Participation and compliance in a 6-month daily diary study among individuals at risk for mental health problems.

Intensive longitudinal (IL) measurement, which involves prolonged self-monitoring, may have important clinical applications but is also burdening. This raises the question who takes part in and successfully completes IL measurements. This preregistered study investigated which demographic, personality, economic, social, psychological, or physical participant characteristics are associated with participation and compliance in an IL study conducted in young adults at enhanced risk for psychopathology. Dutch young adults enrolled in the clinical cohort of the TRacking Adolescents' Individual Lives Survey (TRAILS) were invited to a 6-month daily diary study. Participant characteristics came from five earlier TRAILS assessment waves collected from Age 11 onwards. To evaluate participation, we compared diary study participants (N = 134) to nonparticipants (N = 309) and a sex-matched subsample (N = 1926) of individuals from the general population cohort of TRAILS. To evaluate compliance, we analyzed which characteristics were related to the proportion of completed diary entries. We found that participants (23.6 ± 0.7 years old; 57% male) were largely similar to nonparticipants. In addition, compared to the general population, participants reported more negative scores on nearly all characteristics. Internalizing problems predicted higher compliance. Externalizing problems, antisocial behavior, and daily smoking predicted lower compliance. Thus, in at-risk young adults, who scored lower on nearly every positive characteristic and higher on every negative characteristic relative to the general population, participation in a diary study is unbiased. Small biases in compliance occur, of which researchers should be aware. IL measurement is thus suitable in at-risk populations, which is a requirement for its usefulness in clinical practice. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Screening for Depression in Daily Life: Development and External Validation of a Prediction Model Based on Actigraphy and Experience Sampling Method.

BACKGROUND: In many countries, depressed individuals often first visit primary care settings for consultation, but a considerable number of clinically depressed patients remain unidentified. Introducing additional screening tools may facilitate the diagnostic process. OBJECTIVE: This study aimed to examine whether experience sampling method (ESM)-based measures of depressive affect and behaviors can discriminate depressed from nondepressed individuals. In addition, the added value of actigraphy-based measures was examined. METHODS: We used data from 2 samples to develop and validate prediction models. The development data set included 14 days of ESM and continuous actigraphy of currently depressed (n=43) and nondepressed individuals (n=82). The validation data set included 30 days of ESM and continuous actigraphy of currently depressed (n=27) and nondepressed individuals (n=27). Backward stepwise logistic regression analysis was applied to build the prediction models. Performance of the models was assessed with goodness-of-fit indices, calibration curves, and discriminative ability (area under the receiver operating characteristic curve [AUC]). RESULTS: In the development data set, the discriminative ability was good for the actigraphy model (AUC=0.790) and excellent for both the ESM (AUC=0.991) and the combined-domains model (AUC=0.993). In the validation data set, the discriminative ability was reasonable for the actigraphy model (AUC=0.648) and excellent for both the ESM (AUC=0.891) and the combined-domains model (AUC=0.892). CONCLUSIONS: ESM is a good diagnostic predictor and is easy to calculate, and it therefore holds promise for implementation in clinical practice. Actigraphy shows no added value to ESM as a diagnostic predictor but might still be useful when ESM use is restricted.

Depressive symptoms in Crohn's disease: relationship with immune activation and tryptophan availability.

Crohn's disease (CD) is associated with immune activation and depressive symptoms. This study determines the impact of anti-tumor necrosis factor (TNF)-α treatment in CD patients on depressive symptoms and the degree to which tryptophan (TRP) availability and immune markers mediate this effect. Fifteen patients with CD, eligible for anti-TNF-α treatment were recruited. Disease activity (Harvey-Bradshaw Index (HBI), Crohn's Disease Activity Index (CDAI)), fatigue (Multidimensional Fatigue Inventory (MFI)), quality of life (Inflammatory Bowel Disease Questionnaire (IBDQ)), symptoms of depression and anxiety (Symptom Checklist (SCL-90), Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HDRS)), immune activation (acute phase proteins (APP)), zinc and TRP availability were assessed before treatment and after 2, 4 and 8 weeks. Anti-TNF-α increased IBDQ scores and reduced all depression scores; however only SCL-90 depression scores remained decreased after correction for HBI. Positive APPs decreased, while negative APPs increased after treatment. After correction for HBI, both level and percentage of γ fraction were associated with SCL-90 depression scores over time. After correction for HBI, patients with current/past depressive disorder displayed higher levels of positive APPs and lower levels of negative APPs and zinc. TRP availability remained invariant over time and there was no association between SCL-90 depression scores and TRP availability. Inflammatory reactions in CD are more evident in patients with comorbid depression, regardless of disease activity. Anti-TNF-α treatment in CD reduces depressive symptoms, in part independently of disease activity; there was no evidence that this effect was mediated by immune-induced changes in TRP availability.

Identifying at-risk states beyond positive symptoms: a brief task assessing how neurocognitive impairments impact on misrepresentation of the social world through blunted emotional appraisal / Identificando estados de risco para além dos sintomas positivos: um teste breve que avalia o impacto de disfunções neurocognitivas sobre a interpretação errônea do mundo social resultante de avaliação emocional embotada

OBJECTIVE: Neurocognitive impairments observed in psychotic disorder may impact on emotion recognition and theory of mind, resulting in altered understanding of the social world. Early intervention efforts would be served by further elucidation of this mechanism. METHOD: Patients with a psychotic disorder (n=30) and a reference control group (n=310) were asked to offer emotional appraisals of images of social situations (EASS task). The degree to which case-control differences in appraisals were mediated by neurocognitive alterations was analyzed. RESULTS: The EASS task displayed convergent and discriminant validity. Compared to controls, patients displayed blunted emotional appraisal of social situations (B=0.52, 95 percent CI: 0.30, 0.74, P<0.001; adjusted for age, sex and number of years of education: B=0.44, 95 percent CI: 0.20, 0.68, P<0.001), a difference of 0.88 (adjusted: 0.75) standard deviation. After adjustment for neurocognitive variables, the case-control difference was reduced by nearly 75 percent and was non-significant (B=0.12, 95 percent CI: -0.14, 0.39, P=0.37). CONCLUSIONS: Neurocognitive impairments observed in patients with psychotic disorder may underlie misrepresentation of the social world, mediated by altered emotion recognition. A task assessing the social impact of cognitive alterations in clinical practice may be useful in detecting key alterations very early in the course of psychotic illness.

OBJETIVO: Melhoras neurocognitivas observadas no transtorno psicótico podem ter impacto no reconhecimento de emoções e na teoria da mente, resultando numa alteração na compreensão do mundo social. Esforços para uma intervenção precoce poderiam se beneficiar de uma maior elucidação deste mecanismo. MÉTODO: Pacientes com transtornos psicóticos (n=30) e um grupo controle de referência (n=310) foram convidados a realizar avaliações emocionais de imagens de situações sociais (teste AESS). A relação das diferenças entre casos e controles com as alterações neurocognitivas foi analisada. RESULTADOS: O teste AESS apresentou validade convergente e discriminatória. Quando comparados aos controles, os pacientes apresentaram avaliação emocional embotada das situações sociais (B=0,52, 95 por cento CI: 0,30, 0,74, P<0,001; ajustado para a idade, sexo e número de anos de educação: B=0,44, 95 por cento CI: 0,20, 0,68, P<0001), uma diferença de 0,88 (ajustado: 0,75) desvio-padrão. Após o ajuste para as variáveis neurocognitivas, as diferenças no estudo caso-controle foram reduzidas em quase 75 por cento e deixaram de ser significativas (B=0,12, 95 por cento CI: -0,14, 0.39, P=0,37). CONCLUSÕES: Disfunções neurocognitivas observadas em pacientes com transtornos psicóticos podem ser subjacentes a uma distorção do mundo social, mediada pela alteração no reconhecimento de emoções. Um teste que avalie o impacto social de alterações cognitivas na prática clínica pode ser útil para a detecção das principais alterações nos primeiros estágios de transtornos psicóticos.

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 psychoneuroimmuno-pathophysiology of cytokine-induced depression in humans.

Administration of the cytokines interferon-alpha and interleukin-2 is used for the treatment of various disorders, such as hepatitis C and various forms of cancer. The most serious side-effects are symptoms associated with depression, including fatigue, increased sleepiness, irritability, loss of appetite as well as cognitive changes. However, great differences exist in the prevalence of the development of depressive symptoms across studies. Differences in doses and duration of therapy may be sources of variation as well as individual differences of patients, such as a history of psychiatric illness. In addition, sensitization effects may contribute to differential responses of patients to the administration of cytokines. In animals administration of pro-inflammatory cytokines induces a pattern of behavioural alterations called 'sickness behaviour' which resembles the vegetative symptoms of depression in humans. Changes in serotonin (5-HT) receptors and in levels of 5-HT and its precursor tryptophan in depressed people support a role for 5-HT in the development of depression. In addition, evidence exists for a dysregulation of the noradrenergic system and a hyperactive hypothalamic-pituitary-adrenal (HPA) axis in depression. Some mechanisms exist which make it possible for cytokines to cross the blood-brain barrier. Pro-inflammatory cytokines such as IL-1beta, IFN-alpha, IFN-gamma and TNF-alpha affect the 5-HT metabolism directly and/or indirectly by stimulating the enzyme indoleamine 2,3-dioxygenase which leads to a peripheral depletion of tryptophan. IL-1, IL-2 and TNF-alpha influence noradrenergic activity and IL-1, IL-6 and TNF-alpha are found to be potent stimulators of the HPA axis. Altogether, administration of cytokines may induce alterations in the brain resembling those found in depressed patients, which leads to the hypothesis that cytokines induce depression by their influence on the 5-HT, noradrenergic and HPA system.