Biomedical subjects

Robert M Hamer

Publications and source records attributed to Robert M Hamer.

At least 19 recordsLinked to original sources

PubMed2007

Evaluating binge eating disorder in children: development of the children's binge eating disorder scale (C-BEDS).

OBJECTIVE: Binge eating disorder (BED) may manifest itself differently in children than adults. Recently researchers have proposed provisional criteria for measuring BED in children. The purpose of this study was to develop a brief, simple, structured, interviewer-administered scale (C-BEDS) to measure BED in children according to the provisional criteria and to compare diagnostic results with SCID diagnoses. METHOD: A total of 55 children between the ages of 5 and 13 were interviewed with both the SCID and the C-BEDS. RESULTS: There was a significant association between the two measures (p = .001). Both measures adequately identified children with binge eating behaviors. CONCLUSION: Both the provisional criteria and the C-BEDS may be developmentally appropriate for use with children, although the C-BEDS may be a better screening instrument as it quickly identified children with subsyndromal BED. If used by physicians and other health providers, this brief measure may assist with identifying early onset binge eating behaviors and avoiding the associated consequences, including adult BED, obesity, and other comorbidities.

Adolescent↗

PubMed2007

Relative risk of glucose elevation during antipsychotic exposure in a Veterans Administration population.

Concern is mounting that atypical antipsychotics cause disturbance in glucose regulation ranging from reversible hyperglycemia to diabetic ketoacidosis and death. It is difficult, however, to know what the level of risk of hyperglycemia might be for an individual patient on a particular medication of this class. We conducted a retrospective nonrandomized cohort analysis of glucose measurements in 18,764 patients receiving outpatient prescriptions for olanzapine, risperidone, or typical antipsychotics from 1 October 1998 to 30 June 2003 at six Veterans Affairs Medical Centers in the southeast United States. In patients without a random plasma glucose measurement > or =160 mg/dl before medication exposure (n=1394), treatment with index medications was associated with an incidence of new diabetes-level hyperglycemia of 78.7 cases per 1,000 individuals exposed per year. Olanzapine exposure was associated with a greater rate of developing at least one glucose measurement > or =200 mg/dl than risperidone (odds ratio=2.14, P=0.003). Olanzapine exposure was also associated with a greater rate of development of at least one fasting glucose measurement > or =126 mg/dl than risperidone. Typical antipsychotics were associated with risk intermediate between the two atypicals. These data indicate that patients with no previously observed glucose elevations develop diabetes-level hyperglycemia during antipsychotic treatment, particularly in patients receiving olanzapine.

Antipsychotic Agents↗

PubMed2006

Intracranial hemorrhage in asymptomatic neonates: prevalence on MR images and relationship to obstetric and neonatal risk factors.

PURPOSE: To retrospectively evaluate the prevalence of neonatal intracranial hemorrhage (ICH) and its relationship to obstetric and neonatal risk factors. MATERIALS AND METHODS: Pregnant women were recruited for a prospective study of neonatal brain development; the study was approved by the institutional review board and complied with HIPAA regulations. After informed consent was obtained from a parent, neonates were imaged with 3.0-T magnetic resonance (MR) imaging without sedation. The images were reviewed by a neuroradiologist with 12 years of experience for the presence of ICH. Medical records were prospectively and retrospectively reviewed for selected risk factors, which included method of delivery, duration of labor, and evidence of maternal or neonatal birth trauma. Risk factors were assessed for relationship to ICH by using Fisher exact test statistics. RESULTS: Ninety-seven neonates (mean age at MR imaging, 20.8 days +/- 6.9 [standard deviation]) underwent MR imaging between the ages of 1 and 5 weeks. Eighty-eight (44 male and 44 female) neonates (65 with vaginal delivery and 23 with cesarean delivery) completed the MR imaging evaluation. Seventeen neonates with ICHs (16 subdural, two subarachnoid, and six parenchymal hemorrhages) were identified. Seven infants had two or more types of hemorrhages. All neonates with ICH were delivered vaginally, with a prevalence of 26% in vaginal births. ICH was significantly associated with vaginal birth (P < .005) but not with prolonged duration of labor or with traumatic or assisted vaginal birth. CONCLUSION: Asymptomatic ICH following vaginal birth in full-term neonates appears to be common, with a prevalence of 26% in this study.

Birth Injuries↗

PubMed2006

No evidence for parental imprinting of mouse 22q11 gene orthologs.

Non-Mendelian factors may influence central nervous system (CNS) phenotypes in patients with 22q11 Deletion Syndrome (22q11DS, also known as DiGeorge or Velocardiofacial Syndrome), and similar mechanisms may operate in mice carrying a deletion of one or more 22q11 gene orthologs. Accordingly, we examined the influence of parent of origin on expression of 25 murine 22q11 orthologs in the developing and mature CNS using single nucleotide polymorphism (SNP)-based analysis in interspecific crosses and quantification of mRNA in a murine model of 22q11DS. We found no evidence for absolute genomic imprinting or silencing. All 25 genes are biallelically expressed in the developing and adult brains. Furthermore, if more subtle forms of allelic biasing are present, they are very small in magnitude and most likely beyond the resolution of currently available quantitative approaches. Given the high degree of similarity of human 22q11 and the orthologous region of mmChr16, genomic imprinting most likely cannot explain apparent parent-of-origin effects in 22q11DS.

Alleles↗

PubMed2006

Cognitive-behavioral therapy for somatization disorder: a randomized controlled trial.

BACKGROUND: Patients diagnosed as having somatization disorder (SD) who present with a lifetime history of multiple, medically unexplained physical symptoms represent a significant challenge to health care providers. To date, no psychotherapeutic or pharmacologic intervention has been found to produce clinically meaningful improvement in symptoms or functioning of patients with SD. We examined the efficacy of cognitive-behavioral therapy (CBT) for SD. METHODS: Eighty-four participants meeting criteria for SD were randomly assigned to 1 of 2 conditions: (1) standard medical care augmented by a psychiatric consultation intervention or (2) a 10-session, manualized, individually administered CBT regimen added to the psychiatric consultation intervention. Assessments were conducted at baseline and 3, 9, and 15 months after baseline. The primary outcome measure was the severity scale of the Clinical Global Impression Scale for Somatization Disorder (CGI-SD). Secondary outcome measures were responder status as determined by clinical ratings, self-reported measures of physical functioning and somatic symptoms, and health care utilization assessed via medical records. RESULTS: Fifteen months after baseline, somatization symptoms were significantly less severe in the group treated with CBT (0.84 points on the CGI-SD 7-point scale) (P<.001). Patients treated with CBT also were significantly more likely to be rated as either very much improved or much improved than patients treated with only augmented standard medical care (40% [n = 17] vs 5% [n = 2]). Cognitive-behavioral therapy was associated with greater improvements in self-reported functioning and somatic symptoms and a greater decrease in health care costs. CONCLUSION: For patients diagnosed as having SD, CBT may produce clinical benefits beyond those that result from the current state-of-the-art treatment.

Adolescent↗

PubMed2006

Insight in first-episode psychosis.

BACKGROUND: We report here a study examining the relationships between insight and psychopathology, cognitive performance, brain volume and co-morbid depression in 251 patients experiencing a first episode of psychosis, who were then randomly assigned to 2 years of double-blind treatment with either olanzapine or haloperidol. METHOD: Repeated measures of insight were obtained at baseline and 12, 24, 52 and 104 weeks by the Insight and Treatment Attitudes Questionnaire (ITAQ). RESULTS: Older age, female gender and white ethnicity were associated with more insight. Higher total, positive, negative and general psychopathology scores on the Positive and Negative Syndromes Scale (PANSS) were associated with less insight. Higher depression scores were associated with more insight. Better neurocognitive function and large brain volumes were associated with more insight. More insight throughout the study was associated with longer time to medication non-adherence. However, baseline insight was not significantly related to the probability of discontinuing the study before 2 years. Insight improved significantly over the course of the study, but the improvement in insight was not significantly different between the two antipsychotic treatment groups. CONCLUSIONS: Multiple factors contribute to insight. Patients experiencing a first episode of psychosis who have little insight are at increased risk of discontinuing their medication.

Adolescent↗

PubMed2006

Predictors of antipsychotic medication adherence in patients recovering from a first psychotic episode.

BACKGROUND: Many patients recovering from a first psychotic episode will discontinue medication against medical advice, even before a 1-year treatment course is completed. Factors associated with treatment adherence in patients with chronic schizophrenia include beliefs about severity of illness and need for treatment, treatment with typical versus atypical antipsychotic and medication side effects. METHOD: In this 2-year prospective study of 254 patients recovering from a first episode of schizophrenia, schizophreniform, or schizoaffective disorder we examined the relationship between antipsychotic medication non-adherence and patient beliefs about: need for treatment, antipsychotic medication benefits, and negative aspects of antipsychotic medication treatment. We also examined the relationship between medication non-adherence and treatment with either haloperidol or olanzapine, and objective measures of symptom response and side effects. RESULTS: The likelihood of becoming medication non-adherent for 1 week or longer was greater in subjects whose belief in need for treatment was less (HR=1.75, 95% CI 1.16, 2.65, p=0.0077) or who believed medications were of low benefit (HR=2.88, 95 CI 1.79-4.65, p<0.0001). Subjects randomized to haloperidol were more likely to become medication non-adherent for >or=1 week than subjects randomized to olanzapine (HR-1.51, 95% CI 1.01, 2.27, p=0.045). CONCLUSION: Beliefs about need for treatment and the benefits of antipsychotic medication may be intervention targets to improve likelihood of long-term medication adherence in patients recovering from a first episode of schizophrenia, schizoaffective, or schizophreniform disorder.

Adult↗

PubMed2006

Single-voxel 1H PRESS at 4.0 T: precision and variability of measurements in anterior cingulate and hippocampus.

The precision [coefficient of variation or CV (%) = 100SD/X] of single-voxel point resolved spectroscopic data was characterized bilaterally, in anterior cingulate and in hippocampus, at 4.0 T in a healthy subject. Data acquisition was replicated 10 times after voxel repositioning and readjusting higher order shims. Precision measurements show that the scan-to-scan precision is better in anterior cingulate than in hippocampus, with an average CV of 9.2% (for total NAA, tCho and Cr) in anterior cingulate and 13.9% in hippocampus. Variability measurements made by the same method in 24 healthy subjects and in 29 schizophrenia patients showed that there is substantial biological variability in metabolite levels, even in healthy subjects. Simple calculations suggest that more than 200 subjects would be needed to detect a 5% difference in NAA between patients and controls.

Adult↗

PubMed2006

Clinical trials for antipsychotic drugs: design conventions, dilemmas and innovations.

More than 50 years after the introduction of modern pharmacotherapies for schizophrenia, there remains a tremendous need for therapeutic advances. A second generation of antipsychotic drugs, introduced over the past 15 years, has provided uncertain advantages over the first-generation drugs. This paper reviews the designs of studies that evaluate the effectiveness of putative antipsychotic drugs. Data from the trials needed to achieve regulatory approval do not meet all the needs of clinicians and policy makers. Practical and large, simple trials that evaluate the comparative effectiveness of antipsychotic drugs in real-world settings can help to meet these needs once a drug has reached the market.

Antipsychotic Agents↗

PubMed2006

Neuroactive steroids are altered in schizophrenia and bipolar disorder: relevance to pathophysiology and therapeutics.

Evidence suggests that neuroactive steroids may be candidate modulators of schizophrenia pathophysiology and therapeutics. We therefore investigated neuroactive steroid levels in post-mortem brain tissue from subjects with schizophrenia, bipolar disorder, nonpsychotic depression, and control subjects to determine if neuroactive steroids are altered in these disorders. Posterior cingulate and parietal cortex tissue from the Stanley Foundation Neuropathology Consortium collection was analyzed for neuroactive steroids by negative ion chemical ionization gas chromatography/mass spectrometry preceded by high-performance liquid chromatography. Subjects with schizophrenia, bipolar disorder, nonpsychotic depression, and control subjects were group matched for age, sex, ethnicity, brain pH, and post-mortem interval (n = 14-15 per group, 59-60 subjects total). Statistical analyses were performed by ANOVA with post-hoc Dunnett tests on log transformed neuroactive steroid levels. Pregnenolone and allopregnanolone were present in human post-mortem brain tissue at considerably higher concentrations than typically observed in serum or plasma. Pregnenolone and dehydroepiandrosterone levels were higher in subjects with schizophrenia and bipolar disorder compared to control subjects in both posterior cingulate and parietal cortex. Allopregnanolone levels tended to be decreased in parietal cortex in subjects with schizophrenia compared to control subjects. Neuroactive steroids are present in human post-mortem brain tissue at physiologically relevant concentrations and altered in subjects with schizophrenia and bipolar disorder. A number of neuroactive steroids act at inhibitory GABA(A) and excitatory NMDA receptors and demonstrate neuroprotective and neurotrophic effects. Neuroactive steroids may therefore be candidate modulators of the pathophysiology of schizophrenia and bipolar disorder, and relevant to the treatment of these disorders.

Analysis of Variance↗

PubMed2006

Brain volume in first-episode schizophrenia: systematic review and meta-analysis of magnetic resonance imaging studies.

BACKGROUND: Studies of people with schizophrenia assessed using magnetic resonance imaging (MRI) usually include patients with first-episode and chronic disease, yet brain abnormalities may be limited to those with chronic schizophrenia. AIMS: To determine whether patients with a first episode of schizophrenia have characteristic brain abnormalities. METHOD: Systematic review and meta-analysis of 66 papers comparing brain volume in patients with a first psychotic episode with volume in healthy controls. RESULTS: A total of 52 cross-sectional studies included 1424 patients with a first psychotic episode; 16 longitudinal studies included 465 such patients. Meta-analysis suggests that whole brain and hippocampal volume are reduced (both P<0.0001) and that ventricular volume is increased (P<0.0001) in these patients relative to healthy controls. CONCLUSIONS: Average volumetric changes are close to the limit of detection by MRI methods. It remains to be determined whether schizophrenia is a neurodegenerative process that begins at about the time of symptom onset, or whether it is better characterised as a neurodevelopmental process that produces abnormal brain volumes at an early age.

Adolescent↗

PubMed2006

Comparison of quetiapine and risperidone in the treatment of schizophrenia: A randomized, double-blind, flexible-dose, 8-week study.

OBJECTIVE: To compare the efficacy and tolerability of quetiapine and risperidone in the treatment of schizophrenia. METHOD: In this 8-week, double-blind, multicenter, flexible-dose study, patients with schizophrenia (DSM-IV diagnosis) were randomly assigned to quetiapine (200-800 mg/day) or risperidone (2-8 mg/day). The primary hypothesis was that quetiapine was not inferior to risperidone. The primary efficacy measure was change from baseline in Positive and Negative Syndrome Scale (PANSS) total scores; secondary outcomes included response rate (> or = 40% reduction in PANSS scores), Clinical Global Impression-Change (CGI-C), and cognitive and social functioning. Tolerability assessments included treatment-emergent adverse events and changes in weight, glucose, and prolactin. Patients were recruited from June 2001 to September 2002. RESULTS: Patients (N = 673) were randomly assigned to quetiapine (N = 338, mean dose = 525 mg/day) or risperidone (N = 335, mean dose = 5.2 mg/day). The primary analysis demonstrated noninferiority between treatments (p < .05). Improvements with both treatments were comparable on PANSS total, negative, and general psychopathology subscales. Risperidone-treated patients had a significantly (p = .03) greater improvement in PANSS positive subscale score among all patients, but not among completers. Improvements in PANSS response rates, CGI-C, and cognitive function were similar between treatment groups. Changes in serum glucose and weight were minimal and comparable. The rate of extrapyramidal symptom (EPS)-related adverse events was significantly higher with risperidone (22%) than quetiapine (13%; p < .01). Somnolence was more common with quetiapine (26%) than risperidone (20%; p = .04). Prolactin levels increased with risperidone (+35.5 ng/mL), but decreased with quetiapine (-11.5 ng/mL; p < .001). CONCLUSIONS: Quetiapine and risperidone had broadly comparable clinical efficacy. Both agents improved cognitive and social functioning, and neither had a clinically significant effect on weight or glucose. Somnolence was more common with quetiapine; EPS and elevated prolactin rates were significantly higher with risperidone.

Adult↗

PubMed2005

Quality of life during treatment with haloperidol or olanzapine in the year following a first psychotic episode.

OBJECTIVES: Schizophrenia causes significant impairments of quality of life. As treatment approaches have advanced, more attention has been given to re-integrating patients into their psychosocial environments, rather than simply monitoring psychotic symptoms. The development of the second-generation antipsychotics raised hope that these medications would provide better quality of life improvement than conventional antipsychotics. This improvement is particularly relevant early in the course of schizophrenia. METHODS: To address these considerations, improvements in measures of general health and social function (determined using the SF-36) were assessed in 195 patients with first-episode schizophrenia for up to one year following randomization to either olanzapine or haloperidol in a double blind clinical trial. We hypothesized that olanzapine would demonstrate better improvement on these measures than haloperidol. In order to test this hypothesis, we used a repeated measure model with SF-36 scores as the outcome, and treatment group, time, time2, time-by-treatment group interaction, and time2-by-treatment group interaction as fixed effects. RESULTS: Both treatments demonstrated similar changes on the SF-36. Independent of treatment, patients demonstrated significant improvements in most of the SF-36 subscales, which approached normative scores by the end of one year of treatment. Forty-six of 100 olanzapine-treated patients and 37 of 95 haloperidol-treated patients completed the one year of this study (p<.4). CONCLUSIONS: These results suggest an important initial treatment goal for patients with new onset schizophrenic disorders, namely that they can expect to recover significant quality of life and social function at least initially in treatment.

Adult↗

PubMed2005

Long-term neurocognitive effects of olanzapine or low-dose haloperidol in first-episode psychosis.

BACKGROUND: Neurocognitive deficits are severe in first-episode psychosis. METHODS: Patients (N = 263) with first-episode psychosis (schizophrenia, schizoaffective, or schizophreniform disorders) were randomly assigned to double-blind treatment with olanzapine (mean 11.30 mg/day) or haloperidol (mean 4.87 mg/day) for 104 weeks. A neurocognitive battery was administered at baseline (n = 246) and 12 (n = 167), 24 (n = 126), 52 (n = 89), and 104 (n = 46) weeks during treatment. Weighted principal component and unweighted composite scores were derived from individual tests. RESULTS: Both treatment groups demonstrated significant improvement on both composite scores. On the basis of the weighted composite score, olanzapine had greater improvement than haloperidol only at 12 (p = .014) and 24 (p = .029) weeks. For the unweighted composite, olanzapine had significantly better improvement compared with haloperidol only at week 12 (p = .044). At week 12 only, olanzapine improved performance on the Digit Symbol and Continuous Performance Test significantly more than haloperidol. CONCLUSIONS: Both antipsychotic agents appeared to improve neurocognitive functioning among first-episode psychosis patients with schizophrenia. A significantly greater benefit in terms of neurocognitive improvement was found with olanzapine than with haloperidol at weeks 12 and 24.

Adult↗

PubMed2005

Antipsychotic drug effects on brain morphology in first-episode psychosis.

BACKGROUND: Pathomorphologic brain changes occurring as early as first-episode schizophrenia have been extensively described. Longitudinal studies have demonstrated that these changes may be progressive and associated with clinical outcome. This raises the possibility that antipsychotics might alter such pathomorphologic progression in early-stage schizophrenia. OBJECTIVE: To test a priori hypotheses that olanzapine-treated patients have less change over time in whole brain gray matter volumes and lateral ventricle volumes than haloperidol-treated patients and that gray matter and lateral ventricle volume changes are associated with changes in psychopathology and neurocognition. DESIGN: Longitudinal, randomized, controlled, multisite, double-blind study. Patients treated and followed up for up to 104 weeks. Neurocognitive and magnetic resonance imaging (MRI) assessments performed at weeks 0 (baseline), 12, 24, 52, and 104. Mixed-models analyses with time-dependent covariates evaluated treatment effects on MRI end points and explored relationships between MRI, psychopathologic, and neurocognitive outcomes. SETTING: Fourteen academic medical centers (United States, 11; Canada, 1; Netherlands, 1; England, 1). PARTICIPANTS: Patients with first-episode psychosis (DSM-IV) and healthy volunteers. INTERVENTIONS: Random allocation to a conventional antipsychotic, haloperidol (2-20 mg/d), or an atypical antipsychotic, olanzapine (5-20 mg/d). MAIN OUTCOME MEASURES: Brain volume changes assessed by MRI. RESULTS: Of 263 randomized patients, 161 had baseline and at least 1 postbaseline MRI evaluation. Haloperidol-treated patients exhibited significant decreases in gray matter volume, whereas olanzapine-treated patients did not. A matched sample of healthy volunteers (n = 58) examined contemporaneously showed no change in gray matter volume. CONCLUSIONS: Patients with first-episode psychosis exhibited a significant between-treatment difference in MRI volume changes. Haloperidol was associated with significant reductions in gray matter volume, whereas olanzapine was not. Post hoc analyses suggested that treatment effects on brain volume and psychopathology of schizophrenia may be associated. The differential treatment effects on brain morphology could be due to haloperidol-associated toxicity or greater therapeutic effects of olanzapine.

Adult↗

PubMed2005

Comparing the effects of antidepressants: consensus guidelines for evaluating quantitative reviews of antidepressant efficacy.

With increasing numbers of treatment options available for patients with major depression over the last decade and the growing body of evidence describing their efficacy and safety, clinicians often find it difficult to determine the best and most appropriate evidence-based treatment for each patient. Systematic reviews utilizing statistical methods that synthesize and evaluate data from a number of studies have become increasingly more available over the past decade. We review major findings and lessons learned from salient examples of quantitative analyses of antidepressant research and provide recommendations for meta-analysts, journal and grant reviewers, and research 'consumers' (ie, clinicians) for conducting, reporting, and evaluating such analyses.

Antidepressive Agents↗

PubMed2005

Measurement of brain metabolites by 1H magnetic resonance spectroscopy in patients with schizophrenia: a systematic review and meta-analysis.

A systematic review of the literature identified 64 published English-language papers that used proton (1H) magnetic resonance spectroscopy to measure N-acetylaspartate (NAA) concurrently in healthy controls and in patients with a diagnosis of schizophrenia (SZ). A total of 1209 controls and 1256 patients have been evaluated, with 88% of studies carried out at 1.5 T field strength, and 77% of studies focused on patients with chronic SZ. There is consistent evidence that NAA is reduced in a broad range of tissues in the SZ brain. Broad consensus (> or =10 studies) is emerging that NAA levels are reduced > or =5% in hippocampus and in both cortical gray matter (GM) and white matter (WM) of the frontal lobe. There is no evidence to support a hypothesis that relative NAA levels are reduced to a different degree in frontal lobe GM and WM, nor is there robust evidence of a difference in NAA levels between patients with first-episode and chronic SZ. Study reliability may be a problem, as most studies appear to be underpowered. With simple assumptions about the inherent difference in NAA levels between patients and controls, it can be calculated that a minimum sample size of approximately 39 patients and 39 controls is required for acceptable statistical power. Only three of 64 studies included enough subjects to have 80% power to detect a 10% NAA reduction in patients, and no studies were adequately powered to detect a 5% NAA reduction with 80% power.

Aspartic Acid↗

PubMed2005

The efficacy of light therapy in the treatment of mood disorders: a review and meta-analysis of the evidence.

OBJECTIVE: The purpose of this study was to assess the evidence base for the efficacy of light therapy in treating mood disorders. METHOD: The authors systematically searched PubMed (January 1975 to July 2003) to identify randomized, controlled trials of light therapy for mood disorders that fulfilled predefined criteria. These articles were abstracted, and data were synthesized by disease and intervention category. RESULTS: Only 13% of the studies met the inclusion criteria. Meta-analyses revealed that a significant reduction in depression symptom severity was associated with bright light treatment (eight studies, having an effect size of 0.84 and 95% confidence interval [CI] of 0.60 to 1.08) and dawn simulation in seasonal affective disorder (five studies; effect size=0.73, 95% CI=0.37 to 1.08) and with bright light treatment in nonseasonal depression (three studies; effect size=0.53, 95% CI=0.18 to 0.89). Bright light as an adjunct to antidepressant pharmacotherapy for nonseasonal depression was not effective (five studies; effect size=-0.01, 95% CI=-0.36 to 0.34). CONCLUSIONS: Many reports of the efficacy of light therapy are not based on rigorous study designs. This analysis of randomized, controlled trials suggests that bright light treatment and dawn simulation for seasonal affective disorder and bright light for nonseasonal depression are efficacious, with effect sizes equivalent to those in most antidepressant pharmacotherapy trials. Adopting standard approaches to light therapy's specific issues (e.g., defining parameters of active versus placebo conditions) and incorporating rigorous designs (e.g., adequate group sizes, randomized assignment) are necessary to evaluate light therapy for mood disorders.

Adult↗