Biomedical subjects

D A Shapiro

Publications and source records attributed to D A Shapiro.

At least 19 recordsLinked to original sources

PubMed2006

The effectiveness of computerized cognitive behavioural therapy in routine care.

OBJECTIVES AND DESIGN: The efficacy of a Computerized Cognitive Behavioural Therapy (CCBT) package, Beating the Blues, has been demonstrated in a large randomized controlled trial. The current study tests the generalizability of this finding in a naturalistic non-randomized trial. METHOD: 219 patients with anxiety and/or depression were recruited to receive CCBT in routine care. The Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM) and Work and Social Adjustment scale (WSA) were administered pre-treatment, immediately on completing treatment and at 6 months post-treatment. Single-item self-report measures of anxiety and depression were also collected during each treatment session. RESULTS: Completer and intention-to-treat analysis demonstrated statistically and clinically significant improvements on the CORE-OM, WSA and in self-reported anxiety and depression. Intention-to-treat analysis indicated an average 0.29-point drop on the CORE-OM, equating to an uncontrolled pre-post effect size of 0.50. Research completers achieved an average 0.61-point drop equating to an uncontrolled pre-post size of 1.00 on the same measure. Where data was available (18%), these benefits were maintained at week 32 (6 months follow-up). CONCLUSION: CCBT can be an effective first line tool within a stepped care framework for the management of common mental health problems.

Adult↗

PubMed2005

The effectiveness of psychological treatments for treatment-resistant depression: a systematic review.

OBJECTIVE: A systematic review of all studies (controlled and uncontrolled) to evaluate psychological interventions with treatment-resistant depression. METHOD: A systematic search to identify studies evaluating a psychological intervention with adults with a diagnosis of major depressive disorder who had not responded to at least one course of antidepressant medication. RESULTS: Twelve studies met inclusion criteria, of which four were controlled and eight uncontrolled. Treatment effect sizes were computable for four studies and ranged from 1.23 to 3.10 with a number of better quality studies demonstrating some improvements in patients following a psychological intervention. CONCLUSION: Psychological treatments for depression are commonly delivered and often recommended following the failure of medication. The paucity of evidence for their effectiveness in these situations is a significant problem. There is a need for studies with a strong controlled design investigating the effectiveness of psychological treatments for patients with treatment-resistant depression.

Algorithms↗

PubMed2004

Computerized cognitive-behaviour therapy for anxiety and depression: a practical solution to the shortage of trained therapists.

Computerized cognitive-behaviour therapy (CCBT) programmes have been developed to help meet the enormous need for evidence-based psychological treatment of common mental health problems in the context of a severe shortage of trained therapists to meet that need. Randomized controlled trials have confirmed the efficacy of such programmes. We present the experience of a community mental health team (CMHT) resource centre with one such programme, Beating the Blues, together with outcome data on a small sample of its clients. We conclude that experience and data, taken together, demonstrate the practical benefits of CCBT in routine practice.

Aged↗

PubMed2003

Exploring and enhancing engagement to the psychosocial intervention 'Preparing for Parenthood'.

BACKGROUND: Poor compliance by participants consenting to be randomised to receive both physical and mental health promotion interventions represents a potentially serious threat to external and internal validity of those interventions. Quantitative and qualitative investigation of possible predictors of engagement forms an appropriate basis for efforts to enhance it. METHODS: Eight 'Preparing for Parenthood' intervention courses of a randomized controlled trial (RCT) underpinned a quantitative study. One 'Preparing for Parenthood' (PFP) intervention course, run upon completion of the RCT, formed a qualitative study. All nine courses followed identical procedures to enable clear comparisons. The three factors quantitatively explored with respect to engagement in health promoting behaviours were: locus of control (LOC), psychosocial support, and life events. The qualitative study utilised grounded theory analysis, the participants reflecting upon their experiences of the intervention and/or their reasons for not attending the course; nine interviews were completed. RESULTS: Participants in the quantitative and qualitative studies were divided into three sub-groups: compliant, non-compliant, and refusers. None of the three health promoting variables predicted compliance to a statistically significant degree. However, a variable from the trial analysis was found to reach significance; those women who had had less contact with the National Health Service in the 12 months prior to the baseline assessment were more likely to refuse the invitation to PFP. The qualitative study produced nine main themes that had influenced participant engagement at both the initial recruitment stage and during the course itself. CONCLUSIONS: In combination these findings may contribute to the future design of both effective and acceptable interventions to prevent postnatal depression. One such modified intervention is described and its impact on engagement outlined.

Depression, Postpartum↗

PubMed2003

Practice development in psychological interventions: mental health nurse involvement in the Conversational Model of psychotherapy.

This paper describes a mental health nurse led practice development initiative in psychotherapy. Four mental health nurses have been trained to deliver the Conversational Model of psychotherapy (also known as psychodynamic-interpersonal (PI) psychotherapy) a non-cognitive behavioural therapy (CBT) with a robust evidence base. We report on the robust range of both processes and outcome measures being used to evaluate this initiative. We conclude that good quality evidence-based practice requires careful planning and preparation, adequate financial resources from Trusts, as well as commitment and motivation from the staff expected to be involved in such initiatives.

Behavior Therapy↗

PubMed2003

Personal reflections of mental health nurses training to use Hobson's Conversational Model (psychodynamic-interpersonal) of psychotherapy.

Current mental health policy documents highlight the need for mental health nurses to become increasingly involved in the delivery of evidence-based psychological interventions. However, substantial evidence exists indicating that there is a paucity of training to adequately equip nurses to deliver these interventions and, even when training is available, there are barriers to their implementation into routine clinical practice. This paper reports on the personal reflections and experiences of a group of four mental health nurses undertaking training in the Conversational Model of psychotherapy (also known as psychodynamic-interpersonal 'PI' psychotherapy). These reflections highlight the rewards and challenges arising from the effort to undertake training in an evidence-based model of psychological intervention and from attempting to implement and sustain this training into routine practice.

Attitude of Health Personnel↗

PubMed2003

First clinical trial of a novel caspase inhibitor: anti-apoptotic caspase inhibitor, IDN-6556, improves liver enzymes.

OBJECTIVE: To evaluate the safety of IDN-6556, a novel anti-apoptotic pan-caspase inhibitor, administered in single and multiple ascending doses in normal volunteers and patients with hepatic dysfunction. MATERIALS AND METHODS: IDN-6556 was administered as a 30-minute intravenous infusion in rising doses to 3 groups: Group A, normal volunteers, given as a single infusion, Group B, normal volunteers, given q.i.d. for 7 days, Group C, patients with hepatic impairment (elevated transaminases, alanine transaminase, ALT and aspartate transaminase, AST), given q.i.d. for 7 days. RESULTS: The drug was well tolerated up to 10 mg/kg/infusion for a single dose, and 1.5 mg/kg/infusion q.i.d. for 7 days, with the dose-limiting adverse event of phlebitis or inflammation at the site of the infusion. This toxicity was predicted from animal studies. Clinically and statistically meaningful dose-related falls in transaminases were seen in all but 1 of the hepatic impaired patients. Two-way ANOVA analyses of the changes for all the IDN-6556 groups combined versus placebo were: ALT absolute change: p < 0.0001 and % change: p = 0.012, AST absolute and % changes: p < 0.0001. After discontinuation of the drug (after 7 days of dosing), the transaminases rapidly returned to the pre-treatment levels. CONCLUSIONS: Following intravenous administration of a novel anti-apoptotic caspase inhibitor, adverse events were mild-to-moderate in severity, resolved in a few days and did not result in any subject terminating treatment prematurely. The effects in hepatic impaired patients appear to be consistent with both the administration and subsequent abrupt withdrawal of an effective hepatoprotective drug that delays cell death in hepatocytes.

Adult↗

PubMed2001

Control of serotonergic function in medial prefrontal cortex by serotonin-2A receptors through a glutamate-dependent mechanism.

We examined the in vivo effects of the hallucinogen 4-iodo-2,5-dimethoxyamphetamine (DOI). DOI suppressed the firing rate of 7 of 12 dorsal raphe (DR) serotonergic (5-HT) neurons and partially inhibited the rest (ED(50) = 20 microg/kg, i.v.), an effect reversed by M100907 (5-HT(2A) antagonist) and picrotoxinin (GABA(A) antagonist). DOI (1 mg/kg, s.c.) reduced the 5-HT release in medial prefrontal cortex (mPFC) to 33 +/- 8% of baseline, an effect also antagonized by M100907. However, the local application of DOI in the mPFC increased 5-HT release (164 +/- 6% at 100 microm), an effect antagonized by tetrodotoxin, M100907, and BAY x 3702 (5-HT(1A) agonist) but not by SB 242084 (5-HT(2C) antagonist). The 5-HT increase was also reversed by NBQX (AMPA-KA antagonist) and 1S,3S-ACPD (mGluR 2/3 agonist) but not by MK-801 (NMDA antagonist). AMPA mimicked the 5-HT elevation produced by DOI. Likewise, the electrical-chemical stimulation of thalamocortical afferents and the local inhibition of glutamate uptake increased the 5-HT release through AMPA receptors. DOI application in mPFC increased the firing rate of a subgroup of 5-HT neurons (5 of 10), indicating an enhanced output of pyramidal neurons. Dual-label fluorescence confocal microscopic studies demonstrated colocalization of 5-HT(1A) and 5-HT(2A) receptors on individual cortical pyramidal neurons. Thus, DOI reduces the activity of ascending 5-HT neurons through a DR-based action and enhances serotonergic and glutamatergic transmission in mPFC through 5-HT(2A) and AMPA receptors. Because pyramidal neurons coexpress 5-HT(1A) and 5-HT(2A) receptors, DOI disrupts the balance between excitatory and inhibitory inputs and leads to an increased activity that may mediate its hallucinogenic action.

Amphetamines↗

PubMed2001

Client interpersonal and cognitive styles as predictors of response to time-limited cognitive therapy for depression.

This study examined the relationship between cognitive and interpersonal styles and outcome among 24 clients who received time-limited cognitive therapy for depression. The authors hypothesized that this relationship would be mediated by therapeutic alliance. They found that clients' interpersonal style, particularly an underinvolved style, was predictive of treatment outcome. As predicted, the impact of this style on outcome was mediated through the therapeutic alliance.

Adult↗

PubMed2001

Discovery of a novel member of the histamine receptor family.

We report the discovery, tissue distribution and pharmacological characterization of a novel receptor, which we have named H4. Like the three histamine receptors reported previously (H1, H2, and H3), the H4 receptor is a G protein-coupled receptor and is most closely related to the H3 receptor, sharing 58% identity in the transmembrane regions. The gene encoding the H4 receptor was discovered initially in a search of the GenBank databases as sequence fragments retrieved in a partially sequenced human genomic contig mapped to chromosome 18. These sequences were used to retrieve a partial cDNA clone and, in combination with genomic fragments, were used to determine the full-length open reading frame of 390 amino acids. Northern analysis revealed a 3.0-kb transcript in rat testis and intestine. Radioligand binding studies indicated that the H4 receptor has a unique pharmacology and binds [(3)H]histamine (K(d) = 44 nM) and [(3)H]pyrilamine (K(d) = 32 nM) and several psychoactive compounds (amitriptyline, chlorpromazine, cyproheptadine, mianserin) with moderate affinity (K(i) range of 33-750 nM). Additionally, histamine induced a rapid internalization of HA-tagged H4 receptors in transfected human embryonic kidney 293 cells.

Amino Acid Sequence↗

PubMed2000

Pragmatic randomized trial of antenatal intervention to prevent post-natal depression by reducing psychosocial risk factors.

BACKGROUND: Social support theory and observational risk factor studies suggest that increased antenatal psychosocial support could prevent post-natal depression. We used empirical knowledge of risk and protective factors for post-natal depression not employed previously in order to develop and evaluate an antenatal preventive intervention. METHODS: We conducted a pragmatic randomized controlled trial in antenatal clinics. We screened 1300 primiparous women and 400 screened positive, 69 screen-positive women were untraceable or not eligible. Of 292 women who completed baseline assessment, 209 consented to randomization, of these 190 provided outcome data 3 months post-natally. 'Preparing for Parenthood', a structured antenatal risk factor reducing intervention designed to increase social support and problem-solving skills, was compared with routine antenatal care only. We compared the percentage depressed at 3 months after childbirth using the self-completion General Health Questionnaire Depression scale and Edinburgh Post-natal Depression Scale (EPDS), and the Schedules for Clinical Assessment in Neuropsychiatry a systematic clinical interview. RESULTS: Assignment to the intervention group did not significantly impact on post-natal depression (odds ratio for GHQ-Depression 1.22 (95% CI 0.63-2.39), P = 0.55) or on risk factors for depression. Forty-five per cent of the intervention group women attended sufficient sessions to be likely to benefit from intervention if effective. Attenders benefited no more than non-attenders. CONCLUSIONS: Prevention services targeting post-natal depression should not implement antenatal support programmes on these lines until further research has demonstrated the feasibility and effectiveness of such methods. The development of novel, low cost interventions effective in reducing risk factors should be completed before further trial evaluation.

Adolescent↗

PubMed2000

Differential modes of agonist binding to 5-hydroxytryptamine(2A) serotonin receptors revealed by mutation and molecular modeling of conserved residues in transmembrane region 5.

Site-directed mutagenesis and molecular modeling were used to investigate the molecular interactions involved in ligand binding to, and activation of, the rat 5-hydroxytryptamine(2A) (5-HT(2A)) serotonin (5-HT) receptor. Based on previous modeling studies utilizing molecular mechanics energy calculations and molecular dynamics simulations, four sites (S239[5.43], F240[5.44], F243[5.47], and F244[5.48]) in transmembrane region V were selected, each predicted to contribute to agonist and/or antagonist binding. The F243A mutation increased the affinity of (+/-)4-iodo-2, 5-dimethoxyphenylisopropylamine, decreased the binding of alpha-methyl-5HT, N-omega-methyl-5HT, ketanserin, ritanserin, and spiperone and had no effect on the binding of 5-HT and 5-methyl-N, N-dimethyltryptamine. The F240A mutant had no effect on the binding of any of the ligands tested, whereas F244A caused an agonist-specific decrease in binding affinity (3- to 10-fold). S239A caused a 6- to 13-fold decrease in tryptamine-binding affinity and a 5-fold increase in affinity of 4-iodo-2, 5-dimethoxyphenylisopropylamine. A subset of the agonists used in binding studies were used to determine the efficacies and potencies of these mutants to activate phosphoinositide hydrolysis. The F243A and F244A mutations reduced agonist stimulated phosphoinositide hydrolysis, whereas the S239A and F240A mutations had no effect. There was little correlation between agonist binding and second messenger production. Furthermore, molecular dynamics simulations, considering these data, produced ligand-bound structures utilizing substantially different bonding interactions even among structurally similar ligands (differing by as little as one methyl group). Taken together, these results suggest that relatively minor changes in either receptor or ligand structure can produce drastic and unpredictable changes in both binding interactions and 5-HT(2A) receptor activation. Thus, our finding may have major implications for the future and feasibility of receptor structure-based drug design.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗

PubMed2000

Coding system of therapeutic focus on action and insight.

This study (a) used an established comprehensive process measure to uncover a latent pattern of therapeutic focus in cognitive-behavioral and psychodynamic-interpersonal sessions; (b) used these results to develop the coding system of Therapeutic Focus on Action and Insight, which makes it possible to evaluate therapists' relative emphasis on the Constructing Meaning and Facilitating Action domains of in-session focus; and (c) evaluated its reliability and validity.

Classification↗

PubMed1999

Psychotherapy in two-plus-one sessions: outcomes of a randomized controlled trial of cognitive-behavioral and psychodynamic-interpersonal therapy for subsyndromal depression.

A total of 116 clients with a range of subsyndromal depression received 3 therapy sessions: 2 sessions 1 week apart followed by a 3rd session 3 months later (the 2 + 1 model). Clients were stratified for severity on the Beck Depression Inventory (BDI) as stressed, subclinical, or low-level clinically depressed. In a 2 x 2 design, they received either cognitive-behavioral (CB) or psychodynamic-interpersonal (PI) therapy, either immediately or after a 4-week delay. An initial advantage for the immediate condition disappeared once the delayed-condition clients received treatment. Improvement rates at the end of treatment were 67% (stressed), 72% (subclinical), and 65% (low-level clinically depressed). There were no significant differences between CB and PI treatment methods, with the exception at 1-year follow-up, when the BDI showed a significant advantage for CB. Implications for designing very brief planned interventions are discussed.

Adult↗

PubMed1998

Gamma 3 gene-disrupted mice selectively deficient in the dominant IgG subclass made to bacterial polysaccharides undergo normal isotype switching after immunization with polysaccharide-protein conjugate vaccines.

Bacterial polysaccharides (PS) are T-independent type 2 Ags that elicit restricted Ab responses of IgM and IgG3 in mice and IgM and predominantly IgG2 in humans. Immunodeficiency in the dominant IgG subclass made to PS is associated with chronic sinus and pulmonary infections with PS-encapsulated bacteria. To elucidate the biologic role of the dominant IgG subclass in the immune response to PS and to make an animal model of human IgG subclass deficiency, we generated mice with a targeted disruption of the exon encoding the CH1 domain of the gamma 3 heavy-chain constant region gene. Homozygotes had no detectable serum IgG3, and their splenocytes did not produce IgG3 after LPS stimulation. IgG3(-/-) mice immunized with PS from Pseudomonas aeruginosa LPS O-side chain or Streptococcus pneumoniae type 19F capsule did not produce any IgG3 anti-PS Abs, in contrast to wild-type mice in which IgG3 was the major IgG subclass. Immunizing both wild-type and IgG3(-/-) mice with 19F PS-protein conjugate elicited IgG1 Abs. We conclude that IgG3(-/-) mice have a selective deficiency in the dominant murine IgG subclass made to T-independent type 2 Ags and may be a useful animal model of IgG subclass deficiency. In addition, we show that the anti-PS Ab class switching to IgG1 that occurs when mice are immunized with a PS-protein conjugate vaccine does not require sequential Ig expression or an intact, upstream gamma 3 heavy-chain gene.

Animals↗

PubMed1998

Relations of the alliance with psychotherapy outcome: findings in the Second Sheffield Psychotherapy Project.

Clients (n = 79) and therapists (n = 5) rated their alliance using parallel forms of the Agnew Relationship Measure (ARM) after every session of their time-limited psychodynamic-interpersonal or cognitive-behavioral treatments for depression. The ARM assesses 5 dimensions of the alliance: Bond, Partnership, Confidence, Openness, and Client Initiative. Treatment outcome was assessed as residual gain from pretreatment assessment to end of treatment, 3-month follow-up, and 1-year follow-up on 6 standard measures. Some aspects of the alliance as measured by the ARM were correlated with clients' gains in treatment. The strength of the association varied across assessment measures, occasions of outcome assessment, ARM scales, and the session number when the alliance was measured.

Adult↗

PubMed1998

Alliance structure assessed by the Agnew Relationship Measure (ARM).

OBJECTIVES: We used a new instrument, the Agnew Relationship Measure (ARM), to examine the alliance's dimensionality and to construct scales for use in future studies. DESIGN: We studied the alliance as reported on the ARM by both clients and therapists in the Second Sheffield Psychotherapy Project, a randomized comparison of two contrasting time-limited psychotherapies for depression. METHODS: Clients (N = 95) and therapists (N = 5) completed parallel forms of the (ARM) after every session (N = 1120). RESULTS: Five scales were constructed, based on results of simultaneous components analyses and considerations of conceptual coherence and comparability across client and therapist perspectives. CONCLUSIONS: Bond, partnership, and confidence overlapped statistically (consistent with previous studies), but there are conceptual and empirical reasons for retaining the distinctions. Openness represented a relatively independent dimension. The client initiative scale had low internal consistency but the items may have value for future investigations.

Adult↗

PubMed1998

The role of personal therapy for therapists: a review.

This paper reviews the research literature on personal therapy and makes some recommendations for how future work in this area may be improved. Despite the general acceptance of the importance of personal therapy amongst therapists, there has been relatively little research to evaluate its effectiveness. The vast majority of studies have consisted of surveys of therapists' opinions and experiences of therapy or naturalistic comparisons across therapists who have or have not had therapy. The interpretation of most findings is compromised because of small sample sizes and confounding variables, nevertheless some conclusions can be made. Whilst the majority of therapists feel that they have benefited professionally from personal therapy there is very little empirical evidence that it has any measurable effect on client outcome. However, there is some evidence that personal therapy has a positive effect on those therapist qualities often cited as constructive to client change (e.g. empathy, warmth, genuineness). What is evident is that there is a need for more methodologically sound research as well as a more theoretical understanding of how personal therapy affects clinical practice, before any firm conclusions can be drawn about its usefulness. It is suggested that it may be more useful for future research in this area to focus on therapy process rather than client outcome.

Humans↗