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RESÚMENES JUNIO 2004 |
Child Disorders
Weight and Leptin Changes Among Risperidone-Treated Youths With Autism: 6-Month Prospective Data
Andrés Martin, Lawrence Scahill,
George M. Anderson, Michael Aman, L. Eugene Arnold,
James McCracken, Christopher J. McDougle, Elaine
Tierney, Shirley Chuang, and Benedetto Vitiello, the Research Units on Pediatric
Psychopharmacology Autism Network
Am J Psychiatry 161:1125-1127, June 2004
OBJECTIVE: The
authors examined the developmental impact and temporal
characteristics of risperidone-associated weight
change. METHOD: Weight change was measured for 63 children and
adolescents with autism treated with risperidone
for 6 months. Change in serum leptin
levels after 2 months was examined as a predictor of final weight
gain in mixed regression models that controlled for site, gender,
age, and risperidone dose. RESULTS: Age- and gender-standardized
weight increased after 6 months of treatment (gross: mean=5.6 kg
[SD=3.9]; standardized: mean=0.6 z [SD=0.5]) and was positively
correlated with weight gained after 1 month. Change in leptin levels after 2 months of treatment (mean=–0.3 ng/ml, SD=6.2) (N=48) did not predict final weight gain.
CONCLUSIONS: Chronic risperidone exposure
in children with autism causes weight gain in excess of
developmentally expected norms that follows a curvilinear trajectory
and decelerates over time. Serum leptin
change does not reliably predict risperidone-associated
weight gain.
Divalproex-ER
pharmacokinetics in older children and adolescents.
Dutta S, Zhang Y, Conway JM, Sallee FR, Biton V, Reed MD,
Kearns GL.
Pediatr Neurol. 2004 May;30(5):330-7.
Valproic acid pharmacokinetic profile and
tolerability after administration of divalproex
sodium extended-release tablets was characterized in older children and
adolescents. In this multiple-dose, open-label, pharmacokinetic study, the
patients were divided into two age groups, 8-11 years (older children; n = 15)
and 12-17 years (adolescents; n = 14). Once-daily administration of divalproex sodium extended-release tablets (doses ranged
from 250 to 1750 mg) in older children and adolescents produced relatively flat
plasma valproic acid concentration-time profiles over
the entire 24-hour dosing interval, similar to the pharmacokinetic performance
of this formulation in adults. The mean (standard deviation) oral clearance
values for unbound valproic acid were 94.3 (51.8) and
82.3 (28.2) mL/h/kg and for total valproic
acid were 11.2 (3.77) and 9.06 (2.03) mL/h/kg in
older children and adolescents, respectively. Two patients discontinued for
administrative reasons, whereas one discontinued for an adverse event (flulike
syndrome). Adverse events reported by three or more patients were flu syndrome
(5 patients, 17.2%) and headache (3 patients, 10.3%). Reported adverse events
were generally mild to moderate in severity and similar to those reported in
previous divalproex studies. This study demonstrates
that in older children and adolescents, once-daily administration of divalproex sodium extended-release tablets may potentially
be used to sustain plasma valproic acid
concentrations within the usually accepted therapeutic ranges for various
indications.
A Naturalistic Retrospective Analysis of Psychostimulants in Pervasive Developmental Disorders.
Stigler
KA, Desmond LA, Posey DJ, Wiegand RE, McDougle CJ.
J
Child Adolesc Psychopharmacol
2004;14(1):49-56.
Objective: We
set out to examine the effectiveness and tolerability of psychostimulants
in children and adolescents with pervasive developmental disorders (PDDs). Methods: Medical records of all patients with PDDs treated with a stimulant were retrospectively
reviewed. Demographics, stimulant type, drug dosage, trial duration, and
adverse effects were recorded. Global improvement, focused on symptoms of
hyperactivity and inattention, was measured by the Clinical Global
Impressions-Improvement scale, with positive response defined by a rating of
much improved or very much improved. Results: Of 195 patients (174 males, 21
females; mean age plus or minus sign SD = 7.26 plus or minus sign 3.45 years,
range 2-19 years), 61 had more than one trial, resulting in a total of 274
separate stimulant trials. It was discovered that 24.6%, 23.2%, and 11.1% of
patients with a history of one, two, or three stimulant trials, respectively,
responded to their first stimulant trial. Among first trial nonresponders,
6 (14.0%) of 43 patients responded to a second trial. Of those who did not
respond to their first or second stimulant trial, 2 (14.3%) of 14 patients
responded to a third trial. Patients with Asperger's
disorder, in contrast to those with autistic disorder or PDD not otherwise
specified, were significantly more likely to respond to a stimulant trial (p
< 0.01). Use of concomitant medication (p < 0.007) positively affected
response, whereas no association was found between stimulant type and IQ and
response. Adverse effects, including agitation, dysphoria,
and irritability, often occurred (154 [57.5%] of 268 trials, with 6 missing
values). Conclusions: Overall, stimulants appeared ineffective and poorly
tolerated for the majority of patients with PDDs. Response
may differ with PDD subtype. Controlled studies are needed to further evaluate
these preliminary findings in a systematic manner.
Perinatal
Factors and the Development of Autism .A
Population Study
Emma J. Glasson, Carol Bower, Beverly Petterson, Nick de Klerk, Gervase
Chaney, Joachim F. Hallmayer
Arch Gen Psychiatry. 2004;61:618-627.
Background Autism is considered to have a
genetic basis, although exposure to certain stimuli in the prenatal
period has been implicated to be causal in some cases. Some
investigations have shown an association with obstetric
complications but findings have been inconsistent owing to
differences in sampling and methods.
Objective To examine the association of
obstetric factors with autism spectrum disorders for a cohort of
children, using obstetric data contained in a statutory database
collected at the time of birth.
Design Subjects born in
Results Compared with control subjects, cases
had significantly older parents and were more likely to be
firstborn. Case mothers had greater frequencies of threatened
abortion, epidural caudal anesthesia use, labor induction, and a
labor duration of less than 1 hour. Cases were more likely to have
experienced fetal distress, been delivered by an elective or
emergency cesarean section, and had an Apgar
score of less than 6 at 1 minute. Cases with a diagnosis of autism
had more complications than those with pervasive developmental disorder
not otherwise specified or Asperger
syndrome. Nonaffected siblings of cases were more
similar to cases than control subjects in their profile of complications.
Conclusions Autism is unlikely to be caused
by a single obstetric factor. The increased prevalence of obstetric
complications among autism cases is most likely due to the
underlying genetic factors or an interaction of these factors with
the environment.
Use of
the "Inverse Neuroleptic" Metoclopramide in Tourette
Syndrome: An Open Case Series.
Acosta MT, Castellanos
FX.
J Child Adolesc Psychopharmacol 2004;14(1):123-128.
Neuroleptics are generally
highly effective in suppressing tics, but their many adverse effects limit
their usefulness. Animal studies have shown that, compared with both typical
and atypical neuroleptics, metoclopramide
has effects that are regionally circumscribed to rat motor striatum. Based on
this observation and two prior case reports, metoclopramide
was openly prescribed and individually titrated to diminish tics in 10 patients
with Tourette syndrome. All patients improved on the
Yale Global Tic Severity Scale by an average of 55%. Although we did not
observe frank extrapyramidal symptoms, including tardive dyskinesia, these data
are not sufficient to support clinical recommendations because of many
limitations, including the absence of systematic ratings of nontic
abnormal movements. However, controlled clinical studies and additional basic
investigations of metoclopramide are warranted.
Effects of Risperidone on Destructive Behavior of Persons With
Developmental Disabilities: III. Functional Analysis
Jennifer R. Zarcone,
Steven E. Lindauer, Paige S. Morse, Kimberly A.
Crosland, Maria G. Valdovinos, and Todd L. McKerchar
American
Journal on Mental Retardation: Vol. 109, No. 4, pp. 310–321.
Functional
analyses were conducted during a double-blind, placebo-controlled study of the
atypical antipsychotic medication risperidone with 13
individuals. Risperidone was effective in reducing
destructive behavior (compared to placebo) for 10 participants. For 7 of these
responders, an undifferentiated pattern of responding occurred across their
baseline functional analysis conditions (i.e., a similar rate of responding
across conditions), and risperidone treatment
produced nonspecific reductions of their destructive behavior across functional
analysis conditions. For the remaining 3 responders, a differentiated pattern
of responding occurred across their baseline functional analysis conditions
(i.e., an elevated rate of responding occurred in a specific condition), and risperidone treatment produced function-specific reductions
of their destructive behavior.
Patients' preferences in the treatment of
depressive disorder in primary care
Digna J.F. van Schaik,
Alexandra F.J. Klijn ,
Hein P.J. van Hout , Harm W.J. van Marwijk ,
Aartjan T.F. Beekman
, Marten de Haan and Richard van Dyck
Gen Hosp Psychiatry. Volume 26, Issue 3, Pages
184-189 (May 2004)
Patients'
preferences in the treatment of depression are important in clinical practice
and in research. Antidepressant medication is often prescribed, but adherence
is low. This may be caused by patients preferring psychotherapy, which is often
not available in primary care. In randomized clinical trials, patients'
preferences may affect the external validity. The aim of this article is to
study patients' preferences regarding psychotherapy and antidepressant
medication and the impact of these preferences on treatment outcome. A
systematic review of the literature was performed. The majority of patients
preferred psychotherapy in all available studies. Antidepressants were often
regarded as addictive and psychotherapy was assumed to solve the cause of
depression. Discussing and supporting preferences as part of a quality
improvement program of depression care, resulted in more patients receiving the
treatment that was most suitable to them. In two patient-preference trials,
preferences did not influence treatment outcome. It can be concluded that a
substantial percentage of well-informed patients prefer psychotherapy. Patients
with strong preferences, mostly for psychotherapy, are likely not to enter
antidepressant treatment or randomized clinical trials if their preferences are
not supported.
The Link Between Health-Related Quality of Life and
Clinical Symptoms Among Children with Attention-Deficit Hyperactivity Disorder.
Matza LS, Rentz
AM, Secnik K, Swensen AR, Revicki DA, Michelson D, Spencer T, Newcorn
JH, Kratochvil CJ.
J Dev Behav Pediatr.
2004 Jun;25(3):166-174.
Clinical
research on attention-deficit hyperactivity disorder (ADHD) has begun to
integrate measures of health-related quality of life (HRQL) as part of the
overall assessment of treatment outcomes. This study examines the association
between HRQL and measures of clinical symptoms of ADHD. Data were gathered from
297 children and adolescents in an 8-week, randomized, double-blind,
placebo-controlled, clinical trial of atomoxetine
treatment for ADHD. HRQL was assessed with the Child Health Questionnaire
50-item Parent Form. ADHD symptoms were assessed with the ADHD Rating Scale-IV;
Parent Version and Clinical Global Impressions-ADHD-Severity. Associations
between HRQL and clinical symptoms were assessed with correlations, analyses of
variance with post hoc comparisons, and t tests. The Child Health Questionnaire
50-item Parent Form scales assessing psychosocial domains of HRQL were
significantly negatively correlated with clinical measures. Improvement in
clinical symptoms was associated with corresponding improvement in psychosocial
aspects of HRQL. The findings suggest that HRQL instruments can add important
information to efficacy measures in clinical trials of ADHD treatment.
Primary parental preoccupation: circuits, genes,
and the crucial role of the environment
J.
F. Leckman, R. Feldman, J. E. Swain,
V. Eicher, N. Thompson and L. C. Mayes
Journal of Neural
2004; Volume 111, Number 7: 753 - 771
Parental caregiving
includes a set of highly conserved behaviors and mental states that may reflect
both an individual
s
genetic endowment and the early experience of being cared for as a child. This
review first examines the mental and behavioral elements of early parental caregiving in humans. Second, we consider what is known
about the neurobiological substrates of maternal behaviors in mammalian species
including some limited human data. Third, we briefly review the evidence that
specific genes encode proteins that are crucial for the development of the
neural substrates that underlie specific features of maternal behavior. Fourth,
we review the emerging literature on the 
programming
role of the intrauterine environment and postnatal caregiving
environment in shaping subsequent maternal behavior. We conclude that there are
critical developmental windows during which the genetically determined microcircuitry of key limbic-hypothalamic-midbrain
structures are susceptible to early environmental influences and that these
influences powerfully shape an individuals
responsivity to psychosocial stressors and their
resiliency or vulnerability to various forms of human psychopathology later in
life.
Questioning inhibitory control as the specific
deficit of ADHD – evidence from brain electrical activity
T. Banaschewski, D. Brandeis, H. Heinrich, B. Albrecht,
E. Brunner and A. Rothenberger
Objective: To investigate motor
response control during a cued continuous performance test (CPT-A-X) by performance
and ERP parameters in children with hyperkinetic disorder (HD), hyperkinetic
conduct disorder (HCD) or oppositional deviant/conduct disorder (ODD/CD), to
examine the evidence for an inhibition-specific deficit as indicated by these
parameters, and to analyze whether possible deviations are specific for HD/HCD.
Method: Behavioral parameters and
event-related potentials (ERPs) were recorded during
a CPT-A-X-task in children (aged 8 to 14 years) with either HD (n=15), HCD
(n=16), or ODD/CD (n=15) and normal children (n=18) and analysed.
ICD-10 diagnoses of HD/HCD diagnoses in all children were fully concordant with
the DSM-IV diagnosis of ADHD-combined type.
Results: Children with HCD committed
more dyscontrol errors and differed most from normal
children on ERP measures of motor response control, while children with HD-only
were more impaired during processing of the warning stimuli for motor
preparation. ERP measures specific for response inhibition were not different
between the groups.
Conclusions: The results show that
ADHD cannot be fully explained by an inhibition-specific deficit and implicate
impaired response execution processes as well. This indicates that comorbid children suffer from a reduced ability to control
their prepared motor responses. Further, they seem to have difficulties in
timely switching attention from monitoring the sensory input stream to the
monitoring of own responses and actions.
Age-dependent neuropsychological deficits and
effects of methylphenidate in children with attention-deficit/hyperactivity
disorder: a comparison of pre- and grade-school children
C. Hanisch, K. Konrad, T. Günther and
B. Herpertz-Dahlmann
Journal of Neural
Transmission 2004; Volume 111, Number 7: 865 - 881
Objective: Pre-school and
grade-school children diagnosed with attention-deficit/hyperactivity disorder
(ADHD) were compared in their performance on computerized attention tasks.
Depending on the nature of the specified attention deficit, subjects were
assigned to groups of cognitive subtypes. The effects of methylphenidate (MPH)
were analysed depending on age and cognitive subtype.
Method: The preschool group
comprised 45 children aged 5–7 years; the grade-school group comprised 54
children aged 8–12 years. Children were tested on placebo and on MPH (mean
dose: 0.25–0.3
mg/kg
body weight) employing tasks of alertness, sustained attention, focused
attention, divided attention, and a cognitive conflict task.
Results: Both groups showed
measurable attention deficits. While preschoolers were especially impaired in
supervisory attention functions, grade-schoolers most frequently exhibited
deficits in attention intensity and selectivity. Positive MPH effects were
documented for sustained attention in both age-groups. Analysis of MPH effects
in dependence on the type of attention impairment (supervisory functions vs.
attention intensity/selectivity) revealed a positive relation between deficits
in a specific attention domain and MPH effects.
Conclusions: Age-dependent
differences in attention dysfunctions might be due to brain maturational
processes. Performance on computerized attention tasks was particularly
improved by MPH in children with objectified attention deficits suggesting that
neuropsychological diagnostics can be useful to optimise
treatment outcome.
Association of dopamine D4 receptor (DRD4) gene
with attention-deficit/hyperactivity disorder (ADHD) in a high-risk community
sample: a longitudinal study from birth to 11 years of age
M. El-Faddagh, M. Laucht, A. Maras, L. Vöhringer and M.
H. Schmidt
Journal of Neural
Transmission 2004; Volume 111, Number 7: 883 - 889
Background: In recent years, a
growing number of studies has focused on the dopamine D4 receptor gene (DRD4)
as mediating the susceptibility to attention-deficit/hyperactivity disorder
(ADHD). While their results are contradictory, the reason for this
inconsistency remains as yet unclear.
Method: The present study sought to
examine the association between ADHD and the DRD4 exon
III polymorphism during child development using longitudinal data from a
high-risk community sample (n=265, 129 females, 126 males) who have been followed
from birth to 11 years of age.
Results: Higher rates of ADHD were
observed in boys with the 7 repeat allele of exon III
than in boys with other alleles at the ages of 4 1/2 (Fishers
exact test, p=.061), 8 (p=.026), and 11 years (p=.005). Boys with this allele
also exhibited higher rates of persistent disorder (p=.024). In girls, a trend
towards an association (p=.055) with the 7 repeat allele emerged only at
preschool age.
Conclusions: These findings provide
additional evidence for the role of the dopamine D4 receptor in ADHD during the
course of child development.
Bipolar disorder, schizophrenia, and other
psychotic disorders in adults with childhood onset AD/HD and/or autism spectrum
disorders
O. Stahlberg,
H. Soderstrom, M. Rastam
and C. Gillberg
Journal of Neural
Transmission 2004; Volume 111, Number 7: 891 - 902
Individuals with attention-deficit/hyperactivity
disorder (AD/HD) and autism spectrum disorders (ASD) often display symptoms
from other diagnostic categories. Exclusion criteria in the Diagnostic and
Statistical Manual of Mental Disorders (DSM-IV) and the International
Statistical Classification of Diseases and Related Health Problems (ICD-10)
impede the use of categorical diagnoses to describe the particular problem
constellation in a patient. In this study, we describe the prevalence and
patterns of comorbid bipolar and psychotic disorders
in 241 consecutively referred adult patients with AD/HD and/or ASD. Thirty per
cent of patients with AD/HD had comorbid ASD and 38%
of patients with ASD had comorbid AD/HD. Of the
subjects with ASD, 7% had bipolar disorder with psychotic features, and 7.8%
had schizophrenia or another psychotic disorder. The corresponding figures for
the patients with AD/HD were 5.0% and 5.0%, respectively. Current diagnostic
criteria have to be revised to acknowledge the comorbidity
of bipolar and/or psychotic disorders in AD/HD and ASD.
Review on structural neuroimaging
findings in autism
S. J. M. C. Palmen and H. van Engeland
Journal of Neural
Transmission 2004; Volume 111, Number 7: 903 - 929
Autism is now widely viewed as a neurodevelopmental disorder, although the underlying
biological causes remain to be established. In this review, we examine the
literature in magnetic resonance imaging (MRI) as applied to autism, discuss
the findings that have emerged, and give directions for potential future
research. To date, structural MRI results are inconsistent, partly due to the
heterogeneity of the disorder itself, and partly due to the different
composition and the varied degree of matching of the studied groups. However,
recent studies have begun to elucidate the underlying neuroanatomical
abnormalities and brain-behavior relationships in autism, with the most
consistent finding being increased brain volume in autism. Future large-scale
longitudinal structural imaging studies, starting at very young ages, investigating
homogeneous groups of patients and extensively matched control groups, and
making use of (combinations of) newer and more sophisticated techniques, hold a
great promise to further elucidate the enigma of autism.
Depression,
partnership, social support, and parenting: interaction of maternal factors
with behavioral problems of the child
Judith
E. Herwig, Markus Wirtz and
Jürgen Bengel
Journal of Affective Disorders .Volume 80, Issues 2-3 , June 2004, Pages
199-208
Background:
Children of depressed mothers are at elevated risk to develop behavioral
problems. Besides maternal depression, other risk factors like interpersonal
functioning, are discussed. The object of this study was to investigate the
predictive value of the maternal variables depression, partnership, social
support, and parenting for internal and external behavioral problems of the
children. Methods: A total of 100 mothers and their children who participated
in a German mother–child rehabilitation program were interviewed by
questionnaire. Structural equation modeling was conducted in order to determine
the predictive value of the mentioned maternal variables on behavioral problems
of the children. Results: Behavioral problems of the children can be predicted
by the parenting and the partnership of the mothers. Mothers with more
parenting difficulties and with less containment with partnership report more
behavioral problems of their children. Depression and social support do
indirectly predict the child’s problems. Limitations: The data is from a
cross-sectional sample. Therefore, path models do not demonstrate causation.
All information is based upon maternal report. Conclusions: These findings
suggest the need for intervention programs which focus on the parenting and the
partnership of the mothers. More research with independent assessment is
needed.