Francine S P Mandel
Pfizer Inc, Worldwide Research and Development, Department Member
Objective. This study, like earlier studies that focused on younger abused children, ascertained whether physically abused adolescents exhibited increased internalizing and externalizing behaviors. Relevance to pediatric practice is... more
Objective. This study, like earlier studies that focused on younger abused children, ascertained whether physically abused adolescents exhibited increased internalizing and externalizing behaviors. Relevance to pediatric practice is discussed. Design. A cross-sectional design was used to compare the behavior of physically abused adolescents and comparison adolescents using self-reports, parent reports, and teacher reports. The level of agreement among raters was also examined. Participants. The subjects were 99 physically abused adolescents between the ages of 12 and 18 years, who were recruited from Child Protective Services. Comparison subjects were 99 community-recruited nonabused adolescents who were matched for age, gender, and income with the abused adolescents. Measures. The behavior of the adolescents was assessed using the Child Behavior Checklist, and the comparable Youth Self-Report and Teacher Report Form, which are widely used measures of behavioral and emotional proble...
Research Interests: Evaluation, Adolescent, Comparative Study, Fathers, Medicine, and 15 moreFaculty, Humans, Child Abuse, Female, Male, Acting Out, Functional impairment, Mothers, New York, Analysis of Variance, Behavior Problems, Adjustment Disorders, Cross Sectional Studies, Case Control Studies, and Medical and Health Sciences
A century of clinical research has noted a range of trauma-related psychological problems that are not captured in the DSM-IV framework of posttraumatic stress disorder (PTSD). This study investigated the relationships between exposure to... more
A century of clinical research has noted a range of trauma-related psychological problems that are not captured in the DSM-IV framework of posttraumatic stress disorder (PTSD). This study investigated the relationships between exposure to extreme stress, the emergence of PTSD, and symptoms traditionally associated with "hysteria," which can be understood as problems with stimulus discrimination, self-regulation, and cognitive integration of experience. The DSM-IV field trial for PTSD studied 395 traumatized treatment-seeking subjects and 125 non-treatment-seeking subjects who had also been exposed to traumatic experiences. Data on age at onset, the nature of the trauma, PTSD, dissociation, somatization, and affect dysregulation were collected. PTSD, dissociation, somatization, and affect dysregulation were highly interrelated. The subjects meeting the criteria for lifetime (but not current) PTSD scored significantly lower on these disorders than those with current PTSD, but significantly higher than those who never had PTSD. Subjects who developed PTSD after interpersonal trauma as adults had significantly fewer symptoms than those with childhood trauma, but significantly more than victims of disasters. PTSD, dissociation, somatization, and affect dysregulation represent a spectrum of adaptations to trauma. They often occur together, but traumatized individuals may suffer from various combinations of symptoms over time. In treating these patients, it is critical to attend to the relative contributions of loss of stimulus discrimination, self-regulation, and cognitive integration of experience to overall impairment and provide systematic treatment that addresses both unbidden intrusive recollections and these other symptoms associated with having been overwhelmed by exposure to traumatic experiences.
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Objective. This study, like earlier studies that focused on younger abused children, ascertained whether physically abused adolescents exhibited increased internalizing and externalizing behaviors. Relevance to pediatric practice is... more
Objective. This study, like earlier studies that focused on younger abused children, ascertained whether physically abused adolescents exhibited increased internalizing and externalizing behaviors. Relevance to pediatric practice is discussed. Design. A cross-sectional design was used to compare the behavior of physically abused adolescents and comparison adolescents using self-reports, parent reports, and teacher reports. The level of agreement among raters was also examined. Participants. The subjects were 99 physically abused adolescents between the ages of 12 and 18 years, who were recruited from Child Protective Services. Comparison subjects were 99 community-recruited nonabused adolescents who were matched for age, gender, and income with the abused adolescents. Measures. The behavior of the adolescents was assessed using the Child Behavior Checklist, and the comparable Youth Self-Report and Teacher Report Form, which are widely used measures of behavioral and emotional proble...
Research Interests: Evaluation, Adolescent, Comparative Study, Fathers, Medicine, and 15 moreFaculty, Humans, Child Abuse, Female, Male, Acting Out, Functional impairment, Mothers, New York, Analysis of Variance, Behavior Problems, Adjustment Disorders, Cross Sectional Studies, Case Control Studies, and Medical and Health Sciences
To evaluate the efficacy of pregabalin in facilitating taper off chronic benzodiazepines, outpatients ( N = 106) with a lifetime diagnosis of generalized anxiety disorder (current diagnosis could be subthreshold) who had been treated with... more
To evaluate the efficacy of pregabalin in facilitating taper off chronic benzodiazepines, outpatients ( N = 106) with a lifetime diagnosis of generalized anxiety disorder (current diagnosis could be subthreshold) who had been treated with a benzodiazepine for 8–52 weeks were stabilized for 2–4 weeks on alprazolam in the range of 1–4 mg/day. Patients were then randomized to 12 weeks of double-blind treatment with either pregabalin 300–600 mg/day or placebo while undergoing a gradual benzodiazepine taper at a rate of 25% per week, followed by a 6-week benzodiazepine-free phase during which they continued double-blind study treatment. Outcome measures included ability to remain benzodiazepine-free (primary) as well as changes in Hamilton Anxiety Rating Scale (HAM)-A and Physician Withdrawal Checklist (PWC). At endpoint, a non-significant higher proportion of patients remained benzodiazepine-free receiving pregabalin compared with placebo (51.4% vs 37.0%). Treatment with pregabalin was ...
Research Interests: Psychology, Anxiety Disorders, Psychopharmacology, Cognition, Treatment Outcome, and 14 moreMedicine, Humans, Generalized Anxiety Disorder, Female, Male, Middle Aged, Adult, Randomized Controlled Trial, Alprazolam, Gamma-Aminobutyric Acid, Psychomotor Performance, Psychiatric Status Rating Scales, Psychology and Cognitive Sciences, and Medical and Health Sciences
Research Interests: Psychology, Schizophrenia, Treatment Outcome, Medicine, Humans, and 15 moreHospitalization, Female, Male, Body Mass Index, Adult, Sex Factors, Clinical Psychiatry, Age Factors, Antipsychotic, Age of Onset, Psychiatric Status Rating Scales, Randomized Controlled Trials as Topic, Antipsychotic agents, Psychology and Cognitive Sciences, and Medical and Health Sciences
Research Interests: Psychology, Schizophrenia, Treatment Outcome, Medicine, Humans, and 15 moreHospitalization, Female, Male, Body Mass Index, Adult, Sex Factors, Clinical Psychiatry, Age Factors, Antipsychotic, Age of Onset, Psychiatric Status Rating Scales, Randomized Controlled Trials as Topic, Antipsychotic agents, Psychology and Cognitive Sciences, and Medical and Health Sciences
The relationship between physical abuse and family functioning was investigated in a comparative study of victims of adolescent physical abuse. The sample consisted of 99 physically abused adolescents and 99 nonabused adolescents who were... more
The relationship between physical abuse and family functioning was investigated in a comparative study of victims of adolescent physical abuse. The sample consisted of 99 physically abused adolescents and 99 nonabused adolescents who were administered the Parental Bonding Instrument (PBI) and Family Adaptability and Cohesion Evaluation Scale (FACES III). These measures assess family functioning in terms of adolescents' perception of
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To determine whether mannose ligand receptor and acrosome reaction deficits in sperm from men with varicocele are related to the transition metal content of their semen. Cadmium and zinc in semen and blood plasma were assayed for fertile... more
To determine whether mannose ligand receptor and acrosome reaction deficits in sperm from men with varicocele are related to the transition metal content of their semen. Cadmium and zinc in semen and blood plasma were assayed for fertile males, men without varicocele who required intracytoplasmic sperm injection to achieve fertilization, and men evaluated for potential varicocele-associated infertility. The relationship between actin cytoskeletal distributions and acrosome status was determined for fertile donor sperm in the presence and absence of exogenous cadmium. University hospital-based molecular biology research laboratory. Patients from two university hospital-based IVF-assisted reproductive technology programs and two male urology private practices. Fertile donor sperm were exposed to exogenous cadmium during capacitating incubations followed by culture at temperatures up to 41 degrees C. Metal ion levels in semen and blood plasma were determined by graphite furnace atomic absorption spectroscopy. Motile sperm were examined for mannose ligand binding and the ability to undergo spontaneous and induced acrosome reactions. Unfixed, Triton-permeabilized sperm were probed with antiactin and antimyosin antibodies. Cadmium was elevated and zinc was decreased in the seminal plasma of men with varicocele. The content of these metals in semen and blood was not correlated. Cadmium exposure in vitro reduced mannose receptor expression, acrosome exocytosis, and cytoskeletal formation by fertile donor sperm. Defects in transition metal regulation or excessive cadmium exposure are involved in varicocele-associated infertility.
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Negative symptoms are an important target for intervention in schizophrenia. There is lack of clarity in defining appropriate patients for negative symptom trials. While regulators, drug developers and academics have expressed positions... more
Negative symptoms are an important target for intervention in schizophrenia. There is lack of clarity in defining appropriate patients for negative symptom trials. While regulators, drug developers and academics have expressed positions in this regard, the implications of these definitions are not yet tested in large-scale trials and there is no consensus. We examined the extent to which various operational criteria for inclusion in negative symptoms in schizophrenia clinical trials can impact patient selection and examined the effectiveness of second generation antipsychotics (SGAs) in patients with various degrees of negative symptoms. Using anonymized patient data from AstraZeneca, Janssen Pharmaceuticals, Eli Lilly, Lundbeck, and Pfizer from 20 placebo-controlled trials of SGAs in schizophrenia from the NewMeds repository, we applied different criteria for negative symptoms: prominent, predominant, and EMA criteria, which require predominant and core negative symptoms to be present and examined the impact of these on inclusion and outcome. Operational criteria for negative symptoms in trials vary greatly in their inclusion of patients from "typical" trial samples. Of the patients in our studies, 8.1% and 62.3% met criteria for prominent negative symptoms, 10.2% to 50.2% met criteria for predominant negative symptoms and 7.6% to 40.0% met EMA criteria at baseline. After 6weeks of active treatment, 8% and 33.1% of patients met criteria for prominent residual negative symptoms and 14.9% to 65% met criteria for prominent and 12.2% to 45.5% met EMA criteria. Patients with predominant or prominent negative symptoms showed marked improvement on second generation antipsychotics. Applying various operational criteria for selecting patients for negative symptoms trials provides a great variability in percentage of suitable patients calling into question the extent to which some definitions may be overly narrow.
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The objective of the study was to evaluate the response of generalized anxiety disorder (GAD) patients with prominent gastrointestinal (GI) symptoms to pregabalin (PGB) treatment. Data were pooled from six double-blind, placebo... more
The objective of the study was to evaluate the response of generalized anxiety disorder (GAD) patients with prominent gastrointestinal (GI) symptoms to pregabalin (PGB) treatment. Data were pooled from six double-blind, placebo (PBO)-controlled, 4-6 week trials in outpatients who met Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria for GAD with a minimum Hamilton Anxiety Rating Scale (HAM-A) total score of 20. Treatment response was evaluated for three PGB fixed-dosage groups: 150, 300-450, and ...
Research Interests: Psychology, Agoraphobia, Humans, Generalized Anxiety Disorder, Female, and 10 moreMale, Middle Aged, Adult, Clinical Psychopharmacology, Analgesics, Gamma-Aminobutyric Acid, Gastrointestinal Diseases, Psychiatric Status Rating Scales, Randomized Controlled Trials as Topic, and Pharmacology and pharmaceutical sciences
Research Interests: Education, Eating Disorders, Adolescent Health, Adolescent, Bulimia Nervosa, and 15 moreHumans, Child, Female, Feeding Behavior, New York, Middle Aged, Adult, Age Factors, Body Weight, Eating Disorder, Binge eating, Clinical Presentation, Clinical Pediatrics, Eating Disorder Not Otherwise Specified, and Medical and Health Sciences
To determine the degree to which a proxy measure of remission in schizophrenia correlates with the criteria identified by the Remission in Schizophrenia Working Group, and how well early treatment response to ziprasidone predicts... more
To determine the degree to which a proxy measure of remission in schizophrenia correlates with the criteria identified by the Remission in Schizophrenia Working Group, and how well early treatment response to ziprasidone predicts remission. Data from 10 ziprasidone studies were analyzed to determine rates of remission achieved with ziprasidone using a remission definition of Clinical Global Impression of Improvement (CGI-I) of 1, and compared with rates of remission achieved using the remission working group criteria. Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) scores were then investigated as predictors of remission. A CGI-I score of 1 correlated with the remission criteria developed by the remission working group. In the combined ziprasidone arms, BPRS scores at Weeks 1, 3, and 4 successfully predicted PANSS remission (p<0.01) and BPRS remission (p<0.0001) at study endpoint (44-196weeks). PANSS scores (at Weeks 1, 3, and 4) successfully predicted PANSS remission (p<0.01) at study endpoint. PANSS scores at Week 3 successfully predicted BPRS remission (p=0.02) at study endpoint. A CGI-I score of 1 or 2 at Week 1 also successfully predicted remission in schizophrenia. The findings show a correlation between clinical and research scales (remission working group criteria) for the assessment of remission in schizophrenia. This proxy measure for the assessment of remission should be easy to apply in a clinical setting and facilitates the prediction of remission in schizophrenia.
Research Interests: Schizophrenia, Prediction, Humans, Follow-up studies, ROC Curve, and 11 moreProxy, Clinical Study, Thiazoles, Treatment Response, SECONDARY PREVENTION, Predictive value of tests, Psychiatric Status Rating Scales, Antipsychotic agents, Psychology and Cognitive Sciences, Outcome assessment (Health care), and Medical and Health Sciences
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Behavior problems and family functioning were investigated in a sample of 10 adolescent girls with chronic fatigue syndrome (CFS), 10 matched healthy adolescent girls, and 10 adolescents with childhood cancer in remission. Based on the... more
Behavior problems and family functioning were investigated in a sample of 10 adolescent girls with chronic fatigue syndrome (CFS), 10 matched healthy adolescent girls, and 10 adolescents with childhood cancer in remission. Based on the adolescent girls' reports, the CFS group had significantly higher scores than the cancer and healthy comparison adolescent girls on somatic complaints and also significantly higher scores than the cancer controls on internalizing symptoms and depression. Parent reports resulted in significantly higher scores in the CFS group than the adolescent girls from the healthy comparison groups on internalizing scores and somatic complaints. There were no significant differences on any family variables.
Research Interests: Psychometrics, Depression, Personality Assessment, Family, Chronic Fatigue Syndrome, and 12 moreAdolescent, Comparative Study, Humans, Female, Social Environment, Behavioral and Developmental Pediatrics, Somatoform disorders, Neoplasms, Sick Role, Reference Values, Psychology and Cognitive Sciences, and Medical and Health Sciences
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Clinical and laboratory observations of 133 children and adolescents with Crohn's disease were used to validate an index of severity of illness previously developed by a group of senior pediatric gastroenterologists at a research... more
Clinical and laboratory observations of 133 children and adolescents with Crohn's disease were used to validate an index of severity of illness previously developed by a group of senior pediatric gastroenterologists at a research forum in April 1990. This pediatric Crohn's disease activity index (PCDAI) included (a) subjective reporting of the degree of abdominal pain, stool pattern, and general well-being; (b) presence of extraintestinal manifestations, such as fever, arthritis, rash, and uveitis; (c) physical examination findings; (d) weight and height; and (e) hematocrit, erythrocyte sedimentation rate, and serum albumin. Independent evaluation of each patient by two physician-observers was performed at the time of a visit, and each physician completed a PCDAI index and a modified Harvey-Bradshaw index and made a "global assessment" of disease activity as none, mild, moderate, or severe. Excellent interobserver agreement was noted for the PCDAI, modified Harvey-Bradshaw index, and global assessment. There was a strong correlation between global assessment and both the PCDAI or modified Harvey-Bradshaw. Increasing PCDAI scores were noted with increasing disease severity, and significant differences in scores were noted between the severity groups. We propose that the PCDAI could be used in multicenter projects to facilitate patient stratification by disease severity and that longitudinal PCDAI scores might provide a numerical measure of response to therapeutic regimens.
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To evaluate the efficacy and safety of high-dose sertraline for patients with obsessive-compulsive disorder (OCD) who failed to respond to standard sertraline acute treatment. Sixty-six nonresponders to 16 weeks of sertraline treatment... more
To evaluate the efficacy and safety of high-dose sertraline for patients with obsessive-compulsive disorder (OCD) who failed to respond to standard sertraline acute treatment. Sixty-six nonresponders to 16 weeks of sertraline treatment who met DSM-III-R criteria for current OCD were randomly assigned, in a double-blind continuation phase of a multicenter trial, either to continue on 200 mg/day of sertraline or to increase their dose to between 250 and 400 mg/day for 12 additional weeks. Efficacy measures included the Yale-Brown Obsessive Compulsive Scale (YBOCS), the National Institute of Mental Health Global Obsessive Compulsive Scale (NIMH Global OC Scale), and the Clinical Global Impressions-Severity of Illness and -Improvement (CGI-I) scales. Data were collected from July 26, 1994, to October 26, 1995. The high-dose (250-400 mg/day, mean final dose = 357, SD = 60, N = 30) group showed significantly greater symptom improvement than the 200-mg/day group (N = 36) as measured by the YBOCS (p = .033), NIMH Global OC Scale (p = .003), and CGI-I (p = .011). Responder rates (decrease in YBOCS score of > or = 25% and a CGI-I rating < or = 3) were not significantly different for the 200-mg/day versus the high-dose sertraline group, either on completer analysis, 34% versus 52%, or on endpoint analysis, 33% versus 40%. Both treatments showed similar adverse event rates. Greater symptom improvement was seen in the high-dose sertraline group compared to the 200-mg/day dose group during continuation treatment. Both dosages yielded similar safety profiles. Administration of higher than labeled doses of selective serotonin reuptake inhibitors may be a treatment option for certain OCD patients who fail to respond to standard acute treatment.
Research Interests: Treatment, Treatment Outcome, Strategy, Humans, Female, and 13 moreClinical, Drug Resistance, Male, Obsessive Compulsive Disorder, Placebos, Adult, SERTRALINE, Clinical Psychiatry, Serotonin Uptake Inhibitors, Severity of Illness Index, Psychiatric Status Rating Scales, Psychology and Cognitive Sciences, and Medical and Health Sciences
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This randomized, double-blind, multicentre extension study compared the efficacy, tolerability, and safety of ziprasidone and risperidone for schizophrenia or schizoaffective disorder. Patients who had responded to treatment for an acute... more
This randomized, double-blind, multicentre extension study compared the efficacy, tolerability, and safety of ziprasidone and risperidone for schizophrenia or schizoaffective disorder. Patients who had responded to treatment for an acute exacerbation of illness in an 8-week study received ziprasidone, 80 to 160 mg/day (n = 62), or risperidone, 6 to 10 mg/day (n = 77), for up to 44 additional weeks. Primary efficacy variables included changes in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impression Severity (CGI-S) score. Tolerability and safety assessments included movement disorders, adverse events, study discontinuation rates, and weight and metabolic parameters. Both the ziprasidone and risperidone groups showed statistical improvement from baseline in PANSS and CGI-S scores at study end point with no significant differences between treatment groups. More risperidone-treated patients completed the study (41.6%) than ziprasidone-treated patients (...
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PET has been used to quantify striatal 6-[18F]fluoro-L-dopa (FDOPA) uptake as a measure of presynaptic dopaminergic function. Striatal FDOPA uptake rate constants (Ki) can be calculated using dynamic PET imaging with measurements of the... more
PET has been used to quantify striatal 6-[18F]fluoro-L-dopa (FDOPA) uptake as a measure of presynaptic dopaminergic function. Striatal FDOPA uptake rate constants (Ki) can be calculated using dynamic PET imaging with measurements of the plasma FDOPA input function determined either directly or by several estimation procedures. We assessed the comparative clinical utility of these methods by calculating the striato-occipital ratio (SOR) and striatal Ki values in 12 patients with mild to moderate PD and 12 age-matched normal volunteers. The plasma FDOPA time-activity curve (KiFD); the plasma 18F time-activity curve (KiP); the occipital time-activity curve (KiOCC); and a simplified population-derived FDOPA input function (KiEFD) were used to calculate striatal Ki. Mean values for all striatal Ki estimates and SOR were significantly lower in the PD group. Although all measured parameters discriminated PD patients from normals, KiFD and KiEFD provided the best between-group separation. K...
Research Interests: Nuclear medicine, Comparative Study, Nuclear, Brain, Discriminant Analysis, and 15 moreHumans, Clinical research, PET imaging, Female, Male, Disease Severity, Central Nervous System, Clinical Sciences, Aged, Middle Aged, Adult, Positron, Quantitative Analysis, Nervous System Diseases, and Parkinson Disease
The attention deficit hyperactive disorder (ADHD) is a neurophysiologic problem that is detrimental to children and their parents. Despite previous studies on the role of foods, preservatives and artificial colorings in ADHD this issue... more
The attention deficit hyperactive disorder (ADHD) is a neurophysiologic problem that is detrimental to children and their parents. Despite previous studies on the role of foods, preservatives and artificial colorings in ADHD this issue remains controversial. This investigation evaluated 26 children who meet the criteria for ADHD. Treatment with a multiple item elimination diet showed 19 children (73%) responded favorably, P < .001. On open challenge, all 19 children reacted to many foods, dyes, and/or preservatives. A double-blind placebo controlled food challenge (DBPCFC) was completed in 16 children. There was a significant improvement on placebo days compared with challenge days (P = .003). Atopic children with ADHD had a significantly higher response rate than the nonatopic group. This study demonstrates a beneficial effect of eliminating reactive foods and artificial colors in children with ADHD. Dietary factors may play a significant role in the etiology of the majority of ...
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Research Interests: Geography, Bipolar Disorder, Neuropsychopharmacology, Adolescent, India, and 15 moreHumans, Female, Male, Placebos, Haloperidol, Adult, Internationality, Disease Progression, Psychiatric Status Rating Scales, Randomized Controlled Trials as Topic, cultural characteristics, Antipsychotic agents, Psychology and Cognitive Sciences, healthcare disparities, and Medical and Health Sciences
To determine the degree to which a proxy measure of remission in schizophrenia correlates with the criteria identified by the Remission in Schizophrenia Working Group, and how well early treatment response to ziprasidone predicts... more
To determine the degree to which a proxy measure of remission in schizophrenia correlates with the criteria identified by the Remission in Schizophrenia Working Group, and how well early treatment response to ziprasidone predicts remission. Data from 10 ziprasidone studies were analyzed to determine rates of remission achieved with ziprasidone using a remission definition of Clinical Global Impression of Improvement (CGI-I) of 1, and compared with rates of remission achieved using the remission working group criteria. Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) scores were then investigated as predictors of remission. A CGI-I score of 1 correlated with the remission criteria developed by the remission working group. In the combined ziprasidone arms, BPRS scores at Weeks 1, 3, and 4 successfully predicted PANSS remission (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01) and BPRS remission (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001) at study endpoint (44-196weeks). PANSS scores (at Weeks 1, 3, and 4) successfully predicted PANSS remission (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01) at study endpoint. PANSS scores at Week 3 successfully predicted BPRS remission (p=0.02) at study endpoint. A CGI-I score of 1 or 2 at Week 1 also successfully predicted remission in schizophrenia. The findings show a correlation between clinical and research scales (remission working group criteria) for the assessment of remission in schizophrenia. This proxy measure for the assessment of remission should be easy to apply in a clinical setting and facilitates the prediction of remission in schizophrenia.
Research Interests: Schizophrenia, Prediction, Humans, Follow-up studies, ROC Curve, and 11 moreProxy, Clinical Study, Thiazoles, Treatment Response, SECONDARY PREVENTION, Predictive value of tests, Psychiatric Status Rating Scales, Antipsychotic agents, Psychology and Cognitive Sciences, Outcome assessment (Health care), and Medical and Health Sciences
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Early-stage Parkinson&#39;s disease (EPD) is often clinically asymmetric. We used 18F-fluorodeoxyglucose (FDG) and PET to assess whether EPD can be detected by a characteristic pattern of regional metabolic asymmetry. To identify this... more
Early-stage Parkinson&#39;s disease (EPD) is often clinically asymmetric. We used 18F-fluorodeoxyglucose (FDG) and PET to assess whether EPD can be detected by a characteristic pattern of regional metabolic asymmetry. To identify this pattern, we studied 10 EPD (Hoehn and Yahr stage I) patients (mean age 61.1 +/- 11.1 years) using 18F-FDG and PET to calculate regional metabolic rates for glucose. The scaled subprofile model (SSM) was applied to metabolic asymmetry measurements for the combined group of EPD patients and normal subjects to identify a specific covariation pattern that discriminated EPD patients from normal subjects. To determine whether this pattern could be used diagnostically, we studied a subsequent group of five presumptive EPD patients (mean age 50.9 +/- 18.3), five normal subjects (mean age 44.6 +/- 15.3), and nine patients with atypical drug-resistant early-stage parkinsonism (APD) (mean age 44.6 +/- 14.0). In each member of this prospective cohort, we calculated the expression of the EPD-related covariation pattern (subject scores) on a case-by-case basis. We also studied 11 of the EPD patients, five patients with APD, and 10 normal subjects with 18F-fluorodopa (FDOPA) and PET to measure presynaptic nigrostriatal dopaminergic function, and we assessed the accuracy of differential diagnosis with both PET methods using discrimination analysis. SSM analysis disclosed a significant topographic contrast profile characterized by covariate basal ganglia and thalamic asymmetries. Subject scores for this profile accurately discriminated EPD patients from normal subjects and APD patients (p &lt; 0.0001). Group assignments into the normal or parkinsonian categories with FDG/PET were comparable to those achieved with FDOPA/PET, although APD and EPD patients were not differentiable by the latter method. Metabolic brain imaging with FDG/PET may be useful in the differential diagnosis of EPD.
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In an investigation of the prevalence of post-traumatic stress disorder (PTSD), other Axis I psychiatric disorders, and social and behavioral difficulties, 27 physically abused adolescents were compared with 27 nonabused controls who were... more
In an investigation of the prevalence of post-traumatic stress disorder (PTSD), other Axis I psychiatric disorders, and social and behavioral difficulties, 27 physically abused adolescents were compared with 27 nonabused controls who were recruited through random-digit dialing procedures. The Structured Clinical Interview for Diagnosis (PTSD module), Kiddie-Schedule for Affective Disorders and Schizophrenia, and Youth Self-Report were administered to all subjects; mothers were interviewed regarding their adolescent&#39;s behavior using the Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Age Children and Child Behavior Checklist. The three physically abused adolescents who received a diagnosis of PTSD on the PTSD module of the Structured Clinical Interview for Diagnosis reported their PTSD symptoms were in reaction to extrafamilial sexual assaults and not to physical abuse. In contrast, the abused adolescents showed significantly higher prevalence rates of depression, conduct disorder, internalizing and externalizing behavior problems, and social deficits. Findings suggest that physically abused adolescents may be more at risk for behavioral and social difficulties than for PTSD.
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To evaluate acute onset of anxiolytic activity using a dental anxiety model, 89 patients were randomised to double-blind single dose pregabalin 150 mg, alprazolam 0.5 mg or placebo 4 h before a scheduled dental procedure. A Dental Anxiety... more
To evaluate acute onset of anxiolytic activity using a dental anxiety model, 89 patients were randomised to double-blind single dose pregabalin 150 mg, alprazolam 0.5 mg or placebo 4 h before a scheduled dental procedure. A Dental Anxiety Total score &gt;12 (moderate-to-severe) without meeting Diagnostic and Statistical Manual of Mental Disorders (Fourth edition) (DSM-IV) anxiety disorder criteria was required. Efficacy and safety, assessed 2, 2.5, 3, 3.5 and 4 h postdose, included 100 mm Visual Analogue Scale for Anxiety (VAS-Anxiety; primary outcome), 100 mm VAS-Sedation and Time-to-Onset of Action Scale (TOAS), a patient-rated anti-anxiety drug-benefit scale (no [0] to full benefit [10]). Mixed model analysis found significantly greater VAS-A improvement slopes for pregabalin (t = -2.47; P = 0.014) and alprazolam (t = -2.39; P = 0.018). There was a significant improvement versus placebo in the TOAS from 2 h through endpoint in alprazolam patients and from 3 h onward in pregabalin patients. Pregabalin produced significantly greater increases in VAS-Sedation versus placebo from 2.5 h through 4 h (2 h onward for alprazolam). Notably, there was a higher correlation between TOAS and VAS-Sedation (r = +0.58) than VAS-Anxiety (r = -0.50) on Spearman&#39;s analysis. The majority of Adverse Effects (AEs) were mild, and the most frequent for pregabalin, alprazolam, and placebo, respectively, were fatigue (N = 7, 7, 3), dizziness (N = 6, 3, 3), attention disturbance (N = 3, 1, 0), somnolence (N = 3, 0, 0), feeling abnormal (N = 0, 2, 0) and balance disorder (N = 0, 2, 0). These results suggest that onset of clinically meaningful anxiolytic effect after single-dose pregabalin occurs within the first 3-4 h. Additional research is needed to determine whether anxiolytic effect occurs in generalized anxiety disorder populations by day 1 or within 3-4 h post-first dose.
Research Interests: Evaluation, Anxiety, Humans, Models, Placebo, and 15 moreGeneralized Anxiety Disorder, Female, Male, Mental Disorder, Efficiency, Middle Aged, Dental Anxiety, Adult, ANXIETY, Anxiety Disorder, Pain Measurement, Alprazolam, Adverse effect, Diagnostic and Statistical Manual, and Medical and Health Sciences
The objective of this study was to assess the impact of high levels of insomnia on response to pregabalin (PGB) in patients with generalized anxiety disorder (GAD). Pooled data were analyzed from six double-blind, placebo-controlled, 4-... more
The objective of this study was to assess the impact of high levels of insomnia on response to pregabalin (PGB) in patients with generalized anxiety disorder (GAD). Pooled data were analyzed from six double-blind, placebo-controlled, 4- to 6-week trials of outpatients who met the Diagnostic and Statistical Manual of Mental Disorders (fourth edition) criteria for GAD with a minimum Hamilton Rating Scale for Anxiety (HAM-A) score = 18. Response was evaluated for three fixed-dose PGB groups (150, 300-450, 600 mg/day), and for a benzodiazepine group (alprazolam or lorazepam). A &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;high-insomnia&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; subgroup was defined by a baseline HAM for Depression (HAM-D) insomnia factor score greater than 3 (maximum = 6). At baseline, 1002 (54%) patients met the criteria for the high-insomnia subgroup, and 852 (46%) for the low-insomnia subgroup. Mean baseline HAM-A scores were 1-2 points higher in high-insomnia versus low-insomnia patients. In high-insomnia patients, PGB produced significantly greater improvement in HAM-A total scores at last observation carried forward endpoint on 300-450 mg (-13.1+/-0.6) and 600 mg (-11.2+/-0.5) dose groups compared with placebo (-8.3+/-0.5; P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001 for both comparisons); the improvement on PGB 150 mg was not significant (-9.9+/-0.7; P = 0.051). Improvement was significant in the benzodiazepine group (-11.0+/-0.6; P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001). In the high-insomnia subgroup, treatment with PGB significantly (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) improved the HAM-D insomnia factor scores on both the 300-450 mg (-2.73) and 600 mg (-2.35) doses, and on benzodiazepines (-2.52) compared with placebo (-1.51); improvement on PGB 150 mg (-1.69) was not significant. Rates of treatment-emergent insomnia were lower on PGB compared with placebo in both the high- and low-insomnia subgroups. In conclusion, PGB was well tolerated, and improved overall anxiety symptoms, while specifically improving insomnia in patients with GAD presenting with high levels of concurrent insomnia.