A qualitative approach to guide choices for designing a diary study.

BACKGROUND: Electronic diaries are increasingly used in diverse disciplines to collect momentary data on experienced feelings, cognitions, behavior and social context in real life situations. Choices to be made for an effective and feasible design are however a challenge. Careful and detailed documentation of argumentation of choosing a particular design, as well as general guidelines on how to design such studies are largely lacking in scientific papers. This qualitative study provides a systematic overview of arguments for choosing a specific diary study design (e.g. time frame) in order to optimize future design decisions. METHODS: During the first data assessment round, 47 researchers experienced in diary research from twelve different countries participated. They gave a description of and arguments for choosing their diary design (i.e., study duration, measurement frequency, random or fixed assessment, momentary or retrospective assessment, allowed delay to respond to the beep). During the second round, 38 participants (81%) rated the importance of the different themes identified during the first assessment round for the different diary design topics. RESULTS: The rationales for diary design choices reported during the first round were mostly strongly related to the research question. The rationales were categorized into four overarching themes: nature of the variables, reliability, feasibility, and statistics. During the second round, all overarching themes were considered important for all diary design topics. CONCLUSIONS: We conclude that no golden standard for the optimal design of a diary study exists since the design depends heavily upon the research question of the study. The findings of the current study are helpful to explicate and guide the specific choices that have to be made when designing a diary study.

Susceptibility to depression expressed as alterations in cortisol day curve: a cross-twin, cross-trait study.

OBJECTIVE: To examine, using a cross-twin cross-trait design, the hypotheses 1) that the genetic and environmental susceptibility to depression is expressed, in part, as alterations in cortisol day curves and 2) that cortisol abnormalities are not merely the consequence of depressive states or the stressors associated with its onset. Alteration of diurnal secretion of cortisol is a possible endophenotype of depression, as depressed patients show alterations in cortisol dynamics over the day. METHODS: Salivary cortisol measurements were obtained in a sample of 279 twin pairs at 10 random times a day for 5 days. A structured clinical interview for DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) axis I mood disorder (SCID) was administered. Using multilevel regression analysis, the moderating influence of a lifetime diagnosis of depression in the co-twin on the association between time of day and cortisol concentrations in the proband twin was examined. RESULTS: Diurnal variation in cortisol in the proband twin differed as a function of lifetime diagnosis of depression in the co-twin. In addition, this moderating effect was significantly stronger for dizygotic than for monozygotic twins. CONCLUSIONS: Probands of co-twins with lifetime depression have a different diurnal cortisol profile than those without, suggesting that altered hypothalamic-pituitary-adrenal axis functioning is an indicator of depression susceptibility.

Early prediction of major depression in chronic hepatitis C patients during peg-interferon alpha-2b treatment by assessment of vegetative-depressive symptoms after four weeks.

AIM: To study the predictive value of the vegetative-depressive symptoms of the Zung Depression Rating Scale for the occurrence of depression during treatment with peg-interferon alpha-2b of chronic hepatitis C (CHC) patients. METHODS: The predictive value of vegetative-depressive symptoms at 4 wk of treatment for the occurrence of a subsequent diagnosis of major depressive disorder (MDD) was studied in CHC patients infected after substance use in a prospective, multi-center treatment trial in Belgium. The presence of vegetative-depressive symptoms was assessed using the Zung Scale before and 4 wk after the start of antiviral treatment. RESULTS: Out of 49 eligible patients, 19 (39%) developed MDD. The area under the ROC curve of the vegetative Zung subscale was 0.73, P = 0.004. The sensitivity at a cut-point of > 15/35 was 95% (95% CI: 74-100). The positive predictive value equalled 44% (95% CI: 29-60). CONCLUSION: In this group of Belgian CHC patients infected after substance use, antiviral treatment caused a considerable risk of depression. Seven vegetative-depressive symptoms of the Zung scale at wk 4 of treatment predicted 95% of all emerging depressions, at a price of 56% false positive test results.

Evidence that moment-to-moment variation in positive emotions buffer genetic risk for depression: a momentary assessment twin study.

OBJECTIVE: The negative affective response to daily life stressors, which previous work suggest is a fundamental depression endophenotype, may be moderated by positive emotions. It was investigated whether positive affect (PA) buffers negative affect (NA) reactivity in response to stress and whether PA moderates the genetic predisposition to negative affect reactivity. METHOD: A total of 279 twin pairs participated in a momentary assessment study with the experience sampling method, collecting appraisals of stress and affect in the flow of daily life. Lifetime diagnoses of depression were obtained. RESULTS: There was a significant interaction between stress appraisal of event (STRESS) and PA in the association with NA. The interaction between proband PA, proband STRESS and co-twin lifetime depression showed that higher PA reduced the interaction between proband STRESS and co-twin lifetime depression. CONCLUSION: Positive emotions not only buffer against NA reactivity, but in addition attenuate genetic effects on negative mood bias in daily life.

Interferon-alpha-induced depressive symptoms are related to changes in the cytokine network but not to cortisol.

OBJECTIVE: Proinflammatory cytokines have the potential to activate the hypothalamo-pituitary-adrenocortical (HPA) axis, and HPA axis hyperactivity is also encountered in depression. Therefore, the induction of depressive symptoms by interferon-alpha (IFN-alpha) may be mediated by changes in the cytokine network and the HPA axis. METHODS: In 17 hepatitis C patients undergoing IFN-alpha treatment, depressive symptoms were measured using the Montgomery-Asberg Depression Rating Scale (MADRS). In addition, serum cytokine concentrations were measured. Saliva was collected five times over the course of a day in order to assess daily average cortisol (DAC) and awakening response. Assessments were carried out at baseline and six later time points after starting treatment. RESULTS: During treatment, the increases in the MADRS were significantly and positively correlated with soluble interleukin (IL)-2 receptor, tumor necrosis factor alpha (TNF-alpha), and IL-6. There were no significant associations between the DAC or cortisol awakening response with the MADRS score. CONCLUSION: Results suggest a clear connection between IFN-alpha-induced depressive symptoms and cytokine concentrations, but not cortisol.

Baseline immune activation as a risk factor for the onset of depression during interferon-alpha treatment.

BACKGROUND: Major depression has been associated cross-sectionally with increased cell-mediated immune activation but causality has been difficult to establish. This study prospectively investigated the hypothesis that baseline level of immune activation predicts the development of depression during interferon-alpha (IFN-alpha) treatment. METHODS: Sixteen hepatitis C patients without psychiatric disorder underwent IFN-alpha treatment. Proinflammatory and anti-inflammatory cytokines were determined before starting treatment. Presence of a major depressive disorder (MDD) was assessed at baseline and several times during treatment. RESULTS: Baseline soluble interleukin-2 receptor (sIL-2r), interleukin-6 (IL-6), and interleukin-10 (IL-10) concentrations were significantly increased in the five subjects that developed MDD during treatment compared with those that did not, with standardized effect sizes of 1.08, 1.16, and 1.25, respectively, controlling for marijuana use, cigarette smoking, and baseline level of depressive symptoms. CONCLUSIONS: Results suggest that increased immune activation, rather than an epiphenomenon, is a causal risk factor for the development of MDD.

Cytokines and major depression.

In the research field of psychoneuroimmunology, accumulating evidence has indicated the existence of reciprocal communication pathways between nervous, endocrine and immune systems. In this respect, there has been increasing interest in the putative involvement of the immune system in psychiatric disorders. In the present review, the role of proinflammatory cytokines, such as interleukin (IL)-1, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma, in the aetiology and pathophysiology of major depression, is discussed. The 'cytokine hypothesis of depression' implies that proinflammatory cytokines, acting as neuromodulators, represent the key factor in the (central) mediation of the behavioural, neuroendocrine and neurochemical features of depressive disorders. This view is supported by various findings. Several medical illnesses, which are characterised by chronic inflammatory responses, e.g. rheumatoid arthritis, have been reported to be accompanied by depression. In addition, administration of proinflammatory cytokines, e.g. in cancer or hepatitis C therapies, has been found to induce depressive symptomatology. Administration of proinflammatory cytokines in animals induces 'sickness behaviour', which is a pattern of behavioural alterations that is very similar to the behavioural symptoms of depression in humans. The central action of cytokines may also account for the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity that is frequently observed in depressive disorders, as proinflammatory cytokines may cause HPA axis hyperactivity by disturbing the negative feedback inhibition of circulating corticosteroids (CSs) on the HPA axis. Concerning the deficiency in serotonergic (5-HT) neurotransmission that is concomitant with major depression, cytokines may reduce 5-HT levels by lowering the availability of its precursor tryptophan (TRP) through activation of the TRP-metabolising enzyme indoleamine-2,3-dioxygenase (IDO). Although the central effects of proinflammatory cytokines appear to be able to account for most of the symptoms occurring in depression, it remains to be established whether cytokines play a causal role in depressive illness or represent epiphenomena without major significance.

The role of indoleamine 2,3-dioxygenase (IDO) in the pathophysiology of interferon-alpha-induced depression.

The mechanisms by which administration of interferon-alpha induces neuropsychiatric side effects, such as depressive symptoms and changes in cognitive function, are not clear as yet. Direct influence on serotonergic neurotransmission may contribute to these side effects. In addition, the enzyme indoleamine 2,3-dioxygenase (IDO), which converts tryptophan into kynurenine, may play an important role, first, because IDO activation leads to reduced levels of tryptophan, the precursor of serotonin (5-HT), and thus to reduced central 5-HT synthesis. Second, kynurenine metabolites such as 3-hydroxy-kynurenine (3-OH-KYN) and quinolinic acid (QUIN) have toxic effects on brain function. 3-OH-KYN is able to produce oxidative stress by increasing the production of reactive oxygen species (ROS), and QUIN may produce overstimulation of hippocampal N-methyl-D-aspartate (NMDA) receptors, which leads to apoptosis and hippocampal atrophy. Both ROS overproduction and hippocampal atrophy caused by NMDA overstimulation have been associated with depression.