Kristi-Ann Villagonzalo

Oxidative pathways as a drug target for the treatment of autism

Importance of the field: Autism is a severe, pervasive developmental disorder, the aetiology of which is poorly understood. Current pharmacological treatment options for autism are often focused on addressing comorbid behavioural problems, rather than core features of the disorder. Investigation of a new treatment approach is needed. Areas covered in this review: Recent research has indicated a possible role of abnormalities in oxidative homeostasis in the pathophysiology of autism, based on reports that a range of oxidative biomarkers are significantly altered in people with autism. This article reviews the current findings on oxidative stress in autism, including genetic links to oxidative pathways, changes in antioxidant levels and other oxidative stress markers. We conducted a search of the literature up to June 2010, using Medline, Pubmed, PsycINFO, CINAHL PLUS and BIOSIS Previews. What the reader will gain: This review provides an overview of the current understanding of the role of oxidative stress in autism. This will assist in highlighting areas of future therapeutic targets and potential underlying pathophysiology of this disorder. Take home message: Abnormalities in oxidative homeostasis may play a role in the pathophysiology of autism. Antioxidant treatment may form a potential therapeutic pathway for this complex disorder.

Targeting the mitochondrial electron transport chain in autism, a systematic review and synthesis of a novel therapeutic approach

Autism is a complex developmental disorder with an unknown etiology and without any curative treatment. The mitochondrial electron transfer chains play a major role in the production of ATP, and the generation and management of reactive oxidative stress (ROS). This paper is a systematic review of the role of the mitochondrial electron transport chain in autism, and a consequent hypothesis for treating autism is synthesized. An electronic search with pre-specified inclusion criteria was conducted in order to retrieve all the published articles about the mitochondrial electron transport chain in autism. The two databases of PUBMED and Google Scholar were searched. From one hundred twenty five retrieved titles, 12 (three case control study and 9 case reports) articles met inclusion criteria. All of the included studies indicated dysfunction of electron transport chain in autism. The mitochondrial electron transfer chain seems impaired in some children with autism and ROS production is additionally enhanced. It is hypothesized that interventions involving alternative electron shuttling may improve autism through lowering the production of ROS. In addition, it is expected that this alternative electron shuttling to cytochrome c might enhance the production of ATP which is impaired in the disorder.

The relationship between substance use and posttraumatic stress disorder in a methadone maintenance treatment program.

INTRODUCTION AND AIMS Posttraumatic stress disorder (PTSD) is frequently linked with substance abuse. The self-medication hypothesis suggests that some people may use illicit substances in an attempt to self-treat psychiatric symptoms. This study explores the relationship between substance abuse and PTSD symptom clusters in a methadone maintenance population. DESIGN AND METHODS Clients of a methadone maintenance program at a public Drug and Alcohol Service were invited to complete the PTSD Checklist-Civilian Version, a screening tool for PTSD. Information about their history of substance use was also collected. RESULTS Eighty clients (43 female, 37 male), aged 35 ± 8.0 years (mean ± SD), participated in the study, of which 52.7% screened positive for PTSD. Severity of marijuana use was significantly associated with a number of reexperiencing and hyperarousal symptoms and with overall severity of PTSD symptoms. Opiate, amphetamine, and benzodiazepine use did not appear to be related to PTSD symptoms. DISCUSSION AND CONCLUSIONS In this sample, marijuana may be used to self-treat certain PTSD symptoms, supporting the self-medication hypothesis. Further research is required to confirm the association between a diagnosis of PTSD and substance use. Given the high prevalence of PTSD in the substance-using population, routine PTSD screening in the substance abuse treatment setting may be justified.

A randomised, double blind, placebo-controlled trial of a fixed dose of N-acetyl cysteine in children with autistic disorder.

Objective: Oxidative stress, inflammation and heavy metals have been implicated in the aetiology of autistic disorder. N-acetyl cysteine has been shown to modulate these pathways, providing a rationale to trial N-acetyl cysteine for autistic disorder. There are now two published pilot studies suggesting efficacy, particularly in symptoms of irritability. This study aimed to explore if N-acetyl cysteine is a useful treatment for autistic disorder. Method: This was a placebo-controlled, randomised clinical trial of 500 mg/day oral N-acetyl cysteine over 6 months, in addition to treatment as usual, in children with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis of autistic disorder. The study was conducted in Victoria, Australia. The primary outcome measures were the Social Responsiveness Scale, Children’s Communication Checklist–Second Edition and the Repetitive Behavior Scale–Revised. Additionally, demographic data, the parent-completed Vineland Adaptive Behavior Scales, Social Communication Questionnaire and clinician-administered Autism Diagnostic Observation Schedule were completed. Results: A total of 102 children were randomised into the study, and 98 (79 male, 19 female; age range: 3.1–9.9 years) attended the baseline appointment with their parent/guardian, forming the Intention to Treat sample. There were no differences between N-acetyl cysteine and placebo-treated groups on any of the outcome measures for either primary or secondary endpoints. There was no significant difference in the number and severity of adverse events between groups. Conclusion: This study failed to demonstrate any benefit of adjunctive N-acetyl cysteine in treating autistic disorder. While this may reflect a true null result, methodological issues particularly the lower dose utilised in this study may be confounders.

The utility of the Mood Disorders Questionnaire as a screening tool in a methadone maintenance treatment program

Abstract Objective. Comorbid mental illness amongst methadone maintenance therapy clients may be common and screening may be warranted. The Mood Disorders Questionnaire (MDQ) is a screening tool for bipolar disorder that has been validated in other treatment settings. Its utility for patients with substance use disorders is assessed in this study. Methods. Clients of a methadone maintenance program were invited to complete the MDQ when they attended a public Drug and Alcohol Service for their regular scheduled appointments. Information about their history of substance use was also collected. Results. Eighty clients (43 females, 37 males) aged 35 ± 8.0 years (mean ± SD) participated in the study. Seventy-four clients completed the MDQ of which 36 (48.6%) obtained a positive screen. A check of client files suggested that only three of the 74 participants had a current working diagnosis of bipolar disorder. These three participants had screened positive on the MDQ. Conclusions. There was a high prevalence of manic symptoms reported by participants, suggesting that screening for bipolar disorder in this population may be warranted. However, there is a risk of false positives with the MDQ, as it does not clearly differentiate between symptoms of mania and drug intoxication.

The utility of psychiatric screening tools in a methadone maintenance population

The Australian Schizophrenia Research Bank (ASRB) is a national resource, encompassing clinical, neuropsychological, genetic and anatomical cross-referenced data. ASRB’s aim is to collect data from 2,000 case and 2,000 controls. A clinical assessment battery (CAB) is administered over 3 hours and involves a diagnostic interview (DIP; Castle et al., 2006), measures of neuropsychological and cognitive performance, clinical and family history, symptom and general functioning rating. Instruments were selected following exhaustive consultation with ASRB investigators and clinicians. The large scale data collection across multiple sites has necessitated the development of a quality-controlled, time and cost effective data collection strategy. To this end, the ASRB has developed an electronic version of the CAB (i.e., eCAB)