Group dialectical behavior therapy adapted for obese emotional eaters; a pilot study.

Dialectical Behavior Therapy (DBT) has been shown to effectively target binge eating disorder (BED). This study pilots the effectiveness of group DBT for obese "emotional eaters" to reduce eating psychopathology and achieve weight maintenance. Thirty-five obese male and female emotional eaters receiving 20 group psychotherapy sessions of DBT adapted for emotional eating were assessed at end-of-treatment and 6 month follow-up for reductions in eating psychopathology and weight maintenance. DBT resulted in significant reductions in emotional eating and other markers of eating psychopathology at the end-of-treatment that were maintained at follow-up. The drop-out rate was very low, with only 1 participant dropping from treatment. Thirty-three (94%) of the sample provided data at every assessment point. Of these, 80% achieved either weight reduction or weight maintenance after treatment and throughout the follow-up period. The effect size for weight reduction was small. This pilot study demonstrates group DBT targeting emotional eating in the obese to be a highly acceptable and effective intervention for reducing eating related psychopathology at both at end-of-treatment and during follow-up. The ability of DBT to limit the upward trajectory of weight gain in obese patients with high degrees of emotional eating suggests that DBT may also help limit the increase or even prevent onset of obesity related morbidity in these patients.

Do antidepressants reduce suicide rates?

Investigators from a number of countries have linked temporal declines in the rate of completed suicide in children and adults to the increasing utilization of selective serotonin reuptake inhibitor (SSRI) antidepressants. They suggest that the relationship is causal. We undertook a thorough literature search of the rates of completed suicide using data from 1980 onwards, from the World Health Organization, the US National Center for Health Statistics, and related studies, in order to ascertain if a broad array of epidemiological evidence would or would not support a consistent association between suicide completion and SSRI utilization. The major findings were: (1) within and between countries, suicide rates vary prominently by age group; (2) national differences are marked with respect to a temporal association between rates of completed suicide and SSRI utilization; (3) in nearly half of the countries of the world, the decline in the suicide rate preceded the onset of the use of SSRIs; (4) suicide rates have fluctuated dramatically over the last century; and (5) the association between declining rates of completed suicides and increased SSRI use in the USA between 1990 and 1999 was no longer present between 2000 and 2004. We conclude that available ecological evidence does not support an inverse temporal relationship between rates of completed suicide and SSRI utilization.

Early body mass index and other anthropometric relationships between parents and children.

OBJECTIVE: To assess longitudinally the relationship between measures of adiposity in children over the first 8 y of life with that of their parents and to explore the role of parental adiposity in the development of childhood adiposity. DESIGN: Longitudinal study of measures of adiposity in children. SUBJECTS: A community sample from three health service systems including 114 children followed annually from infancy to age 8 and their 228 biological parents. METHODS: Measurements were assessed at baseline for parents (6 months post-partum for mothers) and at regular intervals for children beginning at age 2 months. Measurements included weight, height, triceps skinfold, subscapular skinfold, midarm circumference, waist and hip. RESULTS: The major findings were: (1) significant correlations between parental body mass index (BMI), both maternal and paternal, and their biological offspring first emerged at age 7; (2) children with two overweight parents had consistently elevated BMI compared to children with either no overweight parents or one overweight parent. These differences became significant beginning at age 7. CONCLUSIONS: This study supports the hypothesis that familial factors (biological and/or environmental) affecting the development of adiposity emerge at specific ages and are related to the adiposity of both parents.

Prolonged bottle feeding in a cohort of children: does it affect caloric intake and dietary composition?

Little is known about the consequences to children of bottle feeding prolonged beyond age 1 year on caloric intake and overall dietary composition. To obtain these data, 165 children, followed up from infancy, were assessed in these respects for a 24-hour period at age 3 1/2 years. Bottle-fed children (n = 14) consumed more milk than their weaned counterparts (p < 0.001), had a higher mean daily calcium intake (p < 0.05), received fewer calories from carbohydrates (p = 0.034), and received a greater percentage of calories from protein (p = 0.033). There were no significant differences between the groups in total caloric intake, total iron intake, total volume ofjuice, or calories from fat. Pediatricians questioned about the effects of continuing to offer children nutritive liquids from bottles as well as cups (versus offering cups alone) may inform parents that this feeding practice is associated with significantly greater milk consumption and daily calcium intake. However, this study could not find evidence that prolonged bottle feeding at age 3 1/2 years is associated with a significantly decreased total daily iron intake or an increased risk for factors associated with adiposity such as a greater daily calorie intake, a higher body mass index, or greater percentage of total calories derived from fat.

Mental health services for youths in foster care and disabled youths.

OBJECTIVES: This study assessed whether mental health services for youths differ with respect to medical assistance aid category. METHODS: Computerized claims for 15,507 youths with Medicaid insurance in a populous county of a mid-Atlantic state were used to establish population-based prevalence estimates of mental disorders and psychotherapeutic treatments during 1996. RESULTS: An analysis of service claims revealed that the prevalence of mental disorders among youths enrolled in foster care (57%) was twice that of youths receiving Supplemental Security Income (SSI; 26%) and nearly 15 times that of other youths receiving other types of aid (4%). Rates of mental health service use were pronounced among foster care youths aged 6 to 14 years. Attention deficit/hyperactivity disorder, depression, and developmental disorders were the most prevalent disorders. Stimulants, antidepressants, and anticonvulsants were the most prevalent medications. CONCLUSIONS: Youths enrolled in foster care and youths receiving SSI use far more mental health services than do youths in other aid categories. Additional research should evaluate the complexity and outcomes of mental health services for youths in foster care.

Dialectical behavior therapy adapted for bulimia: a case report.

OBJECTIVE: This case report describes the application of dialectical behavior therapy (DBT) to the treatment of bulimia nervosa in a 20-session manualized therapy. METHOD: The treatment, based on an affect regulation model of eating disorders, was developed to teach emotion regulation skills to replace eating-disordered behaviors. The patient, a 36-year-old woman, had a long history of binge eating and purging that had not responded to 2 years of counseling. In the 4 weeks before treatment began, she reported 13 objective binges and 21 purging episodes. RESULTS AND DISCUSSION: Upon initiating DBT, her binge eating and purging rapidly declined. She achieved abstinence by the fifth week of treatment and maintained it through treatment. In the 6 months following treatment, she reported a total of two objective binge episodes and two purge episodes.

Pemoline hepatotoxicity and postmarketing surveillance.

OBJECTIVE: To review the numerous reports of hepatotoxic adverse drug reactions (ADRs) ascribed to pemoline that were sent to the U.S. Food and Drug Administration (FDA) between 1975 and 1996 and to describe the medical community's lack of awareness of these reports. METHOD: All ADR reports from 1975 through 1996 wherein pemoline was the suspect agent were obtained from the FDA MedWatch Internet site, and some details of nine pemoline-related deaths in youths were obtained directly from the FDA. The published literature on this subject was fully reviewed. RESULTS: (1) In premarketing clinical trials with pemoline in the early 1970s, hepatic abnormalities were noted in enzyme levels (1%-3% of youths receiving maintenance treatment), during rechallenges (6 of 6), and in biopsies (2 of 2). (2) Between 1975 and 1989, 12 cases of jaundice and 6 deaths in youths ascribed to pemoline hepatotoxicity were reported to the FDA. (3) The first medical literature report of a serious ADR ascribed to pemoline was in a 1989 letter to the editor. (4) Physicians generally only became aware of serious pemoline hepatotoxicity in December 1996. (5) Pemoline use increased until 1997. CONCLUSION: Limitations in postmarketing surveillance and public reporting in the United States, particularly in the 1980s, largely accounted for delays in an appropriate response to pemoline hepatotoxicity.

Services and prevention: pharmacoepidemiology of antidepressant use.

Between 1988 and 1994, data from 3 large sites revealed a 3-5 fold increase in the prevalence of antidepressant (ATD) treatment for U.S. youths aged 2-19 years. In 1994, the ATD prevalence for youths of this age ranged from 13 per 1000 (in the HMO) to 18 per 1000 (in 2 state Medicaid systems). Males predominated in the 10-14-year-olds treated with ATDs, whereas females predominated among 15-19-year-olds. Caucasians were more than twice as likely to receive ATD therapy than their African-American counterparts. Primary care providers were the major source of ATD prescriptions for youths. The leading diagnoses in primary care were ADHD followed by depression, whereas the diagnostic order was reversed for youths who received psychiatric services. This review provides details concerning these patterns and trends in ATD treatment of youths from community-based clinical data sources. In addition, the role of these data in an expanded, comprehensive psychotropic knowledge base is discussed. Finally, the implications of an expanded knowledge base for ATD treatments are discussed in regard to generating research questions on effectiveness and safety and to improve treatment consensus within a public-health perspective.

Dialectical behavior therapy for bulimia nervosa.

OBJECTIVE: The effects of dialectical behavior therapy adapted for the treatment of binge/purge behaviors were examined. METHOD: Thirty-one women (averaging at least one binge/purge episode per week) were randomly assigned to 20 weeks of dialectical behavior therapy or 20 weeks of a waiting-list comparison condition. The manual-based dialectical behavior therapy focused on training in emotion regulation skills. RESULTS: An intent-to-treat analysis showed highly significant decreases in binge/purge behavior with dialectical behavior therapy compared to the waiting-list condition. No significant group differences were found on any of the secondary measures. CONCLUSIONS: The use of dialectical behavior therapy adapted for treatment of bulimia nervosa was associated with a promising decrease in binge/purge behaviors.

Antidepressant treatment in children and adolescents: bridging the gap between efficacy and effectiveness.

This review of antidepressant treatments in children and adolescents emphasizes the gap between efficacy data derived from randomized clinical trials (RCTs) and the limited effectiveness data from community-based practices. Part one is a brief review of data from randomized, double-blind clinical trials to assess the evidence base for the major approved indications for antidepressants in youths. Part two reviews information gaps in the evidence from RCTs. Part three discusses nonexperimental evidence of the use of antidepressants, including surveys of prescription sales, physician surveys, and population-based data. Part four presents a comprehensive model for assessing the use of antidepressants in youths in the community. The model aims to answer a range of public health-oriented questions and is intended to improve treating physicians' and clinical care providers' ability to manage medications for optimal patient benefit. Suggestions are made for engaging health service providers, health insurers, academicians, advocates, and the government in building the necessary infrastructure to make effectiveness as vital as efficacy to the model of drug therapy evaluation.

Stimulant treatment in Maryland public schools.

OBJECTIVE: A statewide school survey was performed to provide naturalistic data on the prevalence of medication administered to Maryland public school students for the treatment of attention deficit hyperactivity disorder (ADHD) to clarify the concern of some state legislators about stimulant treatment for youths. METHODS: In April 1998, school nurses supervised a survey of all Maryland public school students medicated during school hours for ADHD. The data collected on these students included: type of medication administered, gender, school level, race/ethnicity, special education and Section 504 status, and the specialist of the prescriber. RESULTS: Of the 816 465 students surveyed, 20 050 (2. 46%) received methylphenidate and 3721 (0.46%) received other medications for ADHD. Other major findings were: 1) methylphenidate constituted 84% of all the medication administered for ADHD; 2) the male:female ratio of the medication's recipients was 3.5:1 and 4.3:1 in elementary and secondary school, respectively; 3) black and Hispanic students received methylphenidate at approximately half the rate of their white counterparts; 4) 45% of all students receiving methylphenidate had special education status and an additional 8% had Section 504 status; and 5) nurse practitioners were the prescribers of 3% of the methylphenidate prescribed to Maryland students. CONCLUSIONS: This large, population-based, point prevalence study of medication administered to students for ADHD adds new and updated findings on prevalence variations, rates for minority and special education/Section 504 students, and specialty prescriber rates.

Sequestered actin in chick embryo fibroblasts.

Chick embryo fibroblasts contain about 75-100 microM unpolymerized actin and at least four proteins which can bind actin monomers, actin depolymerizing factor (ADF), gelsolin, profilin, and thymosin beta4 (Tbeta4). Fibroblast extracts are analyzed by non-denaturing polyacrylamide gel electrophoresis and immunoblotting where most of the G-actin is detected as a complex with Tbeta4. When fibroblast extracts are fractionated by gel filtration and the fractions are analyzed by PAGE and HPLC, most of the G-actin elutes in a peak that also contains Tbeta4 at an overall molar ratio of 1.9:1 relative to actin. Gelsolin, profilin, and ADF are also detectable in the gel filtration eluate and at least partly coelute with actin, and account for only a minor fraction of the soluble actin pool. These observations indicate that under the growth conditions studied, Tbeta4 is the major actin-sequestering protein in fibroblasts.

Are stimulants overprescribed for youths with ADHD?

Critics of stimulant treatment for youths with attention deficit hyperactivity disorder (ADHD) have increased their rhetoric of late, contending that the leading medication for it, Ritalin, is vastly overprescribed. Additionally, they claim that Ritalin (methylphenidate) is inherently dangerous and that the entire system of the diagnosis and treatment of ADHD is seriously flawed. The critics view the underlying reason for the "epidemic" as societal, due to our modern pace of living, our competitive society, and our consumer emphasis. Rejoinders to and clarifications of the more tangible points of the critics are presented, followed by a discussion of some more practical and legitimate concerns for researchers in this area. These concerns include changes within the ADHD category, the clinical need for multiple sources of diagnostic data, infrequent teacher-physician communication, problematic ADHD/conduct disorder comorbidity in adolescence, and the limited amount of community-based research.

Thymosin-beta(4) changes the conformation and dynamics of actin monomers.

Thymosin-beta(4) (Tbeta(4)) binds actin monomers stoichiometrically and maintains the bulk of the actin monomer pool in metazoan cells. Tbeta(4) binding quenches the fluorescence of N-iodoacetyl-N'-(5-sulfo-1-naphthyl)ethylenediamine (AEDANS) conjugated to Cys(374) of actin monomers. The K(d) of the actin-Tbeta(4) complex depends on the cation and nucleotide bound to actin but is not affected by the AEDANS probe. The different stabilities are determined primarily by the rates of dissociation. At 25 degrees C, the free energy of Tbeta(4) binding MgATP-actin is primarily enthalpic in origin but entropic for CaATP-actin. Binding is coupled to the dissociation of bound water molecules, which is greater for CaATP-actin than MgATP-actin monomers. Proteolysis of MgATP-actin, but not CaATP-actin, at Gly(46) on subdomain 2 is >12 times faster when Tbeta(4) is bound. The C terminus of Tbeta(4) contacts actin near this cleavage site, at His(40). By tritium exchange, Tbeta(4) slows the exchange rate of approximately eight rapidly exchanging amide protons on actin. We conclude that Tbeta(4) changes the conformation and structural dynamics ("breathing") of actin monomers. The conformational change may reflect the unique ability of Tbeta(4) to sequester actin monomers and inhibit nucleotide exchange.

Trends in the prescribing of psychotropic medications to preschoolers.

CONTEXT: Recent reports on the use of psychotropic medications for preschool-aged children with behavioral and emotional disorders warrant further examination of trends in the type and extent of drug therapy and sociodemographic correlates. OBJECTIVES: To determine the prevalence of psychotropic medication use in preschool-aged youths and to show utilization trends across a 5-year span. DESIGN: Ambulatory care prescription records from 2 state Medicaid programs and a salaried group-model health maintenance organization (HMO) were used to perform a population-based analysis of three 1-year cross-sectional data sets (for the years 1991, 1993, and 1995). SETTING AND PARTICIPANTS: From 1991 to 1995, the number of enrollees aged 2 through 4 years in a Midwestern state Medicaid (MWM) program ranged from 146,369 to 158,060; in a mid-Atlantic state Medicaid (MAM) program, from 34,842 to 54,237; and in an HMO setting in the Northwest, from 19,107 to 19,322. MAIN OUTCOME MEASURES: Total, age-specific, and gender-specific utilization prevalences per 1000 enrollees for 3 major psychotropic drug classes (stimulants, antidepressants, and neuroleptics) and 2 leading psychotherapeutic medications (methylphenidate and clonidine); rates of increased use of these drugs from 1991 to 1995, compared across the 3 sites. RESULTS: The 1995 rank order of total prevalence in preschoolers (per 1000) in the MWM program was: stimulants (12.3), 90% of which represents methylphenidate (11.1); antidepressants (3.2); clonidine (2.3); and neuroleptics (0.9). A similar rank order was observed for the MAM program, while the HMO had nearly 3 times more clonidine than antidepressant use (1.9 vs 0.7). Sizable increases in prevalence were noted between 1991 and 1995 across the 3 sites for clonidine, stimulants, and antidepressants, while neuroleptic use increased only slightly. Methylphenidate prevalence in 2- through 4-year-olds increased at each site: MWM, 3-fold; MAM, 1.7-fold; and HMO, 3.1-fold. Decreases occurred in the relative proportions of previously dominant psychotherapeutic agents in the stimulant and antidepressant classes, while increases occurred for newer, less established agents. CONCLUSIONS: In all 3 data sources, psychotropic medications prescribed for preschoolers increased dramatically between 1991 and 1995. The predominance of medications with off-label (unlabeled) indications calls for prospective community-based, multidimensional outcome studies.

Psychotherapeutic medication patterns for youths with attention-deficit/hyperactivity disorder.

OBJECTIVES: (1) To describe temporal patterns of office visits for attention-deficit/hyperactivity disorder (ADHD) and stimulant treatment for 5- to 14-year-old US youths; (2) to compare youth visits for ADHD with and without melication according to patient demographics, physician specialty, reimbursement source, and comorbid diagnoses; and (3) to compare office visits for youths with ADHD in relation to common medication patterns (stimulants alone, stimulants with other psychotherapeutic medication, and nonstimulant psychotherapeutic medications alone). DESIGN: Survey based on a national probability sample of office-based physicians in the United States. SETTING: Physician offices. PARTICIPANTS: A systematically sampled group of office-based physicians. MAIN OUTCOME MEASURES: National estimates of office visits for ADHD and psychotherapeutic drug visits for ADHD for each year and for a combined 8-year period. RESULTS: Youth visits for ADHD as a percentage of total physician visits had a 90% increase, from 1.9% in 1989 to 3.6% in 1996. Stimulant therapy within ADHD youth visits rose from 62.6% in 1989 to 76.6% in 1996. While the majority of non-ADHD youth visits were conducted by primary care physicians, one third of ADHD youth visits were managed by psychiatry and neurology specialists. Health maintenance organization insurance was the reimbursement source for 17.9% of non-ADHD youth visits but only 11.7% of ADHD youth visits. Complex medication therapy was more likely to be prescribed by psychiatrists and less likely to be related to visits with health maintenance organization reimbursement. CONCLUSIONS: National survey estimates in the 1990s confirm the substantial increase in visits for youths diagnosed as having ADHD, with more than three quarters of these visits associated with psychotherapeutic medication treatment. Physician specialty and reimbursement source variables identify distinct patient populations with a gradient in psychotherapeutic medication patterns from single-drug standard (stimulant) therapy to complex multidrug treatment regimens for which evidence-based scientific information is lacking.

Myosin VI is an actin-based motor that moves backwards.

Myosins and kinesins are molecular motors that hydrolyse ATP to track along actin filaments and microtubules, respectively. Although the kinesin family includes motors that move towards either the plus or minus ends of microtubules, all characterized myosin motors move towards the barbed (+) end of actin filaments. Crystal structures of myosin II (refs 3-6) have shown that small movements within the myosin motor core are transmitted through the 'converter domain' to a 'lever arm' consisting of a light-chain-binding helix and associated light chains. The lever arm further amplifies the motions of the converter domain into large directed movements. Here we report that myosin VI, an unconventional myosin, moves towards the pointed (-) end of actin. We visualized the myosin VI construct bound to actin using cryo-electron microscopy and image analysis, and found that an ADP-mediated conformational change in the domain distal to the motor, a structure likely to be the effective lever arm, is in the opposite direction to that observed for other myosins. Thus, it appears that myosin VI achieves reverse-direction movement by rotating its lever arm in the opposite direction to conventional myosin lever arm movement.

Undecagold cluster labeling of proteins at reactive cysteine residues.

Undecagold cluster labeling of reactive cysteine residues in numerous proteins has allowed the labeled sites to be identified by electron microscopy, providing high-resolution information on the location and orientation of subunits in oligomeric enzymes, virus capsids, crystalline sheets of membrane proteins, and muscle thin filaments. The range of applications of undecagold cluster labeling has been greatly extended by the availability of site-directed mutagenesis to introduce cysteine residues at sites of interest. In this paper I discuss factors that can influence the extent and specificity of labeling, methods for biochemical analysis of undecagold-labeled proteins, and the effects of undecagold cluster labeling on biological activity.

A quantitative analysis of G-actin binding proteins and the G-actin pool in developing chick brain.

The large G-actin pool in individual actively motile cells has been shown to be maintained primarily by the actin sequestering protein thymosin beta four (Tbeta4). It is not clear whether Tbeta4 or an isoform also plays a primary role in neural tissue containing highly motile axonal growth cones. To address this question we have made a definitive analysis of the relative contributions of all the known G-actin sequestering proteins: Tbeta4, Tbeta10, profilin, and phosphorylated (inactive) and unphosphorylated (potentially active) forms of both ADF and cofilin, in relation to the G-actin pool in developing chick brain at embryonic days 13 and 17. From our measurements we estimate the intracellular concentration of G-actin as 30-37 microM and of Tbeta4 as 50-60 microM in an 'average' brain cell in embryonic chick brain. No other beta thymosin isoforms were detected in these brain extracts. The ratio of soluble, unphosphorylated ADF to Tbeta4 is only 1:7 at 13 embryonic days, but increases to 1:4 at 17 days. Profilin and cofilin concentrations are an order of magnitude lower than Tbeta4. Combining the contributions of Tbeta4, unphosphorylated ADF and unphosphorylated cofilin, we estimate a mean G-actin critical concentration of approximately 0.45 microM and approximately 0.2 microM, respectively, in day 13 and day 17 embryonic brain extracts, suggesting a significant developmental decrease. We conclude that (a) Tbeta4 is the major actin sequestering protein in embryonic chick brain and the only beta thymosin isoform present; (b) ADF may play a significant developmental role, as its concentration changes significantly with age; (c) the known G-actin binding proteins can adequately account for the G-actin pool in embryonic chick brain.