The status of psychodynamic psychotherapy as an empirically supported treatment for common mental disorders – an umbrella review based on updated criteria

To assess the current status of psychodynamic therapy (PDT) as an empirically supported treatment (EST), we carried out a pre-registered systematic umbrella review addressing the evidence for PDT in common mental disorders in adults, based on an updated model for ESTs. Following this model, we focused on meta-analyses of randomized controlled trials (RCTs) published in the past two years to assess efficacy. In addition, we reviewed the evidence on effectiveness, cost-effectiveness and mechanisms of change. Meta-analyses were evaluated by at least two raters using the proposed updated criteria, i.e. effect sizes, risk of bias, inconsistency, indirectness, imprecision, publication bias, treatment fidelity, and their quality as well as that of primary studies. To assess the quality of evidence we applied the GRADE system. A systematic search identified recent meta-analyses on the efficacy of PDT in depressive, anxiety, personality and somatic symptom disorders. High quality evidence in depressive and somatic symptom disorders and moderate quality evidence in anxiety and personality disorders showed that PDT is superior to (inactive and active) control conditions in reducing target symptoms with clinically meaningful effect sizes. Moderate quality evidence suggests that PDT is as efficacious as other active therapies in these disorders. The benefits of PDT outweigh its costs and harms. Furthermore, evidence was found for long-term effects, improving functioning, effectiveness, cost-effectiveness and mechanisms of change in the aforementioned disorders. Some limitations in specific research areas exist, such as risk of bias and imprecision, which are, however, comparable to those of other evidence-based psychotherapies. Thus, according to the updated EST model, PDT proved to be an empirically-supported treatment for common mental disorders. Of the three options for recommendation provided by the updated model (i.e., “very strong”, “strong” or “weak”), the new EST criteria suggest that a strong recommendation for treating the aforementioned mental disorders with PDT is the most appropriate option. In conclusion, PDT represents an evidence-based psychotherapy. This is clinically important since no single therapeutic approach fits all psychiatric patients, as shown by the limited success rates across all evidence-based treatments.     

Maximizing the value of systematic reviews in ecology when data or resources are limited

Systematic reviews provide a rigorous, repeatable and quantitative method for assessing and synthesizing all available empirical evidence to evaluate a specific research, management, or policy question. They are particularly well suited for evaluating the effectiveness of environmental management actions, and thus for underpinning evidence‐based adaptive natural resource management. However, their current utility may be limited in countries like Australia, where both the amount of research relative to land area and of well‐monitored, active land management for environmental purposes are relatively low. Based on our experience conducting two of the first ecological systematic reviews in Australia, we have developed a number of recommendations for conducting systematic reviews in situations where resources and/or primary research data are limited. We discuss potential modification or augmentation of most aspects of the systematic review process including selection of a review team, question formulation, search strategy, data analysis, and the communication of results, as well as the inherent tradeoffs between systematic thoroughness and available resources that are involved in these changes. We hope that our recommendations will encourage more ecologists to undertake systematic reviews even if primary research and resources to conduct the review appear to be limited, as even a modified systematic review can provide more defensible evidence‐based guidelines for management of natural resources.     

Periodic health examination, 1999 update: 1. Detection,prevention and treatment of obesity

OBJECTIVES: (1) To evaluate the evidence relating to the effectiveness of methods to prevent and treat obesity, and (2) to provide recommendations for the prevention and treatment of obesity in adults aged 18 to 65 years and for the measurement of the body mass index (BMI) as part of a periodic health examination. OPTIONS: In adults with obesity (BMI greater than 27) management options include weight reduction, prevention of further weight gain or no intervention. OUTCOMES: The long-term (more than 2 years) effectiveness of (a) methods to prevent obesity and (b) methods to treat obesity. EVIDENCE: MEDLINE was searched for articles published from 1966 to April 1998 that related to the prevention and treatment of obesity; additional articles were identified from the bibliographies of review articles and the listings of Current Contents. Selection criteria were used to limit the analysis to prospective studies with at least 2 years'' follow-up. BENEFITS, HARM AND COSTS: Health benefits of weight reduction were evaluated in terms of alleviation of symptoms, improved management of obesity-related diseases and a reduction in major clinical outcomes. The health risk of weight-reduction methods were briefly evaluated in terms of increased mortality and morbidity. VALUES: The recommendations of this report reflect the commitment of the Canadian Task Force on Preventive Health Care to provide a structured, evidence-based appraisal of whether a manoeuvre should be part of a periodic health examination. RECOMMENDATIONS: (1) Prevention: There is insufficient evidence to recommend in favour of or against community-based obesity prevention programs; however, because of considerable health risks associated with obesity and the limited long-term effectiveness of weight-reduction methods, the prevention of obesity should be a high priority for health care providers (grade C recommendation). (2) Treatment: (a) For obese adults without obesity-related diseases, there is insufficient evidence to recommend in favour of or against weight-reduction therapy because of a lack of evidence supporting the long-term effectiveness of weight-reduction methods (grade C recommendation); (b) for obese adults with obesity-related diseases (e.g., diabetes mellitus, hypertension), weight reduction is recommended because it can alleviate symptoms and reduce drug therapy requirements, at least in the short term (grade B recommendation). (3) Detection: (a) for people without obesity-related diseases, there is insufficient evidence to recommend the inclusion or exclusion of BMI measurement as part of a periodic health examination, and therefore BMI measurement is left to the discretion of individual health care providers (grade C recommendation); (b) for people with obesity-related diseases, BMI measurement is recommended because weight reduction should be considered with a BMI of more than 27 (grade B recommendation). VALIDATION: The findings of this analysis were reviewed through an iterative process by the members of the Canadian Task Force on Preventive Health Care. SPONSORS: The Canadian Task Force on Preventive Health Care is funded through a partnership between the Provincial and Territorial Ministries of Health and Health Canada.     

Applying Weight-of-Evidence in Retrospective Ecological Risk Assessment When Quantitative Data Are Limited

Retrospective ecological risk assessment attempts to identify likely causal agents to explain adverse effects that have occurred in ecological targets. It can never be decisive since it is post hoc and usually based on limited evidence that is rarely very quantitative. It can, nevertheless, be made more transparent, systematic, and logical, and less subjective. Based on human health epidemiological criteria we develop an approach that moves from systematic consideration of seven basic questions to assigning a likelihood of involvement of putative agents. The questions are: 1. Is there evidence that the target is or has been exposed to the agent? 2. Is there evidence for correlation between adverse effects in the target and exposure to the agent either in time or in space? 3. Do the measured or predicted environmental concentrations exceed quality criteria for water, sediment or body burden? 4. Have the results from controlled experiments in the field or laboratory led to the same effect? 5. Has removal of the agent led to amelioration of effects in the target? 6. Is there an effect in the target known to be specifically caused by exposure to the agent? 7. Does the proposed causal relationship make sense logically and scientifically? We identify 15 common scenarios of answers to the questions and illustrate the approach by reference to three real-world case studies (decline in benthos in a tropical marine bay, decline in fisheries in a temperate sea, decline in marine mollusc populations). The primary challenge in retrospective risk assessment is to make best use of the available evidence to develop rational management strategies and/or guide additional analyses to gain further evidence about likely agents as causes of observed harm.     

The treatable intellectual disability APP www.treatable-id.org: A digital tool to enhance diagnosis & care for rare diseases

ABSTRACT: BACKGROUND: Intellectual disability (ID) is a devastating and frequent condition, affecting 2-3% of the population worldwide. Early recognition of treatable underlying conditions drastically improves health outcomes and decreases burdens to patients, families and society. Our systematic literature review identified 81 such inborn errors of metabolism, which present with ID as a prominent feature and are amenable to causal therapy. The WebApp translates this knowledge of rare diseases into a diagnostic tool and information portal. Methods & Results: Freely available as a WebApp via www.treatable-id.org and mid 2012 via the App store, this diagnostic tool is designed for all specialists evaluating children with global delay / ID and laboratory scientists. Information on the 81 diseases is presented in different ways with search functions: 18 biochemical categories, neurologic and non-neurologic signs & symptoms, diagnostic investigations (metabolic screening tests in blood and urine identify 60% of all IEMs), therapies & effects on primary (IQ/developmental quotient) and secondary outcomes, and available evidence For each rare condition a 'disease page' serves as an information portal with online access to specific genetics, biochemistry, phenotype, diagnostic tests and therapeutic options. As new knowledge and evidence is gained from expert input and pubmed searches this tool will be continually updated. The WebApp is an integral part of a protocol prioritizing treatability in the work-up of every child with global delay / ID. A 3-year funded study will enable an evaluation of its effectiveness. CONCLUSIONS: For rare diseases, a field for which financial and scientific resources are particularly scarce, knowledge translation challenges are abundant. With this WebApp technology is capitalized to raise awareness for rare treatable diseases and their common presenting clinical feature of ID, with the potential to improve health outcomes. This innovative digital tool is designed to motivate health care providers to search actively for treatable causes of ID, and support an evidence-based approach to rare metabolic diseases. In our current -omics world with continuous information flow, the effective synthesis of data into accessible, clinical knowledge has become ever more essential to bridge the gap between research and care.     

Disseminating the best available evidence: New challenges in public reporting of health care

As a direct benefit of the Health Care Reform Act (2010), concerted effort has been deployed to define and characterize the process by which the best available evidence for diagnosis or treatment intervention prognosis can be obtained. The science of research synthesis in health care has established the systematic research protocol by which randomized clinical trials and other clinical studies must be reviewed and compared for the level and quality of the evidence presented, as well as the consensus of the best available evidence synthesized and shared. This process of systematic review yields a reliable and valid approach in comparing different interventions and strategies to prevent, diagnose, treat and monitor health conditions in terms of efficacy, and or of effectiveness. The resulting bioinformation outcome of comparative effectiveness and efficacy research review of the available clinical data is expressed as a consensus of the best available evidence, which finds its way in evidence-based clinical practice guidelines, standards of care and eventually, in policies: hence, the acronym CEERAP (comparative effectiveness and efficacy review and policy). The methodological and the procedural criteria that determine and regulate the public reporting dissemination of this sort of bioinformation, and the extent of benefit to the patient's health literacy, which have remained a bit more elusive to this date, are investigated and discussed in this paper.     

Systematic Analysis of Fly Models with Multiple Drivers Reveals Different Effects of Ataxin-1 and Huntingtin in Neuron Subtype-Specific Expression

The fruit fly, Drosophila melanogaster, is a commonly used model organism for neurodegenerative diseases. Its major advantages include a short lifespan and its susceptibility to manipulation using sophisticated genetic techniques. Here, we report the systematic comparison of fly models of two polyglutamine (polyQ) diseases. We induced expression of the normal and mutant forms of full-length Ataxin-1 and Huntingtin exon 1 in cholinergic, dopaminergic, and motor neurons, and glial cells using cell type-specific drivers. We systematically analyzed their effects based on multiple phenotypes: eclosion rate, lifespan, motor performance, and circadian rhythms of spontaneous activity. This systematic assay system enabled us to quantitatively evaluate and compare the functional disabilities of different genotypes. The results suggest different effects of Ataxin-1 and Huntingtin on specific types of neural cells during development and in adulthood. In addition, we confirmed the therapeutic effects of LiCl and butyrate using representative models. These results support the usefulness of this assay system for screening candidate chemical compounds that modify the pathologies of polyQ diseases.     

The use of computer system in the introduction of countermeasures in agriculture after the Chernobyl accident

In the development of strategies for countermeasures aimed at the rehabilitation of contaminated areas, essential is to identify criteria for assessing their effectiveness and factors influencing the priority of the criteria chosen. A method is suggested for assessing effectiveness of countermeasures in agriculture based on a multicriterium analysis of radiologic, economic, regulatory and socio-psychological indicators characterizing the use of countermeasures. Rating of countermeasures strategies is presented depending on financing of works on the rehabilitation of the Chernobyl affected areas.     

Neutrophil elastase in bronchiectasis

The role of neutrophil elastase (NE) is poorly understood in bronchiectasis because of the lack of preclinical data and so most of the assumptions made about NE inhibitor potential benefit is based on data from CF. In this context, NE seems to be a predictor of long-term clinical outcomes and a possible target of treatment. In order to better evaluate the role of NE in bronchiectasis, a systematic search of scientific evidence was performed.Two investigators independently performed the search on PubMed and included studies published up to May 15, 2017 according to predefined criteria. A final pool of 31 studies was included in the systematic review, with a total of 2679 patients. For each paper data of interest were extracted and reported in table.In this review sputum NE has proved useful as an inflammatory marker both in stable state bronchiectasis and during exacerbations and local or systemic antibiotic treatment. NE has also been associated with risk of exacerbation, time to next exacerbation and all-cause mortality. This study reviews also the role of NE as a specific target of treatment in bronchiectasis. Inhibition of NE is at a very early stage and future interventional studies should evaluate safety and efficacy for new molecules and formulations.     

Risk factors for neck and upper extremity disorders among computers users and the effect of interventions: an overview of systematic reviews

Background

To summarize systematic reviews that 1) assessed the evidence for causal relationships between computer work and the occurrence of carpal tunnel syndrome (CTS) or upper extremity musculoskeletal disorders (UEMSDs), or 2) reported on intervention studies among computer users/or office workers.

Methodology/Principal Findings

PubMed, Embase, CINAHL and Web of Science were searched for reviews published between 1999 and 2010. Additional publications were provided by content area experts. The primary author extracted all data using a purpose-built form, while two of the authors evaluated the quality of the reviews using recommended standard criteria from AMSTAR; disagreements were resolved by discussion. The quality of evidence syntheses in the included reviews was assessed qualitatively for each outcome and for the interventions.Altogether, 1,349 review titles were identified, 47 reviews were retrieved for full text relevance assessment, and 17 reviews were finally included as being relevant and of sufficient quality. The degrees of focus and rigorousness of these 17 reviews were highly variable. Three reviews on risk factors for carpal tunnel syndrome were rated moderate to high quality, 8 reviews on risk factors for UEMSDs ranged from low to moderate/high quality, and 6 reviews on intervention studies were of moderate to high quality. The quality of the evidence for computer use as a risk factor for CTS was insufficient, while the evidence for computer use and UEMSDs was moderate regarding pain complaints and limited for specific musculoskeletal disorders. From the reviews on intervention studies no strong evidence based recommendations could be given.

Conclusions/Significance

Computer use is associated with pain complaints, but it is still not very clear if this association is causal. The evidence for specific disorders or diseases is limited. No effective interventions have yet been documented.     

Estradiol-induced redistribution of lysosomal proteins in rat preputial gland. Evidence from immunologic probes

The influence of estrogen on the subcellular localization and distribution of lysosomal components of preputial gland was investigated in the ovariectomized rat. Antisera of high titer and specificity toward high-density lysosomal lipoproteins of this organ were raised in rabbits. The immunologic effectiveness of the IgG fraction so obtained was confirmed by microcomplement fixation, immunodiffusion, and immunoelectrophoresis. By both direct and indirect immunofluorescence techniques, cryostat sections of preputial gland from the control animals exhibited pinpoint cytoplasmic fluorescence, of dimensions corresponding to those of lysosomes. In contrast, specific immunoreactive material in corresponding target cells from animals receiving 0.1 microng of estradiol-17 beta/100 g body wt only 2 min earlier was distributed more homogeneously, indicating release of antigen from the membrane-bounded organelles. Moreover, specific immunofluorescence became evident at cell surfaces and in peri- and supranuclear localization, sites essentially negative in the controls. These effects were intensified at 15 min, as well as by maximal physiologic dose (0.5 microng/100 g body wt) of hormone. The relatively less active epimer, estradiol-17 alpha, exhibited only very limited effectiveness by some of these criteria. These observations, taken together with independent biochemical and ultrastructural evidence, lead to the conclusion that structural labilization of lysosomal constituents and their translocation to the nuclear compartment are early correlates of estrogen action.     

The impact of eHealth on the quality and safety of health care: a systematic overview

Background

There is considerable international interest in exploiting the potential of digital solutions to enhance the quality and safety of health care. Implementations of transformative eHealth technologies are underway globally, often at very considerable cost. In order to assess the impact of eHealth solutions on the quality and safety of health care, and to inform policy decisions on eHealth deployments, we undertook a systematic review of systematic reviews assessing the effectiveness and consequences of various eHealth technologies on the quality and safety of care.

Methods and Findings

We developed novel search strategies, conceptual maps of health care quality, safety, and eHealth interventions, and then systematically identified, scrutinised, and synthesised the systematic review literature. Major biomedical databases were searched to identify systematic reviews published between 1997 and 2010. Related theoretical, methodological, and technical material was also reviewed. We identified 53 systematic reviews that focused on assessing the impact of eHealth interventions on the quality and/or safety of health care and 55 supplementary systematic reviews providing relevant supportive information. This systematic review literature was found to be generally of substandard quality with regards to methodology, reporting, and utility. We thematically categorised eHealth technologies into three main areas: (1) storing, managing, and transmission of data; (2) clinical decision support; and (3) facilitating care from a distance. We found that despite support from policymakers, there was relatively little empirical evidence to substantiate many of the claims made in relation to these technologies. Whether the success of those relatively few solutions identified to improve quality and safety would continue if these were deployed beyond the contexts in which they were originally developed, has yet to be established. Importantly, best practice guidelines in effective development and deployment strategies are lacking.

Conclusions

There is a large gap between the postulated and empirically demonstrated benefits of eHealth technologies. In addition, there is a lack of robust research on the risks of implementing these technologies and their cost-effectiveness has yet to be demonstrated, despite being frequently promoted by policymakers and “techno-enthusiasts” as if this was a given. In the light of the paucity of evidence in relation to improvements in patient outcomes, as well as the lack of evidence on their cost-effectiveness, it is vital that future eHealth technologies are evaluated against a comprehensive set of measures, ideally throughout all stages of the technology''s life cycle. Such evaluation should be characterised by careful attention to socio-technical factors to maximise the likelihood of successful implementation and adoption. Please see later in the article for the Editors'' Summary     

A systematic review of randomised clinical trials of Tripterygium wilfordii for rheumatoid arthritis.

Tripterygium wilfordii is a Chinese herb with immunosuppressive effects and an established history of use in the treatment of rheumatoid arthritis (RA). We have carried out a systematic review of randomised clinical trials (RCTs) which assess the effectiveness of T. wilfordii in this indication. We included only randomised and controlled studies which tested the effectiveness of T. wilfordii monopreparations in the treatment of RA. Studies in any language were included. A search of five electronic databases from inception to February 2005 identified 18 articles which could potentially meet our inclusion criteria. Only 16 of these could be retrieved from the scientific literature and after reading these in full, only two unique RCTs meeting our inclusion criteria were identified. Both indicated that T. wilfordii has beneficial effects on the symptoms of RA. However, the literature indicates that T. wilfordii is associated with serious adverse events which make the risk-benefit analysis for this herb unfavourable. Therefore, we cannot recommend its use.     

What Should Dental Services for People with Disabilities Be Like? Results of an Irish Delphi Panel Survey

Background

This study aimed to generate prioritised goals for oral health services for people with disabilities as a first step in meeting the need for evidence based oral health services for people with disabilities in Ireland.

Methods

The study used a three round modified e-Delphi method, involving dental service professionals and people with disabilities or their representatives, in Ireland. Three rounds were completed online using SurveyMonkey. Round 1 asked: “List what you think dental services for people with disabilities in Ireland should be like.” Items for subsequent rounds were generated from responses to Round 1. Round 2 and Round 3 used 5 point Likert scales to rank these items by priority: from No Priority (1) to Top Priority (5). Consensus was achieved on each item where at least 80% of respondents considered an item either High or Top Priority. A consensus meeting concluded the process.

Results

Sixty-one panelists started and 48 completed the survey. The Delphi panel agreed on level of priority for 69 items and generated 16 consensus statements. These statements covered a range of topics such as access to care, availability of information and training, quality of care, dental treatment and cost. A recurrent theme relating to the appropriateness of care to individual need arose across topics suggesting a need to match service delivery according to the individual''s needs, wants and expectations rather than the disability type/diagnosis based service which predominates today.

Conclusions

This process produced a list of prioritised goals for dental services for people with disabilities. This creates a foundation for building evidence-based service models for people with disabilities in Ireland.     

Role of epidemiological science and practice in protecting the health of the population of the country

The historical stages of the development of epidemiology as a science with a specific object of study, is summarized. One of the greatest theoretical generalizations is the doctrine on the natural focality of diseases. New principles of theoretical epidemiology, new theories and concepts are analyzed. The role of infectious pathology as one of the main criteria of the population health is emphasized as well as a wide spread of infectious (parasitic) diseases. The specific feature of the present stage of epidemiological situation is the dominating and constantly increasing role of viruses in the etiology of infectious diseases. The effectiveness of vaccinal prophylaxis to control vaccine-preventable infections is substantiated. The role of epidemiological science in revealing the epidemiological regularities of emerging and re-emerging infections is emphasized.     

Physiotherapy for patients with soft tissue shoulder disorders: a systematic review of randomised clinical trials.

OBJECTIVE: To assess the effectiveness of physiotherapy for patients with soft tissue shoulder disorders. DESIGN: A systematic computerised literature search of Medline and Embase, supplemented with citation tracking, for relevant trials with random allocation published before 1996. SUBJECTS: Patients treated with physiotherapy for disorders of soft tissue of the shoulder. MAIN OUTCOME MEASURES: Success rates, mobility, pain, functional status. RESULTS: Six of the 20 assessed trials satisfied at least five of eight validity criteria. Assessment of methods was often hampered by insufficient information on various validity criteria, and trials were often flawed by lack of blinding, high proportions of withdrawals from treatment, and high proportions of missing values. Trial sizes were small: only six trials included intervention groups of more than 25 patients. Ultrasound therapy, evaluated in six trials, was not shown to be effective. Four other trials favoured physiotherapy (laser therapy or manipulation), but the validity of their methods was unsatisfactory. CONCLUSIONS: There is evidence that ultrasound therapy is ineffective in the treatment of soft tissue shoulder disorders. Due to small trial sizes and unsatisfactory methods, evidence for the effectiveness of other methods of physiotherapy is inconclusive. For all methods of treatment, trials were too heterogeneous with respect to included patients, index and reference treatments, and follow up to merit valid statistical pooling. Future studies should show whether physiotherapy is superior to treatment with drugs, steroid injections, or a wait and see policy.     

Clinical guidelines contribute to the health inequities experienced by individuals with intellectual disabilities

ABSTRACT: BACKGROUND: Clinical practice guidelines are developed to improve the quality of healthcare. However, clinical guidelines may contribute to health inequities experienced by disadvantaged groups. This study uses an equity lens developed by the International Clinical Epidemiology Network (INCLEN) to examine how well clinical guidelines address inequities experienced by individuals with intellectual disabilities. METHODS: Nine health problems relevant to the health inequities experienced by persons with intellectual disabilities were selected. Clinical guidelines on these disorders were identified from across the world. The INCLEN equity lens was used as the basis for a purposedesigned, semistructured data collection tool. Two raters independently examined each guideline and completed the data collection tool. The data extracted by each rater were discussed at a research group consensus conference and agreement was reached on a final equity lens rating for each guideline. RESULTS: Thirty-six guidelines were identified, one of which (2.8%) explicitly excluded persons with intellectual disabilities. Of the remaining 35, six (17.1%) met the first criterion of the equity lens, identifying persons with intellectual disabilities at high risk for the specific health problem. Eight guidelines (22.9%) contained any content on intellectual disabilities. Six guidelines addressed the fourth equity lens criterion, by giving specific consideration to the barriers to implementation of the guideline in disadvantaged populations. There were no guidelines that addressed the second, third, and fifth equity lens criteria. CONCLUSIONS: The equity lens is a useful tool to systematically examine whether clinical guidelines address the health needs and inequities experienced by disadvantaged groups. Clinical guidelines are likely to further widen the health inequities experienced by persons with intellectual disabilities, and other disadvantaged groups, by being preferentially advantageous to the general population. There is a need to systematically incorporate methods to consider disadvantaged population groups into the processes used to develop clinical guidelines.     

Somatostatin in Alzheimer's disease and depression.

Somatostatin (somatotropin release-inhibiting factor, SRIF) was originally discovered (1) during the purification of growth hormone-releasing factor from rat hypothalamus and was subsequently isolated and characterized (2) in 1972 from ovine hypothalamus. Since its initial characterization, SRIF has been shown to fulfill criteria for a neurotransmitter and to directly modulate neuronal activity as well as acting as an inhibitory factor regulating endocrine and exocrine secretion. Alterations in cerebrospinal fluid (CSF) concentrations of SRIF have been reported in several diseases exhibiting prominent cognitive dysfunction, including Alzheimer's disease (AD), major depression, Huntington's chorea, multiple sclerosis, schizophrenia and Parkinson's disease, while evidence for regional brain tissue concentration deficits in SRIF are more specific for AD. This mini-review will focus on the studies reporting alterations in CSF and postmortem tissue concentrations of SRIF in AD and depression.