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Distribution of the D-aspartate (NMDA) receptor complex in the frontal cortex of serotonin 5-HT2 receptor family mRNAs: comparison between suicide victims purchase imipramine online pills anxiety symptoms throat. The pharmacology and biochemistry of depres- Arch Pharmacol 1989;339:312–314 discount 50 mg imipramine fast delivery anxiety lack of sleep. Effects of corticotropin- tion of monoamine oxidase A in brainstem monoamine nuclei releasing factor on brain serotonergic activity buy discount imipramine 75mg on-line anxiety symptoms arm pain. Serotonin-dopamine interac- Chapter 73: Neurocircuitry of Mood Disorders 1063 tion in the rat ventral tegmental area: an electrophysiological 161 buy 75 mg imipramine fast delivery anxiety symptoms relief. Identification and charac- by cardiovascular stimuli and various forms of acute stress. Brain terization of antidepressant-sensitive serotonin transporter pro- Res 1995;704:42–50. D-aspartate (NMDA) receptors following antidepressant treat- 143. Mania, depression and ment: implications for the pharmacotherapy of depression. CSF amine metabo- brachial nucleus, stimulates norepinephrine release in the pre- lites in depression. Relapse of depression after cholamines in efferent projections of the nuclei of the solitary rapid depletion of tryptophan [see comments]. Serotonin recep- drugs on the dopamine D2/D3 receptors in the rat brain differ- tors in suicide victims with major depression. Neuropsychophar- entiated by agonist and antagonist binding—an autoradio- macology 1997;16:162–173. Plasma norepinephrine level major depression—postmortem evidence for decreased seroto- in affective disorders: relationship to melancholia. Corticotropic- and depression: toward a unified hypothesis of cortico-striato- releasing hormone and serotonin interact in the human brain- pallido-thalamic function. Discovery of the antidepressant and sustained administration of selective serotonin reuptake inhibi- anti-emetic efficacy of substance P receptor (NK1) antagonists. Afferent connections of the tegmental area of the rat. Lack of behavioral areas of the brain measured by microdialysis. Brain Res 1999; effects of monoamine depletion in healthy subjects. The catecholamine hypothesis of affective disor- area histopathology with adult dementia. Arch Neurol 1988;45: ders: a review of supporting evidence. Repeated admin- ent alpha-noradrenergic receptor binding sites in rat brain: effect istration of desmethylimipramine blocks reserpine-induced in- of 6-hydroxydopamine. Possible role of dopamine release of corticotropin-releasing factor. Brain Res 1991;555: D1 receptor in the behavioural supersensitivity to dopamine 25–34. Clinical and psycho- leus, the nucleus of the solitary tract and the periaqueductal metric correlates of dopamine D2 binding in depression. Reduction of substance P after chronic antidepressants treatment in the releasing factor-containing axon terminals synapse onto cate- striatum, substantia nigra and amygdala of the rat. Brain Res cholamine dendrites and may presynaptically modulate other 1996;739:70–78. Br J Pharmacol 1998;123: cotropin-releasing factor targets locus ceruleus dendrites: sub- 746–752. In: Usdin E, et al, release in the locus ceruleus of conscious rats. New evidence of serotonin-deficient depres- neurochemical changes: An alternative explanaion for the origi- sions. Sympathetic nervous system mal models in human psychobiology. New York: Plenum, 1976: activity in major depression: basal and desipramine-induced al- 133–145. Projections of the dorsal raphe nucleus to Neurol 1997;382:394–400. Dopamine and depression: a review of recent evi- 340:11–26. Dopamine and depression: a review of recent evi- 'D1-like'- 'D2-like' interactions and 'D1-like' receptors not dence. Comparative expression in the locus ceruleus of depression-model rats and localization of serotonin 1A, 1C, and 2 receptor subtype rats exposed to short-and long-term forced walking stress. GABAergic innervation of sero- stimulation: stress and desmethylimipramine. Prog Neuropsycho- tonergic neurons in the dorsal raphe nucleus of the rat studied pharmacol Biol Psychiatry 1984;8:601–606. Is the caudomedial shell of the nucleus accumbens 1992;29:943–948. MINTUN With advances in imaging technology it is now possible precision. Initially primarily focused on older subjects, to examine subtle changes in both structure and regional structural studies have found both generalized and localized function that are associated with the pathophysiology of structural brain changes in major depression and bipolar affective illness. Understanding how these changes fit to- disorder across the age spectrum. Combining Recurrent Unipolar Major Depression anatomic MRI studies with functional studies has improved Studies of neuroanatomic structure in early-onset recurrent the localization of abnormalities in blood flow, metabolism, depression (EORD) have recently found evidence for and neurotransmitter receptor function and has the poten- depression-associated structural change (Table 74. Brain tial to provide a better-integrated model of depression. They comprise a neuroanatomic cir- clinical and treatment applications. In this chapter we re- cuit, which has been termed the limbic–cortical–stria- view studies of structural brain changes associated with tal–pallidal–thalamic (LCSPT) circuit (21). As discussed early-onset recurrent depression (EORD), late-onset depres- herein, functional aspects of this circuit are also altered in sion (LOD), bipolar disorder, and potential etiologic mech- depression as measured by blood flow and metabolism. We also review functional studies in affective illness, Several studies have examined hippocampal volume in including positron emission tomography (PET), functional depression. In some (9–12) but not all (13,14,16,17,19) magnetic resonance imaging (fMRI), and single-photon significant reductions in hippocampal volumes were found emission computed tomography (SPECT) studies. In some studies the volume loss appears to have functional significance with an association between acute depression and abnormalities of declarative memory STRUCTURAL STUDIES (22) as well as an association between severe depression in remission and lower scores on tests of verbal memory (11). Historically, the major psychiatric illnesses, including affec- One study (10) found hippocampal atrophy in patients with tive disorders, were not thought to be associated with struc- chronic depression but not in patients with remitted depres- tural brain pathology. Vakili and colleagues (14) also observed correlations ing tools in the last two decades, increasing evidence has between depression severity and hippocampal volumes, al- accumulated that challenges this assumption.

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Healthcare costs for initial management No eligible health outcomes of children with new-onset type 1 diabetes mellitus in central and northern Alberta buy cheap imipramine on line anxiety symptoms go away. Can J Diabetes 2012;36:128–32 Franklin BE discount imipramine 25 mg otc anxiety pathophysiology, Crisler SC Jr order 25mg imipramine free shipping anxiety symptoms 97, Shappley R buy imipramine 25mg overnight delivery anxiety questionnaire, Armour MM, McCommon DT, Ferry RJ Jr. Real-time Ineligible intervention support of pediatric diabetes self-care by a transport team. Diabetes Care 2014;37:81–7 Garcia-Perez L, Perestelo-Perez L, Serrano-Aguilar P, Del Mar Trujillo-Martin M. Effectiveness No eligible health outcomes of a psychoeducative intervention in a summer camp for children with type 1 diabetes mellitus. Diabetes Educ 2010;36:310–17 Geist R, Heinmaa M, Stephens D, Davis R, Katzman DK. Comparison of family therapy and Absent/ineligible comparator family group psychoeducation in adolescents with anorexia nervosa. Can J Psychiatry 2000;45:173–8 Gerald LB, Redden D, Wittich AR, Hains C, Turner-Henson A, Hemstreet MP, et al. No eligible health outcomes Outcomes for a comprehensive school-based asthma management program. J Sch Health 2006;76:291–6 Gerald LB, Redden D, Wittich AR, Hains C, Turner-Henson A, Hemstreet MP, et al. Ineligible intervention Outcomes for a comprehensive school-based asthma management program. J Sch Health 2006;76:291–6 Gillies J, Barry D, Crane J, Jones D, MacLennan L, Pearce N, et al. A community trial of a Ineligible intervention written self management plant for children with asthma. N Z Med J 1996;109:30–3 Greer D, Grasso DJ, Cohen A, Webb C. Trauma-focused treatment in a state system of No eligible health outcomes care: is it worth the cost? Adm Policy Ment Health Ment Health Serv Res 2014;41:317–23 Greineder DK, Loane KC, Parks P. A randomized controlled trial of a pediatric asthma No eligible health outcomes outreach program. J Allergy Clin Immunol 1999;103:436–40 Grey M, Boland EA, Davidson M, Li J, Tamborlane WV. Coping skills training for youth with No eligible economic diabetes mellitus has long-lasting effects on metabolic control and quality of life. J Pediatr outcomes 2000;137:107–13 Griffiths JD, Martin PR. Clinical- versus home-based treatment formats for children with No eligible economic chronic headache. Br J Health Psychol 1996;1:151–66 outcomes Grimes KE, Schulz MF, Cohen SA, Mullin BO, Lehar SE, Tien S. Pursuing cost-effectiveness No eligible health outcomes in mental health service delivery for youth with complex needs. J Ment Health Policy Econ 2011;14:73–83 Guglani L, Havstad SL, Johnson CC, Ownby DR, Joseph CL. Effect of depressive symptoms No eligible economic on asthma intervention in urban teens. Ann Allergy Asthma Immunol 2012;109:237–42 outcomes Gustafson D, Wise M, Bhatacharya A, Pulvermacher A, Shanovich K, Philips B, et al. No eligible economic The effects of combining web-based eHealth with telephone nurse case management for outcomes pediatric asthma control: a randomized controlled trial. J Med Internet Res 2012;14:41–59 Halterman JS, Fagnano M, Tremblay PJ, Fisher SG, Wang H, Rand C, et al. Prompting Ineligible intervention Asthma Intervention in Rochester-Uniting Parents and Providers (PAIR-UP): a randomized trial. JAMA Pediatrics 2014;168:e141983 Harish Z, Bregante AC, Morgan C, Fann CS, Callaghan CM, Witt MA, et al. A comprehensive No eligible health outcomes inner-city asthma program reduces hospital and emergency room utilization. Ann Allergy Asthma Immunol 2001;86:185–9 106 NIHR Journals Library www. Randomised comparison Absent/ineligible comparator of the effectiveness and costs of community and hospital based mental health services for children with behavioural disorders. BMJ 2000;321:1047–50 Honeycutt AA, Khavjou OA, Jones DJ, Cuellar J, Forehand RL. Helping the noncompliant No eligible economic child: an assessment of program costs and cost-effectiveness. J Child Fam Stud outcomes 2015;24:499–504 Hudson A, Cameron C, Matthews J. The wide-scale implementation of a support program Ineligible population for parents of children with an intellectual disability and difficult behaviour. J Intellect Dev Disabil 2008;33:117–26 Hui SHL, Leung TF, Ha G, Wong E, Li AM, Fok TF. Evaluation of an asthma management Wrong study design program for Chinese children with mild-to-moderate asthma in Hong Kong. Pediatr Pulmonol 2002;33:22–9 Izquierdo R, Morin PC, Bratt K, Moreau Z, Meyer S, Ploutz-Snyder R, et al. School-centered Ineligible intervention telemedicine for children with type 1 diabetes mellitus. J Pediatr 2009;155:374–9 Kamps AWA, Brand PLP, Kimpen JLL, Maille AR, Overgoor-Van De Groes AW, Ineligible intervention Van Helsdingen-Peek LCJAM, et al. Outpatient management of childhood asthma by paediatrician or asthma nurse: randomised controlled study with one year follow up. Thorax 2003;58:968–73 Karnick P, Margellos-Anast H, Seals G, Whitman S, Aljadeff G, Johnson D. The pediatric No eligible health outcomes asthma intervention: a comprehensive cost-effective approach to asthma management in a disadvantaged inner-city community. J Asthma 2007;44:39–44 Kelly CS, Morrow AL, Shults J, Nakas N, Strope GL, Adelman RD. Outcomes evaluation of a No eligible health outcomes comprehensive intervention program for asthmatic children enrolled in Medicaid. Pediatrics 2000;105:1029–35 King CA, Klaus N, Kramer A, Venkataraman S, Quinlan P, Gillespie B. The youth-nominated No eligible economic support team-version ii for suicidal adolescents: a randomized controlled intervention trial. Sick day management using Ineligible intervention blood 3-hydroxybutyrate (3-OHB) compared with urine ketone monitoring reduces hospital visits in young people with T1DM: a randomized clinical trial. Diabet Med 2006;23:278–84 Lara M, Ramos-Valencia G, Gonzalez-Gavillun JA, Lopez-Malpica F, Morales-Reyes B, Marin H, Wrong study design et al. Reducing quality-of-care disparities in childhood asthma: La red de asma infantil intervention in San Juan, Puerto Rico.

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Activators of the cAMP cascade discount imipramine 50mg without prescription anxiety 2 weeks before period, REFERENCES including D1 agonists purchase imipramine online anxiety uptodate, can induce L-LTP (84 generic imipramine 25mg free shipping anxiety hot flashes,85) discount 25 mg imipramine anxiety symptoms dsm. D1 re- ceptor blockade inhibits hippocampal L-LTP (85–87), and 1. The biological, social D1-knockout mice do not show L-LTP (88). Therefore, and clinical bases of drug addiction: commentary and debate. D1 receptor activation in the hippocampus may act to gate 2. Drugs abused by humans preferentially synaptic plasticity, helping to determine whether changes increase synaptic dopamine concentrations in the mesolimbic in synaptic strength are long lasting or merely transient. Proc Natl Acad Sci USA 1988;85: A role for dopamine receptors in the modification of 5274–5278. MK-801 (dizocilpine): synergist and conditioned stimulus in bromocriptine-induced extracellular dopamine can act as a reinforcement learning psychomotor sensitization. From synapse to vesicle: the reuptake and depression)is found at corticostriatal synapses in vivo (90) storage of biogenic amine neurotransmitters. Some groups have found that striatal Acta 1993;1144:249–263. Hyperlocomotion and indiffer- LTP can be modified by dopamine receptor stimulation ence to cocaine and amphetamine in mice lacking the dopamine (91,93,94). Moreover, based on genetic manipulations, transporter. CREB has been implicated in both invertebrate and verte- 6. Altered brain serotonin brate models of synaptic plasticity and long-term memory homeostasis and locomotor insensitivity to 3,4-methylenedioxy- (80–82,95). Moreover, changes in striatal synaptic physiol- methamphetamine ('Ecstasy')in serotonin transporter-deficient mice. At the systems level, dorsal re- norepinephrine transporter are supersensitive to psychostimu- gions of striatum appear to be involved in the learning and lants. Cocaine self- particularly in response to external cues. Ventral striatal administration in dopamine-transporter knockout mice [see com- ments] [published erratum appears in Nat Neurosci 1998;1(4): areas are involved in acting on the motivational significance 330]. Opioids excite dopamine neurons by regions may contribute to drug use through consolidation hyperpolarization of local interneurons. J Neurosci 1992;12: of drug-taking and -seeking behaviors. Destruction of dopa- mine in the nucleus accumbens selectively attenuates cocaine but of genes transiently induced by addictive drugs, the products not heroin self-administration in rats. Psychopharmacology (Berl) of which produce stable remodeling of synapses. Heroin and cocaine intravenous self-administration in rats: mediation by separate CONCLUSION neural systems. Disruption of cocaine and heroin self-administration following kainic acid lesions of All of the initial molecular targets of drugs of abuse have the nucleus accumbens. Pharmacol Biochem Behav 1985;23: been characterized and cloned. Blockade of nucleus accum- zation, and most important, compulsive drug use, and late bens opiate receptors attenuates intravenous heroin reward in the rat. Molecular genetic analysis of the role of GABAergic has been made in identifying large numbers of molecular systems in the behavioral and cellular actions of alcohol. Behav changes initiated by drugs of abuse, but coherent biological Genet 1996;26:313–323. Ethanol enhances 1378 Neuropsychopharmacology: The Fifth Generation of Progress the release of dopamine and serotonin in the nucleus accumbens 38. Alcohol Clin Exp Res 1992;16: phine tolerance on the paw-pressure and tail-shock vocalization 781–785. GABAA receptor antagonism in the ex- pensatory responding. Psychopharmacology (Berl) 1999;145: tended amygdala decreases ethanol self-administration in rats. The phasic reward signal of primate dopamine neu- 17. Naltrexone in the treatment of alco- Res Rev 1993;18:247–291. Addictive drugs as reinforcers: multiple partial ac- 20. Molecular and cellular basis of addic- Trends Pharmacol Sci 1997;18:54–59. Reduction of mor- sumption in null mutant mice lacking 5-HT1B serotonin recep- phine abstinence in mice with a mutation in the gene encoding tors. Genetic analysis of drug addiction: mine lesions on the locomotor stimulant action of nicotine in the role of cAMP response element binding protein. Alteration of GABAA nucleus accumbens and similarity to those of addictive drugs [see receptor alpha 1-subunit mRNA in mouse brain following con- comments]. Ethanol and neurotransmit- tors containing the beta2 subunit are involved in the reinforcing ter interactions—from molecular to integrative effects. Ethanol withdrawal is associated with nicotinic receptor subunit in nicotine-elicited locomotion, dem- onstrated by in vivo antisense oligonucleotide infusion. Neurore- increased extracellular glutamate in the rat striatum. Cocaine addiction: psychology and neurophysiology linergic and opioid receptor mechanisms in nicotine- induced [published erratum appears in Science 1991;253:494]. Drug abuse: hedonic homeostatic dysreg- Neuropsychiatry Clin Neurosci 1997;9:482–497. Cocaine-induced c-fos messenger RNA stimulation reward by 9- tetrahydrocannabinol. Psychopharma- is inversely related to dynorphin expression in striatum. Cocaine self-administra- mu1 opioid receptor mechanism [see comments]. Science 1997; tion differentially alters mRNA expression of striatal peptides.

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Each case was discussed in terms of suitability and application of the PCAM tool l nurses were provided with some examples as to how the PCAM items may be introduced and discussed order imipramine 50mg otc anxiety 5 months postpartum, and then invited to role play l each nurse was encouraged to practice the PCAM with around 10 patients buy imipramine anxiety effects on the body. For the sake of the study purchase cheapest imipramine anxiety 9gag gif, these did not always have to be LTC patients imipramine 50 mg without a prescription anxiety symptoms vibration. In order to build experience and confidence, it was suggested that they begin with just a few domains. They should reflect on each experience and discuss with colleagues as required l a researcher was attached to the practice and provided support in one additional face-to-face session, online and by telephone. In addition, the nursing team were provided with: l hard copies of the presentation slides l a copy of Making it Easy, a Health Literacy Plan for Scotland64 l a copy of Good Mental Health For All. However, after the first session it became apparent that nurses: l would be unlikely to be able to dedicate a full unbroken half-day l may benefit from focusing the evidence further on their own experience l may benefit from time to reflect on the evidence and the PCAM introduction, and some distance in time before trying to integrate it into their practice. In order to respond to this, the training was adapted over the course of the study: l advance creation and sending of three case studies each l 2. An additional two sections comprised information relating to: 1. Within each section, information comprised national resources [e. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals 87 provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 1 Information about each resource comprised: l name of resource (e. Each section was printed on plain white paper and placed together in clip file with a front index for ease of use. To make the pack usable for nurses, the lists of resources were not exhaustive, but were targeted. In addition, the low-technology approach was somewhat influenced by the feasibility nature of the research, but was appreciated by nurses. Copies of example resource packs are available on request from: pcam@stir. However, the support of a PM was helpful in some circumstances for enabling scheduling of time for training. Item 5: who provided each aspect of the intervention? Training was delivered by the research team, led by Carina Hibberd (who developed the training resources for the Keep Well study as well as the adapted training for this study in collaboration with RP). Carina Hibberd has a PhD in biological sciences, in exploring and understanding the links between physical and emotional responses. Each session was delivered by Carina Hibberd and another researcher (EC or PA, both of whom had received 5 hours of training, in a train-the-trainer model, from Carina Hibberd). Training covered use of the PCAM tool and nurses received copies of the PCAM at this stage. Patricia Aitchison developed the bespoke resource packs for each practice; however, these were then reviewed by local PMs and PNs who were encouraged to add and amend these resources as local knowledge emerged. Patricia Aitchison has been engaged in primary care research for over a decade. The modes of delivery (face to face or by some other mechanism, such as internet or telephone) of the intervention and whether it was provided individually or in a group The PCAM training was delivered face to face, but with the option of either a face-to-face follow-up/ review session or a telephone session. Training was provided both individually (when single PNs were involved) or in small groups where more than one PN was involved. The adaptability of delivery of training is an essential feature for making this implementable in primary care. Type(s) of location(s) where the intervention occurred, including any necessary infrastructure or relevant features The PCAM intervention was implemented in primary care practices by PNs. Practices were located in two health board areas of Scotland, covering both highly deprived urban and less deprived small town/semirural locations. Practice nurses then used the PCAM tool and the resource packs in their routine delivery of annual individual face-to-face health checks for patients with LTCs (such as CHD, DM, COPD). The number of times the intervention was delivered and over what period of time, including the number of sessions, their schedule and their duration, intensity or dose Practices (and PNs) varied in the number of visits they required to introduce the overall study to them, from one to three. However, these visits included introducing the PCAM tool, as well as introducing the feasibility trial, and the number of visits/sessions required to introduce the PCAM intervention cannot be separated out. The training intervention received by nurses and its duration and number of sessions has been reported under Item 3 above. Nurses were then requested to practise using the tool on up to 10 patients to familiarise themselves with the PCAM delivery. Practice nurse delivery of the PCAM tool with patients consisted of using the tool throughout the annual LTC review of a patient. PN-delivered annual reviews for LTCs vary in the time allocated and this intervention is designed to be implemented into usual care delivery. This is especially so when an intervention aims to change practitioner behaviour/ outcomes as well as patient behaviour or outcomes. However, after the first training session in one practice, it became apparent that training delivery would have to be tailored to suit individual practice needs. The content of the training was also adapted in response to early nurse feedback in order to maximise learning in the limited time available. The essential element of learning why it is important to conduct a biopsychosocial assessment, and how to use the PCAM tool to facilitate this, was still delivered to all PNs. There was still some attempt in our adaptations to ensure that nurses had received equivalent training intensity and follow-up support. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals 89 provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. APPENDIX 1 When the PCAM tool is being used in LTC annual reviews, the delivery of this is very much dependent on the individual circumstances of the patient, and also with individual practice procedures for patient follow-up if required. Item 10: modifications – if the intervention was modified during the course of the study, describe the changes (what, why, when and how) It was planned that the PCAM tool used in the study should be open to adaptation in response to management and steering group partners, and to focus group and feasibility RCT findings. However, it was important that it did not change during the feasibility RCT and that it remained congruent with the US version. The following changes were all made before the feasibility RCT: l For clarity, abbreviations were expanded. This was consistent with the rest of the document and International Classification of Functioning, Disability and Health (ICF) wording. The modification to the training intervention and delivery has been reported under Item 3 above. The resource packs were designed to be an evolving resource and to encourage local ownership of the resource for ongoing use.

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