Physical Exercise for Late-Life Depression: Customizing an Intervention for Primary Care.

OBJECTIVES: To identify which individual- and context-related factors influence the translation into clinical practice of interventions based on physical exercise (PE) as an adjunct to antidepressants (AD) for the treatment of late-life major depression (LLMD). DESIGN: Secondary analysis of a randomized controlled trial. SETTING: Primary care with psychiatric consultation-liaison programs (PCLPs)-organizational protocols that regulate the clinical management of individuals with psychiatric disorders. PARTICIPANTS: Individuals aged 65 and older with major depression according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (N = 121). INTERVENTION: Participants with LLMD were randomized to AD (sertraline) or AD plus PE (AD + PE). MEASUREMENTS: Participant characteristics that were associated with greater effectiveness of AD + PE (moderators) were identified, and effect sizes were calculated from success rate differences. Whether the characteristics of the study setting influenced participant flow and attendance at exercise sessions was then explored, and primary care physicians (PCPs) were surveyed regarding their opinions on PE as a treatment for LLMD. RESULTS: The following participant characteristics were associated with greater likelihood of achieving remission from depression with AD + PE than with AD alone: aged 75 and older (effect size 0.32), polypharmacy (0.35), greater aerobic capacity (0.48), displaying psychomotor slowing (0.49), and less-severe anxiety (0.30). The longer the PCLP had been established at a particular center, the more individuals were recruited at that center. After participating in the study, PCPs expressed positive views on AD + PE as a treatment for LLMD and were more likely to use this as a therapeutic strategy. CONCLUSIONS: The combination of PE and sertraline could improve the management of LLMD, especially when customized for individuals with specific clinical features. Liaison programs might influence the implementation of similar interventions in primary care, and PCPs viewed them positively.

Biopsychosocial predictors of interferon-related depression in patients with Hepatitis C.

OBJECTIVES: The aim of this study is to examine the role of different bio-psycho-social risk factors for the onset of depression among patients with Hepatitis C (HCV) treated with Interferon alpha (IFN). MATERIAL AND METHODS: Patients with HCV were recruited and assessed prospectively at baseline and after 4, 8, and 24 weeks since the start of IFN treatment. Assessments included the Hamilton Depression and Anxiety Rating Scales (HAM-D and HAM-A), Toronto Alexithymia Scale, Temperament Evaluation of the Memphis, Pisa, Paris and San Diego, 110 item version (TEMPS-A), Young Mania Rating Scale and other assessment tools. Sociodemographic and clinical factors were entered as predictors in logistic regression models, with early-onset depression (4 weeks) or persistent depression (24 weeks) as the outcomes. RESULTS: Early-onset depression was predicted by preexisting depressive symptoms' severity (baseline HAM-D scores: OR=1.24; 95% CI: 1.03, 1.50; p=0.03) and by the presence of additional physical comorbidities (OR=3.74; 95% CI: 1.12, 12.5; p=0.03). Persistent depression was predicted by additional physical comorbidities (OR=7.75; 95% CI: 1.33, 45.0, p=0.02), depressive temperament (OR=8.95; 95% CI: 1.32, 60.6; p=0.03) and, at trend-level, by unknown mode of HCV contagion (OR=5.21; 95% CI: 0.89, 30.4; p=0.07). CONCLUSIONS: The incidence of IFN-related depression is associated with factors related to patients' physical and temperamental characteristics. Further research should include comprehensive biopsychosocial assessments to improve the early detection and treatment of vulnerable patients in the real clinical world.

The "Insight Paradox" in Schizophrenia: Magnitude, Moderators and Mediators of the Association Between Insight and Depression.

The so-called "insight paradox" posits that among patients with schizophrenia higher levels of insight are associated with increased levels of depression. Although different studies examined this issue, only few took in account potential confounders or factors that could influence this association. In a sample of clinically stable patients with schizophrenia, insight and depression were evaluated using the Scale to assess Unawareness of Mental Disorder and the Calgary Depression Scale for Schizophrenia. Other rating scales were used to assess the severity of psychotic symptoms, extrapyramidal symptoms, hopelessness, internalized stigma, self-esteem, and service engagement. Regression models were used to estimate the magnitude of the association between insight and depression while accounting for the role of confounders. Putative psychological and sociodemographic factors that could act as mediators and moderators were examined using the PROCESS macro. By accounting for the role of confounding factors, the strength of the association between insight into symptoms and depression increased from 13% to 25% explained covariance. Patients with lower socioeconomic status (F = 8.5, P = .04), more severe illness (F = 4.8, P = .03) and lower levels of service engagement (F = 4.7, P = .03) displayed the strongest association between insight and depression. Lastly, hopelessness, internalized stigma and perceived discrimination acted as significant mediators. The relationship between insight and depression should be considered a well established phenomenon among patients with schizophrenia: it seems stronger than previously reported especially among patients with lower socioeconomic status, severe illness and poor engagement with services. These findings may have relevant implications for the promotion of insight among patients with schizophrenia.

The HPA axis in bipolar disorder: Systematic review and meta-analysis.

OBJECTIVES: To provide a quantitative and qualitative synthesis of the available evidence on the role of Hypothalamic-Pituitary-Adrenal (HPA) axis in the pathophysiology of Bipolar Disorder (BD). METHODS: Meta-analysis and meta-regression of case-control studies examining the levels of cortisol, ACTH, CRH levels. Systematic review of stress reactivity, genetic, molecular and neuroimaging studies related to HPA axis activity in BD. RESULTS: Forty-one studies were included in the meta-analyses. BD was associated with significantly increased levels of cortisol (basal and post-dexamethasone) and ACTH, but not of CRH. In the meta-regression, case-control differences in cortisol levels were positively associated with the manic phase (p=0.005) and participants' age (p=0.08), and negatively with antipsychotics use (p=0.001). Reviewed studies suggest that BD is associated with abnormalities of stress-related molecular pathways in several brain areas. Variants of HPA axis-related genes seem not associated with a direct risk of developing BD, but with different clinical presentations. Also, studies on unaffected relatives suggest that HPA axis dysregulation is not an endophenotype of BD, but seems related to environmental risk factors, such as childhood trauma. Progressive HPA axis dysfunction is a putative mechanism that might underlie the clinical and cognitive deterioration of patients with BD. CONCLUSIONS: BD is associated with dysfunction of HPA axis activity, with important pathophysiological implications. Targeting HPA axis dysfunctions might be a novel strategy to improve the outcomes of BD.

HPA axis and aging in depression: systematic review and meta-analysis.

One of the most consistent findings in the biology of depression is an altered activity of the hypothalamic-pituitary-adrenal (HPA) axis. However, data concerning this issue have never been examined with a focus on the older population. Here we present a systematic review and meta-analysis, based on studies investigating levels of cortisol, adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) in depressed participants older than 60 and compared with healthy controls. We found 20 studies, for a total of 43 comparisons on different indices of HPA axis functioning. Depression had a significant effect (Hedges' g) on basal cortisol levels measured in the morning (0.89), afternoon (0.83) and night (1.39), but a smaller effect on cortisol measured continuously (0.51). The effect of depression was even higher on post-dexamethasone cortisol levels (3.22), whereas it was non-significant on morning ACTH and CRH levels. Subgroup analyses indicated that various methodological and clinical factors can influence the study results. Overall, older participants suffering from depression show a high degree of dysregulation of HPA axis activity, with differences compared with younger adults. This might depend on several mechanisms, including physical illnesses, alterations in the CNS and immune-endocrinological alterations. Further studies are needed to clarify the implications of altered HPA axis activity in older patients suffering from depression. Novel pharmacological approaches might be effective in targeting this pathophysiological feature, thus improving the clinical outcomes.

Vitamin D and psychosis: mini meta-analysis.

Individuals with psychotic disorders are more likely to have vitamin D (VD) deficiency, while evidence suggests VD could have pathophysiological roles. We summarized meta-analytically the available evidence on VD levels in psychotic disorders in comparison with healthy controls and other psychiatric illnesses. We found seven studies, all reporting insufficient VD levels in patients with psychosis. Schizophrenia had a medium effect size for lower VD than healthy controls, and a trend for lower levels than other psychoses. There were non-significant differences between schizophrenia and major depression. No study has investigated the potential psychotropic effects of VD supplementation in patients with psychosis.