The Use of Antiepileptic Drugs (AEDs) for the Treatment of Pediatric Aggression and Mood Disorders

Aggressive symptomatology presents across multiple psychiatric, developmental, neurological and behavioral disorders, complicating the diagnosis and treatment of the underlying pathology. Anti-Epileptic Drugs (AEDs) have become an appealing alternative in the treatment of aggression, mood lability and impulsivity in adult and pediatric populations, although few controlled trials have explored their efficacy in treating pediatric populations. This review of the literature synthesizes the available data on ten AEDs—valproate, carbamazepine, oxcarbazepine, phenytoin, lamotrigine, topiramate, levetiracetam, zonisamide, gabapentin and tiagabine—in an attempt to assess evidence for the efficacy of AEDs in the treatment of aggression in pediatric populations. Our review revealed modest evidence that some of the AEDs produced improvement in pediatric aggression, but controlled trials in pediatric bipolar disorder have not been promising. Valproate is the best supported AED for aggression and should be considered as a first line of treatment. When monotherapy is insufficient, combining an AED with either lithium or an atypical anti-psychotic can result in better efficacy. Additionally, our review indicates that medications with predominately GABA-ergic mechanisms of action are not effective in treating aggression, and medications which decrease glutaminergic transmission tended to have more cognitive adverse effects. Agents with multiple mechanisms of action may be more effective

Abundance and species composition of non-geniculate coralline red algae epiphytic on the South African populations of the rocky shore seagrass Thalassodendron leptocaule M.C. Duarte, Bandeira & Romeiras

Seagrasses support a great diversity of epiphytic organisms and new research has shown that non-geniculate coralline red algae are important occupiers of space on the fronds of seagrasses. Except for a few scant records, there are no detailed published accounts of non-geniculate coralline algae epiphytic on seagrasses in South Africa. The seagrass Thalassodendron leptocaule (previously known as Thalassodendron ciliatum) is unique among southern African seagrasses in that it occurs on exposed rocky outcrops along the Mozambique and north eastern South African coast; most other seagrasses are restricted to sheltered bays and estuaries. Here we present descriptions of three species of non-geniculate coralline red algae which we have identified growing epiphytically on this seagrass in northern KwaZulu-Natal: Hydrolithon farinosum, Pneophyllum amplexifrons and Synarthrophyton patena. Two of the corallines (P. amplexifrons and S. patena) were restricted to the seagrass' stems while the third (H. farinosum) occurred only on the leaves. Of the three coralline epiphytes, P. amplexifrons contributed most to the biomass (average wet weight per plant 0.6±1.18 g); its wet weight, however, varied between habitats. Hydrolithon farinosum and other smaller turf algae amounted to no more than 0.1 g (wet weight) per leaf. Synarthrophyton patena was far more sparsely evident and contributed to less than 0.1 g (wet weight) per stem. Pneophyllum amplexifrons and H. farinosum appear to be pioneer epiphytes and form additional surfaces onto which other seaweed epiphytes attach and grow. Distribution of these epiphytes is explained by the longevity of the stems and leaves of the seagrass.Web of Scienc

A mathematical model of aging-related and cortisol induced hippocampal dysfunction

<p>Abstract</p> <p>Background</p> <p>The hippocampus is essential for declarative memory synthesis and is a core pathological substrate for Alzheimer's disease (AD), the most common aging-related dementing disease. Acute increases in plasma cortisol are associated with transient hippocampal inhibition and retrograde amnesia, while chronic cortisol elevation is associated with hippocampal atrophy. Thus, cortisol levels could be monitored and managed in older people, to decrease their risk of AD type hippocampal dysfunction. We generated an in silico<it/>model of the chronic effects of elevated plasma cortisol on hippocampal activity and atrophy, using the systems biology mark-up language (SBML). We further challenged the model with biologically based interventions to ascertain if cortisol associated hippocampal dysfunction could be abrogated.</p> <p>Results</p> <p>The in silico<it/>SBML model reflected the in vivo<it/>aging of the hippocampus and increased plasma cortisol and negative feedback to the hypothalamic pituitary axis. Aging induced a 12% decrease in hippocampus activity (HA), increased to 30% by acute and 40% by chronic elevations in cortisol. The biological intervention attenuated the cortisol associated decrease in HA by 2% in the acute cortisol simulation and by 8% in the chronic simulation.</p> <p>Conclusion</p> <p>Both acute and chronic elevations in cortisol secretion increased aging-associated hippocampal atrophy and a loss of HA in the model. We suggest that this first SMBL model, in tandem with in vitro<it/>and in vivo<it/>studies, may provide a backbone to further frame computational cortisol and brain aging models, which may help predict aging-related brain changes in vulnerable older people.</p

Diversidade de resultados no estudo do transtorno de déficit de atenção e hiperatividade

Com este artigo pretende-se abordar a problemática da diversidade de dados na investigação do Transtorno de Déficit de Atenção e Hiperatividade (TDAH). Apresenta-se uma revisão da literatura centrada na heterogeneidade de conclusões relativas à caracterização do transtorno, à distinção dos subtipos, aos contextos de informação, às diferenças de gênero e à comorbidade. Na tentativa de compreender a disparidade de conclusões, salientam-se potenciais fatores explicativos, nomeadamente a heterogeneidade das amostras, a diversidade de metodologias e de procedimentos de investigação, entre outros.With this paper we aimed at addressing the problem of data diversity in Attention-Deficit Hyperactivity Disorder (ADHD) research. We present a literature review based on the heterogeneity of findings about the characterization of the disorder, subtypes differentiation, sources of information, sex differences and comorbidities. In an effort to understand the variety of findings, we underline potential explanations, such as the sample’s heterogeneity or the multiplicity of methods and procedures, among others.(undefined

Serotonin transporter binding of [123I]ADAM in bulimic women, their healthy twin sisters, and healthy women: a SPET study

<p>Abstract</p> <p>Background</p> <p>Bulimia Nervosa (BN) is believed to be caused by an interaction of genetic and environmental factors. Previous studies support the existence of a bulimia-related endophenotype as well as disturbances in serotonin (5-HT) transmission. We studied serotonin transporter (SERT) binding in BN, and to investigate the possibility of a SERT-related endophenotype for BN, did this in a sample of female twins. We hypothesized clearly reduced SERT binding in BN women as opposed to healthy women, and intermediate SERT binding in unaffected co-twins.</p> <p>Methods</p> <p>We studied 13 female twins with BN (9 with purging and 4 with non-purging BN) and 25 healthy women, including 6 healthy twin sisters of BN patients and 19 women from 10 healthy twin pairs. [¹²³I]ADAM, a selective SERT radioligand for single photon emission tomography (SPET) imaging, was used to assess SERT availability in the midbrain and the thalamus.</p> <p>Results</p> <p>No differences in SERT binding were evident when comparing the BN women, their unaffected co-twins and the healthy controls (p = 0.14). The healthy sisters of the BN patients and the healthy control women had similar SERT binding in both brain regions. In a <it>post hoc </it>subgroup analysis, the purging bulimics had higher SERT binding than the healthy women in the midbrain (p = 0.03), but not in the thalamus.</p> <p>Conclusion</p> <p>Our finding of increased SERT binding in the midbrain in the purging BN women raises the possibility that this subgroup of bulimics might differ in serotonergic function from the non-purging ones. The similarity of the unaffected co-twins and the healthy controls doesn't support our initial assumption of a SERT-related endophenotype for BN. Due to the small sample size, our results need to be interpreted with caution and verified in a larger sample.</p

Epilepsy and Psychiatric Comorbidities: Drug Selection.

Purpose of review The pharmacological treatment of patients with epilepsy and psychiatric comorbidities may sometimes represent a therapeutic challenge. This review is focused on the pharmacological management of patients with epilepsy and psychiatric problems in terms of rationalization of the antiepileptic drug (AED) treatment and the pharmacological management of the most clinically relevant psychiatric comorbidities, namely mood and anxiety disorders, psychoses, and attention deficit hyperactivity disorder (ADHD). Recent findings Up to 8% of patients with drug-resistant epilepsy develop treatment-emergent psychiatric adverse events of AED regardless of the mechanism of action of the drug and this is usually related to an underlying predisposition given by the previous psychiatric history and the involvement of mesolimbic structures. Careful history taking, periodic screening for mood and anxiety disorders, low starting doses, and slow titration schedules can reduce the possibility of AED-related problems. A pragmatic checklist for the pharmacological management of patients with epilepsy and psychiatric disorders is presented. Summary patients should be informed of potential behavioral effects of AEDs but no drugs should be excluded a priori. Any psychiatric comorbidity should be addressed in the appropriate setting and full remission and recovery should always represent the first goal of any therapeutic intervention. Neurologists should be aware of the side effects of major psychotropic drug classes in order to fully counsel their patients and other health professionals involved

Effects of STX209 (Arbaclofen) on Neurobehavioral Function in Children and Adults with Fragile X Syndrome: A Randomized, Controlled, Phase 2 Trial

Research on animal models of fragile X syndrome suggests that STX209, a γ-aminobutyric acid type B (GABA[subscript B]) agonist, might improve neurobehavioral function in affected patients. We evaluated whether STX209 improves behavioral symptoms of fragile X syndrome in a randomized, double-blind, placebo-controlled crossover study in 63 subjects (55 male), ages 6 to 39 years, with a full mutation in the FMR1 gene (>200 CGG triplet repeats). We found no difference from placebo on the primary endpoint, the Aberrant Behavior Checklist—Irritability (ABC-I) subscale. In the other analyses specified in the protocol, improvement was seen on the visual analog scale ratings of parent-nominated problem behaviors, with positive trends on multiple global measures. Post hoc analysis with the ABC—Social Avoidance scale, a newly validated scale for the assessment of fragile X syndrome, showed a significant beneficial treatment effect in the full study population. A post hoc subgroup of 27 subjects with more severe social impairment showed improvements on the Vineland II–Socialization raw score, on the ABC—Social Avoidance scale, and on all global measures. STX209 was well tolerated, with 8% incidences of sedation and of headache as the most frequent side effects. In this exploratory study, STX209 did not show a benefit on irritability in fragile X syndrome. Nonetheless, our results suggest that GABA[subscript B] agonists have potential to improve social function and behavior in patients with fragile X syndrome.Seaside Therapeutics Inc

Young children with psychotic symptoms and risk for suicidal thoughts and behaviors: a research note

Abstract Objective Suicidal thoughts and behaviors (STBs) are prevalent among youth with psychotic disorders (PD) relative to the general population. Recent research now suggests that STBs may present during the prodromal phase of the disease, or the clinical high risk (CHR) state. While this knowledge is important for the development of suicide prevention strategies in adolescent and adult populations, it remains unclear whether risk for suicide extends to children with or at risk for psychosis. The current study is an extension of previous work assessing STBs in youth across the psychosis continuum. We examine STBs in 37 CHR and PD children ages 7–13 years old, and further explore the prodromal symptom correlates of STB severity among CHR children. Results CHR and PD children endorsed STBs with a frequency and severity similar to what is observed in older CHR and PD populations. A number of children had never previously vocalized their suicidal plans or intent. Among CHR children, Social Anhedonia and Odd Behavior or Appearance were significantly correlated with STB severity. These findings underscore the importance of screening for STBs even in young children presenting with psychotic symptoms

The Use of Antiepileptic Drugs (AEDs) for the Treatment of Pediatric Aggression and Mood Disorders

Aggressive symptomatology presents across multiple psychiatric, developmental, neurological and behavioral disorders, complicating the diagnosis and treatment of the underlying pathology. Anti-Epileptic Drugs (AEDs) have become an appealing alternative in the treatment of aggression, mood lability and impulsivity in adult and pediatric populations, although few controlled trials have explored their efficacy in treating pediatric populations. This review of the literature synthesizes the available data on ten AEDs – valproate, carbamazepine, oxcarbazepine, phenytoin, lamotrigine, topiramate, levetiracetam, zonisamide, gabapentin and tiagabine – in an attempt to assess evidence for the efficacy of AEDs in the treatment of aggression in pediatric populations. Our review revealed modest evidence that some of the AEDs produced improvement in pediatric aggression, but controlled trials in pediatric bipolar disorder have not been promising. Valproate is the best supported AED for aggression and should be considered as a first line of treatment. When monotherapy is insufficient, combining an AED with either lithium or an atypical anti-psychotic can result in better efficacy. Additionally, our review indicates that medications with predominately GABA-ergic mechanisms of action are not effective in treating aggression, and medications which decrease glutaminergic transmission tended to have more cognitive adverse effects. Agents with multiple mechanisms of action may be more effective