore encourage patients to keep trying to obtain relief. [ABSTRACT FROM AUTHOR]

BackgroundIncreasing understanding of the neural correlates of anxiety symptoms in late-life depression (LLD) could inform the development of more targeted and effective treatments.MethodsGrey matter volume (GMV) was assessed with volumetric magnetic resonance imaging in a sample of 113 adults ≥60 years with MDD using the following regions of interest: amygdala, anterior cingulate cortex (ACC), insula, orbitofrontal cortex (OFC), and temporal cortex.ResultsAfter controlling for demographic (age, sex, education) and clinical variables (antidepressant use, anxiolytic use, duration of illness, medical comorbidity, cognitive functioning), greater severity of anxiety symptoms was associated with lower GMV bilaterally in the insula, F(1,102) = 6.63, p = 0.01, and OFC, F(1,102) = 8.35, p = 0.005. By contrast, depressive symptom severity was significantly associated with lower bilateral insula volumes, F(1,102) = 6.43, p = 0.01, but not OFC volumes, F(1,102) = 5.37, p = 0.02.LimitationsLimitations include (1) the relatively mild nature of anxiety symptoms in our sample; (2) the cross-sectional research design, which prohibits inferences of directionality; (3) the relatively homogenous demographic of the sample, and (4) the exclusion of participants with significant psychiatric comorbidity, suicidality, or cognitive impairment.ConclusionsDecreased OFC volumes may serve as a unique biomarker of anxiety symptoms in LLD. Future longitudinal and clinical studies with long-term follow up and more diverse samples will help further elucidate the biological, psychological, and social factors affecting associations between anxiety and brain morphology in LLD.

Anxious depression is one of the subtypes of major depressive disorder (MDD), usually defined as "patients with MDD and high levels of anxiety symptoms". Compared to non-anxious MDD (naMDD), patients with anxious MDD (aMDD) have more severe depressive symptoms and suicidal ideation, worse treatment outcomes and remission rates, and poorer prognosis. Current research suggests that the Papez circuit is an important brain structure closely related to emotion, memory, and cognition. This study applied DTI to explore the altered white matter integrity in Papez circuit of patients with aMDD. DTI data were acquired from 30 medication-naive outpatients with naMDD and 55 with aMDD and 88 demographically similar healthy control (HC) subjects. Voxel-based analysis (VBM) and region of interest (ROI) analysis were conducted to explore the significant difference of fractional anisotropy (FA) values among 3 groups. Pearson's correlations were performed to analyze the correlation between FA values and the score of HAMA-14 and HAMD-17. We found that aMDD patients had significantly higher FA values in left fornix (belong to Papez circuit) and left posterior thalamic radiation and right anterior corona radiata (belong to limbic-thalamo-cortical circuitry) compared with HC. And there was variability in the white matter integrity in right posterior thalamic radiation (belong to limbic-thalamo-cortical circuitry) and left fornix (belong to Papez circuit) between aMDD and naMDD patients. The cross-sectional study and the population vary between aMDD group and naMDD group are limitations. Abnormal white matter integrity in Papez circuit and Limbic-Thalamo-Cortical circuitry may play an important role in the neuropathology of aMDD and might help to identify aMDD. • Anxious depression patients had significantly higher FA values in left fornix (belong to Papez circuit) and left posterior thalamic radiation and right anterior corona radiata (belong to Limbic-Thalamo-Cortical circuitry) compared with healthy controls. • There was variability in the white matter integrity in right posterior thalamic radiation and left fornix between anxious depression and non-anxious MDD patients. • Abnormal white matter integrity in Papez circuit and Limbic-Thalamo-Cortical circuitry may play an important role in the neuropathology of anxious depression and might help to identify anxious depression. [ABSTRACT FROM AUTHOR]

Background: Anxious depression is a common subtype of major depressive disorder (MDD) associated with adverse outcomes and severely impaired social function. The aim of this study was to explore the relationships between child maltreatment, family functioning, social support, interpersonal problems, dysfunctional attitudes, and anxious depression.Methods: Data were collected from 809 MDD patients. The Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale-17 (HAMD-17), Family Assessment Device (FAD), Childhood Trauma Questionnaire (CTQ), Social Support Rating Scale (SSRS), Interpersonal Relationship Integrative Diagnostic Scale (IRIDS), and Dysfunctional Attitudes Scale (DAS) were administered and recorded. Anxious depression was defined as an anxiety/somatization factor score ≥ 7 on the HAMD-17. Chi-squared tests, Mann-Whitney U tests, distance correlations, and structural equation models were used for data analysis.Results: Two-fifths of MDD patients had comorbid anxiety, and there were significant differences in child maltreatment, family functioning, social support, interpersonal problems, and dysfunctional attitudes between groups. Of these factors, interpersonal relationships were most related to anxiety in MDD patients, and dysfunctional attitudes mediated the relationship between interpersonal relationships and anxiety in MDD patients.Limitations: This study used cross-sectional data with no further follow-up to assess patient outcomes. This study did not include information about pharmacological treatments. A larger sample size is needed to validate the results.Conclusions: Psychosocial factors were significantly associated with anxious depression. Interpersonal relationships and dysfunctional attitudes have a direct effect on anxious depression, and interpersonal relationships also mediate the effects of anxious depression via dysfunctional attitudes. [ABSTRACT FROM AUTHOR]

Objectives: To explore differences in the diversity and composition of the gut microbiome between major depressive disorder (MDD) with and without anxious distress.Methods: The study comprised 117 participants (79 female, 36 male, 2 other, mean age 38.2 ± 13.4 years) with a current major depressive episode (MDE) with (n = 63) and without (n = 54) the anxious distress specifier. A clinical psychologist administered the structured clinical interview for the DSM-5-RV to confirm a diagnosis of depression. Participants provided stool samples which were immediately frozen and stored at -80 °C. These samples were analysed using the Illumina 16S Metagenomics sequencing protocol in which the sequencing primers target the V3 and V4 regions of the 16S rRNA gene. Participants also completed mental health questionnaires to assess severity of depression (BDI-II), generalized anxiety (GAD-7), and stress (PSS).Results: There were no significant group differences in α-diversity (Shannon's diversity Index; Simpson Index), richness (ACE; Chao1), (Pielou's) evenness, or beta diversity (Bray-Curtis dissimilarity index and weighted UniFrac distance) of gut bacteria. Significant group differences in the relative abundance of gut microbiota however were observed at each taxonomical level, including across 15 genera and 18 species.Limitations: This was an exploratory study that needs to be replicated across larger samples and compared with a healthy control group.Conclusions: The research contributes to knowledge of the depressive gut microbial profile unique to the anxious distress subtype of MDD. [ABSTRACT FROM AUTHOR]

Background: The 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.Methods: Thirty-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.Results: The 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.Limitations: The sample size is rather small.Conclusions: Our 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. [ABSTRACT FROM AUTHOR]

Abstract Background Diagnostic criteria are not always useful to discriminate major depression with anxious distress (ADS-D; Diagnostic and Statistical Manual for Mental Disorders, version-5 [DSM-5] criteria) from mixed depression (Koukopoulos’ criteria; KMX-D). So, clinicians need alternative tools to improve their diagnostic ability and to choose the most appropriate treatment. The aim of the present study is to identify socio-demographic and clinical features that discriminate patients with ADS-D from those with KMX-D. Methods Two hundred and forty-one consecutive outpatients with unipolar (51%) and bipolar (49%) disorder, fulfilling DSM-5 criteria for a current major depressive episode (MDE) and with a 21-item Hamilton Depression Rating Scale score ≥ 14, were recruited and treated in a prospective observational study. Results Ten percent of patients met criteria for KMX-D, 22% ADS-D, and 37% for both. Irritable premorbid temperament, mixed depression polarity at onset, mixed depression recurrence, and a high number of mania symptoms at intake were typical features of patients with KMX-D. Depressive polarity at onset, a low number of mania symptoms at intake, and generalized anxiety disorder comorbidity were typical features of patients with ADS-D. Multinomial logistic regression confirmed that higher rate of irritable temperament and higher Young Mania Rating Scale total score differentiated patients with KMX-D from patients with pure MDE. Conclusion Our findings suggest some clinical features that could help differentiate between ADS-D and KMX-D in patients meeting both conditions and to select the appropriate treatment. However, the small sample size may have limited the power to detect differences between the groups. Further research is needed to confirm the results of present study.

ObjectiveThe purpose of this study is to examine the association between verbal learning, fluency, and processing speed with anxious depression symptomatology (ADS) among diverse Hispanics. We hypothesized an inverse association of anxious depression with neurocognition among Hispanics of different heritage.DesignData are from the Hispanic Community Health Study/Study of Latinos. The sample included 9,311participants aged 45-74 years (mean: 56.5 years). A latent class analysis of items from the Center for Epidemiological Studies for Depression scale and the Spielberger Trait Anxiety Inventory was used to derive an anxious depression construct. Neurocognitive measures included scores on the Brief Spanish English Verbal Learning Test (B-SEVLT, learning and recall trials), Word Fluency (WF), Digit Symbol Substitution (DSS) test, and a Global Cognitive Score (GCS). We fit survey linear regression models to test the associations between anxious depression symptomatology and cognitive function. We tested for effect modification by sex, Hispanic heritage, and age groups.ResultsAmong men, 71.6% reported low, 23.3% moderate, and 5.1% high ADS. Among women, 55.1% reported low, 33.2% moderate, and 11.8% high ADS. After controlling for age, sex, sociodemographic characteristics, cardiovascular risk factors and disease, and antidepressant use, we found significant inverse associations between moderate and high anxious depression (ref:low) with B-SEVLT learning and recall, DSS and GCS. Moderate, but not high, anxious depression was inversely associated with WF. Associations were not modified by sex, Hispanic heritage, or age.ConclusionsIncreased anxious depression symptomatology is associated with decreased neurocognitive function among Hispanics. Longitudinal studies are needed to establish temporality and infer if negative emotional symptoms precede cognitive deficits.

Background: Anxious depression is a serious mental disorder characterized by comorbidity of anxiety and depression, and its symptoms are similar to those of non-anxious depression. This study aimed to use functional near-infrared spectroscopy (fNIRS) as a tool to distinguish between patients with anxious and non-anxious depression based on differences in hemodynamic changes in the right prefrontal cortex during the verbal fluency task. It is helpful to improve the diagnostic accuracy of the two disorders to further promote their therapeutic effect and prognosis.Methods: A total of 105 subjects, comprising 39 patients with anxious depression, 32 patients with non-anxious depression, and 32 healthy controls, were evaluated using 53-channel fNIRS and the Depression and Anxiety Clinical Scale.Results: Hemodynamic activation was significantly enhanced in the right dorsolateral prefrontal cortex (DLPFC) and right frontopole cortex (FPC) in the anxious depressed group compared with the non-anxious depressed and healthy groups.Limitations: First, Hospital Anxiety and Depression Scale (HADS) was used to evaluate the scores of anxiety and depression among the three groups in our study. Different scales may result in different research results. Therefore, other scales (HAM, the Montgomery Asberg Depression Rating Scale, or the Beck Depression Inventory) should be used for further verification. Second, although all the samples we have chosen were patients with the diagnosis of anxious depression or no-anxious depression, we did not distinguish between different severity of anxious depression or no-anxious depression. Third, pure anxiety was not included as the control condition in our study.Conclusions: There are significant differences in activation patterns of the right DLPFC and right FPC areas between patients with and without anxious depression. Moreover, the right FPC area is promising as a brain region to assess the severity of anxious depression. fNIRS may be a potential tool to improve diagnostic accuracy for both disorders. [ABSTRACT FROM AUTHOR]

Aim: In the DSM-5, it is specified that severe cases of major depressive disorder with anxious distress (ANXD) may be accompanied with motor agitation. Agitation, on the other hand, is one of the main characteristics of major depressive disorder with melancholic features (MEL). The purpose of this study was to compare ANXD and MEL in terms of psychomotor disturbance., Methods: A total of 106 patients with major depressive disorder were included in the study. Psychomotor disturbance was assessed using the CORE measure. The associations of ANXD and MEL with the CORE measure subscales of psychomotor retardation, agitation, and noninteractiveness were analyzed using multivariate logistic analysis., Results: Retardation scores (odds ratio [OR] = 0.63, 95% confidence interval [CI] = 0.52-0.77) were associated with fewer diagnoses of ANXD, whereas agitation scores (OR = 2.23, 95% CI = 1.60-3.13) were associated with more diagnoses of ANXD. Both noninteractiveness (OR = 1.23, 95% CI = 1.06-1.42) and agitation (OR = 1.27, 95% CI = 1.02-1.58) scores were associated with increased diagnoses of MEL., Conclusion: Among the characteristics of psychomotor disturbance, agitation is a common feature of both ANXD and MEL, and ANXD and the agitated type of MEL may be overlapping concepts. On the other hand, ANXD is distinguished from the retarded type of MEL by its low level of retardation, whereas MEL but not ANXD is characterized by noninteractiveness., Competing Interests: Hiroyuki Toda is a Field Editor of Psychiatry and Clinical Neurosciences Reports and a co‐author of this article. He was excluded from editorial decision‐making related to the acceptance and publication of this article. Yu Tamada has received honoraria from Otsuka Pharmaceutical, Sumitomo Pharma, Eisai, MSD, and Meiji Seika Pharma. Takeshi Inoue has received personal compensation from Mochida Pharmaceutical, Takeda Pharmaceutical, Eli Lilly, Janssen Pharmaceutical, MSD, Taisho Toyama Pharmaceutical, Yoshitomiyakuhin, and Daiichi Sankyo; grants from Shionogi, Astellas, Tsumura, and Eisai; and grants and personal compensation from Otsuka Pharmaceutical, Sumitomo Pharma, Mitsubishi Tanabe Pharma, Kyowa Pharmaceutical Industry, Pfizer, Novartis Pharma, and Meiji Seika Pharma; and is a member of the advisory boards of Pfizer, Novartis Pharma, and Mitsubishi Tanabe Pharma. Atsushi Sekine has received personal compensation from Otsuka Pharmaceutical, Meiji Seika Pharma, Takeda Pharmaceutical, and Sumitomo Pharma. Hiroyuki Toda has received lecture fees from Sumitomo Pharma, Otsuka Pharmaceutical, Takeda Pharmaceutical, Pfizer, Yoshitomi Pharmaceutical, and Viatris. Minoru Takeshima has received lecture fees from Kyowa Pharmaceutical, Otsuka Pharmaceutical, Sumitomo Pharma, Takeda Pharmaceutical, and Lundbeck. Masaaki Sasaki has received lecture fees from Viatris. Yota Fujimura has received honoraria from Sumitomo Pharma, and research grants from Shionogi and Sumitomo Pharma. Susumu Ohmae has received honoraria from Viatris and Takeda Pharmaceutical., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences Reports published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Objectives: Patents 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.Methods: One 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.Results: In 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).Conclusion: This 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. [ABSTRACT FROM AUTHOR]

Abstract Background Anxious-depressive attack (ADA) is a symptom complex that comprises sudden intense feelings of anxiety or depression, intrusive rumination of regretful memories or future worries, emotional distress due to painful thoughts, and coping behaviors to manage emotional distress. ADA has been observed trans-diagnostically across various psychiatric disorders. Although the importance of ADA treatment has been indicated, a scale to measure the severity of ADA has not been developed. This study aimed to develop an Anxious-Depressive Attack Severity Scale (ADAS) to measure the severity of ADA symptoms and examine its reliability and validity. Methods A total of 242 outpatients responded to a questionnaire and participated in an interview, which were designed to measure the severity of ADA, depressive, anxiety, anxious depression, and social anxiety symptoms. Based on the diagnostic criteria for ADA, 54 patients were confirmed to have ADA and were included in the main study analyses. Results The exploratory factor analysis of the ADAS identified a two factor structure: severity of ADA symptoms and ADA frequency and coping behaviors. McDonald’s ωt coefficients were high for the overall scale and the first factor (ωt = .78 and ωt = .83, respectively) but low for the second factor (ωt = .49). The ADAS score was significantly positively correlated with clinical symptoms related to anxiety and depression. Conclusion The present study demonstrated that the ADAS has sufficient reliability and validity; however, internal consistency was insufficient for the second factor. Overall, the ADAS has potential to be a valuable tool for use in clinical trials of ADA.

Introduction: Although anxiety symptoms frequently co-occur with major depressive disorder, few studies examined the prediction of treatment outcomes among participants with anxious depression receiving antidepressants. We investigated whether baseline anxiety, and early improvements in anxiety and depression symptoms predict eventual treatment outcomes.Methods: 111 participants with anxious depression, defined using ≥ 10 on GAD-7, received escitalopram (10-20 mg) for 8 weeks. Covariate-adjusted logistic regression was conducted to examine the impact of baseline anxiety, and to assess the extent week 2 anxiety (GAD-7) and depression (QIDS-SR) percentage improvement associates with week 8 anxiety (GAD-7) and depression (MADRS) response/remission. Optimum improvement thresholds were identified using receiving-operating-curve analysis and their predictive values assessed.Results: Greater percentage improvement in anxiety and depression after the first 2 weeks of treatment significantly increased odds of achieving week 8 anxiety and depression response/remission (OR:1.01-1.04, p<0.05). Early anxiety (68.4%/87.2%) and depression (52.2%/83.0%) improvement thresholds around 30 and 40% provided moderate to high positive predictive value (PPV) for predicting week 8 anxiety response/remission, as well as moderate to high negative predictive value (NPV) for predicting week 8 depression response/remission (anxiety:70.8%/91.7%; depression:72.2%/90.1%). Baseline anxiety severity predicted anxiety outcomes at weeks 2 and 8.Limitations: Trial lacked placebo group.Conclusion: In anxious depression, early improvement in anxiety may be better than depression in predicting anxiety outcomes, with similar or higher PPVs. Both improvement types perform similarly in predicting depression outcomes, with the lack of improvement predictive of non-response and non-remission. Finally, baseline anxiety predicts eventual anxiety but not depression outcomes. [ABSTRACT FROM AUTHOR]

Background: γ-aminobutyric acid (GABA) and its main receptor, the GABA A 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 GABA A receptors. Although the GABAergic deficit hypothesis of MDD is generally accepted, few studies have demonstrated how GABA A receptor gene polymorphisms affect the functions of specific brain regions, in particular, the amygdala and the DLPFC., Methods: The sample comprised 83 patients with AD, 70 patients with non-anxious depression (NAD), and 62 healthy controls (HC). All participants underwent genotyping for polymorphisms of GABA A 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, GABA A 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 GABA A receptor gene MGPS and AD clinical features., Results: Compared with the NAD group, the AD group had a higher GABA A 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 GABA A receptor MGPS and anxiety/somatic symptoms in patients with AD., Conclusion: The decreased FC between the right MFG and right CM subregion mediates the association between GABA A receptor MGPS and AD., Competing Interests: The authors declare that this study was performed without any business or financial relationships that could be interpreted as potential conflicts of interest., (© 2024 Qiao et al.)

Background: Comorbid anxiety is generally associated with poorer response to antidepressant treatment. This post hoc analysis explored the efficacy of esketamine plus an antidepressant in patients with treatment-resistant depression (TRD) with or without comorbid anxiety.Methods: TRANSFORM-2, a double-blind, flexible-dose, 4-week study (NCT02418585), randomized adults with TRD to placebo or esketamine nasal spray, each with a newly-initiated oral antidepressant. Comorbid anxiety was defined as clinically noteworthy anxiety symptoms (7-item Generalized Anxiety Disorder scale [GAD-7] score ≥10) at screening and baseline or comorbid anxiety disorder diagnosis at screening. Treatment effect based on change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score, and response and remission were examined by presence/absence of comorbid anxiety using analysis of covariance and logistic regression models.Results: Approximately 72% (162/223) of patients had baseline comorbid anxiety. Esketamine-treated patients with and without anxiety demonstrated significant reductions in MADRS (mean [SD] change from baseline at day 28: -21.0 [12.51] and -22.7 [11.98], respectively). Higher rates of response and remission, and a significantly greater decrease in MADRS score at day 28 were observed compared to antidepressant/placebo, regardless of comorbid anxiety (with anxiety: difference in LS means [95% CI] -4.2 [-8.1, -0.3]; without anxiety: -7.5 [-13.7, -1.3]). There was no significant interaction of treatment and comorbid anxiety (p = .371). Notably, in the antidepressant/placebo group improvement was similar in those with and without comorbid anxiety.Conclusion: Post hoc data support efficacy of esketamine plus an oral antidepressant in patients with TRD, regardless of comorbid anxiety. [ABSTRACT FROM AUTHOR]

Objective: In a retrospective study, we analyzed if anxious depression impacts outcomes in patients with treatment resistant depression (TRD) receiving IV Ketamine infusions at an academic center Ketamine clinic. Methods: Forty-three patients with TRD received six IV Ketamine infusions over a three-week period. Anxious depression (ANX-TRD) was defined as a Hamilton Depression Rating Scale Anxiety/Somatization factor score of ≥ 7 at the baseline evaluation. Beck Depression Inventory (BDI-II) and Generalized Anxiety Disorder-7 (GAD-7) scales were used through the infusion course to assess symptom change. Results: Twenty-three patients were categorized as ANX-TRD and 20 as non-anxious TRD. Generalized estimating equation (GEE) models revealed BDI-II and GAD-7 scores for ANX-TRD and NANX-TRD groups did not differ significantly during any time point. Symptoms of anxiety and depression improved after treatment in both groups, though the degree of change was significant and greater for depression. Limitations: This was a naturalistic, retrospective study, without a control group. Conclusions: Symptoms of depression show greater improvement than symptoms of anxiety. IV Ketamine is effective in the treatment of depression, regardless of the baseline anxiety level.

Background: Anxious-depressive attack (ADA) is a symptom complex that comprises sudden intense feelings of anxiety or depression, intrusive rumination of regretful memories or future worries, emotional distress due to painful thoughts, and coping behaviors to manage emotional distress. ADA has been observed trans-diagnostically across various psychiatric disorders. Although the importance of ADA treatment has been indicated, a scale to measure the severity of ADA has not been developed. This study aimed to develop an Anxious-Depressive Attack Severity Scale (ADAS) to measure the severity of ADA symptoms and examine its reliability and validity. Methods: A total of 242 outpatients responded to a questionnaire and participated in an interview, which were designed to measure the severity of ADA, depressive, anxiety, anxious depression, and social anxiety symptoms. Based on the diagnostic criteria for ADA, 54 patients were confirmed to have ADA and were included in the main study analyses. Results: The exploratory factor analysis of the ADAS identified a two factor structure: severity of ADA symptoms and ADA frequency and coping behaviors. McDonald's ωt coefficients were high for the overall scale and the first factor (ωt =.78 and ωt =.83, respectively) but low for the second factor (ωt =.49). The ADAS score was significantly positively correlated with clinical symptoms related to anxiety and depression. Conclusion: The present study demonstrated that the ADAS has sufficient reliability and validity; however, internal consistency was insufficient for the second factor. Overall, the ADAS has potential to be a valuable tool for use in clinical trials of ADA. [ABSTRACT FROM AUTHOR]

Introduction There are different clinical forms combining anxiety and depression and it is essential to identify them because they will require different management. Among these clinical forms, there is that including anxiety as a symptom within the depressive episode: the anxious depression. Objectives The objective is to find the characteristics of this anxious depression. Methods We conducted a literature review on the PubMed® site giving access to the MEDLINE® database, as well as on the Google Scholar® search engine and retained 127 articles. Results By studying anxiety as a symptom of the depression, we identify on the pathophysiological level different neurobiological mechanisms (neuroanatomical, biological, immunological and endocrinological) involved in types of symptoms of different anxiety. Thus, by adopting a dimensional point of view, we can say that there are various anxiety symptoms which can be included in multiple forms of anxiety within the depression: psychic anxiety (anxiety and irritability), somatic anxiety (hypochondria, sweating, cardiological, respiratory, gastrointestinal and urinary symptoms), motor anxiety (agitation), anxious arousal (somatic anxiety, fear, panic) or anxious apprehension (anticipatory anxiety and worry). The prognosis which emerges from it is of a more pejorative evolution, and has specificities on which an increased attention is required, such as suicidal behavior which is more frequently described for example. The treatment must be psychotherapeutic, sociotherapeutic, and medication by antidepressant treatment, with SSRIs in the first line. Conclusions It is therefore essential to identify the clinical presentation of the anxious depression because it has specific semiological, neurobiological, prognostic and therapeutic characteristics. Disclosure No significant relationships.

Fear conditioning and generalization are well-known mechanisms in the pathogenesis of anxiety disorders. Extinction of conditioned fear responses is crucial for the psychotherapeutic treatment of these diseases. Anxious depression as a subtype of major depression shares characteristics with anxiety disorders. We therefore aimed to compare fear learning mechanisms in patients with anxious versus non-anxious depression. Fear learning mechanisms in patients with major depression (n = 79; for subgroup analyses n = 41 patients with anxious depression and n = 38 patients with non-anxious depression) were compared to 48 healthy participants. We used a well-established differential fear conditioning paradigm investigating acquisition, generalization, and extinction. Ratings of valence, arousal and probability of expected threat were assessed as well as skin conductance response as an objective psychophysiological measure. Patients with major depression showed impaired acquisition of conditioned fear. In addition, depressed patients showed impaired extinction of conditioned fear responses after successful fear conditioning. Generalization was not affected. However, there was no difference between patients with anxious and non-anxious depression. Results differed between objective and subjective measures. Our findings show altered fear acquisition and extinction in major depression as compared to healthy controls, but they do not favor differential fear learning and extinction mechanisms in the pathogenesis of anxious versus non-anxious depression. The results of impaired extinction warrant future studies addressing extinction learning elements in the treatment of depression. [ABSTRACT FROM AUTHOR]

A relationship between anxious depression has been proposed in patients with diabetes, which may contribute to the lack of medication adherence. The aim of this study was to investigate if there is a relationship between depression and / or anxiety with medication adherence and glycemic control in patients with type 2 Diabetes Mellitus (DM2). An analytical, cross-sectional study was carried out in the internal medicine outpatient clinic of a Hospital in Mexico. Patients with DM2 participated over a period from November 2015 to January 2016. The Morisky scale for medication adherence, and the Goldberg anxiety and depression scale were conducted for each patient. Data was collected from a total of 179 patients. There was a significant difference between anxious depression and medication adherence (p < 0.001) using logistic regression with an R2 of 0.136. There was also a significant difference between anxiety and glycemic control (p < 0.001) with an R2 of 0.175, however no significant difference was found between glycemic control and anxious depression. Our findings demonstrate that patients who suffer from anxious depression also tend to have reduced medication adherence, and anxiety was associated with poor glycemic control in patients with DM2 within the Mexican population. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This study compared enhanced serotonin (5-HT) synthesis roles of γ-[Glu]n-Trp (EW) and whey protein hydrolysate (WPH, Val-Ala-Gly-Thr-Trp-Tyr, Val-Ala-Gly-Thr-Trp, Ser-Ala-Trp-Tyr, Trp-Tyr-Ser, Gly-Thr-Trp) using anxious depression C57BL/6 mice. As an index of serotonergic activity, we assessed 5-HT levels in response to Trp oligopeptide ingestion. The neuroprotective and hypothalamic-pituitaryadrenal (HPA) axis hormones were examined in order to characterize the suggested improvements of anxious depression observed in mice after ingestion Trp oligopeptide. The 5-HT levels were increasingly enhanced by the EW and WPH diet, with the EW being more effective. But WPH had higher capacity on anti-oxidative than EW. EW and WPH could normalize the levels of HPA axis hormones, and promote brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB) signaling. In conclusion, Trp oligopeptide ingestion neuroprotective and HPA regulation effects possibly related to serotonergic activation and anti-oxidation. Consumed Trp oligopeptide diets may induce beneficial effects on 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.

Weiping Xia,1,2 Rubai Zhou,1 Guoqing Zhao,1 Fan Wang,1 Ruizhi Mao,1 Daihui Peng,1 Tao Yang,1 Zuowei Wang,1,3 Jun Chen,1 Yiru Fang1,4,5 1Division of Mood Disorders, Shanghai Mental Health Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Medical Psychology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Mood Disorder Department, Hongkou District Mental Health Center of Shanghai, Shanghai, People’s Republic of China; 4State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, CAS, Shanghai, People’s Republic of China; 5Shanghai Key Laboratory of Psychotic Disorders, Shanghai, People’s Republic of China Background: Almost half of patients with major depressive disorder (MDD) also have clinically meaningful levels of anxiety. Anxious depression is a distinct clinical subtype of MDD, which has poor response to pharmacotherapy; however, the neural mechanisms behind are largely unknown. In the present study, we explored the white matter (WM) integrity traits of anxious depression in first-episode and medication-free (medication-naïve and medication washout) Chinese young adult patients by detecting differences in diffusion tensor imaging (DTI) with the tract-based spatial statistics (TBSS) method.Subjects and methods: DTI was obtained from 39 first-episode, medication-free anxious depressive patients, 45 nonanxious depressive patients, and 50 demographically similar healthy controls. All subjects underwent clinical assessments. TBSS was carried out to investigate the difference in WM integrity among three groups within DTI parameter maps. WM integrity was measured using fractional anisotropy (FA), mean diffusivity, axial diffusivity, and radial diffusivity (RD). The correlations between WM integrity and clinical features were also computed.Results: When compared with nonanxious patients, lower FA values in anxious depressive patients were found in multiple regions of the brain, mainly involving left uncinate fasciculus (UF), superior longitudinal fasciculus (SLF), and forceps major and minor. Higher RD in forceps major and minor and SLF were also detected. The decreased FA values and increased RD values correlated with both anxiety level and depression level in the pooled depressive group.Conclusion: The anxious depressive patients had more abnormalities in WM integrity at the early phase than the nonanxious group. Alternations in WM integrity in fiber pathways, including SLF, UF, and forceps major and minor, may play a critical role in the neuropathology of anxious depression and might help to identify anxious MDD from nonanxious MDD. Further study with larger sample size, larger age range, and longitudinal design is needed to confer a robust inference to better understand the dynamic neurological change and neuropathology of WM integrity in anxious MDD. Keywords: diffusion tensor imaging, anxious depression, tract-based spatial statistics, micro-structure of whiter matter

The World Health Organization, Department of Mental Health and Substance Abuse is currently revising the international classification of disease10 (ICD-10) chapter on mental, behavioral, and neurodevelopmental disorders. This revision aims to improve the clinical utility of the ICD-primary health-care (ICD-PHC) classification system in the primary health-care settings, where the presentation of common mental health conditions vary from that of the specialist centers. The salient changes proposed in the ICD-11 PHC version are the category of anxious depression, health anxiety, and bodily stress syndrome. The ICD-11 PHC field trails have positively supported the proposed changes. The changes in the classification will have to be widely disseminated, complemented with training, and supervision for it to be of use to the people suffering from common mental health conditions in the community.

Background: Functional 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.Methods: Eighty-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.Results: Patients 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.Conclusion: The 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. [ABSTRACT FROM AUTHOR]

Background: Anxious 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. Method: The 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. Results: In 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). Conclusions: AD 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. [ABSTRACT FROM AUTHOR]

Background: Major Depressive Disorder (MDD), anxiety disorders, and high levels of anxious symptoms are associated with impaired cognitive functioning. However, little is known of how cognitive functioning is impaired in people with anxious depression. Here, we compared cognitive functioning between people with anxious depression, non-anxious depression, and healthy controls. We also tested whether anxious depression moderated the relationship between cognitive functioning and treatment outcome.Methods: 1008 adults with MDD and 336 healthy controls completed IntegNeuro: a computerized cognitive functioning test battery. Participants were then randomised to one of three antidepressants and reassessed at 8 weeks using the 17-item Hamilton Depression Rating Scale (HRSD17) and the 16-Item Quick Inventory of Depressive Symptomatology-Self-Rated for remission and response. Syndromal anxious depression was defined as MDD with a comorbid anxiety disorder. HRSD anxious depression was defined as MDD with a comorbid HRSD17 anxiety/somatisation factor score ≥ 7.Results: Syndromal anxious depression was associated with better psychomotor functioning and poorer working memory, cognitive flexibility and information processing speed compared to their non-anxious counterparts. HRSD anxious depression was associated with better psychomotor functioning compared to their non-anxious counterparts. Syndromal anxious depression moderated the relationship between verbal memory and treatment outcome. In people with syndromal anxious depression, poorer baseline verbal memory predicted poorer treatment outcome.Limitations: As DSM-IV criteria was used, the DSM-5 anxious distress specifier characterisation of anxious depression could not be assessed CONCLUSIONS: Syndromal anxious depression is characterised by impaired executive functions and moderates the relationship between verbal memory functioning and treatment outcome. [ABSTRACT FROM AUTHOR]