Recent advances in autism spectrum disorders

OBJECTIVE: This review article provides an overview of the most recent developments in the literature regarding autism spectrum disorders including epidemiology, etiology, assessment, and management/treatment. METHOD: A review of the recent literature was conducted using Medline and the search term "Autism Spectrum Disorders." RESULTS: Autism Spectrum Disorders are more common than previously believed (1 in 166), and etiology appears to be multifaceted including both heritable and non-heritable factors. State of the art treatment includes comprehensive medical monitoring as well as behavioral intervention. CONCLUSIONS: Current and anticipated federal funding, policy changes, and large scale research projects provide promise for increasing knowledge about Autism Spectrum Disorders.     

Recent advances in the prevention of mental disorders

Purpose

Prevention of mental disorders is a rapidly growing area of research with substantial potential benefits for population health. This paper reviews the evidence base for prevention of depression, anxiety, and schizophrenia.

Methods

We synthesized evidence from recent systematic reviews and meta-analyses published between 2013 and 2018 on prevention of depression, anxiety, and first-episode psychosis. We included reviews of randomized controlled trials testing psychological, psychosocial, and pharmacological preventive interventions.

Results

There is good evidence that depression and anxiety can be prevented, although effect sizes are generally small. Indicated prevention of first-episode psychosis appears promising. Economic evaluations provide support for prevention of depression, anxiety, and first-episode psychosis, but more studies evaluating costs and benefits are needed to strengthen the knowledge base, particularly regarding long-term outcomes, which include chronicity of the prevented disorder, as well as later occurence of important comorbid mental and physical health problems. Promising areas for further development include internet- or computer-based prevention strategies, mindfulness-based interventions, and integration of prevention programs within occupational settings.

Conclusions

A number of interventions to prevent mental disorders are efficacious. While intervention effect sizes are generally small for prevention of depression and anxiety, they may nonetheless be of significant population benefit. Using the growing evidence base to inform policy and dissemination of evidence-based prevention programs is critical for moving prevention science into real-world settings.

     

Neuroplasticity in addictive disorders

Compulsive drug-taking behavior develops in vulnerable individuals who ingest substances that activate the reward system. This intense activation produces learned associations to cues that predict drug availability. With repetition the reward system becomes reflexively activated by cues alone, leading to a drive toward drug-taking. The central nervous system changes underlying this conditioned behavior are just beginning to be understood. New treatments aimed at this neuroplasticity are being tested in animal models. The clinical significance of these brain changes is that addiction, once established, becomes a chronic illness with relapses and remissions, it therefore requires chronic treatment with medications and behavioral therapies based on an understanding of the fundamental nature of these changes in the brain.     

Recent advances of the treatment in metabolic disorders]

Familial amyloid polyneuropathy (FAP) and adult type (type II) citrullinemia are caused by metabolic disorders in liver: the vast majority of serum amyloid precursors (variant forms of transthyretin) in FAP are produced in liver and adult citrullinemia is ascribed to a deficiency of argininosuccinate synthetase (ASS), one of the five urea cycle enzymes in liver. Liver transplantation is, therefore, expected to correct the underlying metabolic abnormalities in both diseases. We performed partial liver transplantation using grafts from living donors for 13 patients with FAP and outcomes of 10 patients are satisfactory: polyneuritic and autonomic symptoms are gradually improving. The remaining 3 patients, all of whom were at advanced stages of the disease, had adverse postoperative results, presumably because of serious dysfunctions of amyloid-laden systemic organs. Similarly seven patients with adult citrullinemia received this transplantation and all recovered uneventfully. After operation plasma levels of ammonia and citrulline were soon normalized and five patients had returned to their previous social lives. Liver transplantation is a very promising therapy for the liver-based metabolic disorders.     

Recent advances in the psychopharmacological treatment of anxiety disorders

The authors review recent progress in the pharmacological treatment of anxiety disorders. Most research within the last five years has focused on panic disorder; the findings include support for the usefulness of imipramine and clomipramine and probably other agents; evidence that the benzodiazepines alprazolam, diazepam, lorazepam, and clonazepam are approximately equally effective as antipanic agents; and high variability in relapse rates after discontinuation of drug treatment. Further work is required to determine whether buspirone and other forthcoming serotonin agonist drugs have a role in treating panic disorder and other anxiety disorders. For generalized anxiety disorder, scientific studies do not support the effectiveness of beta blocker; tricyclics may be potentially useful. Psychopharmacological treatments for social phobia, obsessive-compulsive disorder, and posttraumatic stress disorder are also reviewed.     

Recent advances in atypical parkinsonian disorders.

Recent advances in epidemiologic, diagnostic, pathologic, and management aspects of atypical parkinsonian disorders are reviewed and placed in perspective. The implications of considering progressive supranuclear palsy and corticobasal degeneration as tauopathies, and multiple system atrophy and dementia with Lewy bodies as alpha-synucleopathies are discussed.     

Recent advances in the diagnosis and treatment of balance disorders

Here we summarize the recent progress made in the diagnosis and treatment of balance and gait disorders. Focusing on work published in the Journal of Neurology in 2010 and 2011, we have found evidence for the following clinically relevant statements: (1) the exclusion of stroke in acute vestibular syndromes is based on the bedside clinical findings; (2) the risk of developing secondary somatoform vertigo is predictable; it is especially high in patients with vestibular migraine; (3) postural imbalance and falls in Parkinson syndromes are related to dysfunction of the cholinergic midbrain thalamic axis; (4) aminopyridines improve a variety of cerebellar parameters including central nystagmus and gait variability.     

Sex differences in addictive disorders

Gender-dependent differences in the rate of initiation and frequency of misuse of addicting drugs have been widely described. Yet, men and women also differ in their propensity to become addicted to other rewarding stimuli (e.g., sex, food) or activities (e.g., gambling, exercising). The goal of the present review is to summarize current evidence for gender differences not only in drug addiction, but also in other forms of addictive behaviours. Thus, we first reviewed studies showing gender-dependent differences in drug addiction, food addiction, compulsive sexual activity, pathological gambling, Internet addiction and physical exercise addiction. Potential risk factors and underlying brain mechanisms are also examined, with particular emphasis given to the role of sex hormones in modulating addictive behaviours. Investigations on factors allowing the pursuit of non-drug rewards to become pathological in men and women are crucial for designing gender-appropriate treatments of both substance and non-substance addictions.     

Recent advances in newborn screening for neurometabolic disorders

PURPOSE OF REVIEW: Newborn screening for neurometabolic disorders offers a unique and promising opportunity to practice preventive medicine in children with diverse inborn errors of metabolism. The benefits of the early identification and presymptomatic treatment of these disorders are now recognized. RECENT FINDINGS: The rapid pace of developments in the field of expanded newborn screening has been made possible by technological advances in the ability to detect multiple compounds diagnostic of diverse inborn errors of metabolism in neonatal dried blood specimens. Launched by the success of newborn screening for phenylketonuria, experts in this area are optimistic that further public health benefits will follow the same pathway. This review highlights the population model and public health issues inherent in advances in newborn screening for selected neurometabolic disorders. Current and future diagnostic and therapeutic, as well as social and ethical, dilemmas are discussed. SUMMARY: Newborn screening represents one of the major child health advances of this past century. As developments in the field of expanded newborn screening for neurometabolic disease progress forward, the long-term success of this important project will pose future challenges and opportunities.     

Children's language disorders: Recent research advances

Between 3 and 8% of preschool children in Britain and the United States are delayed in their language development by more than a year below the normal range. Evidence suggests that such children are Particularly impaired in acquiring syntactic and morphological rules, although well-defined syndromes of impaired language development have not yet been determined. The effects of preschool impairments in language development on subsequent school achievement are significant: 60% of these children are in special classes for the learning impaired at 9 years of age. Auditory processing deficits have been demonstrated in language-impaired children, but the contributions of such deficits to language development difficulties have yet to be determined. While autistic children have severe cognitive disorders and visual and auditory perceptual disturbances, the difficulties of nonautistic languageimpaired children seem confined more to language expression and comprehension. Recent neuropsychological evidence concerning brain organization for language behavior suggests that these children have deficiencies in language function which normally depend on left hemisphere functioning.     

Recent advances in the theories of and interventions with attachment disorders

PURPOSE OF REVIEW: The present review examines the available literature to consider recent advances in the theories of, and interventions with, disorders of attachment. We discuss the existing evidence to argue that the conceptualization of attachment disorders remains problematic despite their clinical significance. RECENT FINDINGS: Research into clinical disorders of attachment is limited, but there is some recent evidence that a standardized approach to diagnosis may improve identification. The current classificatory systems do not accommodate all clinical presentations and proposed broader approaches have greater clinical utility. A recent review of interventions for attachment disordered children confirms that 'coercive' interventions have no empirical support and are not biased on coherent principles of attachment theory. SUMMARY: Clinical interest in identification and treatment of attachment disorders has remained high. This is despite continuing confusion regarding terminology, phenomenology and diagnosis. The lack of agreed definition and conceptualization of these conditions is reflected in disparate approaches to intervention and limited empirical data. Interventions have little demonstrated benefit and some potential risk.     

Recent advances in the understanding of tau protein and movement disorders

Tau plays an important role in movement disorders. The accumulation of pathological tau is a major substrate of frontotemporal dementia and parkinsonism linked to chromosome 17, progressive supranuclear palsy, and corticobasal degeneration. Over the past year, several new mutations on the tau gene have been found. These mutations have been classified into three groups: (i) mutations in constitutively spliced exons; (ii) mutations in the alternatively spliced exon 10; and (iii) mutations of the exon 10 5' splice site. Some patients presenting with frontotemporal dementia and parkinsonism linked to chromosome 17 transiently respond to levodopa therapy. The significance of Pick bodies was recognized by a recent study on kindred with the Glu342Val tau mutation. In sporadic cases of progressive supranuclear palsy, the presence of the H1 haplotype was found to be a risk factor. Corticobasal degeneration shares a common genetic background with progressive supranuclear palsy. This opens the question of whether corticobasal degeneration represents a separate disorder or a spectrum of disease with progressive supranuclear palsy. However, distinguishing features are observed, and include oculomotor abnormalities, which may help to differentiate these two disorders on clinical grounds. Despite recent advances in the understanding of the tauopathies, there are still no curative therapies available. It is hoped that studies in transgenic tau animal models will lead to the development of successful treatments.     

Medical comorbidity in addictive disorders.

Greater risks exist for medical comorbidities in persons with addictive disorders. Clinicians should screen for early comorbidities such as hepatitis C and HIV. During acute intoxications and overdoses, patients are at greater risk for major respiratory and cardiac events. Long-term management of persons with addictions and medical disorders requires integrative care programs involving comprehensive primary and psychiatric care.     

Continuing care in the treatment of addictive disorders

Newer models of continuing care in the addictions are designed to improve the long-term management of substance use disorders by engaging patients into flexible, or “adaptive,” treatment algorithms that change in focus and intensity as symptoms wax and wane over time. This article describes some of these newer approaches to the management of substance use disorders and presents recent research on their effectiveness. Findings suggest the following: 1) Continuing care interventions of a year or longer are more likely to show significant positive effects; 2) Continuing care treatments that are less burdensome to patients appear to promote higher rates of sustained engagement; 3) More structured and intensive continuing care may be more effective for patients with severe substance dependence and associated problems and for those who fail to achieve reasonable progress while in the initial phase of treatment; and 4) Use of medications as part of continuing care is increasing.     

Dependency and suicidality in addictive disorders

Excessive interpersonal dependency has been described in depression and addictive disorders. Moreover, excessive dependency and suicidality are linked in psychiatric subjects, but their relationships have not been studied in specific addictions. Separate samples of female anorectic patients (n=150), female bulimic patients (n=95), male (n=150) or female (n=68) alcoholics, male (n=94) or female (n=54) drug abusers and non-psychiatric control subjects (n=683) were included in the study. On the basis of a structured interview, suicidal ideations, number of previous suicide attempts and diagnoses of dependent personality disorder (DSM-IV) were collected, and the subjects completed the Interpersonal Dependency Inventory and the Beck Depression Inventory. Logistic regression analysis revealed that excessive dependency and notably dependent personality disorder increased the likelihood of suicidal ideation or suicide attempts with a range of 2.65 to 9.42 in bulimic patients, female alcoholics and male drug abusers. Excessive dependency in specific addictive disorders as well as in male non-psychiatric subjects could constitute a risk factor for suicide. This hypothesis must be confirmed using prospective studies.     

The genetic basis of addictive disorders

Addictions are common, chronic, and relapsing diseases that develop through a multistep process. The impact of addictions on morbidity and mortality is high worldwide. Twin studies have shown that the heritability of addictions ranges from 0.39 (hallucinogens) to 0.72 (cocaine). Twin studies indicate that genes influence each stage from initiation to addiction, although the genetic determinants may differ. Addictions are by definition the result of gene × environment interaction. These disorders, which are in part volitional, in part inborn, and in part determined by environmental experience, pose the full range of medical, genetic, policy, and moral challenges. Gene discovery is being facilitated by a variety of powerful approaches, but is in its infancy. It is not surprising that the genes discovered so far act in a variety of ways: via altered metabolism of drug (the alcohol and nicotine metabolic gene variants), via altered function of a drug receptor (the nicotinic receptor, which may alter affinity for nicotine but as discussed may also alter circuitry of reward), and via general mechanisms of addiction (genes such as monoamine oxidase A and the serotonin transporter that modulate stress response, emotion, and behavioral control). Addiction medicine today benefits from genetic studies that buttress the case for a neurobiologic origin of addictive behavior, and some general information on familially transmitted propensity that can be used to guide prevention. A few well-validated, specific predictors such as OPRM1, ADH1B, ALDH2, CHRNA5, and CYP26 have been identified and can provide some specific guidance, for example, to understand alcohol-related flushing and upper GI cancer risk (ADH1B and AKLDH2), variation in nicotine metabolism (CYP26), and, potentially, naltrexone treatment response (OPRM1). However, the genetic predictors available are few in number and account for only a small portion of the genetic variance in liability, and have not been integrated into clinical nosology or care.     

Recent advances in behavioral assessment of individuals with disorders of consciousness

PURPOSE OF REVIEW: The burden of proof for establishing diagnosis and prognosis in patients with disorders of consciousness lies with behavioral assessment methods. The current review discusses recent advances in understanding the strengths and weaknesses of this methodology. RECENT FINDINGS: Behavioral assessment methods remain the 'gold standard' for establishing diagnosis and prognosis in patients with disorders of consciousness, although their psychometric integrity and clinical utility remain largely unproven. While the Glasgow Coma Scale maintains its standing in the trauma setting, there are ongoing concerns regarding testing confounds and interrater reliability. The Full Outline of UnResponsiveness, an emerging alternative, is more sensitive to detection of locked-in syndrome but may fail to identify patients in the minimally conscious state. Recent studies investigating the relationship between behavioral and neurophysiologic measures of conscious awareness have revealed important dissociations between behavioral response profiles and corresponding neural activity. SUMMARY: Further research is needed on the psychometric properties of existing behavioral assessment methods for disorders of consciousness. Although dissociations between behavioral and neurophysiologic findings caution against overreliance on behavioral metrics for detection of conscious awareness, we expect there will be increased effort toward combining these methodologies to increase diagnostic accuracy and prognostic specificity in patients with disorders of consciousness.