ADHD
Autism
Bipolar
Disorder
2007/8/24/8
Neurosci Lett. 2006 Mar
21; [Epub ahead of print] The VNTR polymorphism
in the human dopamine transporter gene: improved detection and absence of association
of VNTR alleles with attention-deficit hyperactivity disorder. Pharmacol Biochem Behav. 2006 Feb 24; [Epub
ahead of print] Biol Psychiatry. 2006 Feb 21; [Epub ahead of print] Neuropsychopharmacol Hung. 2005 Sep;7(3):125-31. Neurosci Lett. 2006 Feb
18; [Epub ahead of print]
Association of
attention-deficit/hyperactivity disorder with serotonin 4 receptor gene
polymorphisms in Han Chinese subjects.
Li J, Wang Y, Zhou R, Wang B, Zhang H, Yang L, Faraone
SV.
Attention-deficit/hyperactivity disorder (ADHD) is an important public
health problem. Although serotonin is believed to be an important
neurotransmitter in the etiology of this disorder, it remains unclear which
specific 5-HT receptors are involved in regulating the symptoms of ADHD.
Previous studies have provided favorable evidence for the association of
ADHD with both the serotonin transporter gene and serotonin 1B receptor
gene. To further investigate the role of other genes of the serotonergic pathway in ADHD, the current study
examined variants of the serotonin 4 receptor gene in a relatively large
sample of ADHD nuclear families. The T allele of the 83097 C>T
polymorphism of HTR4 showed a tendency of preferential transmission to probands with ADHD (chi(2)=2.699,
P=0.100). When haplotype TDT analysis of HTR4 was
performed, we further found that the C/G haplotype
of the 83097 C>T and 83198 A>G polymorphisms (chi(2)=8.783,
P=0.003) and the C/G/C haplotype of these and the
-36 C>T polymorphism (chi(2)=5.762, P=0.016) were under-transmitted to probands with ADHD. These results suggest that the HTR4
gene may play a role in the genetic predisposition to ADHD.
PMID: 16563621 [PubMed - as supplied by
publisher]
Simsek M, Al-Sharbati M,
Al-Adawi S,
Lawatia K.
Department of Biochemistry,
The human dopamine transporter (DAT1) gene contains a variable number
tandem repeat (VNTR) in its 3'-untranslated region because of repetition of
a 40-bp core sequence. Methods available for the diagnosis of this
polymorphism are limited in number. We have developed a new polymerase
chain reaction (PCR) test, which is similar to that described originally by
Vandenbergh's group, but provides a better
detection of the VNTR alleles in the human DAT1 gene. Using two independent
PCR methods, we have determined the distribution of VNTR alleles in 110 healthy
Omani subjects, and in 92 children with attention-deficit hyperactivity
disorder (ADHD). The frequency of the risk allele (DAT1*10) was similar in
the healthy subjects and ADHD cases, indicating absence of association of
this allele with ADHD in
PMID: 16545000 [PubMed - in process]
Orally active vasopressin V1a receptor
antagonist, SRX251, selectively blocks aggressive behavior.
Ferris CF,
Lu SF, Messenger T,
Guillon
CD, Heindel
N, Miller M, Koppel G, Robert Bruns F, Simon NG.
Center for Comparative Neuroimaging, University
of Massachusetts Medical School, Worcester, MA, USA; Azevan
Pharmaceuticals, Inc., Bethlehem, PA, USA.
Arginine vasopressin functions as a neurochemical signal in the brain to affect social
behavior. There is an expanding literature from animal and human studies
showing that vasopressin, through the vasopressin 1A receptor (V1A), can
stimulate aggressive behavior. Using a novel monocylic
beta lactam platform, a series of orally active
vasopressin V1a antagonists was developed with high affinity for the human
receptor. SRX251 was chosen from this series of V1a antagonists to screen for
effects on serenic activity in a
resident-intruder model of offensive aggression. Resident, male Syrian
golden hamsters were given oral doses of SRX251 or intraperitoneal
Manning compound, a selective V1a receptor antagonist with reduced brain penetrance, at doses of 0.2 mug, 20 mug, 2 mg/kg or
vehicle. When tested 90-120 min later, SRX251, but not Manning compound,
caused a significant dose-dependent reduction in offensive aggression
toward intruders as measured by latency to bite and number of bites. The
reduction in aggression persisted for over 6 h and was no longer present 12
h post treatment. SRX251 did not alter the amount of time the resident
investigated the intruder, olfactory communication, general motor activity,
or sexual motivation. These data corroborate previous studies showing a
role for vasopressin neurotransmission in aggression and suggest that V1a
receptor antagonists may be used to treat interpersonal violence
co-occurring with such illness as ADHD, autism, bipolar disorder, and substance
abuse.
ABT-089, A
Neuronal Nicotinic Receptor Partial Agonist, for the Treatment of
Attention-Deficit/Hyperactivity Disorder in Adults: Results of a Pilot
Study.
Wilens
TE, Verlinden
MH, Adler LA, Wozniak PJ,
West SA.
Department of Psychiatry (TEW),
BACKGROUND: This pilot study was designed to evaluate ABT-089, a neuronal
nicotinic receptor partial agonist, as treatment for adult
attention-deficit/hyperactivity disorder (ADHD). METHODS: Adults with ADHD
received placebo, 2 mg, 4 mg, or 20 mg of ABT-089 for 2 weeks each in a
randomized, double-blind, placebo-controlled, 4 x 4 Latin square design for a total of 8 weeks. In addition to the
primary outcome, the Conner's Adult ADHD Rating Scale (CAARS), secondary
rating scales, and neuropsychological and safety assessments were
completed. RESULTS: A total of 11 adults with well-characterized ADHD
completed this crossover study. ABT-089 b.i.d.
was superior to placebo for the CAARS Total Symptom Score, which was the
primary endpoint (placebo: 38.0 +/- 1.9; 2 mg b.i.d.:
32.2 +/- 1.9, one-tail p = .021; 4 mg b.i.d.:
33.2 +/- 1.9, p = .047; 20 mg b.i.d.: 33.5 +/-
1.9, p = .056). ABT-089 was also superior to placebo for the CAARS ADHD
Index and Hyperactive/Impulsive scores and the Clinical Global
Impression-ADHD Severity score. On the clinical efficacy endpoints, CAARS
Total Symptom Score and CAARS Hyperactive/Impulsive score, a shallow
inverted U-shaped dose-response curve was observed; however, the
dose-response curve for attention and memory effects as measured by
computerized cognitive testing seemed dose-linear. No clinically meaningful
findings in safety assessments or side effect profile were observed.
CONCLUSIONS: Data from this pilot study suggest that ABT-089 might be
effective in treating adult ADHD and that it is well tolerated. On the
basis of these promising results, larger, parallel-group ABT-089 studies of
longer duration are warranted.
[Effects of the D4 dopamine receptor gene
variation on behavior problems at 6 years of age]
[Article in Hungarian]
Birkas E, Lakatos K,
Nemoda Z, Ney K, Toth I, Novak A, Sasvari-Szekely M,
Gervai J.
Magyar Tudomanyos Akademia
Pszichologiai Kutatointezet,
Association of the 7-repeat allele of the D4 dopamine receptor (DRD4) exon 3 polymorphism with attention
deficit/hyperactivity disorder is well-established, and a link with
mother-reported aggressiveness was also found in healthy pre-schoolers assessed by the quantitative scale of the
Child Behavior Checklist. In the present study, we hypothesized that
children carrying the 7-repeat allele would show more attention problems
and externalizing (aggressive and delinquent) behavior at 6 years of age.
Further, we hypothesized a potential mediating role of early temperament in
the relationship of DRD4 gene with behavior problems. Mothers filled in the
Achenbach Child Behavior Checklist for 88 six-year-old firstborn children
(51 boys, 35 girls) followed from birth. Mother-reported temperament for
the same children was assessed by the Rothbart
Infant Behavior Questionnaire at 12 months. Genotypes of the DRD4 repeat
polymorphism were determined using buccal cells.
Significant main effects of gender and DRD4 genotype were observed on
6-year behavioral problems. Boys showed more attention problems and
externalizing behavior, and children lacking the 7-repeat variant showed
more externalizing and internalizing behavior. These effects remained
significant after controlling for 1-year temperament. Our results did not
confirm the negative effect of the 7-repeat allele on attention problems
and externalizing behavior measured on quantitative scales. On the
contrary, we found elevated problem scores in the absence of the 7-repeat
allele. Further research including environmental risk factors is needed to
clarify the role of the DRD4 gene in the development of externalizing
behavior.
PMID: 16493876 [PubMed - indexed for MEDLINE]
Characterization of the
neuronal dopamine transporter DAT in human blood platelets.
Frankhauser
P, Grimmer Y,
Bugert
P, Deuschle
M, Schmidt M,
Schloss
P.
Department Psychiatry, Central Institute of Mental
Health,
Compelling evidence suggests a monoaminergic
dysfunction in the aetiology of various neuro-psychiatric diseases such as depression,
attention deficit hyperactivity disorder (ADHD), schizophrenia, addiction
and Parkinson's disease. The efficiency of monoaminergic
neurotransmission is controlled by rapid and efficient reuptake of dopamine
out of the synaptic cleft by specific transporters for dopamine, serotonin
and noradrenalin. In case of the serotonin transporter, many investigators
have determined its function and expression also on peripheral cells such
as blood platelets under the assumption that changes in protein expression
in these cells might reflect neuronal changes. No comparable studies have
so far been performed with respect to the dopamine transporter due to the
lack of information about the existence of this protein in platelets. Here,
we present pharmacological, immunological as well as microarray
and PCR data that human blood platelets express the dopamine transporter
protein (DAT), which is identical to that first identified in neurons.
Because DAT expression is modulated also in non-neuronal cells
independently of gene transcription, platelets may well serve as an easy
accessible peripheral system to study DAT regulation in mental diseases or
during drug treatment or drug abuse.
PMID: 16490314 [PubMed - as supplied by
publisher]