By V. Mortis. Stevens Institute of Technology.
Differential inhibitory mine binding in the brains of patients with depressive illness discount finax 1 mg online. The growth hormone [123I]-2-beta-carbomethoxy-3-beta-(4-iodophenyl)tropane and response to clonidine in acute and remitted depressed male pa- single photon emission computed tomography best 1 mg finax. Increased serotonin1 (5-HT2) receptor rine systems in mood disorders purchase finax 1mg on line. New York: in the blood platelets of depressed patients finax 1 mg fast delivery. Serotonin 5-HT2 receptor in the brain of suicide victims: increased receptor density associ- binding on blood platelets as a state dependant marker in major ated with major depression. Brain alpha- receptor binding sites in depression and suicide. Biol Psychiatry adrenoceptors in depressed suicides. Effects of selective 1048 Neuropsychopharmacology: The Fifth Generation of Progress serotonin reuptake inhibitors on platelet serotonin parameters 73. Serotonin transporter gene in major depressive disorders. Biol Psychiatry 1997;41(2): polymorphism and antidepressant response. Serotonin and the demonstration of increase serotonin 5-HT2 and beta-adrenergic neurobiology of depression. Effects of tryptophan depletion in receptor binding sites in the brain of suicide victims. Arch Gen Psychiatry 1994;51(11): Psychiatry 1990;47:1038–1047. Serotonin 5-HT2 receptor tomography measurement of cerebral metabolic correlates of imaging in major depression: Focal changes in orbito-insular tryptophan depletion-induced depressive relapse. Rapid serotonin deple- receptors in depression: An [18F] setoperone PET imaging tion as a provocative challenge test for patients with major study. Lack of relapse with receptors studied in depressive patients during chronic treat- tryptophan depletion following successful treatment with ACT. Decrease in brain seroto- cal consequences of rapid tryptophan depletion. Neuropsycho- nin 2 receptor binding in patients with major depression follow- pharmacology 2000;23:601–622. Protein kinase C in Proc Natl Acad Sci USA 1997;94:5308–5313. Hormonal responses to fenfluramine in pholipase C 1 protein in the prefrontal cortex of teenage sui- depressed and control subjects. Growth-associated protein fenfluramine in major depression: evidence of diminished re- (GAP43), its mRNA, and protein Kinase C (PKc) izoenzymes sponsivity of central serotonergic function. Am J Psychiatry in brain regions of depressed suicides. Altered brain protein depression is not associated with normalization of serotonergic kinase C in depression: a post-mortem study. Serotonergic measures in dopamine transmission among patients with depression who suicide brain: 5-HT1A binding sites in frontal cortex of suicide attempted suicide. Serotonin recep- creased in depression: CSF dopamine, noradrenaline and their tors in suicide victims with major depression. Neuropsychophar- metabolites in depressed patients and controls. Urinary monoamines and porter gene promoter polymorphism (5-HT TLPR) and pre- monoamine metabolites in subtypes of unipolar depressive dis- frontal cortical binding in major depression and suicide.
The potential linkage of a particular charac- ple genes buy 1mg finax overnight delivery, and the lack of precision of the definition of the teristic to a specific signpost helps identify areas of chromo- broad phenotype purchase finax 1 mg without prescription, alcohol abuse order finax 1mg without prescription, or dependence (1 buy finax 1 mg visa,4). This chapter describes some of the more promising re- Most of the genetic studies have used variations in two ap- sults of the application of such approaches to alcohol use proaches described in more detail in Chapter 99, as well as disorders, and briefly synthesizes the wide range of pheno- in additional recent review articles (1,3,6). Candidate gene typic and genotypic markers into a framework focusing on studies (also called case-control, association, or forward ge- the several possible themes of potentially related characteris- netic investigations) begin with the hypothesis that a specific tics described in Table 98. Reflecting space limitations, gene is related to the characteristic under study (7). If a emphasis is placed on genetic factors relating to alcoholism, limited number of multiple forms, or polymorphisms, of rather than to drugs in general; most studies focus on human the gene are known, the proportion of individuals with and rather than animal work; and review articles are often high- without the characteristic who have the specified polymor- lighted rather than a series of primary data sources. Although this approach is an important step in identifying specific genes related to a phe- notype, it is prone to false-positive results that occur if there are additional differences between groups with and without the characteristic (8). POSSIBLE BROAD FAMILIES OF RISK FACTORS fication, can be overcome by two variations of case-control studies where the relationship between the genetic marker Level of response (LR) and the characteristic, or phenotype, is evaluated among P3/disinhibition/ASPD/type 2/B Independent axis I disorders Opioids Alcohol metabolizing enzymes M. Schuckit: Department of Psychiatry, Veterans Affairs San Diego Healthcare System, San Diego, California. In Alcohol has impact on many neurochemical systems, humans, the LR is more similar in identical than fraternal whereas the use and consequences associated with this drug twin pairs, and among first-degree relatives compared to relate to many additional factors including personality traits, unrelated individuals (28,32,33). A candidate gene study reported additive relationships This panoply of phenomena has produced a wide range of to LR for alleles for the -aminobutyric acid receptor A 6 hypotheses regarding how different phenotypes and candi- (GABAA 6) and the serotonin transporter gene, whereas a date genes might contribute to the acquisition of drinking separate sample revealed areas of potential linkages on chro- behaviors and the development of associated problems. Additional candidate genes po- Thus, judgment was needed to decide which potential phe- tentially tied to LRs include neuropeptide Y (NPY), neuro- notypic or genetic markers to highlight, and the reader is tensin, adenylyl cyclase (AC) systems, protein kinase, encouraged to turn to additional reviews (1,6,11–13). The aspects of serotonin (5-HT), and the hypothalamic-pitui- information offered below is, somewhat arbitrarily, divided tary-adrenal (HPA) axis. However, a low LR appears to into results relevant to more broadly based phenotypes and operate relatively independently of the event-related poten- those related to specific enzymes or genes. Phenotypes A Low Level of Response (LR) to Alcohol Low Voltage or Low Alpha and EEGs This characteristic, first proposed in 1975, reflects the need An overall low-voltage EEG pattern and a relative paucity for higher doses of alcohol to produce an effect (1,10,14). The importance of the EEG results reflects reports with similar drinking habits, and facilitate the acquisition that alcohol increases alpha power, and that alcoholics of tolerance. LR is classically measured as the level of change might show lower amounts of alpha, higher beta activity, in subjective feelings of intoxication, motor performance, and/or lower voltage on the EEG overall (24,36). Such EEG hormone levels, and/or electrophysiologic measures ob- patterns might have impact on the risk for alcoholism via served at specific blood alcohol concentrations, but can also several different mechanisms, including higher levels of anx- be evaluated by a self-report of the number of drinks re- iety. Low LRs are seen in Some children of alcoholics exhibit lower amounts of about 40% of the estimated 700 children of alcoholics eval- slower alpha and/or higher levels of faster alpha or beta uated in the majority of the studies, and has been reported EEG activity, and alcohol increases the proportion of slower to characterize Native Americans, while high LRs and lower alpha, whereas other offspring demonstrate lower overall alcoholism risks have been noted for Jews and some Asian EEG voltage (6,24,34–37). A 10-year follow-up of 64 sons of alcoholics (38,39). Some relevant EEG characteristics might relate to and controls in Denmark found a significant relationship genes on chromosome 20, although not all reports agree between less alcohol-induced physiologic changes and a (40). Finally, a 10-year follow-up of almost 400 members Conduct disorder (CD) in childhood and subsequent ASPD of Australian twin pairs confirmed the relationship of the represent persisting patterns of impulsivity and difficulty intensity of response to the alcoholic outcome for men (28). These disorders are potentially Chapter 98: Vulnerability Factors for Alcoholism 1401 related to personality characteristics of novelty- or sensation controlled for the potential impact of CD and ASPD, the seeking, extroversion, neuroticism, and the absence of harm results are consistent with the relationship between P3 am- avoidance, attributes that might increase the risk for alcohol plitude and the alcoholism risk. Related concepts that overlap As is true of many electrophysiologic measures, P3 ampli- with ASPD include type 2 and type B subgroups of alcohol- tudes are genetically influenced (56,57). Data supporting ics whose early onset and more severe course is often associ- these conclusions come from twin investigations, family ated with criminality and dependence on other drugs (42, studies, and a genetic linkage study that highlighted findings 43). Almost two-thirds of people with ASPD are alcoholics, There are several interesting potential crossovers between although only about 20% of alcoholic men fulfill criteria for P3 amplitude and other phenotypic or genetic markers of this disorder (41–43). There is impressive familial crossover the alcoholism risk (19,52,53). Some investigators believe between CD/ASPD and alcoholism, and offspring of ASPD that most of the variance explained by P3 relates to CD parents are likely to have a more severe alcoholic course (44, or ASPD, or that finding might reflect activities of several 45). Genetic factors are important in personality traits and dopamine (DA) receptors, which, in turn, might be related some personality disorders, and ASPD and alcohol depen- to impulsiveness or CD (41,52,53,58). At the same time, dence are often inherited together (44–47). The high levels of impulsivity and sensation seeking in CD and Independent Major Psychiatric Disorders ASPD might, in turn, relate to aspects of 5-HT functioning, and/or to subtypes of GABA receptors (49,50).
The table above describes four direct indicators and two indirect indicators of protection which can be measured by household expenditure surveys that include spending on health order 1 mg finax free shipping, as illustrated in the main text discount finax 1 mg mastercard. The techniques used to measure these indicators are well established as a result of investment in relevant research purchase 1mg finax otc, and the survey data are readily available (45) quality finax 1mg. To assess inequalities in financial risk protection, these indicators can also be measured for different population groups, and can be stratified by income (or expenditure or wealth), place of residence, migrant status and so on. In reality, there is a diversity of ser- vated and skilled health workers who are accessible to vices delivered on several levels, depending on the people they serve; (iii) integrated, high-quality, the nature of the health condition and the type patient-centred services at all levels from primary of intervention. Te elements of each row in to tertiary care; (iv) a combination of priority pro- Fig. A framework for measuring and monitoring the coverage of health services Levels of health system/service delivery Priority health conditions Non- Community- Primary Secondary Tertiary personal based (facility) (hospital) (hospital) MNCH Indicators of HIV/TB/malaria service coverage, including NCDs and promotion, risk factors prevention and treatment Injuries Health system inputs Outputs: availability, readiness, quality, utilization HIV, human immunodefciency virus; MNCH, maternal, newborn and child health; NCDs, noncommunicable diseases; TB, tuberculosis. Note: “Non-personal” health services are actions applied either to communities or populations – such as mass health educa- tion, policy development or taxation – or to the nonhuman components of the environment – such as environmental health measures. Community-based health services are defned as individual and community health actions delivered in the commu- nity (e. They are often considered to be part of the primary health care service. In Mexico, for example, 472 interventions and to whole populations (nonpersonal) (49). As were covered by fve separate health protection illustrated by its position in Fig. It is feasible, applied either to communities or to populations; however, to take a selection of interventions broadly, they are educational, environmental, and indicators, and use them as “tracers” of the public health and policy measures in a range of overall progress towards universal coverage. For HIV/ combined with measures of fnancial risk pro- AIDS, “universal access” to antiretroviral ther- tection, give an overview of service coverage in apy is currently defined as treatment of at least the Philippines and Ukraine. By 2010, 47% of are similar with respect to the coverage of health eligible people were receiving treatment. Te diferences are in the incidence of the target was missed globally, but national data catastrophic health expenditure and of poverty show that it was reached in 10 countries, includ- due to out-of-pocket payments. For instance, in the comparison coverage, it includes the target to reduce by half, in Box 1. Notwithstanding some methodo- catastrophic expenditure and poverty represent logical limitations in measurement, more than aspects of fnancial risk protection that difer two billion people gained access to improved between the two countries? And there is always drinking-water sources between 1990 and 2010, the question: “Are the underlying data accurate? Te Te coverage of services depends on how those MDG target was met by 2010, although access to services are provided. Te inputs can be investi- improved water supplies was generally lower in gated in addition to, or as a proxy for, direct meas- rural areas than in urban ones (50, 55). For instance, WHO 16 Chapter 1 The role of research for universal health coverage Fig. Towards universal health coverage: examples of the growing coverage of interventions for the control of HIV/AIDS, tuberculosis, malaria and neglected tropical diseases ACT, artemisinin-based combination therapies; AIDS, acquired immunodefciency syndrome; ART, antiretroviral therapy; HIV, human immunodefciency virus; ITN, insecticide-treated bed nets; PMTCT, prevention of mother-to-child transmission. Note: Between 2003 and 2008, the denominator for ART coverage was all HIV-infected people with CD4 cell counts of ≤ 200 cells/μL, but in 2009 and 2010 the denominator was all people with ≤ 350 CD4 cells/μL. Hence the apparent fall in coverage between 2008 and 2009. For PMTCT with ART, the numerator in 2010 excludes treatment with single-dose nevirapine. For malaria, data on household coverage with ITN and on suspected cases tested are for the WHO African Region. The interpretation of universal coverage is 100% coverage for all interventions, except for interim targets of ≥ 80% coverage for ART, ≥ 90% for the percentage of tuberculosis patients cured, and variable coverage targets for neglected tropical diseases (23, 51–53). Reproduced, by permission of the publisher, from Dye et al. Measuring the coverage of health services It is not usually possible to measure all aspects of service coverage even in high-income countries, but it is feasible to define a set of “tracer” conditions, with associated indicators and targets for interventions, to track progress towards universal coverage.