Dopamine effects on evidence gathering and integration

BackgroundDisturbances in evidence gathering and disconfirmatory evidence integration have been associated with the presence of or propensity for delusions. Previous evidence suggests that these 2 types of reasoning bias might be differentially affected by antipsychotic medication. We aimed to investigate the effects of a dopaminergic agonist (L-dopa) and a dopaminergic antagonist (haloperidol) on evidence gathering and disconfirmatory evidence integration after single-dose administration in healthy individuals.MethodsThe study used a randomized, double-blind, placebo-controlled, 3-way crossover design. Participants were healthy individuals aged 18–40 years. We administered a new data-gathering task designed to increase sensitivity to change compared with traditional tasks. The Bias Against Disconfirmatory Evidence (BADE) task was used as a measure of disconfirmatory evidence integration.ResultsWe included 30 individuals in our study. In the data-gathering task, dopaminergic modulation had no significant effect on the amount of evidence gathered before reaching a decision. In contrast, the ability of participants to integrate disconfirmatory evidence showed a significant linear dopaminergic modulation pattern (highest with haloperidol, intermediate with placebo, lowest with L-dopa), with the difference between haloperidol and L-dopa marginally reaching significance.LimitationsAlthough the doses used for haloperidol and L-dopa were similar to those used in previous studies, drug plasma level measurements would have added to the validity of findings.ConclusionEvidence gathering and disconfirmatory evidence integration might be differentially influenced by dopaminergic agents. Our findings are in support of a dual-disturbance account of delusions and provide a plausible neurobiological basis for the use of interventions targeted at improving reasoning biases as an adjunctive treatment in patients with psychotic disorders.     

Efficacy and Effectiveness of Child and Adolescent Psychotherapy and Pharmacotherapy

Decades of intervention research have produced a rich body of evidence on the effects of psychotherapies and pharmacotherapies with children and adolescents. Here we summarize and critique that evidence. We review findings bearing on the efficacy of psychosocial treatments and medications under controlled experimental conditions. We also report evidence, where available, on the effectiveness of both classes of treatment with clinically referred youth treated in real-world clinical contexts. In general, the large body of evidence on efficacy contrasts sharply with the small base of evidence on effectiveness. Addressing this gap through an enriched research agenda could contribute importantly to linking scientific inquiry and clinical practice—to the benefit of both ventures. This is one element of a multifaceted agenda for future research and for synthesis of research, which will require the interplay of multiple disciplines related to child and adolescent mental health.     

Perceptual Gains and Losses in Synesthesia and Schizophrenia

Individual differences in perception are widespread. Considering inter-individual variability, synesthetes experience stable additional sensations; schizophrenia patients suffer perceptual deficits in, eg, perceptual organization (alongside hallucinations and delusions). Is there a unifying principle explaining inter-individual variability in perception? There is good reason to believe perceptual experience results from inferential processes whereby sensory evidence is weighted by prior knowledge about the world. Perceptual variability may result from different precision weighting of sensory evidence and prior knowledge. We tested this hypothesis by comparing visibility thresholds in a perceptual hysteresis task across medicated schizophrenia patients (N = 20), synesthetes (N = 20), and controls (N = 26). Participants rated the subjective visibility of stimuli embedded in noise while we parametrically manipulated the availability of sensory evidence. Additionally, precise long-term priors in synesthetes were leveraged by presenting either synesthesia-inducing or neutral stimuli. Schizophrenia patients showed increased visibility thresholds, consistent with overreliance on sensory evidence. In contrast, synesthetes exhibited lowered thresholds exclusively for synesthesia-inducing stimuli suggesting high-precision long-term priors. Additionally, in both synesthetes and schizophrenia patients explicit, short-term priors—introduced during the hysteresis experiment—lowered thresholds but did not normalize perception. Our results imply that perceptual variability might result from differences in the precision afforded to prior beliefs and sensory evidence, respectively.     

Anticonvulsants in bipolar disorders: current research and practice and future directions

Objectives:  To determine the clinical effectiveness of drugs with anticonvulsant properties for interventions in persons with bipolar disorder and to place these findings in the context of clinicians' practices and their implications for future research to more effectively manage bipolar disorders.
Methods:  Major electronic databases were searched up to February 2009 for clinical trial data, both original studies and reviews, on drugs with anticonvulsant properties studied for bipolar disorders.
Results:  Valproate, principally as divalproex, has strong evidence for effectiveness in mania, moderately strong evidence for benefits in prophylaxis of recovered states, and recent proof-of-concept evidence for benefits in bipolar depression. Lamotrigine has strong evidence for evidence for effectiveness in maintenance treatment of bipolar disorder, principally for benefits in depressive states. Lamotrigine has been established as ineffective in mania and has lacked efficacy in acute bipolar depression in most randomized trials. Carbamazepine has strong evidence for effectiveness in mania, but lacks adequate studies in other aspects of bipolar disorder treatment. Its adverse effect profile and pharmacokinetic interference with a wide range of drugs, including many employed in bipolar disorder, warrants limitation of use to patients who have responded inadequately to other regimens.
Conclusions:  Three drugs, valproate, lamotrigine, and carbamazepine, have strong evidence-based support for use in clinical states of bipolar disorder. Other anticonvulsant drugs investigated in bipolar disorder either have evidence of lack of benefits in bipolar disorder or have been inadequately studied to determine possible effectiveness.     

Endogenous vasopressin and baroreflex mechanisms

This article reviews the anatomical and functional evidence for ascending pathways from specific brain regions to the PVN and SON which could influence AVP release. The majority of evidence favours the main projection being from a region in the caudal VLM which may coincide with the noradrenergic neurons of the A₁ cell group. However, the transmitter(s) involved have yet to be identified, and whether the pathway is excitatory and/or inhibitory remains to be fully resolved.Anatomical and functional evidence is reviewed for descending projections from the SON and PVN to specific brain regions involved in cardiovascular control, and their possible involvement in baroreflex mechanisms is discussed. However, there is little unequivocal evidence that AVP is the main neurotransmitter utilized by descending projections from PVN to NTS and DMX. While, in some situations, circulating endogenous AVP exerts cardiovascular effects, details of its putative influences on baroreflex mechanisms are lacking.     

The Influence of Limiting Instructions on Processing and Judgments of Emotionally Evocative Evidence

Most jury instructions are issued after all the evidence has been presented in a trial; however, some are given during the trial. When gruesome photographs form part of the evidence in criminal culpability proceedings, the judge will usually instruct jurors to be dispassionate in examining the evidence. This study investigated whether time of presentation affects the ability of limiting instructions to cure the potentially prejudicial effects of gruesome photographic evidence by measuring the emotions, cognitions and verdicts of 108 mock jurors in a simulated murder trial. Pre-instructed participants processed evidence in the defendant's favour and rendered significantly fewer convictions than did post-instructed participants and those who received no limiting instructions. Gruesome photographs did not bias processing of other items in evidence or verdicts, although they elicited significantly greater victim compassion and crime negativity than did neutral photographs. Results suggest that jury instructions are more conducive to compliance when presented early in the evidence-processing task than when presented late.     

Are psychological interventions effective and accepted by cancer patients? I. Standards and levels of evidence

Different standards and levels of evidence for evaluating the effectiveness of psychological interventions for managing distress in cancer patients are presented and discussed. We conclude that the strongest evidence comes from systematic qualitative and quantitative (i.e., meta-analyses) reviews of the relevant literature and that the most appropriate standard of evidence is the “preponderance of evidence” rather than “beyond a reasonable doubt.” Results of four selected qualitative and quantitative systematic reviews of the literature are described. The preponderance of evidence furnished by these systematic reviews, particularly that gleaned from meta-analyses, suggests that psychological interventions are effective in managing distress in cancer patients. Although effectiveness may vary as a function of the specific nature of the intervention, overall, effectiveness appears strongest for anxiety-related outcomes and when participants are prescreened for distress. Different standards and indexes for evaluating evidence regarding the acceptability of psychological interventions with cancer patients are presented and discussed. The use of simple study accrual rates as an index of intervention acceptability is deemed inappropriate. We suggest alternative indexes of acceptability and conclude that sufficient information does not exist at the present time to draw the conclusion that contemporary psychological interventions for managing distress in cancer patients are unacceptable.     

The Pharmacological Management of Oppositional Behaviour,Conduct Problems,and Aggression in Children and Adolescents With Attention-Deficit Hyperactivity Disorder,Oppositional Defiant Disorder,and Conduct Disorder: A Systematic Review and Meta-Analysis. Part 2: Antipsychotics and Traditional Mood Stabilizers

Objective:

Attention-deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) are among the most common psychiatric diagnoses in childhood. Aggression and conduct problems are a major source of disability and a risk factor for poor long-term outcomes.

Methods:

We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) of antipsychotics, lithium, and anticonvulsants for aggression and conduct problems in youth with ADHD, ODD, and CD. Each medication was given an overall quality of evidence rating based on the Grading of Recommendations Assessment, Development and Evaluation approach.

Results:

Eleven RCTs of antipsychotics and 7 RCTs of lithium and anticonvulsants were included. There is moderate-quality evidence that risperidone has a moderate-to-large effect on conduct problems and aggression in youth with subaverage IQ and ODD, CD, or disruptive behaviour disorder not otherwise specified, with and without ADHD, and high-quality evidence that risperidone has a moderate effect on disruptive and aggressive behaviour in youth with average IQ and ODD or CD, with and without ADHD. Evidence supporting the use of haloperidol, thioridazine, quetiapine, and lithium in aggressive youth with CD is of low or very-low quality, and evidence supporting the use of divalproex in aggressive youth with ODD or CD is of low quality. There is very-low-quality evidence that carbamazepine is no different from placebo for the management of aggression in youth with CD.

Conclusion:

With the exception of risperidone, the evidence to support the use of antipsychotics and mood stabilizers is of low quality.     

Psychiatric and psychological evidence in the Supreme Court of Iceland—2001 to 2007

Background: Little is known about expert psychiatric and psychological evidence in appeal cases. Aims: To review the frequency, nature and impact of expert psychiatric and psychological evidence in the Supreme Court in Iceland over a 7-year period where all appeals in Iceland are heard. Method: All cases listed on the Supreme Court's Website between 2001 and 2007 were identified. The judgements were carefully screened for relevant information. Details of the nature of the criminal offences for the sample were obtained from official records. Results: 3367 cases were identified. Psychiatric and psychological evidence was considered in 213 (6.3%) cases (2.7% and 4.2% for the two disciplines, respectively), with only 10% cases involving reports from both disciplines. Psychiatrists focused primarily on assessing violent offenders, diminished responsibility issues, restraining orders, and mental state examinations and diagnosis, whereas psychologists were more commonly involved in custody disputes and credibility assessments of victims of sexual offending. No oral expert evidence was heard in the Supreme Court. Psychiatric and psychological evidence was typically that previously presented in the District Courts. Conclusions: This is the first comprehensive study to investigate the contribution of forensic psychiatry and psychology in appeal cases. Psychiatrists and psychologists have complementary skills for the assessment of court referrals. Their evidence and recommendations in appeal cases in Iceland are accepted by the Supreme Court in the great majority (78%) of cases.     

Adjuvant use of nutritional and herbal medicines with antidepressants, mood stabilizers and benzodiazepines

Adjuvant use of nutritional and herbal medicines has potential to increase the efficacy of synthetic pharmaceuticals, and perhaps also decrease their side-effects by allowing lower doses to be prescribed. We evaluated current evidence for adjuvant use of nutritional and herbal medicines with antidepressants, mood stabilizers and benzodiazepines; and explored novel future areas of research. The paper also critiques current evidence for co-administration of St. John’s wort with synthetic antidepressants. We performed a systematic search of MEDLINE, CINAHL, PsycINFO, The Cochrane database, China National Knowledge Infrastructure and the Chinese Science Citation Database. Search results were supplemented by a review of reference lists and a forward search using the Web of Science. Where possible we calculated effect sizes. Encouraging evidence exists for the use of omega-3 fatty acids, SAMe, folic acid and l-tryptophan adjuvantly with antidepressants to enhance response and improve efficacy. Various nutrients also have emerging evidence as effective adjuncts with antipsychotics and mood stabilizers. While some evidence supports nutritional adjuvancy with various psychopharmacotherapies, adjuvant use of herbal therapies has not been sufficiently studied to warrant standard clinical application. This remains a promising area of research via robust, safety-conscious studies.     

European Academy of Neurology and European Stroke Organization consensus statement and practical guidance for pre‐hospital management of stroke

Background and purpose

The reduction of delay between onset and hospital arrival and adequate pre‐hospital care of persons with acute stroke are important for improving the chances of a favourable outcome. The objective is to recommend evidence‐based practices for the management of patients with suspected stroke in the pre‐hospital setting.

Methods

The GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to define the key clinical questions. An expert panel then reviewed the literature, established the quality of the evidence, and made recommendations.

Results

Despite very low quality of evidence educational campaigns to increase the awareness of immediately calling emergency medical services are strongly recommended. Moderate quality evidence was found to support strong recommendations for the training of emergency medical personnel in recognizing the symptoms of a stroke and in implementation of a pre‐hospital ‘code stroke’ including highest priority dispatch, pre‐hospital notification and rapid transfer to the closest ‘stroke‐ready’ centre. Insufficient evidence was found to recommend a pre‐hospital stroke scale to predict large vessel occlusion. Despite the very low quality of evidence, restoring normoxia in patients with hypoxia is recommended, and blood pressure lowering drugs and treating hyperglycaemia with insulin should be avoided. There is insufficient evidence to recommend the routine use of mobile stroke units delivering intravenous thrombolysis at the scene. Because only feasibility studies have been reported, no recommendations can be provided for pre‐hospital telemedicine during ambulance transport.

Conclusions

These guidelines inform on the contemporary approach to patients with suspected stroke in the pre‐hospital setting. Further studies, preferably randomized controlled trials, are required to examine the impact of particular interventions on quality parameters and outcome.     

Dopamine and depression: A review of recent evidence. I. Empirical studies

This paper reviews evidence from human, predominantly clinical, studies, relevant to the hypothesis that depression involves reduced levels of dopamine (DA) function. With the exception of Parkinson's disease, there is little evidence that treatments which decrease DA function are potent inducers of depression, but it is argued that such a relationship might not necessarily be expected. There is good evidence that the nigro-striatal DA system is underactive in retarded depressions, and some evidence that DA agonists are therapeutically effective in these cases. It remains unclear whether changes in DA function are primary or secondary.     

Translating the evidence for gene association with depression into mouse models of depression-relevant behaviour: Current limitations and future potential

Depression is characterised by high prevalence and complex, heterogeneous psychopathology. At the level of aetio-pathology, considerable research effort has been invested to identify specific gene polymorphisms associated with increased depression prevalence. Genome-wide association studies have not identified any risk polymorphisms, and candidate gene case–control studies have identified a small number of risk polymorphisms. It is increasingly recognised that interaction between genotype and environmental factors (G × E), notably stressful life events, is the more realistic unit of depression aetio-pathology, with G × E evidence described for a small number of risk polymorphisms. An important complementary approach has been to describe genes exhibiting brain region-specific expression changes in depression. Mouse models of depression informed by the human evidence allow for the study of causality, but to-date have also yielded limited insights into depression aetio-pathology. This review of the translational evidence integrates human and mouse research approaches and evidence. It also makes specific recommendations in terms of how future research in human and mouse should be designed in order to deliver evidence for depression aetio-pathology and thereby to inform the development of novel and improved antidepressant treatments.     

A Self-Report Scale for Mental and Motor Slowness: Preliminary Results

A self-report slowness scale (SRSS) was developed to rate the severity of mental and motor slowness with items approximating general activities of daily life: housekeeping, personal care, recreation and leisure, cognitive skills, and reaction time. The scale was administered to 95 persons infected with HIV and 24 uninfected persons in the context of a comprehensive neurobehavioral evaluation. Analysis of internal consistency for the entire sample (Alpha = .9485) provided strong evidence of internal reliability, and strong evidence of stability was provided by SRSS scores taken 6 months apart, r(58) = .69, p < .001. Construct validity evidence was also strong: point biserial correlations of item-to-total scores for the entire sample were all above .77 (p < .001), and factor analysis for the HIV+ subjects yielded one factor accounting for 66.7% of the variance. Moderate evidence for criterion-related validity was illustrated through significant correlations of SRSS ratings with neuropsychological tests in which timing and memory are primary features.     

Psychological treatment of sexual problems. A review of literature published between 2001 and 2010. Presentation of method and preliminary results

While the quality of treatment traditionally has been a reflection of educational diplomas and professional licences, clinicians are now challenged to document treatment methods based on updated research. The American Psychological Association published a report on evidence-based practice in psychology in 2006, where best available research evidence is based on multiple types of research evidence. The report focuses on clinical expertise and patient characteristics, culture and preferences as factors in evidence-based practice in psychology. There has been a call for more randomized and controlled research as basis for evidence for the effect of treatment. The complexity of psychological treatment of sexual problems calls for more varied evidence. A literature search of publications between 2001 and 2010 was done in order to explore what kind of evidence is referred to in the literature. The first results of this search will be presented in this article. One question to be discussed is difficulties related to collecting literature through databases. Additional search methods like snow-balling and manual searches give important additional results, but limit the stringency of the search. Further results will be presented in future publications.     

The Pharmacological Management of Oppositional Behaviour,Conduct Problems,and Aggression in Children and Adolescents With Attention-Deficit Hyperactivity Disorder,Oppositional Defiant Disorder,and Conduct Disorder: A Systematic Review and Meta-Analysis. Part 1: Psychostimulants,Alpha-2 Agonists,and Atomoxetine

Objective:

Children with attention-deficit hyperactivity disorder (ADHD) may have oppositional behaviour, conduct problems, and aggression. These symptoms vary in severity, and may be related to a comorbid diagnosis of oppositional defiant disorder (ODD) or conduct disorder (CD). Critical evaluation of the efficacy of ADHD medications may guide the clinician regarding the usefulness of medications for these symptoms.

Method:

We performed a systematic review and meta-analysis of psychostimulants, alpha-2 agonists, and atomoxetine for oppositional behaviour, conduct problems, and aggression in youth with ADHD, ODD, and CD. The quality of evidence for medications was rated using the Grading of Recommendations Assessment, Development and Evaluation approach.

Results:

Two systematic reviews and 20 randomized controlled trials were included. There is high-quality evidence that psychostimulants have a moderate-to-large effect on oppositional behaviour, conduct problems, and aggression in youth with ADHD, with and without ODD or CD. There is very-low-quality evidence that clonidine has a small effect on oppositional behaviour and conduct problems in youth with ADHD, with and without ODD or CD. There is moderate-quality evidence that guanfacine has a small-to-moderate effect on oppositional behaviour in youth with ADHD, with and without ODD. There is high-quality evidence that atomoxetine has a small effect on oppositional behaviour in youth with ADHD, with and without ODD or CD.

Conclusions:

Evidence indicates that psychostimulants, alpha-2 agonists, and atomoxetine can be beneficial for disruptive and aggressive behaviours in addition to core ADHD symptoms; however, psychostimulants generally provide the most benefit.     

Immunization and MS: a summary of published evidence and recommendations

OBJECTIVE: To review the risk of MS exacerbations after infectious episodes potentially preventable by vaccination, and the risks and benefits of immunizing patients with MS. METHODS: The authors searched MEDLINE (1966 to January 2001; U.S. National Library of Medicine, Bethesda, MD), HealthSTAR, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) database (Cinahl Information Systems, Glendale, CA) for English-language articles. Each study was summarized and rated for quality of evidence. Then feasible data were pooled and analyzed in meta-analysis. RESULTS: The risk of contracting common infectious diseases in patients with MS is not well established. There is strong evidence for an increased risk of MS exacerbations during weeks around an infectious episode. There is strong evidence against an increased risk of MS exacerbation after influenza immunization. There is no evidence that hepatitis B, varicella, tetanus, or Bacille Calmette-Guerin vaccines increase the risk of MS exacerbations. Insufficient evidence was found for other vaccines. CONCLUSIONS: Evidence supports 1) strategies to minimize the risk of acquiring infectious diseases that may trigger exacerbations of MS; and 2) the safety of using influenza, hepatitis B, varicella, tetanus, and Bacille Calmette-Guerin (BCG) vaccines in patients with MS.     

The Impact of State and Trait Anger on Processing of Evidential Inconsistencies

The courtroom can be an emotional place, and these emotions may impact on a juror's ability to process and evaluate evidence. This study investigated the effects of mock-jurors’ state and trait anger on the detection of evidential inconsistencies. Community members eligible for jury duty (N = 123) were randomly assigned to hear one of four audio trials differing in evidence consistency and emotion-inducing content. State anger increased endorsement of guilty verdicts, and angry mock-jurors were more careful processors of evidence, detecting more inconsistencies and recalling significantly more trial details. The results lend support to motivational theories of emotional influence on information processing.     

‘Material likely to harm or disturb them’: testing the alignment between film and game classification decisions and psychological research evidence

This article analyses the practical operation of Australia’s National Classification System (NCS) for films and games, to evaluate its alignment with the findings of psychological research.¹ Twenty-nine decisions of the Classification Review Board are examined to determine the factors applied in assessing the impact of violent content and drawing the line between the different classification categories. The language used in referring to violent content is analysed to determine the concepts that influence the Board’s view about the correct classification. These concepts are then tested against the research evidence on the depictions of violence that create the greatest risk of adverse outcomes for viewers and players. Not all of the concepts used in classification have a basis in the research evidence, and some are directly at odds with that evidence. The article concludes by recommending changes to the rules that could lead to better alignment between classification decisions and the research evidence.Key words: content factors, evidence-based policy, film and game classification, media effects, media law, media violence, obscenity