Dementia and depression with ischemic heart disease: a population-based longitudinal study comparing interventional approaches to medical management

Background

We compared the proportion of ischemic heart disease (IHD) patients newly diagnosed with dementia and depression across three treatment groups: percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG) and medical management alone (IHD-medical).

Methods and Findings

De-identified, individual-level administrative records of health service use for the population of Manitoba, Canada (approximately 1.1 million) were examined. From April 1, 1993 to March 31, 1998, patients were identified with a diagnosis of IHD (ICD-9-CM codes). Index events of CABG or PCI were identified from April 1, 1998 to March 31, 2003. Outcomes were depression or dementia after the index event. Patients were followed forward to March 31, 2006 or until censored. Proportional hazards regression analysis was undertaken. Independent variables examined were age, sex, diabetes, hypertension and income quintile, medical management alone for IHD, or intervention by PCI or CABG. Age, sex, diabetes, and presence of hypertension were all strongly associated with the diagnosis of depression and dementia. There was no association with income quintile. Dementia was less frequent with PCI compared to medical management; (HR = 0.65; p = 0.017). CABG did not provide the same protective effect compared to medical management (HR = 0.90; p = 0.372). New diagnosis depression was more frequent with interventional approaches: PCI (n = 626; hazard ratio = 1.25; p = 0.028) and CABG (n = 1124, HR = 1.32; p = 0.0001) than non-interventional patients (n = 34,508). Subsequent CABG was nearly 16-fold higher (p<0.0001) and subsequent PCI was 22-fold higher (p<0.0001) for PCI-managed than CABG-managed patients.

Conclusions

Patients managed with PCI had the lowest likelihood of dementia—only 65% of the risk for medical management alone. Both interventional approaches were associated with a higher risk of new diagnosed depression compared to medical management. Long-term myocardial revascularization was superior with CABG. These findings suggest that PCI may confer a long-term protective effect from dementia. The mechanism(s) of dementia protection requires elucidation.     

Proteomic approaches to identify blood-based biomarkers for depression and bipolar disorders

Introduction: Major depressive disorder (MDD) and bipolar disorder (BD) are leading causes of disability worldwide, yet many people remain undiagnosed, are misdiagnosed, and/or ineffectively treated. Diagnosis relies on the clinical assessment of symptoms, and there is currently no molecular or brain-imaging diagnostic test available. Identifying and validating protein biomarkers could provide a more accurate and objective means of diagnosis.

Areas covered: Proteomics is a powerful tool that enables the identification and quantification of novel candidate biomarkers of disease. In this review, we discuss the role of proteomic technologies in biomarker discovery and validation, peripheral blood as a source of protein biomarkers, statistical methods for analyzing proteomic data, and some existing challenges in the field. We also review a selection of previously published studies focused on identifying blood-based diagnostic protein biomarkers of MDD and BD within a ten-year period.

Expert commentary: Proteomic studies have led to the identification of numerous potential biomarkers of MDD and BD. However, clinical validation and translation into clinical practice have not yet been achieved. Conducting large-scale validation studies and addressing various factors that limit the reproducibility of the proteomic findings are key to ensure that robust and reliable biomarker tests are developed and clinically validated.     

New medical approaches in pituitary adenomas

Recently, the medical approach to patients with secreting and clinically non-functioning pituitary adenomas has received great impulse thanks to the availability of new, selective and long-lasting compounds with dopaminergic activity, such as cabergoline, and of somatostatin analogues provided in slow-release formulations, such as lanreotide and octreotide long acting release (LAR). In particular, the use of cabergoline has induced control of hyperprolactinaemia and tumour shrinkage in the great majority of patients with micro- and macroprolactinomas. Cabergoline treatment restores fertility both in women and men, and partially improves osteoporosis, one of the major complications of hyperprolactinaemia. In acromegaly, disease control (growth hormone [GH] <2.5-1.0 microg/l as a fasting or glucose-suppressed value, respectively, together with age-normalised insulin-like growth factor [IGF]-I) is achievable in more than half of patients receiving treatment with lanreotide or octreotide-LAR. Improvement in cardiomyopathy, sleep apnoea and arthropathy has been reported during GH/IGF-I suppression after pharmacotherapy. A synthetic GH analogue, B2036-PEG, that antagonises endogenous GH binding to its receptor-binding sites and a GH-releasing hormone antagonist that blocks the effect of this releasing factor on the hypothalamus and pituitary are presently under investigation in acromegaly. Preliminary studies have clearly demonstrated the effectiveness of the GH receptor antagonist in suppressing IGF-I levels in acromegalic patients previously unresponsive to somatostatin analogues. Beneficial effects of subcutaneous octreotide and lanreotide have also been reported in adenomas secreting thyroid-stimulating hormone, while the results of treatment with dopamine agonists or somatostatin analogues remain disappointing in patients with clinically non-functioning adenomas. In these patients the possibility of visualising in vivo the expression of D(2) receptors using specific radiotracers such as (123)I-methoxybenzamide has allowed selection of patients likely to respond to cabergoline. Scant effects of pharmacotherapy have also been reported in patients with adenomas secreting adrenocorticotropic hormone. However, some preliminary data suggest a potential use of cabergoline in combination with ketoconazole, or alone, in selected cases of Cushing's disease or Nelson's syndrome.     

The association between chronotype and perceived academic stress to depression in medical students

Depression is a multifactorial illness that is highly prevalent among medical students (MS). Chronotypes, which reflect circadian preference in humans, as well as academic stress have been associated with depression in different populations. However, it is not known how chronotype and stress might alone or in combination, associate with depression in MS. Thus, we aimed to evaluate the association between stress, chronotype and depression in MS. In a cross-sectional study, we evaluated a total of 1068 medical students from a public Medical School in Mexico City. The Patient Health Questionnaire-9 (PHQ-9) was used to evaluate depressive symptom severity and the presence of a current depressive episode with a cutoff score of 10 or higher. The Morning-Evening Questionnaire (MEQ) was used to establish chronotype and the Academic Stress Inventory was used to measure perceived academic stress (PAS). We observed that depressive symptom severity was higher in non-morning chronotypes and moderate/severe PAS groups. A factorial ANOVA showed an association between PAS groups and depressive symptom severity. Linear regression showed an association between depressive symptom severity and variables such as PAS scores (p = 0.001), family history of depression (p = 0.001), gender (p = 0.001) and academic year (p = 0.029). Logistic regression analysis showed that evening chronotype (OR: 2.3, 95% CI: 1.2–4.3, p = 0.01) and severe PAS (OR: 4.4, 95% CI: 2.8–7.0, p = 0.0001) were associated with depression. Further, MS with the combination of severe PAS and morning (OR: 5.9, 95% CI: 1.6–22.2, p = 0.01), intermediate (OR: 7.5, 95% CI: 2.3–24.4, p = 0.001) or evening (OR: 10.6, 95% CI: 2.8–40.0, p = 0.001) chronotypes showed a greater association with depression than any PAS or chronotype group alone. Being female, perceiving restricted or limited economic resources, having severe scores of academic stress, and evening chronotype were associated with an increased probability to suffer a current depressive episode. Collectively, these results show that chronotype and PAS are factors associated with depression in MS, and when combined promote this association. Our results might aid in early identification of MS susceptible to depression. Future research could focus on the implementation of simple, low cost preventive strategies, such as chronotype-oriented academic schedules.