Providing Mental Health Services in the Primary Care Setting: the Experiences and Perceptions of General Practitioners at a New York City Clinic.

Mental illness is a significant cause of disability worldwide, including here in the United States. Given the shortage of trained mental health professionals, a significant portion of patients needing care are managed in the primary care setting. Accountable Care Organizations (ACOs), for example, are seeking to improve the quality of care for this vulnerable population, but many are facing significant challenges relating to integration of new services. We sought to elucidate barriers faced by primary care practitioners (PCPs)-physicians, physician trainees and nurse practitioners-at a New York primary care clinic, which impede delivery of optimal care to those suffering from mental illness. The study was conducted with 32 PCPs in 2016-2017 at Mount Sinai Internal Medicine Associates in New York City. For the quantitative component of the study, a 54-item questionnaire was devised to assess their attitude, behavior and confidence in managing psychiatric patients. For the qualitative component, data was obtained from 3 open-ended questions. Responses were coded for salient themes. Analysis revealed a range of difficulties faced by PCPs. Overall, participants felt that the need to integrate mental health care into primary care was important, however they reported significant barriers in terms of lack of time, lack of resources, low confidence in treating more complex mental health conditions and difficulties with referring patient to mental health specialists. Despite a growing body of evidence that integration of mental health services in primary care leads to improved outcomes, addressing barriers to care will be key to ensuring feasibility of integration measures.

Brain-derived neurotrophic factor deficiency restricts proliferation of oligodendrocyte progenitors following cuprizone-induced demyelination.

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors that through its neurotrophic tyrosine kinase, receptor, type 2 (TrkB) receptor, increases 5-bromo-2-deoxyuridine incorporation in oligodendrocyte progenitor cells (OPCs) in culture. Roles in vivo are less well understood; however, increases in numbers of OPCs are restricted in BDNF+/- mice following cuprizone-elicited demyelination. Here, we investigate whether these blunted increases in OPCs are associated with changes in proliferation. BDNF+/+ and BDNF+/- mice were fed cuprizone-containing or control feed. To assess effects on OPC numbers, platelet-derived growth factor receptor alpha (PDGFRα)+ or NG2+ cells were counted. To monitor DNA synthesis, 5-ethynyl-2'-deoxyuridine (EdU) was injected intraperitoneally and colocalized with PDGFRα+ cells. Alternatively, proliferating cell nuclear antigen (PCNA) was colocalized with PDGFRα or NG2. Labeling indices were determined in the BDNF+/+ and BDNF+/- animals. After 4 or 5 weeks of control feed, BDNF+/- mice exhibit similar numbers of OPCs compared with BDNF+/+ animals. The labeling indices for EdU and PCNA also were not significantly different, suggesting that neither the DNA synthesis phase (S phase) nor the proliferative pool size was different between genotypes. In contrast, when mice were challenged by cuprizone for 4 or 5 weeks, increases in OPCs observed in BDNF+/+ mice were reduced in the BDNF+/- mice. This difference in elevations in cell number was accompanied by decreases in EdU labeling and PCNA labeling without changes in cell death, indicating a reduction in the DNA synthesis and the proliferative pool. Therefore, levels of BDNF influence the proliferation of OPCs resulting from a demyelinating lesion.

Transcultural aspects of somatic symptoms in the context of depressive disorders.

Somatic symptoms are a common presentation of mental disorders or psychological distress worldwide, and may often coexist with depressive and anxiety symptoms, thus accounting for what might be the most frequent psychiatric syndrome in primary care. Indeed, physical symptoms accompanying the clinical presentations of a variety of mental disorders may be considered as universal 'idioms of distress' that may vary across cultures, depending on attitudes and explanations embedded in each one of them. These variations in symptom presentations are the result of various interacting factors that ultimately determine how individuals identify and classify bodily sensations, perceive illness, and seek medical attention. This chapter examines the impact of culture on the experiencing of somatic symptoms, based on an inclusive review of the topic from ethnic, nosological, clinical and social perspectives. Particular attention is paid to the association of somatic symptoms with mood symptoms, since depressive disorders appear to be the most common, costly and disabling psychiatric entities worldwide. The review shows that racial/ethnic variations in somatic symptoms in the context of depression are common, and seem to be related to depression severity. Sociocultural factors, particularly stigma, may influence the unique emphasis placed on somatic symptoms within depression, and may account for some racial/ethnic differences in somatic symptom reporting.

Regulated release of BDNF by cortical oligodendrocytes is mediated through metabotropic glutamate receptors and the PLC pathway.

A number of studies suggest that OLGs (oligodendrocytes), the myelinating cells of the central nervous system, are also a source of trophic molecules, such as neurotrophins that may influence survival of proximate neurons. What is less clear is how the release of these molecules may be regulated. The present study investigated the effects of BDNF (brain-derived neurotrophic factor) derived from cortical OLGs on proximate neurons, as well as regulatory mechanisms mediating BDNF release. Initial work determined that BDNF derived from cortical OLGs increased the numbers of VGLUT1 (vesicular glutamate transporter 1)-positive glutamatergic cortical neurons. Furthermore, glutamate acting through metabotropic, and not AMPA/kainate or NMDA (N-methyl-d-aspartate), receptors increased BDNF release. The PLC (phospholipase C) pathway is a key mediator of metabotropic actions to release BDNF in astrocytes and neurons. Treatment of OLGs with the PLC activator m-3M3FBS [N-(3-trifluoromethylphenyl)-2,4,6-trimethylbenzenesulfonamide] induced robust release of BDNF. Moreover, release elicited by the metabotropic receptor agonist ACPD [trans-(1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid] was inhibited by the PLC antagonist U73122, the IP3 (inositol triphosphate 3) receptor inhibitor 2-APB (2-aminoethoxydiphenylborane) and the intracellular calcium chelator BAPTA/AM [1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid tetrakis(acetoxymethyl ester)]. Taken together, these results suggest that OLG lineage cells release BDNF, a molecule trophic for proximate neurons. BDNF release is regulated by glutamate acting through mGluRs (metabotropic glutamate receptors) and the PLC pathway. Thus glutamate and BDNF may be molecules that support neuron-OLG interactions in the cortex.

Neurotrophin-induced melanoma cell migration is mediated through the actin-bundling protein fascin.

Expression of the p75 neurotrophin receptor (p75(NTR)) in primary melanomas is associated with deeply invasive lesions. In turn, there is expression of high levels of neurotrophins at the invasion front of normal tissue adjacent to brain metastases, thus implicating this growth factor-receptor system in melanoma tumorigenesis. The neurotrophins nerve growth factor (NGF) and neurotrophin-3 (NT-3) are potent chemotactic agents for human melanoma cells which express p75(NTR)in vitro. Here we show that the actin-bundling protein fascin specifically interacts with p75(NTR) in an NGF-dependent manner by co-immunoprecipitation and colocalization in melanoma cells that express the two proteins endogenously. In addition, expression of a fascin point mutant at the serine phosphorylation site (serine 39) regulating actin binding abrogates neurotrophin-induced migration. These results suggest a causal role for NGF-mediated dephosphorylation of serine 39 on fascin in mediating actin binding and subsequent melanoma cell migration.