Citalopram treatment of social anxiety disorder with comorbid major depression

Treatment of patients with both social anxiety disorder and major depression has been little studied although social anxiety disorder and depression frequently co-occur. Each disorder has been shown to respond to serotonin reuptake inhibitor treatment. Objectives of this study were to characterize a sample of these comorbid patients and to assess response to treatment with citalopram. Patients with primary DSM-IV generalized subtype of social anxiety disorder and comorbid major depression (N = 21) were assessed for symptoms of each disorder, including atypical depressive features, and functional impairment. Patients were treated with a flexible dose of open label citalopram for 12 weeks. Response rates for the intention-to-treat sample at week 12 were 14/21 (66.7%) for social anxiety disorder and 16/21 (76.2%) for depression. All continuous measures of social anxiety, depression, and functional impairment improved significantly with treatment, but depression symptoms responded more rapidly and more completely than social anxiety symptoms. Mean dose of citalopram at study endpoint was 37.6 mg/day. Only three patients (14.3%) fulfilled DSM-IV criteria for atypical features of depression, although 18 (85.7%) fulfilled the criterion for interpersonal rejection sensitivity. Citalopram treatment may benefit patients with primary social anxiety disorder and comorbid major depression, and it should be further studied in controlled trials. Improvement in social anxiety disorder symptoms lagged behind improvement in depression, and greater than 12 weeks of treatment may be required to assess full social anxiety response in patients with comorbid depression. The overlap of social anxiety disorder with atypical features of depression may primarily be due to the shared feature of rejection sensitivity.     

Personality disorder comorbidity in panic disorder patients with or without current major depression

To investigate the relationship between current or past major depressive disorder (MDD) on comorbid personality disorders in patients with panic disorder, we compared the comorbidity of personality disorders using the Structured Clinical Interview for DSM-III-R personality disorders (SCID-II) in 34 panic disorder patients with current MDD (current-MD group), 21 with a history of MDD but not current MDD (past-MD group), and 32 without lifetime MDD comorbidity (non-MD group). With regard to personality disorders, patients in the current-MD group met criteria for at least one personality disorder significantly more often than patients in the past-MD group or the non-MD group (82.4% vs. 52.4% and 56.3%, respectively). The current-MD group showed statistically significantly more borderline, dependent, and obsessive-compulsive personality disorders than the past-MD group or non-MD group. With stepwise regression analyses, number of MDD episodes emerged as an indicator of the comorbidity of cluster C personality disorder and any personality disorders. Future studies should determine whether aggressive treatment of comorbid personality disorders improves the outcome (e.g., lowers the likelihood of comorbid MDD) of patients with panic disorder.     

小学生焦虑抑郁障碍共病调查

目的：探讨小学生焦虑抑郁障碍共病情况。方法：用儿童焦虑障碍筛查量表（SCRED）对县城2900名及农村1800名8～14岁小学生进行筛查,对筛查出的焦虑障碍儿童进行抑郁障碍诊断,对焦虑与抑郁障碍共病儿童实施相关量表及问卷测量。结果：儿童焦虑抑郁障碍共病率为12.7%,其中县城12.9%,农村12.3%,两地差异无统计学意义（χ2=0.011,P=0.915）。焦虑抑郁障碍共病儿童与仅有焦虑障碍儿童在焦虑量表及家庭功能评定量表上得分差异均无显著性（P均〉0.05）,抑郁量表分与焦虑量表的躯体焦虑、广泛焦虑及焦虑总分呈显著相关（P〈0.001）。结论：小学生焦虑与抑郁障碍共病率较高。     

Distinguishing generalized anxiety disorder from major depression: prevalence and impairment from current pure and comorbid disorders in the US and Ontario

Estimation of comparative disease burden in epidemiological surveys is complicated by the fact that high comorbidities exist among many chronic conditions. The easiest way to take comorbidity into consideration is to distinguish between pure and comorbid conditions and to evaluate the incremental effects of comorbid conditions in prediction equations. This approach is illustrated here in an analysis of the effects of pure and comorbid major depression (MD) and generalized anxiety disorder (GAD) on a number of different measures of role impairment in the US National Comorbidity Survey (NCS) and the Mental Health Supplement to the Ontario (Canada) Health Survey (the Supplement). Pure MD and pure GAD were found to have roughly equal independent associations with role impairments. The incremental effects of having comorbid MD and GAD were found to vary depending on the outcome under investigation. The paper closes with a discussion of the methodological complexities associated with generalizing to comorbidities that involve rare conditions or more than two disorders.     

Maladaptive self-focused attention and default mode network connectivity: a transdiagnostic investigation across social anxiety and body dysmorphic disorders

Maladaptive self-focused attention (SFA) is a bias toward internal thoughts, feelings and physical states. Despite its role as a core maintaining factor of symptoms in cognitive theories of social anxiety and body dysmorphic disorders (BDDs), studies have not examined its neural basis. In this study, we hypothesized that maladaptive SFA would be associated with hyperconnectivity in the default mode network (DMN) in self-focused patients with these disorders. Thirty patients with primary social anxiety disorder or primary BDD and 28 healthy individuals were eligible and scanned. Eligibility was determined by scoring greater than 1SD or below 1SD of the Public Self-Consciousness Scale normative mean, respectively, for each group. Seed-to-voxel functional connectivity was computed using a DMN posterior cingulate cortex (PCC) seed. There was no evidence of increased DMN functional connectivity in patients compared to controls. Patients (regardless of diagnosis) showed reduced functional connectivity of the PCC with several brain regions, including the bilateral superior parietal lobule (SPL), compared to controls, which was inversely correlated with maladaptive SFA but not associated with social anxiety, body dysmorphic, depression severity or rumination. Abnormal PCC-SPL connectivity may represent a transdiagnostic neural marker of SFA that reflects difficulty shifting between internal versus external attention.     

Social anxiety disorder and depression in Saudi Arabia

The purpose of this study was to estimate the prevalence of depression in patients with social anxiety disorder (SAD) and to assess the relationship between the severity of SAD symptoms and depression. Ninety-eight consecutive patients with generalized SAD according to DSM-IV criteria were included in a cross-sectional case-control study. Patients were referred to a psychiatric outpatient clinic in a general hospital in Saudi Arabia. The Liebowitz Social Anxiety Scale was used to estimate the severity of SAD. Fifty-eight (59%) of the patients with SAD had another current psychiatric disorder. Forty (41%) patients had current depression, and 37 (92.5%) of them had it after SAD onset. Eleven of 16 patients with severe SAD (69%) had depression whereas only 29 of 82 of SAD patients with mild or moderate subtypes (35%) had depression. Patients with severe SAD were four times more likely to have depression than the patients with mild or moderate SAD even after controlling for confounding sociodemographic and clinical factors. Depression is common among patients with SAD, particularly the severe subtype. Early recognition and treatment of SAD, especially the severe subtype, may prevent the occurrence of depression. Prospective studies are needed to investigate the risk factors that may lead to depression in SAD.     

Spatiotemporal,metabolic, and therapeutic characterization of altered functional connectivity in major depressive disorder

Although imbalanced functional integration has been increasingly reported in major depressive disorder (MDD), there still lacks a general framework to characterize common characteristic and origin shared by the integrative disturbances. Here we examined spatial selectivity, temporal uniqueness, metabolic basis, and therapeutic response of altered functional connectivity (FC) in MDD by analyzing both cross‐sectional and longitudinal multimodal functional magnetic resonance imaging data from 35 patients and 34 demographically matched healthy controls. First, based on a voxel‐wise, data‐driven, graph‐based degree centrality approach, the bilateral anterior cingulate gyri, middle frontal gyri and superior frontal gyri, and the right parahippocampal gyrus were robustly identified to show decreased FC in MDD. Further spatiotemporal analyses revealed that these regions exhibited hub‐like features and were selectively located in limbic and default mode networks spatially and, relative to other areas in the brain, exhibited unique, frequency‐dependent oscillation power (stronger within 0.01–0.027 Hz and weaker within 0.027–0.073 Hz) and less dynamical variability of whole‐brain FC profiles temporally. Moreover, a cross‐modality fusion analysis showed that all MDD‐related FC impairments were associated with reduced cerebral blood flow (CBF); however, there existed multiple regions that showed reduced CBF but had intact FC in the patients, which resulted in a decreased FC‐CBF coupling and implied an earlier emergence of reduced CBF than impaired FC in MDD. Finally, the disrupted FC in MDD gradually recovered over the course of drug treatment (2 and 12 weeks). Altogether, these findings could help establish a general framework to provide mechanistic insights into integrative dysfunctions in MDD.     

Intra-episode hypomanic symptoms during major depression and their correlates

Recent studies have shown that 40-50% of major depressive disorders (MDD) may become bipolar with time. Intra-episode hypomanic symptoms in MDD may be a first step in this shift. The purpose of the present study was to find factors associated with intra-episode hypomanic symptoms in MDD. Two hundred and forty-three consecutive MDD outpatients were interviewed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM-IV), Clinician Version (SCID-CV), as modified by Benazzi and Akiskal (J. Affect. Disord. 2003; 73: 33-38). History of hypomania and presence of hypomanic symptoms during major depressive episode (MDE) were systematically assessed. Intra-episode hypomanic symptoms were defined as an MDE combined with three or more hypomanic symptoms, following Akiskal and Benazzi (J. Affect. Disord. 2003; 73: 113-122). Major depressive disorder with intra-episode hypomanic symptoms (MDD + H) was compared to MDD without hypomanic symptoms on classic bipolar validators. It was found that MDD + H (usually irritability, distractibility, racing thoughts, psychomotor agitation, and more talkativeness) was present in 32.5% of patients. Patients with MDD + H versus MDD had significantly lower age at onset, more atypical depressions, and more bipolar family history. Recurrences were not significantly different. Multivariate logistic regression found that bipolar family history and atypical depression were significantly and independently associated with MDD + H. Findings suggest that MDD + H may be associated with a bipolar vulnerability. Duration of illness and recurrences do not seem to be important for the onset of MDD + H. Bipolar genetic vulnerability seems to be required for onset of intra-episode hypomanic symptoms in MDD. Intra-episode hypomanic symptoms might be the first step of a process leading to the switch of MDD to bipolar disorders. Predicting the switch might have important treatment implications, because antidepressants used alone may worsen the course of bipolar disorders. Prospective studies are required to support these findings and hypotheses.     

Subtypes of depression and their overlap in a naturalistic inpatient sample of major depressive disorder

Subtyping depression is important in order to further delineate biological causes of depressive syndromes. The aim of this study was to evaluate clinical and outcome characteristics of distinct subtypes of depression and to assess proportion and features of patients fulfilling criteria for more than one subtype. Melancholic, atypical and anxious subtypes of depression were assessed in a naturalistic sample of 833 inpatients using DSM‐IV specifiers based on operationalized criteria. Baseline characteristics and outcome criteria at discharge were compared between distinct subtypes and their overlap. A substantial proportion of patients (16%) were classified with more than one subtype of depression, 28% were of the distinct anxious, 7% of the distinct atypical and 5% of the distinct melancholic subtype. Distinct melancholic patients had shortest duration of episode, highest baseline depression severity, but were more often early improvers; distinct anxious patients had higher NEO‐Five Factor Inventory (NEO‐FFI) neuroticism scores compared with patients with unspecific subtype. Melancholic patients with overlap of anxious features had worse treatment outcome compared to distinct melancholic and distinct anxious subtype. Distinct subtypes differed in only few variables and patients with overlap of depression subtypes may have independent clinical and outcome characteristics. Studies investigating biological causes of subtypes of depression should take influence of features of other subtypes into account.     

Comorbidity of cardiovascular diseases with mood and anxiety disorder: A population based 4-year study

Aims:  Accumulating evidence from Caucasian patients has shown that depression, bipolar and anxiety disorders are associated with an increased risk of cardiovascular diseases (CVD), but reports in the Asian population are limited, and age effect is rarely investigated. This population-based study was carried out to examine and compare the CVD comorbidities among patients with mood and anxiety disorders in different age groups.
Method:  A 4-year cross-sectional survey was carried out using the Taiwan National Health Insurance Research Database from 2000 to 2003.
Results:  An average total of 1 031 557 patients with mood and anxiety disorders were enrolled as study participants, including 76 430 cases of major depressive disorder, 41 557 cases of bipolar disorder, and 913 570 cases of anxiety disorder. When compared with the insured population without mood or anxiety disorders (average 21 356 304 people), the average relative risk (RR) of developing ischemic heart disease and hypertensive disorders in 1 031 557 study participants was 2.0 and 2.05, respectively. The highest RR was found in the age group under 20 years (RR = 4.74 and 4.08, respectively), and the lowest RR in the age group equal to or older than 65 years (RR = 0.47 and 0.58, respectively).
Conclusions:  Taiwanese patients with mood and anxiety disorders experience high cardiovascular morbidity, especially patients with anxiety disorders. Age acted as an important modifier variable that influenced the relationship between mood, anxiety disorder and CVD. This study highlights the need for future research in different age groups, in order to elucidate the causality and the trajectory of developing CVD among patients with mental disorders.     

Hair cortisol concentrations and cortisol stress reactivity in generalized anxiety disorder,major depression and their comorbidity

Studies investigating cortisol secretion in patients with generalized anxiety disorder (GAD) have reported heterogeneous findings. Further, current knowledge on the specificity of endocrine changes for GAD and/or comorbid major depression (MD) is limited. Hence, the current study investigated long-term integrated cortisol secretion, as indexed by hair cortisol concentrations (HCC), and experimentally-induced cortisol stress reactivity in relation to GAD, MD and their comorbidity. Carefully characterized groups of 17 GAD patients including 8 with comorbid MD (GAD-MD), 12 MD patients and 21 healthy controls were recruited. Alongside psychometric data, HCC (N = 43) and salivary cortisol stress reactivity in response to the Trier Social Stress Test (N = 45) were determined. Findings revealed that MD patients exhibited lower HCC compared to controls and GAD patients, with no differences between the latter two groups. Interestingly, when the GAD group was separated into two groups based on MD comorbidity, lower HCC in MD patients were found compared to controls and GAD-noMD patients, but did not show differences when compared to GAD-MD patients. No HCC differences were seen between GAD-MD or GAD-noMD patients and healthy controls. No TSST group differences emerged. Our findings suggest MD to be related to long-term attenuation in cortisol secretion. While no group differences emerged between patients with GAD, neither with nor without MD, and controls, the current results provide tentative evidence that MD determines long-term endocrine changes, with pure GAD showing a distinct pattern. Future studies are needed to confirm our findings in larger samples of pure and comorbid groups.     

Anxiety and major depression comorbidity in a family study of obsessive-compulsive disorder

To understand the familial relationship between obsessive-compulsive disorder (OCD), other anxiety disorders, and major depressive disorder (MDD), we examined the rates of anxiety disorders and MDD in first-degree relatives of OCD probands and controls, the association between age at onset of OCD and the occurrence of other anxiety disorders and major depressive disorder in relatives of probands, and the co-transmission of specific anxiety disorders, MDD, and OCD within families of probands. Recurrence risks were estimated from 466 first-degree relatives of 100 probands with OCD and 113 first-degree relatives of 33 non-psychiatric controls. Rates of non-OCD anxiety disorders and MDD were comparable in relatives of OCD probands and controls. Rates of anxiety disorders and MDD were higher among case relatives with OCD than among case relatives without OCD and control relatives. Fifty percent of case relatives with OCD had at least one comorbid anxiety disorder. Early age at onset (<10 years) in probands was associated with higher rates of anxiety and depression comorbidity among case relatives with OCD but not among case relatives without OCD. The occurrence of specific anxiety disorders and MDD in case relatives was independent of the same comorbid diagnosis in the OCD probands. OCD, panic disorder, generalized anxiety disorder, and MDD occurred together more often than expected by chance among individuals with OCD. Furthermore, age at onset in probands is associated with specific anxiety and affective comorbidity among case relatives. These findings support the hypothesis that early- and late-onset OCD represent different etiologic variants.     

Generalized Anxiety Disorder and major depressive disorder comorbidity in the National Survey of Mental Health and Well-Being

We report population data on DSM-IV Generalized Anxiety Disorder (GAD) from the Australian National Survey of Mental Health and Well-Being, obtained from a nationwide household survey of adults using a stratified multistage sampling process. A response rate of 78.1% resulted in 10,641 persons being interviewed. Diagnoses were made using the Composite International Diagnostic Interview. The interview was computerised and conducted by trained lay interviewers. We investigated comorbidity between GAD and major depressive disorder (MDD). The results indicate that sociodemographic correlates of GAD, and associated disablement and service use, are influenced by the presence of a comorbid depressive disorder but cannot be fully explained by the presence of that disorder. In addition, GAD was confirmed as significantly disabling, even as a single disorder. We conclude that the results are consistent with the view that GAD has a significant and independent impact on the burden of mental disorders.     

Comorbid depression and anxiety spectrum disorders

The relationship between depression and anxiety disorders has long been a matter of controversy. The overlap of symptoms associated with these disorders makes diagnosis, research, and treatment particularly difficult. Recent evidence suggests genetic and neurobiologic similarities between depressive and anxiety disorders. Comorbid depression and anxiety are highly prevalent conditions. Patients with panic disorder, generalized anxiety disorder, social phobia, and other anxiety disorders are also frequently clinically depressed. Approximately 85% of patients with depression also experience significant symptoms of anxiety. Similarly, comorbid depression occurs in up to 90% of patients with anxiety disorders. Patients with comorbid disorders do not respond as well to therapy, have a more protracted course of illness, and experience less positive treatment outcomes. One key to successful treatment of patients with mixed depressive and anxiety disorders is early recognition of comorbid conditions. Antidepressant medications, including the selective serotonin reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors, are highly effective in the management of comorbid depression and anxiety. The high rates of comorbid depression and anxiety argue for well-designed treatment studies in these populations. Depression and Anxiety 4:160–168, 1996/1997. © 1997 Wiley-Liss, Inc.