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The seven-item Hospital Anxiety and Depression Scale Depression subscale (HADS-D) and the total score of the 14-item HADS (HADS-T) are both used for major depression screening. Compared to the HADS-D, the HADS-T includes anxiety items and requires more time to complete. We compared the screening accuracy of the HADS-D and HADS-T for major depression detection. We conducted an individual participant data meta-analysis and fit bivariate random effects models to assess diagnostic accuracy among participants with both HADS-D and HADS-T scores. We identified optimal cutoffs, estimated sensitivity and specificity with 95% confidence intervals, and compared screening accuracy across paired cutoffs via two-stage and individual-level models. We used a 0.05 equivalence margin to assess equivalency in sensitivity and specificity. 20,700 participants (2,285 major depression cases) from 98 studies were included. Cutoffs of ≥7 for the HADS-D (sensitivity 0.79 [0.75, 0.83], specificity 0.78 [0.75, 0.80]) and ≥15 for the HADS-T (sensitivity 0.79 [0.76, 0.82], specificity 0.81 [0.78, 0.83]) minimized the distance to the top-left corner of the receiver operating characteristic curve. Across all sets of paired cutoffs evaluated, differences of sensitivity between HADS-T and HADS-D ranged from -0.05 to 0.01 (0.00 at paired optimal cutoffs), and differences of specificity were within 0.03 for all cutoffs (0.02-0.03). The pattern was similar among outpatients, although the HADS-T was slightly (not nonequivalently) more specific among inpatients. The accuracy of HADS-T was equivalent to the HADS-D for detecting major depression. In most settings, the shorter HADS-D would be preferred. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Objectives: Validated diagnostic interviews are required to classify depression status and estimate prevalence of disorder, but screening tools are often used instead. We used individual participant data meta-analysis to compare prevalence based on standard Hospital Anxiety and Depression Scale - depression subscale (HADS-D) cutoffs of ≥8 and ≥11 versus Structured Clinical Interview for DSM (SCID) major depression and determined if an alternative HADS-D cutoff could more accurately estimate prevalence., Methods: We searched Medline, Medline In-Process & Other Non-Indexed Citations via Ovid, PsycINFO, and Web of Science (inception-July 11, 2016) for studies comparing HADS-D scores to SCID major depression status. Pooled prevalence and pooled differences in prevalence for HADS-D cutoffs versus SCID major depression were estimated., Results: 6005 participants (689 SCID major depression cases) from 41 primary studies were included. Pooled prevalence was 24.5% (95% Confidence Interval (CI): 20.5%, 29.0%) for HADS-D ≥8, 10.7% (95% CI: 8.3%, 13.8%) for HADS-D ≥11, and 11.6% (95% CI: 9.2%, 14.6%) for SCID major depression. HADS-D ≥11 was closest to SCID major depression prevalence, but the 95% prediction interval for the difference that could be expected for HADS-D ≥11 versus SCID in a new study was -21.1% to 19.5%., Conclusions: HADS-D ≥8 substantially overestimates depression prevalence. Of all possible cutoff thresholds, HADS-D ≥11 was closest to the SCID, but there was substantial heterogeneity in the difference between HADS-D ≥11 and SCID-based estimates. HADS-D should not be used as a substitute for a validated diagnostic interview., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Importance: The Patient Health Questionnaire depression module (PHQ-9) is a 9-item self-administered instrument used for detecting depression and assessing severity of depression. The Patient Health Questionnaire-2 (PHQ-2) consists of the first 2 items of the PHQ-9 (which assess the frequency of depressed mood and anhedonia) and can be used as a first step to identify patients for evaluation with the full PHQ-9., Objective: To estimate PHQ-2 accuracy alone and combined with the PHQ-9 for detecting major depression., Data Sources: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, PsycINFO, and Web of Science (January 2000-May 2018)., Study Selection: Eligible data sets compared PHQ-2 scores with major depression diagnoses from a validated diagnostic interview., Data Extraction and Synthesis: Individual participant data were synthesized with bivariate random-effects meta-analysis to estimate pooled sensitivity and specificity of the PHQ-2 alone among studies using semistructured, fully structured, or Mini International Neuropsychiatric Interview (MINI) diagnostic interviews separately and in combination with the PHQ-9 vs the PHQ-9 alone for studies that used semistructured interviews. The PHQ-2 score ranges from 0 to 6, and the PHQ-9 score ranges from 0 to 27., Results: Individual participant data were obtained from 100 of 136 eligible studies (44 318 participants; 4572 with major depression [10%]; mean [SD] age, 49 [17] years; 59% female). Among studies that used semistructured interviews, PHQ-2 sensitivity and specificity (95% CI) were 0.91 (0.88-0.94) and 0.67 (0.64-0.71) for cutoff scores of 2 or greater and 0.72 (0.67-0.77) and 0.85 (0.83-0.87) for cutoff scores of 3 or greater. Sensitivity was significantly greater for semistructured vs fully structured interviews. Specificity was not significantly different across the types of interviews. The area under the receiver operating characteristic curve was 0.88 (0.86-0.89) for semistructured interviews, 0.82 (0.81-0.84) for fully structured interviews, and 0.87 (0.85-0.88) for the MINI. There were no significant subgroup differences. For semistructured interviews, sensitivity for PHQ-2 scores of 2 or greater followed by PHQ-9 scores of 10 or greater (0.82 [0.76-0.86]) was not significantly different than PHQ-9 scores of 10 or greater alone (0.86 [0.80-0.90]); specificity for the combination was significantly but minimally higher (0.87 [0.84-0.89] vs 0.85 [0.82-0.87]). The area under the curve was 0.90 (0.89-0.91). The combination was estimated to reduce the number of participants needing to complete the full PHQ-9 by 57% (56%-58%)., Conclusions and Relevance: In an individual participant data meta-analysis of studies that compared PHQ scores with major depression diagnoses, the combination of PHQ-2 (with cutoff ≥2) followed by PHQ-9 (with cutoff ≥10) had similar sensitivity but higher specificity compared with PHQ-9 cutoff scores of 10 or greater alone. Further research is needed to understand the clinical and research value of this combined approach to screening.

Background: Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9., Methods: We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy., Results: 16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (-0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01)., Conclusions: PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.

Objective: Two previous individual participant data meta-analyses (IPDMAs) found that different diagnostic interviews classify different proportions of people as having major depression overall or by symptom levels. We compared the odds of major depression classification across diagnostic interviews among studies that administered the Depression subscale of the Hospital Anxiety and Depression Scale (HADS-D)., Methods: Data accrued for an IPDMA on HADS-D diagnostic accuracy were analysed. We fit binomial generalized linear mixed models to compare odds of major depression classification for the Structured Clinical Interview for DSM (SCID), Composite International Diagnostic Interview (CIDI), and Mini International Neuropsychiatric Interview (MINI), controlling for HADS-D scores and participant characteristics with and without an interaction term between interview and HADS-D scores., Results: There were 15,856 participants (1942 [12%] with major depression) from 73 studies, including 15,335 (97%) non-psychiatric medical patients, 164 (1%) partners of medical patients, and 357 (2%) healthy adults. The MINI (27 studies, 7345 participants, 1066 major depression cases) classified participants as having major depression more often than the CIDI (10 studies, 3023 participants, 269 cases) (adjusted odds ratio [aOR] = 1.70 (0.84, 3.43)) and the semi-structured SCID (36 studies, 5488 participants, 607 cases) (aOR = 1.52 (1.01, 2.30)). The odds ratio for major depression classification with the CIDI was less likely to increase as HADS-D scores increased than for the SCID (interaction aOR = 0.92 (0.88, 0.96))., Conclusion: Compared to the SCID, the MINI may diagnose more participants as having major depression, and the CIDI may be less responsive to symptom severity., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Screening for major depression with the Patient Health Questionnaire-9 (PHQ-9) can be done using a cutoff or the PHQ-9 diagnostic algorithm. Many primary studies publish results for only one approach, and previous meta-analyses of the algorithm approach included only a subset of primary studies that collected data and could have published results., Objective: To use an individual participant data meta-analysis to evaluate the accuracy of two PHQ-9 diagnostic algorithms for detecting major depression and compare accuracy between the algorithms and the standard PHQ-9 cutoff score of ≥10., Methods: Medline, Medline In-Process and Other Non-Indexed Citations, PsycINFO, Web of Science (January 1, 2000, to February 7, 2015). Eligible studies that classified current major depression status using a validated diagnostic interview., Results: Data were included for 54 of 72 identified eligible studies (n participants = 16,688, n cases = 2,091). Among studies that used a semi-structured interview, pooled sensitivity and specificity (95% confidence interval) were 0.57 (0.49, 0.64) and 0.95 (0.94, 0.97) for the original algorithm and 0.61 (0.54, 0.68) and 0.95 (0.93, 0.96) for a modified algorithm. Algorithm sensitivity was 0.22-0.24 lower compared to fully structured interviews and 0.06-0.07 lower compared to the Mini International Neuropsychiatric Interview. Specificity was similar across reference standards. For PHQ-9 cutoff of ≥10 compared to semi-structured interviews, sensitivity and specificity (95% confidence interval) were 0.88 (0.82-0.92) and 0.86 (0.82-0.88)., Conclusions: The cutoff score approach appears to be a better option than a PHQ-9 algorithm for detecting major depression., (© 2019 S. Karger AG, Basel.)

Background: Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.AimsTo evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics., Method: Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit., Results: A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15-3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98-10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7-15) (OR = 0.96; 95% CI = 0.56-1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26-0.97)., Conclusions: The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.Declaration of interestDrs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.

Background: Major depressive disorder (MDD) causes a massive disease burden worldwide. Cognitive behavioural therapy (CBT) is an important treatment approach for depression. Cost-utility analysis (CUA) is a method to support decisions on efficient allocation of resources in health policy. The objective of our study was to systematically review CUA of CBT in the treatment of patients suffering from MDD., Methods: We conducted a systematic literature search in Medline, Embase, PsycINFO and National Health Service Economic Evaluation Database (NHS EED) to identify CUA of CBT for MDD. Cost data were inflated to the year 2011 and converted into USD using purchasing power parities (USD PPP) to ensure comparability of the data. Quality assessment of CUA was performed., Results: Twenty-two studies were included in this systematic review. No study employed a time horizon of more than 5 years. In most studies, individual and group CBT as well as CBT for maintenance showed acceptable incremental cost-utility ratios (<50,000 USD PPP/quality-adjusted life year). The CUA results of CBT for children and adolescents and of computerized CBT were inconsistent., Discussion: We found consistent evidence that individualized CBT is cost-effective from the perspective of a third-party payer for short-term treatment and for relapse prevention of MDD in the adult population., (© 2014 S. Karger AG, Basel.)

Objective: Patients with major depressive disorder (MDD) often suffer from impaired declarative, episodic and working memory. Further, MDD is associated with alterations in the noradrenergic system. There is evidence that presynaptic α2 receptors that inhibit release of noradrenaline are upregulated in MDD. Results from our recent study demonstrated that increasing noradrenergic activity by blocking the α2 receptor with yohimbine leads to stronger memory consolidation in MDD patients. In the current study, we further examined the role of noradrenaline on memory in MDD by administering clonidine that activates presynaptic α2 receptors and thereby globally suppresses the noradrenergic output., Methods: In a placebo-controlled, within-subject crossover design, 20 patients with MDD and 20 healthy controls received either 0.15 mg of clonidine or placebo orally before memory testing. A word list paradigm (memory consolidation), an autobiographical memory test (retrieval) and a working memory test were applied. Salivary alpha-amylase and blood pressure were measured., Results: Across groups, clonidine decreased blood pressure and alpha-amylase. Clonidine impaired memory consolidation (word list learning) in depressed patients and controls. Memory retrieval and working memory were not affected by clonidine., Conclusions: Reducing noradrenergic activity had a specific effect on memory consolidation in patients with MDD and healthy controls. The underlying mechanisms need further scrutiny., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Early life stress is said to play a critical role in the development of borderline personality disorder (BPD) and major depressive disorder (MDD), but the underlying mediating factors remain uncertain. This study aimed to investigate self-reported childhood trauma, emotion regulation difficulties, and their associations in a sample of BPD (n = 49) and MDD (n = 48) patients and healthy control participants (n = 63). Multiple regressions were used to evaluate the impact of the quality and severity of self-reported childhood trauma on self-reported emotion regulation. The results supported an association between self-reported maltreatment experiences, especially emotional abuse and neglect, and emotion regulation difficulties. Additional analyses showed that emotion regulation difficulties influence the association between self-reported emotional abuse and acute symptomatology in the BPD subgroup. Emotion regulation difficulties may be 1 pathway through which early life stress, particularly emotional abuse, increases the risk for developing BPD symptomatology.

Glucocorticoids (GCs) have repeatedly been shown to impair hippocampus-mediated, declarative memory retrieval and prefrontal cortex-based working memory in healthy subjects. However, recent experimental studies indicated that patients with major depressive disorder (MDD) lack these impairing effects. These missing effects have been suggested to result from dysfunctional brain GC receptors. The purpose of the present study was to investigate whether response inhibition, an executive function relying on the integrity of the prefrontal cortex, would be impaired after cortisol administration in patients with MDD. In a placebo-controlled, double blind crossover study, 50 inpatients with MDD and 54 healthy control participants conducted an emotional go/no-go task consisting of human face stimuli (fearful, happy, and neutral) after receiving a dose of 10 mg hydrocortisone and after placebo. GC administration had an enhancing effect on inhibitory performance in healthy control participants, indicated by faster responses, while no GC effect was revealed for the patients group. Moreover, patients showed an overall worse performance than healthy participants. In conclusion, this study further supports the hypothesis of impaired central glucocorticoid receptor function in MDD patients. Regarding the importance of inhibitory functioning for daily living, further studies are needed to examine the impact of glucocorticoids on response inhibition., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Major depressive disorder (MDD) has been associated with alterations in the noradrenergic system and impaired memory function. In turn, enhanced memory function has been associated with noradrenergic stimulation. In this study, we examined whether noradrenergic stimulation would differentially improve memory function in patients with MDD and healthy controls. In a placebo-controlled crossover study, 20 patients with MDD and 18 age- and sex-matched healthy controls received either placebo or 5 mg of yohimbine, an alpha-2-adrenoceptor antagonist that causes increased noradrenergic activity, orally before memory testing. A word list paradigm was used to test memory consolidation. Furthermore, the autobiographical memory test assessing memory retrieval and a working memory test were administered. Salivary alpha-amylase and blood pressure were measured. Yohimbine improved memory consolidation (word list learning) across groups (main effect of yohimbine: p = 0.05). This effect was more prominent in depressed patients compared with controls (post hoc t-test: MDD p = 0.01, controls p = 0.77). Memory retrieval (autobiographical memory specificity) and working memory were not affected by yohimbine. Across groups, yohimbine administration resulted in an increase in blood pressure and alpha-amylase. In sum, these results further support the hypothesis that noradrenergic stimulation enhances memory consolidation. The mechanism by which yohimbine leads to stronger memory consolidation in depressed patients compared with healthy controls remains to be elucidated.

Background: Stress and cortisol administration are known to have impairing effects on memory retrieval in healthy humans. These effects are reported to be altered in patients with major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) but they have not yet been investigated in borderline personality disorder (BPD)., Method: In a placebo-controlled cross-over study, 71 women with BPD and 40 healthy controls received either placebo or 10 mg of hydrocortisone orally before undertaking a declarative memory retrieval task (word list learning) and an autobiographical memory test (AMT). A working memory test was also applied., Results: Overall, opposing effects of cortisol on memory were observed when comparing patients with controls. In controls, cortisol had impairing effects on memory retrieval whereas in BPD patients cortisol had enhancing effects on memory retrieval of words, autobiographical memory and working memory. These effects were most pronounced for specificity of autobiographical memory retrieval. Patients with BPD alone and those with co-morbid PTSD showed this effect. We also found that co-morbid MDD influenced the cortisol effects: in this subgroup (BPD + MDD) the effects of cortisol on memory were absent., Conclusions: The present results demonstrate beneficial effects of acute cortisol elevations on hippocampal-mediated memory processes in BPD. The absence of these effects in patients with co-morbid MDD suggests that these patients differ from other BPD patients in terms of their sensitivity to glucocorticoids (GCs).

Background: Alterations of the hypothalamus-pituitary-adrenal (HPA) axis are hallmarks in major depressive disorder (MDD) and there is some evidence about similar patterns in borderline personality disorder (BPD). This study examines HPA axis abnormalities with respect to clinical characteristics in both BPD (n=24) and MDD patients (n=33) as well as in healthy control participants (n=41)., Method: A 0.5mg dexamethasone suppression test was administered to evaluate basal cortisol release and HPA feedback sensitivity via salivary cortisol. Traumatic experiences in childhood as well as severity of borderline and depressive symptom severity and dissociation were obtained by self-report questionnaires., Results: Compared to the healthy control group, BPD and MDD patients exhibited both enhanced cortisol concentrations before and after the administration of 0.5mg dexamethasone. Higher cortisol levels were positively correlated to a history of childhood trauma, current dissociative symptoms and severity of borderline and depressive symptoms. Regression analyses revealed that some aspects of early trauma were associated with cortisol release before and after dexamethasone, whereas psychopathology did not contribute to the regression model., Conclusions: HPA dysfunctions appear to be related rather to childhood trauma than to psychopathology in adulthood. Exposure to childhood trauma may contribute to long-lasting alterations in HPA activity and might enhance the risk for the development of later mental disorder., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: Major depressive disorder (MDD) has been associated with hypercortisolism, reduced glucocorticoid feedback sensitivity, and impaired memory function. In healthy subjects, administration of hydrocortisone impairs declarative memory. The aim of this study was to examine the effects of acute hydrocortisone administration on memory retrieval in MDD patients and healthy controls. We further tested whether the enhancing or impairing effects of hydrocortisone would prevail when it was given after encoding and when delayed retrieval was tested at a time point when glucocorticoid levels were still elevated., Method: In a placebo-controlled, double-blind crossover study, 44 patients with DSM-IV MDD and 51 healthy control participants received either placebo or 10 mg of hydrocortisone orally before memory testing. A word list paradigm and the Logical Memory Test from the Wechsler Memory Scale were applied. The study was conducted from April 2008 until April 2010 at sites in Bielefeld and Hamburg, Germany., Results: In both memory tests, patients with MDD performed worse than controls. Healthy controls showed impaired memory performance after hydrocortisone administration compared to placebo. In contrast, hydrocortisone had no effects on memory in MDD patients. Furthermore, in healthy controls we found that administration of hydrocortisone immediately after learning did not lead to an enhanced free recall during increased cortisol levels., Conclusions: It appears that the impairing effects of hydrocortisone on memory performance are missing in patients with MDD. This might be interpreted in the context of reduced central glucocorticoid receptor functioning., (© Copyright 2011 Physicians Postgraduate Press, Inc.)

Objective: Several studies have shown that stress or the administration of glucocorticoids can impair hippocampus-based declarative memory retrieval and prefrontal dependent working memory performance in healthy subjects. Major Depressive Disorder (MDD) is often characterized by memory impairment and increased cortisol secretion. Studies indicate that the impairing effects of glucocorticoids on declarative memory performance are missing in patients with MDD. The purpose of our study was to investigate whether the finding of missing effects of acute cortisol administration on memory performance in MDD is also seen when examining prefrontal-based working memory., Methods: In a placebo-controlled study, 57 patients with MDD and 56 sex- and age-matched healthy control subjects received either placebo or 10 mg of hydrocortisone orally before memory testing. To test the verbal modality of working memory, the Word Suppression Test was applied with one negative and one neutral test part., Results: After hydrocortisone intake, healthy subjects showed a significantly poorer working memory performance compared to placebo treatment when negative interference words were administered. In contrast, memory performance of MDD patients was not affected by hydrocortisone treatment., Conclusions: The missing effects of glucocorticoid administration on working memory in MDD might be interpreted in the context of reduced central glucocorticoid receptor function.

Objective: Overgeneral autobiographical memory has become a well established phenomenon within major depressive disorder (MDD). Neuroendocrinologically, MDD is often characterized by a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, i.e. hypercortisolemia and reduced feedback sensitivity. In healthy participants cortisol administration has been found to impair autobiographical memory retrieval. The purpose of this study was to compare the effects of acute cortisol administration on autobiographical memory in MDD patients with the effects observed in healthy controls. We hypothesized that in contrast to healthy control subjects acute cortisol administration would not affect autobiographical memory performance in MDD due to reduced central glucocorticoid sensitivity., Methods: In a placebo-controlled, double-blind crossover study, 16 patients with MDD and 16 healthy control subjects received a placebo or 10mg of hydrocortisone orally before autobiographical memory testing (AMT)., Results: In the placebo condition depressed patients performed poorer than controls. After hydrocortisone intake, healthy subjects reported significantly fewer specific memories on the AMT compared to placebo treatment. In contrast, memory specificity of MDD patients was not affected by hydrocortisone treatment., Conclusions: The present findings replicate previous findings of impaired autobiographical memory retrieval after hydrocortisone treatment in healthy subjects and of impaired AMT performance in depressed patients. We speculate that the missing acute impairing effect of hydrocortisone on autobiographical memory in depressed patients might reflect reduced central glucocorticoid sensitivity. However alternative explanations cannot be ruled out., (2009 Elsevier Ltd. All rights reserved.)

Objective: To determine diagnostic overlap of depression, anxiety and somatization as well as their unique and overlapping contribution to functional impairment., Method: Two thousand ninety-one consecutive primary care clinic patients participated in a multicenter cross-sectional survey in 15 primary care clinics in the United States (participation rate, 92%). Depression, anxiety, somatization and functional impairment were assessed using validated scales from the Patient Health Questionnaire (PHQ) (PHQ-8, eight-item depression module; GAD-7, seven-item Generalized Anxiety Disorder Scale; and PHQ-15, 15-item somatic symptom scale) and the Short-Form General Health Survey (SF-20). Multiple linear regression analyses were used to investigate unique and overlapping associations of depression, anxiety and somatization with functional impairment., Results: In over 50% of cases, comorbidities existed between depression, anxiety and somatization. The contribution of the commonalities of depression, anxiety and somatization to functional impairment substantially exceeded the contribution of their independent parts. Nevertheless, depression, anxiety and somatization did have important and individual effects (i.e., separate from their overlap effect) on certain areas of functional impairment., Conclusions: Given the large syndrome overlap, a potential consideration for future diagnostic classification would be to describe basic diagnostic criteria for a single overarching disorder and to optionally code additional diagnostic features that allow a more detailed classification into specific depressive, anxiety and somatoform subtypes.

Background: It is well established that subjects participating in controlled clinical trials may not be representative of patients seen in actual practice. Given that efficacy and safety of sertraline have been investigated almost exclusively in controlled clinical trials, the aim of this study was to investigate efficacy, safety, and predictors of treatment response to sertraline in routine clinical practice., Methods: A total of 1878 depressed outpatients (69.5% female; mean age, 50.3 years) participated in this prospective, open-label, non-interventional, postmarketing surveillance study of sertraline. The primary study outcome was change in depression severity as assessed independently with the Patient Health Questionnaire (PHQ-9) depression scale and Clinical Global Impression (CGI) scales after 12 weeks of treatment. Stepwise logistic regression analyses were used to identify independent predictors of treatment response., Results: Using standard criteria to define clinical improvement, responder rates were 87.7% (PHQ-9) and 87.2% (CGI), respectively. Remission, i.e. a PHQ-9 score of 5 or below, occurred in 56.9% of patients. Independent baseline predictors of CGI treatment response were: non-chronic course of depression (OR=2.8, p < 0.001), non-psychiatric treatment setting (OR=2.5, p < 0.001), absence of comorbid physical disease (OR=1.9, p < 0.001), depression-related work disability (OR=1.9, p < 0.001), and no previous antidepressant medication (OR=1.5, p=0.03). Adverse events were reported by 4.8% of patients., Limitations: Lack of a control group limits the conclusions that can be drawn from this study., Conclusions: For treatment of depressive disorders in routine outpatient settings, sertraline is safe and efficacious. Patients without prior episodes of depression, without medical comorbidity, and those with higher levels of depression-related functional limitations are most likely to respond to sertraline treatment.

Background: Although effective treatment of depressed patients requires regular follow-up contacts and symptom monitoring, an efficient method for assessing treatment outcome is lacking. We investigated responsiveness to treatment, reproducibility, and minimal clinically important difference of the Patient Health Questionnaire-9 (PHQ-9), a standard instrument for diagnosing depression in primary care., Methods: This study included 434 intervention subjects from the IMPACT study, a multisite treatment trial of late-life depression (63% female, mean age 71 years). Changes in PHQ-9 scores over the course of time were evaluated with respect to change scores of the SCL-20 depression scale as well as 2 independent structured diagnostic interviews for depression during a 6-month period. Test-retest reliability and minimal clinically important difference were assessed in 2 subgroups of patients who completed the PHQ-9 twice exactly 7 days apart., Results: The PHQ-9 responsiveness as measured by effect size was significantly greater than the SCL-20 at 3 months (-1.3 versus -0.9) and equivalent at 6 months (-1.3 versus -1.2). With respect to structured diagnostic interviews, both the PHQ-9 and the SCL-20 change scores accurately discriminated patients with persistent major depression, partial remission, and full remission. Test-retest reliability of the PHQ-9 was excellent, and its minimal clinically important difference for individual change, estimated as 2 standard errors of measurement, was 5 points on the 0 to 27 point PHQ-9 scale., Conclusions: Well-validated as a diagnostic measure, the PHQ-9 has now proven to be a responsive and reliable measure of depression treatment outcomes. Its responsiveness to treatment coupled with its brevity makes the PHQ-9 an attractive tool for gauging response to treatment in individual patient care as well as in clinical research.

Background: The nine-item depression module from the Patient Health Questionnaire (PHQ-9) is well validated and widely used as a brief diagnostic and severity measure, but its validity as an outcome measure for depression has not yet been established. Therefore, we investigated the sensitivity to change of the PHQ-9 in three groups of patients whose depression status either improved, remained unchanged, or deteriorated over time., Methods: From three cohorts of medical outpatients, with an equal distribution of major depressive disorder, other depressive disorders, or no depressive disorder, 167 patients (82.7%) were followed up after a mean of 12.3 +/- 3.0 months. The PHQ-9 and the Structured Clinical Interview for DSM-IV (SCID) were completed at both baseline and follow-up. Depression diagnoses from the SCID were used as the criterion standard to divide patients into subgroups with (a) improved depression status, (b) unchanged depression status, and (c) deteriorated depression status., Results: Effect sizes (ES) of PHQ-9 change scores were ES = -1.33 for the improved depression status subgroup (n = 52), ES = -0.21 for the unchanged status subgroup (n = 91), and ES = 0.47 for the deteriorated status subgroup (n = 24). PHQ-9 change scores differed significantly between the three depression outcome groups., Limitations: The PHQ-9 and the SCID were completed in person at baseline, whereas they were completed in a telephone interview at follow-up., Conclusions: This study demonstrates the ability of the PHQ-9 to detect depression outcome and changes over time. Data from treatment trials will help further establish the sensitivity to change of the PHQ-9 in comparison to other depression severity measures.