While considerable attention has focused on improving the detection of depression, assessment of severity is also important in guiding treatment decisions. Therefore, we examined the validity of a brief, new measure of depression severity.
The Patient Health Questionnaire (PHQ) is a self-administered version of the PRIME-MD diagnostic instrument for common mental disorders. The PHQ-9 is the depression module, which scores each of the 9 DSM-IV criteria as "0" (not at all) to "3" (nearly every day). The PHQ-9 was completed by 6,000 patients in 8 primary care clinics and 7 obstetrics-gynecology clinics. Construct validity was assessed using the 20-item Short-Form General Health Survey, self-reported sick days and clinic visits, and symptom-related difficulty. Criterion validity was assessed against an independent structured mental health professional (MHP) interview in a sample of 580 patients.
As PHQ-9 depression severity increased, there was a substantial decrease in functional status on all 6 SF-20 subscales. Also, symptom-related difficulty, sick days, and health care utilization increased. Using the MHP reinterview as the criterion standard, a PHQ-9 score > or =10 had a sensitivity of 88% and a specificity of 88% for major depression. PHQ-9 scores of 5, 10, 15, and 20 represented mild, moderate, moderately severe, and severe depression, respectively. Results were similar in the primary care and obstetrics-gynecology samples.
In addition to making criteria-based diagnoses of depressive disorders, the PHQ-9 is also a reliable and valid measure of depression severity. These characteristics plus its brevity make the PHQ-9 a useful clinical and research tool.
Despite the prevalence of sleep complaints among psychiatric patients, few questionnaires have been specifically designed to measure sleep quality in clinical populations. The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate seven "component" scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these seven components yields one global score. Clinical and clinimetric properties of the PSQI were assessed over an 18-month period with "good" sleepers (healthy subjects, n = 52) and "poor" sleepers (depressed patients, n = 54; sleep-disorder patients, n = 62). Acceptable measures of internal homogeneity, consistency (test-retest reliability), and validity were obtained. A global PSQI score greater than 5 yielded a diagnostic sensitivity of 89.6% and specificity of 86.5% (kappa = 0.75, p less than 0.001) in distinguishing good and poor sleepers. The clinimetric and clinical properties of the PSQI suggest its utility both in psychiatric clinical practice and research activities.
The construction of a depression rating scale designed to be particularly sensitive to treatment effects is described. Ratings of 54 English and 52 Swedish patients on a 65 item comprehensive psychopathology scale were used to identify the 17 most commonly occurring symptoms in primary depressive illness in the combined sample. Ratings on these 17 items for 64 patients participating in studies of four different antidepressant drugs were used to create a depression scale consisting of the 10 items which showed the largest changes with treatment and the highest correlation to overall change. The inner-rater reliability of the new depression scale was high. Scores on the scale correlated significantly with scores on a standard rating scale for depression, the Hamilton Rating Scale (HRS), indicating its validity as a general severity estimate. Its capacity to differentiate between responders and non-responders to antidepressant treatment was better than the HRS, indicating greater sensitivity to change. The practical and ethical implications in terms of smaller sample sizes in clinical trials are discussed.
In a prospective-longitudinal study of a representative birth cohort, we tested why stressful experiences lead to depression in some people but not in others. A functional polymorphism in the promoter region of the serotonin transporter (5-HT T) gene was found to moderate the influence of stressful life events on depression. Individuals with one or two copies of the short allele of the 5-HT T promoter polymorphism exhibited more depressive symptoms, diagnosable depression, and suicidality in relation to stressful life events than individuals homozygous for the long allele. This epidemiological study thus provides evidence of a gene-by-environment interaction, in which an individual's response to environmental insults is moderated by his or her genetic makeup.
In response to a peripheral infection, innate immune cells produce pro-inflammatory cytokines that act on the brain to cause sickness behaviour. When activation of the peripheral immune system continues unabated, such as during systemic infections, cancer or autoimmune diseases, the ensuing immune signalling to the brain can lead to an exacerbation of sickness and the development of symptoms of depression in vulnerable individuals. These phenomena might account for the increased prevalence of clinical depression in physically ill people. Inflammation is therefore an important biological event that might increase the risk of major depressive episodes, much like the more traditional psychosocial factors.
Patients with metastatic non-small-cell lung cancer have a substantial symptom burden and may receive aggressive care at the end of life. We examined the effect of introducing palliative care early after diagnosis on patient-reported outcomes and end-of-life care among ambulatory patients with newly diagnosed disease.
We randomly assigned patients with newly diagnosed metastatic non-small-cell lung cancer to receive either early palliative care integrated with standard oncologic care or standard oncologic care alone. Quality of life and mood were assessed at baseline and at 12 weeks with the use of the Functional Assessment of Cancer Therapy-Lung (FACT-L) scale and the Hospital Anxiety and Depression Scale, respectively. The primary outcome was the change in the quality of life at 12 weeks. Data on end-of-life care were collected from electronic medical records.
Of the 151 patients who underwent randomization, 27 died by 12 weeks and 107 (86% of the remaining patients) completed assessments. Patients assigned to early palliative care had a better quality of life than did patients assigned to standard care (mean score on the FACT-L scale [in which scores range from 0 to 136, with higher scores indicating better quality of life], 98.0 vs. 91.5; P=0.03). In addition, fewer patients in the palliative care group than in the standard care group had depressive symptoms (16% vs. 38%, P=0.01). Despite the fact that fewer patients in the early palliative care group than in the standard care group received aggressive end-of-life care (33% vs. 54%, P=0.05), median survival was longer among patients receiving early palliative care (11.6 months vs. 8.9 months, P=0.02).
Among patients with metastatic non-small-cell lung cancer, early palliative care led to significant improvements in both quality of life and mood. As compared with patients receiving standard care, patients receiving early palliative care had less aggressive care at the end of life but longer survival. (Funded by an American Society of Clinical Oncology Career Development Award and philanthropic gifts; ClinicalTrials.gov number, NCT01038271.)
We derived and tested a short form of the Center for Epidemiologic Studies Depression Scale (CES-D) for reliability and validity among a sample of well older adults in a large Health Maintenance Organization. The 10-item screening questionnaire, the CESD-10, showed good predictive accuracy when compared to the full-length 20-item version of the CES-D (kappa = .97, P < .001). Cutoff scores for depressive symptoms were > or = 16 for the full-length questionnaire and > or = 10 for the 10-item version. We discuss other potential cutoff values. The CESD-10 showed an expected positive correlation with poorer health status scores (r = .37) and a strong negative correlation with positive affect (r = -.63). Retest correlations for the CESD-10 were comparable to those in other studies (r = .71). We administered the CESD-10 again after 12 months, and scores were stable with strong correlation of r = .59.
To estimate the odds and prevalence of clinically relevant depression in adults with type 1 or type 2 diabetes. Depression is associated with hyperglycemia and an increased risk for diabetic complications; relief of depression is associated with improved glycemic control. A more accurate estimate of depression prevalence than what is currently available is needed to gauge the potential impact of depression management in diabetes.
MEDLINE and PsycINFO databases and published references were used to identify studies that reported the prevalence of depression in diabetes. Prevalence was calculated as an aggregate mean weighted by the combined number of subjects in the included studies. We used chi(2) statistics and odds ratios (ORs) to assess the rate and likelihood of depression as a function of type of diabetes, sex, subject source, depression assessment method, and study design.
A total of 42 eligible studies were identified; 20 (48%) included a nondiabetic comparison group. In the controlled studies, the odds of depression in the diabetic group were twice that of the nondiabetic comparison group (OR = 2.0, 95% CI 1.8-2.2) and did not differ by sex, type of diabetes, subject source, or assessment method. The prevalence of comorbid depression was significantly higher in diabetic women (28%) than in diabetic men (18%), in uncontrolled (30%) than in controlled studies (21%), in clinical (32%) than in community (20%) samples, and when assessed by self-report questionnaires (31%) than by standardized diagnostic interviews (11%).
The presence of diabetes doubles the odds of comorbid depression. Prevalence estimates are affected by several clinical and methodological variables that do not affect the stability of the ORs.
A number of self-administered questionnaires are available for assessing depression severity, including the 9-item Patient Health Questionnaire depression module (PHQ-9). Because even briefer measures might be desirable for use in busy clinical settings or as part of comprehensive health questionnaires, we evaluated a 2-item version of the PHQ depression module, the PHQ-2.
The PHQ-2 inquires about the frequency of depressed mood and anhedonia over the past 2 weeks, scoring each as 0 ("not at all") to 3 ("nearly every day"). The PHQ-2 was completed by 6000 patients in 8 primary care clinics and 7 obstetrics-gynecology clinics. Construct validity was assessed using the 20-item Short-Form General Health Survey, self-reported sick days and clinic visits, and symptom-related difficulty. Criterion validity was assessed against an independent structured mental health professional (MHP) interview in a sample of 580 patients.
As PHQ-2 depression severity increased from 0 to 6, there was a substantial decrease in functional status on all 6 SF-20 subscales. Also, symptom-related difficulty, sick days, and healthcare utilization increased. Using the MHP reinterview as the criterion standard, a PHQ-2 score > or =3 had a sensitivity of 83% and a specificity of 92% for major depression. Likelihood ratio and receiver operator characteristic analysis identified a PHQ-2 score of 3 as the optimal cutpoint for screening purposes. Results were similar in the primary care and obstetrics-gynecology samples.
The construct and criterion validity of the PHQ-2 make it an attractive measure for depression screening.
Depression and anxiety are common in medical patients and are associated with diminished health status and increased health care utilization. This article presents a quantitative review and synthesis of studies correlating medical patients' treatment noncompliance with their anxiety and depression.
Research on patient adherence catalogued on MEDLINE and PsychLit from January 1, 1968, through March 31, 1998, was examined, and studies were included in this review if they measured patient compliance and depression or anxiety (with n>10); involved a medical regimen recommended by a nonpsychiatrist physician to a patient not being treated for anxiety, depression, or a psychiatric illness; and measured the relationship between patient compliance and patient anxiety and/or depression (or provided data to calculate it).
Twelve articles about depression and 13 about anxiety met the inclusion criteria. The associations between anxiety and noncompliance were variable, and their averages were small and nonsignificant. The relationship between depression and noncompliance, however, was substantial and significant, with an odds ratio of 3.03 (95% confidence interval, 1.96-4.89).
Compared with nondepressed patients, the odds are 3 times greater that depressed patients will be noncompliant with medical treatment recommendations. Recommendations for future research include attention to causal inferences and exploration of mechanisms to explain the effects. Evidence of strong covariation of depression and medical noncompliance suggests the importance of recognizing depression as a risk factor for poor outcomes among patients who might not be adhering to medical advice.
Current treatments for depression are inadequate for many individuals, and progress in understanding the neurobiology of depression is slow. Several promising hypotheses of depression and antidepressant action have been formulated recently. These hypotheses are based largely on dysregulation of the hypothalamic-pituitary-adrenal axis and hippocampus and implicate corticotropin-releasing factor, glucocorticoids, brain-derived neurotrophic factor, and CREB. Recent work has looked beyond hippocampus to other brain areas that are also likely involved. For example, nucleus accumbens, amygdala, and certain hypothalamic nuclei are critical in regulating motivation, eating, sleeping, energy level, circadian rhythm, and responses to rewarding and aversive stimuli, which are all abnormal in depressed patients. A neurobiologic understanding of depression also requires identification of the genes that make individuals vulnerable or resistant to the syndrome. These advances will fundamentally improve the treatment and prevention of depression.
Increasing amounts of data suggest that inflammatory responses have an important role in the pathophysiology of depression. Depressed patients have been found to have higher levels of proinflammatory cytokines, acute phase proteins, chemokines and cellular adhesion molecules. In addition, therapeutic administration of the cytokine interferon-alpha leads to depression in up to 50% of patients. Moreover, proinflammatory cytokines have been found to interact with many of the pathophysiological domains that characterize depression, including neurotransmitter metabolism, neuroendocrine function, synaptic plasticity and behavior. Stress, which can precipitate depression, can also promote inflammatory responses through effects on sympathetic and parasympathetic nervous system pathways. Finally, depression might be a behavioral byproduct of early adaptive advantages conferred by genes that promote inflammation. These findings suggest that targeting proinflammatory cytokines and their signaling pathways might represent a novel strategy to treat depression.
The rapid antidepressant response after ketamine administration in treatment-resistant depressed patients suggests a possible new approach for treating mood disorders compared to the weeks or months required for standard medications. However, the mechanisms underlying this action of ketamine [a glutamate N-methyl-D-aspartic acid (NMDA) receptor antagonist] have not been identified. We observed that ketamine rapidly activated the mammalian target of rapamycin (mTOR) pathway, leading to increased synaptic signaling proteins and increased number and function of new spine synapses in the prefrontal cortex of rats. Moreover, blockade of mTOR signaling completely blocked ketamine induction of synaptogenesis and behavioral responses in models of depression. Our results demonstrate that these effects of ketamine are opposite to the synaptic deficits that result from exposure to stress and could contribute to the fast antidepressant actions of ketamine.
The psychometric properties of the Depression Anxiety Stress Scales (DASS) were evaluated in a normal sample of N = 717 who were also administered the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI). The DASS was shown to possess satisfactory psychometric properties, and the factor structure was substantiated both by exploratory and confirmatory factor analysis. In comparison to the BDI and BAI, the DASS scales showed greater separation in factor loadings. The DASS Anxiety scale correlated 0.81 with the BAI, and the DASS Depression scale correlated 0.74 with the BDI. Factor analyses suggested that the BDI differs from the DASS Depression scale primarily in that the BDI includes items such as weight loss, insomnia, somatic preoccupation and irritability, which fail to discriminate between depression and other affective states. The factor structure of the combined BDI and BAI items was virtually identical to that reported by Beck for a sample of diagnosed depressed and anxious patients, supporting the view that these clinical states are more severe expressions of the same states that may be discerned in normals. Implications of the results for the conceptualisation of depression, anxiety and tension/stress are considered, and the utility of the DASS scales in discriminating between these constructs is discussed.
Unravelling the pathophysiology of depression is a unique challenge. Not only are depressive syndromes heterogeneous and their aetiologies diverse, but symptoms such as guilt and suicidality are impossible to reproduce in animal models. Nevertheless, other symptoms have been accurately modelled, and these, together with clinical data, are providing insight into the neurobiology of depression. Recent studies combining behavioural, molecular and electrophysiological techniques reveal that certain aspects of depression result from maladaptive stress-induced neuroplastic changes in specific neural circuits. They also show that understanding the mechanisms of resilience to stress offers a crucial new dimension for the development of fundamentally novel antidepressant treatments.