Effect of dorsolateral prefrontal cortex structural measures on neuroplasticity and response to paired-associative stimulation in Alzheimer's dementia.

Long-term potentiation (LTP)-like activity can be induced by stimulation protocols such as paired associative stimulation (PAS). We aimed to determine whether PAS-induced LTP-like activity (PAS-LTP) of the dorsolateral prefrontal cortex (DLPFC) is associated with cortical thickness and other structural measures impaired in Alzheimer's dementia (AD). We also explored longitudinal relationships between these brain structures and PAS-LTP response after a repetitive PAS (rPAS) intervention. Mediation and regression analyses were conducted using data from randomized controlled trials with AD and healthy control participants. PAS-electroencephalography assessed DLPFC PAS-LTP. DLPFC thickness and surface area were acquired from T1-weighted magnetic resonance imaging. Fractional anisotropy and mean diffusivity (MD) of the superior longitudinal fasciculus (SLF)-a tract important to induce PAS-LTP-were measured with diffusion-weighted imaging. AD participants exhibited reduced DLPFC thickness and increased SLF MD. There was also some evidence that reduction in DLPFC thickness mediates DLPFC PAS-LTP impairment. Longitudinal analyses showed preliminary evidence that SLF MD, and to a lesser extent DLPFC thickness, is associated with DLPFC PAS-LTP response to active rPAS. This study expands our understanding of the relationships between brain structural changes and neuroplasticity. It provides promising evidence for a structural predictor to improving neuroplasticity in AD with neurostimulation. This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.

Scaling Up Maternal Mental healthcare by Increasing access to Treatment (SUMMIT) through non-specialist providers and telemedicine: a study protocol for a non-inferiority randomized controlled trial.

BACKGROUND: Depression and anxiety impact up to 1 in 5 pregnant and postpartum women worldwide. Yet, as few as 20% of these women are treated with frontline interventions such as evidence-based psychological treatments. Major barriers to uptake are the limited number of specialized mental health treatment providers in most settings, and problems with accessing in-person care, such as childcare or transportation. Task sharing of treatment to non-specialist providers with delivery on telemedicine platforms could address such barriers. However, the equivalence of these strategies to specialist and in-person models remains unproven. METHODS: This study protocol outlines the Scaling Up Maternal Mental healthcare by Increasing access to Treatment (SUMMIT) randomized trial. SUMMIT is a pragmatic, non-inferiority test of the comparable effectiveness of two types of providers (specialist vs. non-specialist) and delivery modes (telemedicine vs. in-person) of a brief, behavioral activation (BA) treatment for perinatal depressive and anxiety symptoms. Specialists (psychologists, psychiatrists, and social workers with ≥ 5 years of therapy experience) and non-specialists (nurses and midwives with no formal training in mental health care) were trained in the BA protocol, with the latter supervised by a BA expert during treatment delivery. Consenting pregnant and postpartum women with Edinburgh Postnatal Depression Scale (EPDS) score of ≥ 10 (N = 1368) will be randomized to one of four arms (telemedicine specialist, telemedicine non-specialist, in-person specialist, in-person non-specialist), stratified by pregnancy status (antenatal/postnatal) and study site. The primary outcome is participant-reported depressive symptoms (EPDS) at 3 months post-randomization. Secondary outcomes are maternal symptoms of anxiety and trauma symptoms, perceived social support, activation levels and quality of life at 3-, 6-, and 12-month post-randomization, and depressive symptoms at 6- and 12-month post-randomization. Primary analyses are per-protocol and intent-to-treat. The study has successfully continued despite the COVID-19 pandemic, with needed adaptations, including temporary suspension of the in-person arms and ongoing randomization to telemedicine arms. DISCUSSION: The SUMMIT trial is expected to generate evidence on the non-inferiority of BA delivered by a non-specialist provider compared to specialist and telemedicine compared to in-person. If confirmed, results could pave the way to a dramatic increase in access to treatment for perinatal depression and anxiety. TRIAL REGISTRATION: ClinicalTrials.gov NCT04153864 . Registered on November 6, 2019.

Getting to precision psychopharmacology: Combining clinical and genetic information to predict fat gain from aripiprazole.

INTRODUCTION: All atypical antipsychotics are associated with some degree of weight gain. We applied a novel statistical approach to identify moderators of aripiprazole-induced fat gain using clinical and genetic data from a randomized clinical trial (RCT) of treatment resistant depression in older adults. MATERIALS AND METHODS: Adults aged ≥60 years with non-response to a prospective trial of venlafaxine were randomized to 12 weeks of aripiprazole augmentation (n = 91) or placebo (n = 90). Dual energy x-ray absorptiometry (DEXA) measured adiposity at baseline and 12 weeks. Independent moderators of total body fat gain were used to generate two combined multiple moderators, one including clinical data alone and one including both clinical and genetic data to characterize individuals who gained fat during aripiprazole augmentation. RESULTS: The value of the combined genetic + clinical multiple moderator (Mcg) was 0.57 [95% CI 0.46, 0.68] (effect size: 0.57), compared to the combined clinical moderator (Mc) value of 0.49 [0.34, 0.63] (effect size: 0.49). Individuals who gained adiposity in this study were more likely to be female and younger in age, have lower weight, fasting glucose and lipids at baseline and positive for the HTR2C polymorphism. DISCUSSION: These results demonstrate a combined multiple moderator approach, including both clinical and genetic moderators, can be applied to existing clinical trial data to understand adverse treatment effects. This method allowed for more specific characterization of individuals at risk for the outcome of interest. Further work is needed to identify additional genetic moderators and to validate the approach.

Using an Integrated Care Pathway for Late-Life Schizophrenia Improves Monitoring of Adverse Effects of Antipsychotics and Reduces Antipsychotic Polypharmacy.

OBJECTIVE: Antipsychotic use in older patients is associated with many adverse effects, including tardive dyskinesia and extrapyramidal symptoms, which, in turn, increase the risk of falling. Antipsychotics are also associated with metabolic syndrome and cognitive impairment in older patients. Integrated care pathways (ICPs) are designed to manage specific conditions using standardized assessments and measurement-based interventions. This study aims to compare the use of recommended tools to monitor for adverse effects associated with antipsychotics in older patients managed within an ICP and those managed under usual care conditions-i.e., treatment as usual (TAU). METHODS: We reviewed and compared the health records of 100 older patients enrolled in an ICP for late-life schizophrenia with those of 100 older patients treated with antipsychotics under TAU conditions. RESULTS: Monitoring rates were significantly higher in the ICP group than in the TAU group for all assessments: extrapyramidal symptoms (94% versus 5%), metabolic disturbances (91% versus 25%), fall risk (82% versus 35%), and cognitive impairment (72% versus 28%). Rates of antipsychotic polypharmacy were also six times higher in the TAU group. CONCLUSION: Older patients with schizophrenia treated with antipsychotics within an ICP experience higher rates of monitoring and less psychotropic polypharmacy than older patients treated with antipsychotics under TAU conditions. These findings suggest that an ICP can improve the quality of antipsychotic pharmacotherapy in older patients and thus possibly its effectiveness. This needs to be confirmed by a randomized controlled trial.

Stabilization treatment of remitted psychotic depression: the STOP-PD study.

OBJECTIVE: We conducted a 12-week double-blind study of stabilization pharmacotherapy in patients with remitted psychotic depression (PD). METHODS: Seventy-one persons aged 18 years or older who had achieved remission of PD when randomized to either olanzapine plus sertraline or olanzapine plus placebo were continued on the double-blind treatment associated with remission. Symptoms of depression and psychosis, and weight, were measured once every 4 weeks. Cholesterol, triglycerides, and glucose were measured at stabilization phase baseline and Week 12/termination. RESULTS: The effect of treatment did not significantly change with time for depression, weight, or metabolic measures in the stabilization phase. Eight of the 71 participants (11.3%; 95% CI: 5.8, 20.7) experienced a relapse of major depression, psychosis, or both. Treatment groups did not differ in the frequency of relapse. In the entire study group, the adjusted estimate for change in weight was an increase of 1.66 kg (95% CI: 0.83, 2.48) and the adjusted estimate for change in total cholesterol was a decrease of 14.8 mg/dL (95% CI: 3.5, 26.1) during the 12-week stabilization phase; the remaining metabolic measures did not significantly change. CONCLUSION: Continuation of acute treatment was associated with stability of remission.

Low medical morbidity and mortality after acute courses of electroconvulsive therapy in a population-based sample.

BACKGROUND: To determine event rates for specific medical events and mortality among individuals receiving electroconvulsive therapy (ECT). METHOD: Population-based cohort study using health administrative data of acute ECT treatments delivered in Ontario, Canada, from 2003 to 2011. We measured the following medical event rates, per 10 000 ECT treatments, up to 7 and 30 days post-treatment: stroke, seizure, acute myocardial infarction, arrhythmia, pneumonia, pulmonary embolus, deep vein thrombosis, gastrointestinal bleeding, falls, hip fracture, and mortality. RESULTS: A total of 135 831 ECT treatments were delivered to 8810 unique patients. Overall medical event rates were 9.1 and 16.8 per 10 000 ECT treatments respectively. The most common medical events were falls (2.7 and 5.5 per 10 000 ECT treatments) and pneumonia (1.8 and 3.8 per 10 000 ECT treatments). Fewer than six deaths occurred on the day of an ECT treatment. This corresponded to a mortality rate of less than 0.4 per 10 000 treatments. Deaths within 7 and 30 days of an ECT treatment, excluding deaths due to external causes (e.g., accidental and intentional causes of death), were 1.0 and 2.4 per 10 000 ECT treatments respectively. CONCLUSION: Morbidity and mortality events after ECT treatments were relatively low, supporting ECT as a low-risk medical procedure.

Neurobiological mechanisms of repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex in depression: a systematic review.

Depression is one of the most prevalent mental illnesses worldwide and a leading cause of disability, especially in the setting of treatment resistance. In recent years, repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising alternative strategy for treatment-resistant depression and its clinical efficacy has been investigated intensively across the world. However, the underlying neurobiological mechanisms of the antidepressant effect of rTMS are still not fully understood. This review aims to systematically synthesize the literature on the neurobiological mechanisms of treatment response to rTMS in patients with depression. Medline (1996-2014), Embase (1980-2014) and PsycINFO (1806-2014) were searched under set terms. Three authors reviewed each article and came to consensus on the inclusion and exclusion criteria. All eligible studies were reviewed, duplicates were removed, and data were extracted individually. Of 1647 articles identified, 66 studies met both inclusion and exclusion criteria. rTMS affects various biological factors that can be measured by current biological techniques. Although a number of studies have explored the neurobiological mechanisms of rTMS, a large variety of rTMS protocols and parameters limits the ability to synthesize these findings into a coherent understanding. However, a convergence of findings suggest that rTMS exerts its therapeutic effects by altering levels of various neurochemicals, electrophysiology as well as blood flow and activity in the brain in a frequency-dependent manner. More research is needed to delineate the neurobiological mechanisms of the antidepressant effect of rTMS. The incorporation of biological assessments into future rTMS clinical trials will help in this regard.

Rating scales measuring the severity of psychotic depression.

OBJECTIVE: Unipolar psychotic depression (PD) is a severe and debilitating syndrome, which requires intensive monitoring. The objective of this study was to provide an overview of the rating scales used to assess illness severity in PD. METHOD: Selective review of publications reporting results on non-self-rated, symptom-based rating scales utilized to measure symptom severity in PD. The clinical and psychometric validity of the identified rating scales was reviewed. RESULTS: A total of 14 rating scales meeting the predefined criteria were included in the review. These scales grouped into the following categories: (i) rating scales predominantly covering depressive symptoms, (ii) rating scales predominantly covering psychotic symptoms, (iii) rating scales covering delusions, and (iv) rating scales covering PD. For the vast majority of the scales, the clinical and psychometric validity had not been tested empirically. The only exception from this general tendency was the 11-item Psychotic Depression Assessment Scale (PDAS), which was developed specifically to assess the severity of PD. CONCLUSION: In PD, the PDAS represents the only empirically derived rating scale for the measurement of overall severity of illness. The PDAS should be considered in future studies of PD and in clinical practice.

In-vivo imaging of grey and white matter neuroinflammation in Alzheimer's disease: a positron emission tomography study with a novel radioligand, [18F]-FEPPA.

Our primary aim was to compare neuroinflammation in cognitively intact control subjects and patients with Alzheimer's disease (AD) by using positron emission tomography (PET) with translocator protein 18 kDa (TSPO)-specific radioligand [(18)F]-FEPPA. [(18)F]-FEPPA PET scans were acquired on a high-resolution research tomograph in 21 patients with AD (47- 81 years) and 21 control subjects (49-82 years). They were analyzed by using a 2-tissue compartment model with arterial plasma input function. Differences in neuroinflammation, indexed as [(18)F]-FEPPA binding were compared, adjusting for differences in binding affinity class as determined by a single polymorphism in the TSPO gene (rs6971). In grey matter areas, [(18)F]-FEPPA was significantly higher in AD compared with healthy control subjects. Large increases were seen in the hippocampus, prefrontal, temporal, parietal and occipital cortex (average Cohen's d= 0.89). Voxel-based analyses confirmed significant clusters of neuroinflammation in the frontal, temporal and parietal cortex in patients with AD. In white matter, [(18)F]-FEPPA binding was elevated in the posterior limb of the internal capsule, and the cingulum bundle. Higher neuroinflammation in the parietal cortex (r= -0.7, P= 0.005), and posterior limb of the internal capsule (r= -0.8, P=0.001) was associated with poorer visuospatial function. In addition, a higher [(18)F]-FEPPA binding in the posterior limb of the internal capsule was associated with a greater impairment in language ability (r= -0.7, P=0.004). Elevated neuroinflammation can be detected in AD patients throughout the brain grey and white matter by using [(18)F]-FEPPA PET. Our results also suggest that neuroinflammation is associated with some cognitive deficits.

Measuring psychotic depression.

OBJECTIVE: Psychotic depression (PD) is a highly debilitating condition, which needs intensive monitoring. However, there is no established rating scale for evaluating the severity of PD. The aim of this analysis was to assess the psychometric properties of established depression rating scales and a number of new composite rating scales, covering both depressive and psychotic symptoms, in relation to PD. METHOD: The psychometric properties of the rating scales were evaluated based on data from the Study of Pharmacotherapy of Psychotic Depression. RESULTS: A rating scale consisting of the 6-item Hamilton melancholia subscale (HAM-D6 ) plus five items from the Brief Psychiatric Rating Scale (BPRS), named the HAMD-BPRS11 , displayed clinical validity (Spearman's correlation coefficient between HAMD-BPRS11 and Clinical Global Impression - Severity (CGI-S) scores = 0.79-0.84), responsiveness (Spearman's correlation coefficient between change in HAMD-BPRS11 and Clinical Global Impression - Improvement (CGI-I) scores = -0.74--0.78) and unidimensionality (Loevinger's coefficient of homogeneity = 0.41) in the evaluation of PD. The HAM-D6 fulfilled the same criteria, whereas the full 17-item Hamilton Depression Scale failed to meet criteria for unidimensionality. CONCLUSION: Our results suggest that the HAMD-BPRS11 is a more valid measure than pure depression scales for evaluating the severity of PD.

The SORL1 gene and convergent neural risk for Alzheimer's disease across the human lifespan.

Prior to intervention trials in individuals genetically at-risk for late-onset Alzheimer's disease, critical first steps are identifying where (neuroanatomic effects), when (timepoint in the lifespan) and how (gene expression and neuropathology) Alzheimer's risk genes impact the brain. We hypothesized that variants in the sortilin-like receptor (SORL1) gene would affect multiple Alzheimer's phenotypes before the clinical onset of symptoms. Four independent samples were analyzed to determine effects of SORL1 genetic risk variants across the lifespan at multiple phenotypic levels: (1) microstructural integrity of white matter using diffusion tensor imaging in two healthy control samples (n=118, age 18-86; n=68, age 8-40); (2) gene expression using the Braincloud postmortem healthy control sample (n=269, age 0-92) and (3) Alzheimer's neuropathology (amyloid plaques and tau tangles) using a postmortem sample of healthy, mild cognitive impairment (MCI) and Alzheimer's individuals (n=710, age 66-108). SORL1 risk variants predicted lower white matter fractional anisotropy in an age-independent manner in fronto-temporal white matter tracts in both samples at 5% family-wise error-corrected thresholds. SORL1 risk variants also predicted decreased SORL1 mRNA expression, most prominently during childhood and adolescence, and significantly predicted increases in amyloid pathology in postmortem brain. Importantly, the effects of SORL1 variation on both white matter microstructure and gene expression were observed during neurodevelopmental phases of the human lifespan. Further, the neuropathological mechanism of risk appears to primarily involve amyloidogenic pathways. Interventions targeted toward the SORL1 amyloid risk pathway may be of greatest value during early phases of the lifespan.

The genome-wide supported microRNA-137 variant predicts phenotypic heterogeneity within schizophrenia.

We examined the influence of the genome-wide significant schizophrenia risk variant rs1625579 near the microRNA (miRNA)-137 (MIR137) gene on well-established sources of phenotypic variability in schizophrenia: age-at-onset of psychosis and brain structure. We found that the MIR137 risk genotype strongly predicts an earlier age-at-onset of psychosis across four independently collected samples of patients with schizophrenia (n=510; F1,506=17.7, P=3.1 × 10(-5)). In an imaging-genetics subsample that included additional matched controls (n=213), patients with schizophrenia who had the MIR137 risk genotype had reduced white matter integrity (F3,209=13.6, P=3.88 × 10(-8)) throughout the brain as well as smaller hippocampi and larger lateral ventricles; the brain structure of patients who were carriers of the protective allele was no different from healthy control subjects on these neuroimaging measures. Our findings suggest that MIR137 substantially influences variation in phenotypes that are thought to have an important role in clinical outcome and treatment response. Finally, the possible consequences of genetic risk factors may be distinct in patients with schizophrenia compared with healthy controls.

Serotonin-norepinephrine reuptake inhibitor therapy in late-life depression is associated with increased marker of bone resorption.

UNLABELLED: Antidepressants are associated with bone loss and fractures in older adults. We treated depressed older adults with an antidepressant and examined its effects on bone turnover by comparing blood samples before and after treatment. Bone resorption increased after antidepressant treatment, which may increase fracture risk. INTRODUCTION: Antidepressants have been associated with increased bone loss and fractures in older adults in observational studies, but the mechanism is unclear. We examined the effects of a serotonin-norepinephrine reuptake inhibitor, venlafaxine, on biomarkers of bone turnover in a prospective treatment study of late-life depression. METHODS: Seventy-six individuals aged 60 years and older with current major depressive disorder received a 12-week course of venlafaxine XR 150-300 mg daily. We measured serum C-terminal cross-linking telopeptide of type I collagen (ß-CTX) and N-terminal propeptide of type I procollagen (P1NP), measures of bone resorption and formation, respectively, before and after treatment. We then analyzed the change in ß-CTX and P1NP within each participant. Venlafaxine levels were measured at the end of the study. We assessed depression severity at baseline and remission status after treatment. RESULTS: After 12 weeks of venlafaxine, ß-CTX increased significantly, whereas P1NP did not significantly change. The increase in ß-CTX was significant only in participants whose depression did not remit (increase by 10 % in non-remitters vs. 4 % in remitters). Change in ß-CTX was not correlated with serum levels of venlafaxine or norvenlafaxine. CONCLUSION: Our findings suggest that the primary effect of serotonergic antidepressants is to increase bone resorption. However, such an increase in bone resorption seemed to depend on whether or not participants' depression remitted. Our results are in agreement with prior observational studies reporting increased bone loss in older adults taking serotonergic antidepressants. These negative effects on bone homeostasis could potentially contribute to increased fracture risk in older adults.

Two-year course of cognitive function and instrumental activities of daily living in older adults with bipolar disorder: evidence for neuroprogression?

BACKGROUND: While bipolar disorder (BD) is a leading cause of disability, and an important contributor to disability in BD is cognitive impairment, there is little systematic research on the longitudinal course of cognitive function and instrumental activities of daily living (IADLs) in late-life. In this report, we characterize the 2-year course of cognitive function and IADLs in older adults with BD. Method We recruited non-demented individuals 50 years and older with BD I or BD II (n = 47) from out-patient clinics or treatment studies at the University of Pittsburgh. Comparator subjects ('controls') were 22 individuals of comparable age and education with no psychiatric or neurologic history, but similar levels of cardiovascular disease. We assessed cognitive function and IADLs at baseline, 1- and 2-year time-points. The neuropsychological evaluation comprised 21 well-established and validated tests assessing multiple cognitive domains. We assessed IADLs using a criterion-referenced, performance-based instrument. We employed repeated-measures mixed-effects linear models to examine trajectory of cognitive function. We employed non-parametric tests for analysis of IADLs. RESULTS: The BD group displayed worse cognitive function in all domains and worse IADL performance than the comparator group at baseline and over follow-up. Global cognitive function and IADLs were correlated at all time-points. The BD group did not exhibit accelerated cognitive decline over 2 years. CONCLUSIONS: Over 2 years, cognitive impairment and associated functional disability of older adults with BD appear to be due to long-standing neuroprogressive processes compounded by normal cognitive aging rather than accelerated cognitive loss in old age.

Age at onset and cognition in schizophrenia: meta-analysis.

BACKGROUND: The relationship between cognition and age at onset of schizophrenia is largely unknown. AIMS: To compare cognitive deficits in individuals with youth-onset and late-onset schizophrenia with those in adults with first-episode schizophrenia. METHOD: Twenty-nine databases (including EMBASE, MEDLINE and PsycINFO) were searched from 1980 to 2008. Selected publications had to include healthy controls and analyse separately individuals diagnosed with schizophrenia or a related disorder and individuals with first-episode, youth-onset or late-onset schizophrenia. Descriptive and cognitive data were extracted and the latter aggregated into 22 cognitive measures. Cohen's effect size raw and weighted means of cognitive deficits were generated and compared in the three groups. RESULTS: Individuals with youth-onset and first-episode schizophrenia demonstrate large deficits (mean effect size >or=0.8) on almost all cognitive measures. Individuals with youth-onset schizophrenia demonstrate larger deficits than those with first-episode schizophrenia on arithmetic, executive function, IQ, psychomotor speed of processing and verbal memory. In contrast, those with late-onset schizophrenia demonstrate minimal deficits on arithmetic, digit symbol coding and vocabulary, but larger ones on attention, fluency, global cognition, IQ and visuospatial construction. CONCLUSIONS: Individuals with youth-onset schizophrenia have severe cognitive deficits, whereas those with late-onset schizophrenia have some relatively preserved cognitive functions. This finding supports the view that severity of the disease process is associated with different ages at onset. In addition, the cognitive pattern of people with late-onset schizophrenia suggests that their deficits are specific rather than solely as a result of ageing and related factors.

Primary care physicians attitude toward diagnosis and treatment of late-life depression.

Underdiagnosis and undertreatment of late-life depression is common, especially in primary care settings. To help assess whether physicians attitude and confidence in diagnosing and managing depression serve as barriers to care, a total of 176 physicians employed in 18 primary care groups were administered surveys to assess attitudes towards diagnosis, treatment, and management of depression in elderly patients, (individuals over 65 years of age). Logistic regression was performed to assess the association of physician characteristics on attitudes. Nearly all of the physicians surveyed felt that depression in the elderly was a primary care problem, and 41% reported late-life depression as the most common problem seen in older patients. Physicians were confident in their ability to diagnose and manage depression, yet 45% had no medical education on depression in the previous three years. Physicians confidence in their ability to diagnose, treat, and manage depression, and their reported adequacy of training, do not appear to correspond to the amount of continuing medical education in depression, suggesting that physician overconfidence may potentially be serving as a barrier to care.

Assessment of behavioral and psychological symptoms of dementia.

In spite of their prevalence and persistence, why are behavioral and psychological symptoms of dementia difficult for clinicians to assess and manage? This paper provides an overview of the methodological challenges encountered in measuring behavioral disturbances of dementia. Specifically, conceptual constructs of behavioral and psychological symptoms of dementia, the strengths and weaknesses of the currently existing rating instruments, analytic methodologies, and the utility of technological devices are outlined in the service of formulating future directions in behavioral and psychological symptoms of dementia assessment research.

Anxiety disorders in late life: an evolving picture.

Although anxiety disorders are the most prevalent group of disorders in the United States, little is known about the efficacy of treatments for these disorders in elderly patients. Anxiety disorders, especially generalized anxiety disorder and phobias, are highly prevalent in older people. Anxiety symptoms and disorders are associated with increased mortality and disability in older people. Risk factors for anxiety disorders include chronic medical illness, disability, low education, low social network, and poor social support. The newer antidepressant medications, in particular the selective serotonin reuptake inhibitors and venlafaxine-extended relief, are recommended as first-line pharmacotherapy of these disorders in elderly. Cognitive-behavioral therapy is recommended as first-line psychotherapy for these disorders. However, these recommendations are based on extrapolation of data from younger adults or retrospective analysis of datasets, the results need to be confirmed with controlled studies in an elderly age group.

The establishment of a brain bank for the study of late-life depression: a feasibility study of factors facilitating consent.

BACKGROUND: Studies of postmortem brain tissue are advancing the understanding of the pathophysiology of major depressive disorder (MDD). The nature and quality of subject samples, however, limit their applicability to late-life MDD. OBJECTIVE: To examine the feasibility of establishing a brain bank for late-life MDD, and identify clinical, demographic, and procedural factors that might facilitate subject enrollment. METHODS: Elderly subjects participating in clinical trials associated with the Mental Health Intervention Research Center for Late-Life Mood Disorders (MHIRC/LLMD) at the University of Pittsburgh were approached by clinical research staff for consent to future brain-only autopsy. Subjects who consented to participation were compared with those who refused participation on demographic and clinical variables. MHIRC/LLMD clinical research staff were interviewed to determine factors that may have facilitated or hindered the consent process and reasons for subject consent or refusal. RESULTS: Eighty out of 242 subjects (33%) subjects approached for participation in the brain bank provided consent. Consent to participate was associated with higher level of education and with lower Mini-Mental State Examination score. Several factors facilitating and hindering the consent process were identified. CONCLUSION: We provide preliminary evidence for the feasibility of establishing a brain bank for the study of late-life MDD. Future efforts may be guided by the factors identified as facilitating the consent process, especially the inclusion of family in the consent process.