Early Diagnosis and Targeted Treatment Strategy for Improved Therapeutic Outcomes in Alzheimer's Disease.

There have been repeated failures of clinical studies in the development of new efficacious treatments for Alzheimer's disease. This may be due to the fact that Alzheimer's disease is a heterogeneous disorder caused by person-to-person differences in genetic background, epigenetic profiles, environmental triggers, or the presence of other diseases. Furthermore, most Alzheimer's disease patients are diagnosed in the middle to late stages of the illness, when irreversible damage to the brain has already occurred. With this in mind, a strategy is presented involving identification and implementation of biomarker tests for diagnosis during the prodromal or early stages of the disease. In addition, it is proposed that targeting specific components of the amyloid deposition, tau oligomerization and neuroinflammation pathways may lead to improved outcomes in clinical studies.

Early Detection and Treatment of Patients with Alzheimer's Disease: Future Perspectives.

Alzheimer's disease affects approximately 6% of people over the age of 65 years. It is characterized as chronic degeneration of cortical neurons, with loss of memory, cognition and executive functions. As the disease progresses, it is accompanied by accumulation of amyloid plaques and neurofibrillary tangles in key areas of the brain, leading to a loss of neurogenesis and synaptic plasticity in the hippocampus, along with changes in the levels of essential neurotransmitters such as acetylcholine and glutamate. Individuals with concomitant diseases such as depression, diabetes and cardiovascular disorders have a higher risk of developing Alzheimer's disease, and those who have a healthier diet and partake in regular exercise and intellectual stimulation have a lower risk of developing the disorder. This chapter describes the advances made in early diagnosis of Alzheimer's disease as this could help to improve outcomes for the patients by facilitating earlier treatment.

Developmental Origins of Stress and Psychiatric Disorders.

Over the last few decades, evidence has emerged that the pathogenesis of psychiatric disorders such as schizophrenia can involve perturbations of the hypothalamic-pituitary-adrenal (HPA) axis and other neuroendocrine systems. Variations in the manifestation of these effects could be related to differences in clinical symptoms between affected individuals and to differences in treatment response. Such effects can also arise from the complex interaction between genes and environmental factors. Here, we review the effects of maternal stress on abnormalities in HPA axis regulation and the development of psychiatric disorders such as schizophrenia. Studies in this area may prove critical for increasing our understanding of the multidimensional nature of mental disorders and could lead to the development of improved diagnostics and novel therapeutic approaches for treating individuals who suffer from these conditions.

Point-of-Care Testing and Personalized Medicine for Metabolic Disorders.

This chapter describes innovations in biomarker testing that can facilitate earlier and better treatment of patients who suffer from metabolic disorders. The use of new microfluidic devices along with miniaturized biosensors and transducers enables analysis of a single drop of a blood within the time frame of a typical visit to a doctor's office. Steps are underway so that these approaches will incorporate both biochemical and clinical data, resulting in unique bioprofiles for each patient. This will allow earlier, personalized, and more effective therapeutic options. In addition, smartphone apps for self-monitoring will be used increasingly for the best possible patient outcomes.

Proteomic Approaches to Enable Point-of-Care Testing and Personalized Medicine for Psychiatric Disorders.

This chapter describes how innovations that are driven by proteomic biomarker techniques can facilitate earlier and better treatment of patients who suffer from psychiatric disorders. The application of new micro-fluidic devices along with miniaturized biosensors and transducers will enable the development of handheld point-of-care testing instruments which can analyse a drop of a blood within the time span of a single visit to the doctor's office. It is anticipated that these approaches will incorporate both biochemical and clinical information, resulting in unique profiles for each test subject. These profiles can in turn be used to drive personalized medicine approaches in this devastating disease area. In addition, smartphone applications (apps) for self-monitoring will see increasing use for improved patient outcomes.

The emergence of point-of-care blood-based biomarker testing for psychiatric disorders: enabling personalized medicine.

For psychiatric disorders, repeated failures in converting scientific discoveries into novel drugs has precipitated a crisis and eroded confidence in drug discovery. This review describes how current and future innovations driven by application of biomarkers can help to re-initiate research in this area. This will have positive impact on the field of psychiatry and result in application of sensitive and specific biochemical tests in parallel with the traditional questionnaires for improved diagnosis. Furthermore, application of emerging biosensor tools will facilitate point-of-care testing by fusion of biochemical and clinical data. In this way, patient data will be comprised of past medical histories, biopatterns and prognosis information, resulting in personalized profiles or molecular fingerprints for patients with these conditions.

Making Sense of Blood-Based Proteomics and Metabolomics in Psychiatric Research.

This manuscript describes the basics of proteomic and metabolic profiling of blood serum and plasma from patients with psychiatric disorders. It will also explain the rationale behind the use of these bodily fluids, due to the need for user-friendly and rapid tests in clinics with simple sampling procedures. It has become evident over the last 15 years or so that psychiatric disorders are whole-body diseases and the bloodstream is a means of molecular transport that therefore provides a conduit for two-way communication with the brain. Here we also describe some of the basic biomarker findings from studies of serum or plasma from patients with psychiatric disorders like schizophrenia, major depression, and bipolar disorder. Finally, we will discuss potential future advancements in this area, which include the development of hand-held devices containing miniature proteomic and metabolic assays which can be used for facilitating diagnoses in a point-of-care setting and yield results in less than 15 minutes from a single drop of blood.

Os efeitos do estresse na função do eixo hipotalâmico-pituitário-adrenal em indivíduos com esquizofrenia / The effects of stress on hypothalamic-pituitary-adrenal (HPA) axis function in subjects with schizophrenia

Nas últimas décadas, têm surgido evidências sugerindo que a patogênese de desordens psiquiátricas, tais como a esquizofrenia, pode envolver perturbações no eixo hipotalâmico-pituitário-adrenal (HPA). Variações na manifestação desses efeitos poderiam estar relacionadas a diferenças em sintomas clínicos entre os indivíduos afetados, assim como a diferenças na resposta ao tratamento. Tais efeitos podem também ser originados de complexas interações entre genes e fatores ambientais. Aqui, revisamos os efeitos do estresse maternal em anormalidades na regulação do eixo HPA e desenvolvimento de desordens psiquiátricas, incluindo a esquizofrenia. Estudos nessa área podem gerar o aumento do nosso entendimento da natureza multidimensional da esquizofrenia. Posterior pesquisa nesse campo poderia, em última instância, levar ao desenvolvimento de melhores diagnósticos e novas abordagens terapêuticas para essa debilitante condição psiquiátrica

Over the last few decades, evidence has been emerging that the pathogenesis of psychiatric disorders such as schizophrenia can involve perturbations of the hypothalamic-pituitary-adrenal (HPA) axis. Variations in the manifestation of these effects could be related to the differences in clinical symptoms between affected individuals as well as to differences in treatment response. Such effects can also arise from the complex interaction between genes and environmental factors. Here, we review the effects of maternal stress on abnormalities in HPA axis regulation and the development of psychiatric disorders including schizophrenia. Studies in this area may prove critical for increasing our understanding of the multi-dimensional nature of schizophrenia. Further research in this area could ultimately lead to the development of improved diagnostics and novel therapeutic approaches for treating this debilitating psychiatric condition

Characterization of the human primary visual cortex and cerebellum proteomes using shotgun mass spectrometry-data-independent analyses.

We present the first characterization of the human occipital lobe (primary visual cortex) and cerebellum proteomes. Proteins were identified using a combination of gel electrophoresis and data-independent nanoflow liquid chromatography mass spectrometry (nLC-MS(E) ). The resulting data sets comprised 391 and 330 unique proteins in occipital lobe and cerebellum, respectively, present in at least 75% of the analyzed samples with 297 proteins found in common. These proteins have been associated previously with conditions, such as neurological disorder, progressive motor neuropathy, Parkinson's disease and schizophrenia. The unique proteins identified in the occipital lobe included the interesting finding of growth hormone and several members of the Ca²âº-dependent calmodulin kinase and serine/threonine protein phosphatase families. The complete mapping of these and other brain proteomes may help in the elucidation of neurological processes and identify potential targets for therapeutic strategies.