Clinical trials of N-acetylcysteine in psychiatry and neurology: A systematic review

N-acetylcysteine (NAC) is recognized for its role in acetaminophen overdose and as a mucolytic. Over the past decade, there has been growing evidence for the use of NAC in treating psychiatric and neurological disorders, considering its role in attenuating pathophysiological processes associated with these disorders, including oxidative stress, apoptosis, mitochondrial dysfunction, neuroinflammation and glutamate and dopamine dysregulation. In this systematic review we find favorable evidence for the use of NAC in several psychiatric and neurological disorders, particularly autism, Alzheimer's disease, cocaine and cannabis addiction, bipolar disorder, depression, trichotillomania, nail biting, skin picking, obsessive-compulsive disorder, schizophrenia, drug-induced neuropathy and progressive myoclonic epilepsy. Disorders such as anxiety, attention deficit hyperactivity disorder and mild traumatic brain injury have preliminary evidence and require larger confirmatory studies while current evidence does not support the use of NAC in gambling, methamphetamine and nicotine addictions and amyotrophic lateral sclerosis. Overall, NAC treatment appears to be safe and tolerable. Further well designed, larger controlled trials are needed for specific psychiatric and neurological disorders where the evidence is favorable.

Does gender moderate the subjective measurement and structural paths in behavioural and cognitive aspects of gambling disorder in treatment-seeking adults?

Introduction
Gender differences have been observed in the pathogenesis of gambling disorder and gambling related urge and cognitions are predictive of relapse to problem gambling. A better understanding of these mechanisms concurrently may help in the development of more directed therapies.
Methods
We evaluated gender effects on behavioural and cognitive paths to gambling disorder from self-report data. Participants (N = 454) were treatment-seeking problem gamblers on first presentation to a gambling therapy service between January 2012 and December 2014. We firstly investigated if aspects of gambling related urge, cognitions (interpretive bias and gambling expectancies) and gambling severity were more central to men than women. Subsequently, a full structural equation model tested if gender moderated behavioural and cognitive paths to gambling severity.
Results
Men (n = 280, mean age = 37.4 years, SD = 11.4) were significantly younger than women (n = 174, mean age = 48.7 years, SD = 12.9) (p < 0.001). There was no gender difference in conceptualising latent constructs of problem gambling severity, gambling related urge, interpretive bias and gambling expectancies. The paths for urge to gambling severity and interpretive bias to gambling severity were stronger for men than women and statistically significant (p < 0.001 and p = 0.004, respectively) whilst insignificant for women (p = 0.164 and p = 0.149, respectively). Structural paths for gambling expectancies to gambling severity were insignificant for both men and women.
Conclusion
This study detected an important signal in terms of theoretical mechanisms to explaining gambling disorder and gender differences. It has implications for treatment development including relapse prevention.

Effectiveness and efficiency in the treatment of gambling disorder : reflections on the Dodo Bird Conjecture

In the field of research into the treatment of problem gambling, researchers have been attempting to identify the treatment pathways that are effective in remediating gambling disorder among people seeking help. In spite of these efforts, research results remain equivocal in relation to which components of the various treatment options are effective, echoing the familiar claim that all psychotherapy treatments are effective, the Dodo Bird Conjecture.This recent tendency towards the revival of the Dodo Bird Conjecture in the field of gambling research is due to factors ranging from a continuing lack of clarity about the effective components of treatments, subjective therapist effects and the lack of validated repeated measures of outcome to assess changes in self-reported data on gambling urge: anxiety, depression and changes in the 'gambling disorder' diagnosis over time.

Guideline-based programs in the treatment of complex PTSD

The term “post-traumatic stress disorder” (PTSD) is a relatively new diagnostic label, being formally recognized in 1980 in the Diagnostic Statistical Manual for Psychiatric Illness – Third Edition (DSM-III) of the American Psychiatric Association (APA, 1980). Complex Post-Traumatic Stress Disorder (CP) is a more recently discussed, and newly-classified, phenomenon, initially discussed in the early 1990s (Herman, 1992a). Thus, as research into effective treatments for CP is sparse, the treatment of CP is the topic of this study, in which a guideline-based treatment program developed by the researcher for the treatment of CP is implemented and evaluated. Ten individuals participated in this study, undertaking individualized, guideline-based treatment programs spanning a period of six months. In providing background information relevant to this study, an explanation is provided regarding the nature of CP, and the reasons for its consideration as a separate phenomenon to PTSD. The adequacy of the PTSD formulation in enabling effective assessment and treatment of CP is also explored, with endorsement of previous researchers’ conclusions that the CP construct is more useful than the PTSD construct for assessing and treating survivors of long-term and multiple forms of abuse. The PTSD classification is restrictive, and not necessarily appropriate for certain forms of trauma (such as prolonged trauma, or multiple forms of trauma), as such trauma experiences may lead to specific effects that lay outside those formerly associated with PTSD. Such effects include alterations in affect regulation, consciousness, self-perception, interpersonal relationships, and in systems of meaning. Following discussion regarding the PTSD/CP classification, an examination of treatment methods currently used in the treatment of PTSD, and a review of treatment outcome studies, takes place. The adequacy of primary treatment methods in treating CP symptoms is then examined, with the conclusion that a range of treatment methods could potentially be useful in the treatment of CP symptoms. Individuals with a diagnosis of CP may benefit from the adoption of an eclectic approach, drawing on different treatment options for different symptoms, and constantly evaluating client progress and re-evaluating interventions. This review of treatment approaches is followed by details of an initial study undertaken to obtain feedback from individuals who had suffered long-term/multiple trauma and who had received treatment. Participants in this initial study were asked open-ended questions regarding the treatment approach they had experienced, the most useful aspect of the treatment, the least useful aspect, and other strategies/treatment approaches that may have been useful – but which were not used. The feedback obtained from these individuals was used to inform the development of treatment guidelines for use in the main study, as were recommendations made by Chu (1998). The predominant focus of the treatment guidelines was “ego strengthening”, a term coined by Chu (1998) to describe the “initial (sometimes lengthy) period of developing fundamental skills in maintaining supportive relationships, developing self-care strategies, coping with symptomatology, improving functioning, and establishing a positive self identity” (p.75). Using a case study approach, data are then presented relating to each of the ten individuals involved in the treatment program: details of his/her trauma experience(s)and the impact of the trauma (as perceived by each individual); details of each individual’s treatment program (as planned, and as implemented); post-treatment evaluation of the positive and negative aspects of the treatment program (from the therapist’s perspective); and details of the symptoms reported by the individual post-treatment, via psychometric assessment and also during interview. Analysis and discussion of the data relating to the ten participants in the study are the focal point of this study. The evaluation of the effectiveness of each individual’s treatment has been based predominantly on qualitative data, obtained from an analysis of language (discourse analysis) used by participants to describe their symptoms pre- and post-treatment. Both blatant and subtle changes in the language used by participants to describe themselves, their behaviour, and their relationships pre- and post-treatment have provided an insight into the possible changes that occurred as a result of the treatment program. The language used by participants has been a rich source of data, one that has enabled the researcher to obtain information that could not be obtained using psychometric assessment methods. Most of the participants in this study portrayed notable changes in many of the CP symptoms, including being more stable and having improved capacity to explore their early abuse. Although no direct cause-effect relationship between the participants’ treatment program and the improvements described can be established from this study, the participants’ perception that the program assisted them with their symptoms, and reported many aspects of “ego strengthening”, is of major importance. Such self-perception of strength and empowerment is important if an individual is going to be able to deal with past trauma experiences. In fact, abreactive work may have a greater chance of succeeding if those who have experienced long-term or multiple trauma are feeling more empowered, and more stable, as were the participants in this study (post-intervention). In concluding this study, recommendations have been made in regard to the use of guideline-based treatment programs in the responsible treatment of CP. Strengths and limitations of this study have also been highlighted, and recommendations have been made regarding possibilities for future research related to CP treatment. On the whole, this study has supported strongly other research that highlights the importance of focusing on “ego strengthening” in assisting those who have suffered long-term/multiple trauma experiences. Thus, a guideline-based program focusing on assisting sufferers of long-term trauma with some, or all, of the symptoms of CP, is recommended as an important first stage of any treatment of individuals who have experienced long-term/multiple trauma, allowing them to develop the emotional and psychological strength required to deal with past traumatic events. Clinicians who are treating patients whose history depicts long-term or multiple trauma experiences (either from their childhood, or at some stage in their adult life) need, therefore, to be mindful of assessing individuals for symptoms of CP – so that they can treat these symptoms prior to engaging in any work associated directly with the past traumatic experiences.

Clinical, ethical and legal considerations in the treatment of newborns with non-ketotic hyperglycinaemia

Non-ketotic hyperglycinaemia (NKH) is a devastating neurometabolic disorder leading, in its classical form, to early death or severe disability and poor quality of life in survivors. Affected neonates may need ventilatory support during a short period of respiratory depression. The transient dependence on ventilation dictates urgency in decision-making regarding withdrawal of therapy. The occurrence of patients with apparent transient forms of the disease, albeit rare, adds uncertainty to the prediction of clinical outcome and dictates that the current practice of withholding or withdrawing therapy in these neonates be reviewed. Both bioethics and law take the view that treatment decisions should be based on the best interests of the patient. The medical-ethics approach is based on the principles of non-maleficence, beneficence, autonomy and justice. The law relating to withholding or withdrawing life-sustaining treatment is complex and varies between jurisdictions. Physicians treating newborns with NKH need to provide families with accurate and complete information regarding the disease and the relative probability of possible outcomes of the neonatal presentation and to explore the extent to which family members are willing to take part in the decision making process. Cultural and religious attitudes, which may potentially clash with bioethical and juridical principles, need to be considered.

Parent management training, comorbidity, and treatment of children with oppositional defiant disorder

This study found that Parent Management Training was a successful treatment for promary school aged children who were referred to a mental health clinic and diagnosed with Oppositional Defiant Disorder. The positive outcome was not affected by the child having comorbid disorders. These findings have relevance to the clinical field.

PTSD symptomatology in children and adolescents : treatment development and evaluation

This thesis developed, implemented and evaluated a cognitive-behavioural group treatment programme for children and adolescents experiencing symptoms of PTSD (Post-traumatic stress disorder). Results of the study indicate that symptoms of sleep disturbance and flashbacks, reduced markedly in the participants, providing a useful tool in reducing synptoms experiences by individuals exposed to trauma. The Professional portfolio presents four case studies that demonstrate the clinical application of the affect of chronic illness on the psychological adjustment of the sufferer and their families.

Clinical characteristics and management of bipolar disorder in women across the life span

Though prevalent in both genders, specific consideration needs to be given when treating a woman suffering from bipolar disorder over her lifetime. Bipolar disorder is a serious and incapacitating illness affecting an estimated 5% of women. The first episode of illness in women is usually a depressive episode. Female gender has been associated with greater axis-one comorbidity, more depressive episodes, rapid cycling and mixed affective states. Special consideration is required for the treatment of bipolar disorder during reproductive events. More studies are required to better understand the course, outcome and gender-specific treatment strategies of this disorder.

Disrupting disordered neurocircuitry : treating refractory psychiatric illness with neuromodulation

Despite the premature and somewhat infamous rise and fall of psychosurgery in the mid-20th century, the current era of functional neuromodulation proffers immense opportunity for surgical intervention in treatment-resistant psychiatric disorders. On the basis of recent successes with novel, focused, less invasive, and reversible treatment strategies for movement disorders, several therapeutic trials have been conducted to investigate the effectiveness of deep brain stimulation (DBS) in treatment-resistant depression, obsessive-compulsive disorder (OCD), and Tourette syndrome. The many anatomic targets for these psychiatric disorders are indicative of both the system-wide effects of DBS and the network-level dysfunction mediating the emotional and cognitive disturbances. To gain insight into the application of neuromodulation therapies and their further advancement, we must elucidate neuroanatomic networks involved in refractory psychiatric illness, the neurophysiological anomalies that contribute to disordered information processing therein, and the local and system-wide modulatory effects of DBS. This review discusses the history of psychosurgical procedures, recent DBS clinical data, current anatomic models of psychopathology, and possible therapeutic mechanisms of action of DBS neuromodulation. Our search criteria for PubMed included combinations of the following terms: neuromodulation, DBS, depression, OCD, Tourette syndrome, mechanism of action, and history. Dates were not restricted. As clinical and basic scientific investigations probe the neuromodulatory effects of DBS in the treatment of refractory neuropsychiatric illness, our knowledge of these disorders and our potential to treat them are rapidly expanding. Indeed, this modern era of neuromodulation may provide the key that unlocks many of the mysteries pertaining to the biological basis of disordered emotional neurocircuitry.

Youth (in)justice : oral language competence in early life and risk for engagement in antisocial behaviour in adolescence

Youth offenders are complex and challenging for policymakers and practitioners alike and face high risks for long-term disadvantage and social marginalisation. In many cases, this marginalisation from the mainstream begins in early life, particularly in the classroom, where they have difficulty both with language/literacy tasks and with the interpersonal demands of the classroom. Underlying both sets of skills is oral language competence—the ability to use and understand spoken language in a range of situations and social exchanges, in order to successfully negotiate the business of everyday life. This paper highlights an emerging field of research that focuses specifically on the oral language skills of high-risk young people. It presents evidence from Australia and overseas that demonstrates that high proportions (some 50% in Australian studies) of young offenders have a clinically significant, but previously undetected, oral language disorder. The evidence presented in this paper raises important questions about how young offenders engage in forensic interviews, whether as suspects, victims or witnesses. The delivery of highly verbally mediated interventions such as counselling and restorative justice conferencing is also considered in the light of emerging international evidence on this topic.

The relationship between body dysmorphic disorder symptoms and self-construals

Background:  Cognitive models of body dysmorphic disorder (BDD) suggest that beliefs and evaluations related to self-concept are central to the maintenance of the disorder, but such beliefs have received little empirical attention. This study examined the relative importance of contingent self-worth and self-ambivalence to BDD symptoms in comparison to their importance to obsessive–compulsive disorder and social phobia symptoms.

Method:  The sample comprised 194 non-clinical participants (female, N = 148; males, N = 46) with a mean age of 24.70 years (standard deviation = 9.34). Participants were asked to complete a battery of self-report questionnaires. Results:  While significant relationships were found between the self-beliefs and symptoms of all three disorders, some specificity was found in the relationships.

Conclusions:  Self-worth based upon appearance was most important in BDD, while contingent self-worth based on the approval of others was important in social phobia. Self-ambivalence was associated with each disorder. Implications and limitations are discussed.

The influence of confidence in memory on checking behaviours

Recent theories of Obsessive Compulsive Disorder have suggested that meta-cognitive beliefs, particular confidence in memory, may relate to the maintenance of symptoms. For example, individuals who worry that their memory is deficient may check in order to ensure that the doors are locked, regardless of their actual memory ability. While studies have related meta-memory beliefs to OCD symptoms, and have found that memory is affected by checking behaviours; to date, no experimental literature has attempted to ascertain whether lowered confidence in memory directly leads to greater checking behaviours. In the current study 46 non-clinical participants completed a battery of questionnaires measuring these constructs, before undertaking a “memory task” designed to manipulate their level of confidence in their memory. The effect of the manipulation on the level of checking on a visuomemory task was subsequently assessed. The questionnaires indicated that cognitive confidence predicted variation in obsessive-compulsive symptoms over-and-above the influence of depressive symptoms and other OCD-related beliefs. However, while confidence in memory was successfully manipulated, the group with increased memory confidence was not found to have lower checking behaviours. Limitations of the study are discussed and directions for further research are suggested.

Cost-utility analysis of different treatments for post-traumatic stress disorder in sexually abused children

Post-traumatic stress disorder (PTSD) is diagnosed in 20% to 53% of sexually abused children and adolescents. Living with PTSD is associated with a loss of health-related quality of life. Based on the best available evidence, the NICE Guideline for PTSD in children and adolescents recommends cognitive behavioural therapy (TF-CBT) over non-directive counselling as a more efficacious treatment.