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Showing papers in "Dialogues in Clinical Neuroscience in 2017"


Journal ArticleDOI
TL;DR: The treatment recommendations given in this article are based on guidelines, meta-analyses, and systematic reviews of randomized controlled studies as mentioned in this paper, and are the most prevalent psychiatric disorders, and are associated with a high burden of illness.
Abstract: Anxiety disorders (generalized anxiety disorder, panic disorder/agoraphobia, social anxiety disorder, and others) are the most prevalent psychiatric disorders, and are associated with a high burden of illness. Anxiety disorders are often underrecognized and undertreated in primary care. Treatment is indicated when a patient shows marked distress or suffers from complications resulting from the disorder. The treatment recommendations given in this article are based on guidelines, meta-analyses, and systematic reviews of randomized controlled studies. Anxiety disorders should be treated with psychological therapy, pharmacotherapy, or a combination of both. Cognitive behavioral therapy can be regarded as the psychotherapy with the highest level of evidence. First-line drugs are the selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. Benzodiazepines are not recommended for routine use. Other treatment options include pregabalin, tricyclic antidepressants, buspirone, moclobemide, and others. After remission, medications should be continued for 6 to 12 months. When developing a treatment plan, efficacy, adverse effects, interactions, costs, and the preference of the patient should be considered.

346 citations


Journal ArticleDOI
TL;DR: Methods that have been historically used for this type of research are described and new approaches that align with recent conceptualizations of disease symptomatology are highlighted that may ultimately prove to be more fruitful in facilitating the development of improved therapeutics.
Abstract: Stress is a precipitating factor for anxiety-related disorders, which are among the leading forms of psychiatric illness and impairment in the modern world. Rodent-based behavioral tests and models are widely used to understand the mechanisms by which stress triggers anxiety-related behaviors and to identify new treatments for anxiety-related disorders. Although substantial progress has been made and many of the key neural circuits and molecular pathways mediating stress responsiveness have been characterized, these advances have thus far failed to translate into fundamentally new treatments that are safer and more efficacious in humans. The purpose of this article is to describe methods that have been historically used for this type of research and to highlight new approaches that align with recent conceptualizations of disease symptomatology and that may ultimately prove to be more fruitful in facilitating the development of improved therapeutics.

186 citations


Journal ArticleDOI
TL;DR: It is emphasized that anxiety disorders are the most prevalent of the psychiatric conditions, and that rather than merely contrasting cross-national prevalence in anxiety disorders, it is more productive to delineateCross-national themes that emerge about the epidemiology of these conditions.
Abstract: On the basis of epidemiological survey findings, anxiety disorders are the most prevalent mental disorders around the world and are associated with significant comorbidity and morbidity. Such surveys rely on advances in psychiatric nosology and may also contribute usefully to revisions of the nosology. There are a number of questions at the intersection of psychiatric epidemiology and nosology. This review addresses the following: What is the prevalence of anxiety disorders and how do we best explain cross-national differences in prevalence estimates? What are the optimal diagnostic criteria for anxiety disorders, and how can epidemiological data shed light on this question? What are the comorbidities of anxiety disorders, and how do we best understand the high comorbidities seen in these conditions? What is the current treatment gap for anxiety disorders, and what are the implications of current understandings of psychiatric epidemiology and nosology for policy-making relevant to anxiety disorders? Here, we emphasize that anxiety disorders are the most prevalent of the psychiatric conditions, and that rather than merely contrasting cross-national prevalence in anxiety disorders, it is more productive to delineate cross-national themes that emerge about the epidemiology of these conditions. We discuss that optimizing diagnostic criteria for anxiety disorders is an iterative process to which epidemiological data can make a crucial contribution. Additionally, high comorbidity in anxiety disorders is not merely artefactual; it provides key opportunities to explore pathways to mental disorders and to intervene accordingly. Finally, work on the epidemiology and nosology of anxiety disorders has provided a number of important targets for mental health policy and for future integrative work to move between bench and bedside, as well as between clinic and community.

152 citations


Journal ArticleDOI
TL;DR: The objective of this article is to summarize current developments concerning cannabis and the spread of synthetic cannabinoid (SC) use, and to further explore the benefit-risk profile of medical cannabis use.
Abstract: Cannabis (also known as marijuana) is the most frequently used illicit psychoactive substance in the world. Though it was long considered to be a "soft" drug, studies have proven the harmful psychiatric and addictive effects associated with its use. A number of elements are responsible for the increased complications of cannabis use, including the increase in the potency of cannabis and an evolution in the ratio between the two primary components, Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (toward a higher proportion of Δ9-THC), Synthetic cannabinoid (SC) use has rapidly progressed over the last few years, primarily among frequent cannabis users, because SCs provide similar psychoactive effects to cannabis. However, their composition and pharmacological properties make them dangerous substances. Cannabis does have therapeutic properties for certain indications. These therapeutic applications pertain only to certain cannabinoids and their synthetic derivatives. The objective of this article is to summarize current developments concerning cannabis and the spread of SCs. Future studies must further explore the benefit-risk profile of medical cannabis use.

148 citations


Journal ArticleDOI
TL;DR: It is argued that animal models of voluntary drug intake—under nonoperant and operant conditions—and addiction models based on the Diagnostic and Statistical Manual of Mental Disorders are crucial and informative tools for the identification of pathological mechanisms, target identification, and drug development.
Abstract: In recent years, animal models in psychiatric research have been criticized for their limited translational value to the clinical situation. Failures in clinical trials have thus often been attributed to the lack of predictive power of preclinical animal models. Here, I argue that animal models of voluntary drug intake-under nonoperant and operant conditions-and addiction models based on the Diagnostic and Statistical Manual of Mental Disorders are crucial and informative tools for the identification of pathological mechanisms, target identification, and drug development. These models provide excellent face validity, and it is assumed that the neurochemical and neuroanatomical substrates involved in drug-intake behavior are similar in laboratory rodents and humans. Consequently, animal models of drug consumption and addiction provide predictive validity. This predictive power is best illustrated in alcohol research, in which three approved medications-acamprosate, naltrexone, and nalmefene-were developed by means of animal models and then successfully translated into the clinical situation.

141 citations


Journal Article
TL;DR: An increased level of inducible nitric oxide synthase observed in the substantia nigra and striatum of PD patients suggests that both cytokine—and chemokine-induced toxicity and inflammation lead to oxidative stress that contributes to degeneration of dopaminergic neurons and to disease progression.
Abstract: Parkinson disease (PD) is a neurodegenerative disorder characterized by dopaminergic neurons affected by inflammatory processes. Post-mortem analyses of brain and cerebrospinal fluid from PD patients show the accumulation of proinflammatory cytokines, confirming an ongoing neuroinflammation in the affected brain regions. These inflammatory mediators may activate transcription factors-notably nuclear factor κB, Ying-Yang 1 (YY1), fibroblast growth factor 20 (FGF20), and mammalian target of rapamycin (mTOR)-which then regulate downstream signaling pathways that in turn promote death of dopaminergic neurons through death domain-containing receptors. Dopaminergic neurons are vulnerable to oxidative stress and inflammatory attack. An increased level of inducible nitric oxide synthase observed in the substantia nigra and striatum of PD patients suggests that both cytokine-and chemokine-induced toxicity and inflammation lead to oxidative stress that contributes to degeneration of dopaminergic neurons and to disease progression. Lipopolysaccharide activation of microglia in the proximity of dopaminergic neurons in the substantia nigra causes their degeneration, and this appears to be a selective vulnerability of dopaminergic neurons to inflammation. In this review, we will look at the role of various transcription factors and signaling pathways in the development of PD.

111 citations


Journal ArticleDOI
TL;DR: This review serves as a systematic guide to the genetics of generalized anxiety disorder (GAD) and further focuses on anxiety-relevant endophenotypes, such as pathological worry fear of uncertainty, and neuroticism.
Abstract: This review serves as a systematic guide to the genetics of generalized anxiety disorder (GAD) and further focuses on anxiety-relevant endophenotypes, such as pathological worry fear of uncertainty, and neuroticism. We inspect clinical genetic evidence for the familialityl heritability of GAD and cross-disorder phenotypes based on family and twin studies. Recent advances of linkage studies, genome-wide association studies, and candidate gene studies (eg, 5-HTT, 5-HT1A, MAOA, BDNF) are outlined. Functional and structural neuroimaging and neurophysiological readouts relating to peripheral stress markers and psychophysiology are further integrated, building a multilevel disease framework. We explore etiologic factors in gene-environment interaction approaches investigating childhood trauma, environmental adversity, and stressful life events in relation to selected candidate genes (5-HTT, NPSR1, COMT, MAOA, CRHR1, RGS2), Additionally, the pharmacogenetics of selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor treatment are summarized (5-HTT, 5-HT2A, COMT, CRHR1). Finally, GAD and trait anxiety research challenges and perspectives in the field of genetics, including epigenetics, are discussed.

111 citations


Journal ArticleDOI
TL;DR: Anxiety disorders are the most prevalent psychiatric disorders and there is a high comorbidity between anxiety (especially generalized anxiety disorders or panic disorders) and depressive disorders or between anxiety disorders, which renders treatment more complex.
Abstract: Anxiety disorders are the most prevalent psychiatric disorders. There is a high comorbidity between anxiety (especially generalized anxiety disorders or panic disorders) and depressive disorders or between anxiety disorders, which renders treatment more complex. Current guidelines do not recommend benzodiazepines as first-line treatments due to their potential side effects. Selective serotonin reuptake inhibitors and selective serotonin norepinephrine reuptake inhibitors are recommended as first-line treatments. Psychotherapy, in association with pharmacotherapy, is associated with better efficacy. Finally, a bio-psycho-social model is hypothesized in anxiety disorders.

109 citations


Journal Article
TL;DR: The syndromic versus nonsyndromic designation should ultimately be replaced by classification of ASD according to its genetic etiology, which will inform about the associated spectrum and penetrance of neurobehavioral and somatic manifestations.
Abstract: Autism spectrum disorder (ASD) encompasses a group of neurodevelopmental conditions diagnosed solely on the basis of behavioral assessments that reveal social deficits. Progress has been made in understanding its genetic underpinnings, but most ASD-associated genetic variants, which include copy number variants (CNVs) and mutations in ASD-risk genes, account for no more than 1 % of ASD cases. This high level of genetic heterogeneity leads to challenges obtaining and interpreting genetic testing in clinical settings. The traditional definition of syndromic ASD is a disorder with a clinically defined pattern of somatic abnormalities and a neurobehavioral phenotype that may include ASD. Most have a known genetic cause. Examples include fragile X syndrome and tuberous sclerosis complex. We propose dividing syndromic autism into the following two groups: (i) ASD that occurs in the context of a clinically defined syndrome-recognizing these disorders depends on the familiarity of the clinician with the features of the syndrome, and the diagnosis is typically confirmed by targeted genetic testing (eg, mutation screening of FMR1); (ii) ASD that occurs as a feature of a molecularly defined syndrome-for this group of patients, ASD-associated variants are identified by genome-wide testing that is not hypothesis driven (eg, microarray, whole exome sequencing). These ASD groups cannot be easily clinically defined because patients with a given variant have variable somatic abnormalities (dysmorphism and birth defects). In this article, we review common diagnoses from the above categories and suggest a testing strategy for patients, guided by determining whether the individual has essential or complex ASD; patients in the latter group have multiple morphologic anomalies on physical examination. Finally, we recommend that the syndromic versus nonsyndromic designation ultimately be replaced by classification of ASD according to its genetic etiology, which will inform about the associated spectrum and penetrance of neurobehavioral and somatic manifestations.

92 citations


Journal ArticleDOI
TL;DR: A systematic literature review focuses on peer-reviewed studies that have used a qualitative approach to examine the development of an opioid-use disorder from the point of initial exposure, indicating that terms used in structured interviews poorly capture the complex range of needs opioids satisfy.
Abstract: Most research designed to answer the "why" of the prescription opioid epidemic has relied on structured interviews, which rigidly attempt to capture the complex reasons people use opioids. In contrast this systematic literature review focuses on peer-reviewed studies that have used a qualitative approach to examine the development of an opioid-use disorder from the point of initial exposure. Rather than simply providing a "high," opioids reportedly relieve psychological/emotional problems or provide an escape from life stressors. As use continues, avoidance of withdrawal sickness becomes an overriding concern, with all other benefits playing minor roles in persistent use. These studies indicate that terms used in structured interviews, such as "nontherapeutic use" or variations thereof, poorly capture the complex range of needs opioids satisfy. Both quantitative/structured studies and more qualitative ones, as well as more focused studies, have an important role in better informing prevention and treatment efforts.

78 citations


Journal ArticleDOI
TL;DR: Characterization of the neuropsychological mechanisms that underlie individual differences in addiction-like behaviors is the key to understanding the mechanisms of addiction and development of personalized pharmacotherapy.
Abstract: Drug addiction or substance-use disorder is a chronically relapsing disorder that progresses through binge/intoxication, withdrawal/negative affect and preoccupation/anticipation stages. These stages represent diverse neurobiological mechanisms that are differentially involved in the transition from recreational to compulsive drug use and from positive to negative reinforcement. The progression from recreational to compulsive substance use is associated with downregulation of the brain reward systems and upregulation of the brain stress systems. Individual differences in the neurobiological systems that underlie the processing of reward, incentive salience, habits, stress, pain, and executive function may explain (i) the vulnerability to substance-use disorder; (ii) the diversity of emotional, motivational, and cognitive profiles of individuals with substance-use disorders; and (iii) heterogeneous responses to cognitive and pharmacological treatments. Characterization of the neuropsychological mechanisms that underlie individual differences in addiction-like behaviors is the key to understanding the mechanisms of addiction and development of personalized pharmacotherapy.

Journal ArticleDOI
TL;DR: This paper focuses in particular on evidence from neuroimaging, genetic, and neurochemical measurements in GAD in order to better understand potential biomarkers involved in its etiology and treatment.
Abstract: Generalized anxiety disorder (GAD) is a prevalent and highly disabling mental health condition; however, there is still much to learn with regard to pertinent biomarkers, as well as diagnosis, made more difficult by the marked and common overlap of GAD with affective and anxiety disorders. Recently, intensive research efforts have focused on GAD, applying neuroimaging, genetic, and blood-based approaches toward discovery of pathogenetic and treatment-related biomarkers. In this paper, we review the large amount of available data, and we focus in particular on evidence from neuroimaging, genetic, and neurochemical measurements in GAD in order to better understand potential biomarkers involved in its etiology and treatment. Overall, the majority of these studies have produced results that are solitary findings, sometimes inconsistent and not clearly replicable. For these reasons, they have not yet been translated into clinical practice. Therefore, further research efforts are needed to distinguish GAD from other mental disorders and to provide new biological insights into its pathogenesis and treatment.

Journal ArticleDOI
TL;DR: This review focuses on the peptide oxytocin as a potential therapeutic option for individuals with social anxiety and its role in facilitation of prosocial behaviors and its anxiolytic effects.
Abstract: Social anxiety is a form of anxiety characterized by continuous fear of one or more social or performance situations. Although multiple treatment modalities (cognitive behavioral therapy, selective serotonin reuptake inhibitors/selective norepinephrine reuptake inhibitors, benzodiazepines) exist for social anxiety, they are effective for only 60% to 70% of patients. Thus, researchers have looked for other candidates for social anxiety treatment. Our review focuses on the peptide oxytocin as a potential therapeutic option for individuals with social anxiety. Animal research both in nonprimates and primates supports oxytocin's role in facilitation of prosocial behaviors and its anxiolytic effects. Human studies indicate significant associations between social anxiety and oxytocin receptor gene alleles, as well as social anxiety and oxytocin plasma levels. In addition, intranasal administration of oxytocin in humans has favorable effects on social anxiety symptomology. Other disorders, including autism, schizophrenia, and anorexia, have components of social anxiety in their pathophysiology. The therapeutic role of oxytocin for social dysfunction in these disorders is discussed.

Journal ArticleDOI
TL;DR: The current state of the science in the pursuit of early brain and behavioral markers of autism during infancy is highlighted and the potential implications of these findings for treatment of this condition are examined.
Abstract: Autism spectrum disorder (ASD) is a heterogeneous condition that affects 1 in 68 children. Diagnosis is based on the presence of characteristic behavioral impairments that emerge in the second year of life and thus is not typically made until 3 to 4 years of age. Recent studies of early brain and behavior development have provided important new insights into the nature of this condition. Autism-specific brain imaging features have been identified as early as 6 months of age, and age-specific brain and behavior changes have been demonstrated across the first 2 years of life, highlighting the developmental nature of ASD. New findings demonstrate that early brain imaging in the first year of life holds great promise for presymptomatic prediction of ASD. There is a general understanding in medicine that earlier treatment has better outcomes than later treatment, and in autism, there is an emerging consensus that earlier intervention results in more successful outcomes for the child. Examining early brain and behavior trajectories also has the potential to parse the etiologic heterogeneity in ASD, a well-recognized impediment to developing targeted, mechanistic treatments. This review highlights the current state of the science in the pursuit of early brain and behavioral markers of autism during infancy and examines the potential implications of these findings for treatment of this condition.

Journal ArticleDOI
TL;DR: Evidence pointing to the role inflammatory processes play in the pathogenesis of major psychiatric disorders is pointed to, and various immunological aspects of treatment of such disorders are looked at.
Abstract: Schizophrenia and major depression (MD) have been associated with immune system dysfunction. One example of this is the altered level of cytokines-important inflammatory mediators-in blood, and a proinflammatory immune state has been described in some subgroups of patients. A knock to the immune system in early life might trigger a life-long increased immune reactivity, and infections and autoimmune disorders are now known to be risk factors for development of schizophrenia and MD. Pro- and anti-inflammatory cytokines mediate indoleamine 2,3-dioxygenase activity; this enzyme drives metabolism of tryptophan and kynurenin in the central nervous system and degrades serotonin. Alterations of serotonergic, noradrenergic, and glutamatergic neurotransmission have been associated with low-level neuroinflammation, and anti-inflammatory compounds have a therapeutic benefit in MD and schizophrenia, as shown in meta-analyses. Moreover, antidepressants and antipsychotics have intrinsic immunomodulatory effects. With evidence pointing to the role inflammatory processes play in the pathogenesis of major psychiatric disorders, this review will look at various immunological aspects of treatment of such disorders.

Journal ArticleDOI
TL;DR: From the 19th century into the 20th century, the terms used to diagnose generalized anxiety included “pantophobia” and “anxiety neurosis,” but since the revised DSM-III, worry about a number of life circumstances has been gradually emphasized as the distinctive symptom of GAD.
Abstract: From the 19th century into the 20th century, the terms used to diagnose generalized anxiety included "pantophobia" and "anxiety neurosis." Such terms designated paroxysmal manifestations (panic attacks) as well as interparoxysmal phenomenology (the apprehensive mental state). Also, generalized anxiety was considered one of numerous symptoms of neurasthenia, a vaguely defined illness. Generalized anxiety disorder (GAD) appeared as a diagnostic category in the third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) in 1980, when anxiety neurosis was split into GAD and panic disorder. The distinct responses these two disorders had to imipramine therapy was one reason to distinguish between the two. Since the revised DSM-III (DSM-III-R), worry about a number of life circumstances has been gradually emphasized as the distinctive symptom of GAD. Thus, a cognitive aspect of anxiety has become the core criterion of GAD. The validity of GAD as an independent category has been questioned from DSM-III up to preparation of DSM-5. Areas of concern have included the difficulty to establish clear boundaries between GAD and (i) personality dimensions, (ii) other anxiety-spectrum disorders, and (iii) nonbipolar depression. The National Institute of Mental Health has recently proposed the Research Domain Criteria (RDoC), a framework destined to facilitate biological research into the etiology of mental symptoms. Within the RDoC framework, generalized anxiety might be studied as a dimension denominated "anxious apprehension" that would typically fit into the research domain called "negative valence systems" and the more specific construct termed "potential threat."

Journal ArticleDOI
TL;DR: The crosstalk between the emotional and immunological systems and the need for a new scientific area of research called affective immunology will allow a better understanding and appreciation of the immunological basis of mental disorders and the emotional side of immune diseases.
Abstract: Affect and emotion are defined as "an essential part of the process of an organism's interaction with stimuli." Similar to affect, the immune response is the "tool" the body uses to interact with the external environment. Thanks to the emotional and immunological response, we learn to distinguish between what we like and what we do not like, to counteract a broad range of challenges, and to adjust to the environment we are living in. Recent compelling evidence has shown that the emotional and immunological systems share more than a similarity of functions. This review article will discuss the crosstalk between these two systems and the need for a new scientific area of research called affective immunology. Research in this field will allow a better understanding and appreciation of the immunological basis of mental disorders and the emotional side of immune diseases.

Journal ArticleDOI
TL;DR: It is proposed that the cardinal symptom of GAD—worry—predominantly reflects stimulus-independent mental processes that impose abnormal, inflexible functional brain configurations, ie, the overall pattern of information transfer among behaviorally relevant neural circuits at a given point in time.
Abstract: Affective neuroimaging has contributed to our knowledge of generalized anxiety disorder (GAD) through measurement of blood oxygenation level-dependent (BOLD) responses, which facilitate inference on neural responses to emotional stimuli during task-based functional magnetic resonance imaging (fMRI). In this article, the authors provide an integrated review of the task-based affective fMRI literature in GAD. Studies provide evidence for variable presence and directionality of BOLD abnormalities in limbic and prefrontal regions during reactivity to, regulation of, and learning from emotional cues. We conclude that understanding the sources of this variability is key to accelerating progress in this area. We propose that the cardinal symptom of GAD-worry-predominantly reflects stimulus-independent mental processes that impose abnormal, inflexible functional brain configurations, ie, the overall pattern of information transfer among behaviorally relevant neural circuits at a given point in time. These configurations that are inflexible to change from the incoming flux of environmental stimuli may underlie inconsistent task-based findings.

Journal ArticleDOI
TL;DR: Large clinical trials comparing effective pharmacotherapies for opioid addiction (naltrexone, methadone, and buprenorphine) are needed for pharmacogenetic progress.
Abstract: Increased physician prescribing of opioids to treat chronic nonprogressive pain has been accompanied by an increase in opioid addiction. Twin studies of opioid addiction are consistent with an inherited component of risk, approximately 50%. Several genome-wide association study (GWAS) reports indicate that genetic risk for opioid addiction is conveyed by many alleles of small effect (odds ratios <1.5). These reports have detected alleles in potassium-ion-channel genes (KCNC1 and KCNG2) and in a glutamate receptor auxiliary protein (CNIH3). Additionally, a variant at the µ-opioid receptor gene (OPRM1), which regulates OPRM1 expression appears promising. In pharmacogenetics of opioid addictions, methadone dose may be regulated by variants in cytochrome P450 2B6 (CYP2B6), a methadone-metabolizing enzyme, and by a locus 300 kb 5' to OPRM1. A δ-opioid-receptor gene single-nucleotide polymorphism may predict treatment response to methadone versus buprenorphine. To achieve better progress, larger sample sizes are needed for GWAS research, including controls with chronic opioid exposure, but no addiction. Large clinical trials comparing effective pharmacotherapies for opioid addiction (naltrexone, methadone, and buprenorphine) are needed for pharmacogenetic progress.

Journal ArticleDOI
TL;DR: Novel findings on the frequency of normal sexual behaviors in high-functioning ASD individuals and those about the assessment of hypersexual and paraphilic fantasies and behaviors in ASD individuals are presented from the authors' own study.
Abstract: Like nonaffected adults, individuals with autism spectrum disorders (ASDs) show the entire range of sexual behaviors. However, due to the core symptoms of the disorder spectrum, including deficits in social skills, sensory hypo- and hypersensitivities, and repetitive behaviors, some ASD individuals might develop quantitatively above-average or nonnormative sexual behaviors and interests. After reviewing the relevant literature on sexuality in high-functioning ASD individuals, we present novel findings on the frequency of normal sexual behaviors and those about the assessment of hypersexual and paraphilic fantasies and behaviors in ASD individuals from our own study. Individuals with ASD seem to have more hypersexual and paraphilic fantasies and behaviors than general-population studies suggest. However, this inconsistency is mainly driven by the observations for male participants with ASD. This could be due to the fact that women with ASD are usually more socially adapted and show less ASD symptomatology. The peculiarities in sexual behaviors in ASD patients should be considered both for sexual education and in therapeutic approaches.

Journal ArticleDOI
TL;DR: It is concluded that parents with GAD may bias their children's processing of potential threats in the environment by conveying the message that the world is not safe, that uncertainty is intolerable, that strong emotions should be avoided, and that worry helps to cope with uncertainty, thereby transmitting cognitive styles that characterize GAD.
Abstract: Generalized anxiety disorder (GAD) runs in families. Building on recent theoretical approaches, this review focuses on potential environmental pathways for parent-to-child transmission of GAD. First, we address child acquisition of a generalized pattern of fearful/anxious and avoidant responding to potential threat from parents via verbal information and via modeling. Next, we address how parenting behaviors may contribute to maintenance of fearful/anxious and avoidant reactions in children. Finally, we consider intergenerational transmission of worries as a way of coping with experiential avoidance of strong negative emotions and with intolerance of uncertainty. We conclude that parents with GAD may bias their children's processing of potential threats in the environment by conveying the message that the world is not safe, that uncertainty is intolerable, that strong emotions should be avoided, and that worry helps to cope with uncertainty, thereby transmitting cognitive styles that characterize GAD. Our review highlights the need for research on specific pathways for parent-to-child transmission of GAD.

Journal ArticleDOI
TL;DR: A narrative of the origin of the myths around autism is presented, showing how myths that vaccines or mercury are associated with autism have been amplified by misguided scientists; frustrated, but effective parent groups; and politicians.
Abstract: Despite significant progress in the study of the epidemiology and genetics of autism, the etiology and patho-physiology of this condition is far from being elucidated and no curative treatment currently exists. Although solid scientific research continues, in an attempt to find explanations and solutions, a number of nonscientific and pure myths about autism have emerged. Myths that vaccines or mercury are associated with autism have been amplified by misguided scientists; frustrated, but effective parent groups; and politicians. Preventing the protection provided by vaccination or administration of mercury-chelating agents may cause real damage to autistic individuals and to innocent bystanders who as a result may be exposed to resurgent diseases that had already been "extinguished. " That such myths flourish is a consequence of the authority of scientific evidence obtained by scientific methodology losing ground to alternative truths and alternative science. This article presents a narrative of the origin of the myths around autism.

Journal ArticleDOI
TL;DR: There is a great need for further research on the safety and efficacy of existing psychotropic medications in youth with ASD, as well as the development of new treatment modalities for the core and associated behavioral symptoms.
Abstract: Autism spectrum disorder (ASD) is characterized by impairment in social communication and restricted patterns of behavior. Although there is no pharmacological treatment approved by the US Food and Drug Administration (FDA) for the core symptoms of ASD, there is mounting support in the literature for the management of behavioral symptoms associated with this developmental disorder, in particular, irritability and hyperactivity. Aripiprazole and risperidone are currently approved by the FDA for the treatment of irritability in youth with ASD. Though not FDA-approved, methylphenidate and guanfacine are effective for the management of hyperactivity in children with ASD. Selective serotonin reuptake inhibitors are often used in clinical practice to target anxiety and compulsions; however, there is little evidence to support its use in this population. There is a great need for further research on the safety and efficacy of existing psychotropic medications in youth with ASD, as well as the development of new treatment modalities for the core and associated behavioral symptoms.

Journal ArticleDOI
TL;DR: CBT is an effective treatment for GAD, typically leading to reductions in worry, and a study has shown that such therapy is equal to pharmaceutical treatment and more effective 6 months after study completion.
Abstract: As a form of therapy, cognitive behavioral therapy (CBT) is more than a mere "toolbox." CBT allows us to better understand how the human mind is functioning because it is based on neuroscience and experimental and scientific psychology. At the beginning, the Diagnostic and Statistical Manual of Mental Disorders (DSM) was "nontheoretical," but nowadays (the most recent version being DSM-5), it is increasingly based on CBT paradigms (with the insertion of important notions such as cognitions and behaviors). This Brief Report presents what we currently know about generalized anxiety disorder (GAD) and how we can treat this condition by nonpharmaceutical means. In the last few years, GAD theories have evolved, becoming more precise about the cognitive functioning of GAD sufferers. Here, we look at current theoretical models and the main techniques of therapeutic care, as well as the advances in research about the "transdiagnostic" process and GAD in childhood. CBT is an effective treatment for GAD, typically leading to reductions in worry, and a study has shown that such therapy is equal to pharmaceutical treatment and more effective 6 months after study completion.

Journal ArticleDOI
TL;DR: The prevalence and phenomenology of various disorders, such as generalized anxiety disorder, panic disorder, social anxiety, and phobic disorder, as well as culture-specific syndromes such as dhat and koro in India are reviewed.
Abstract: Cultural factors have influenced the presentation, diagnoses, and treatment of anxiety disorders in India for several centuries. This review covers the antecedents, prevalence, phenomenology, and treatment modalities of anxiety disorders in the Indian cultural context. It covers the history of the depiction of anxiety in India and the concept of culture in the classification of anxiety disorders, and examines the cultural factors influencing anxiety disorders in India. We review the prevalence and phenomenology of various disorders, such as generalized anxiety disorder, panic disorder, social anxiety, and phobic disorder, as well as culture-specific syndromes such as dhat and koro in India. Finally, the review examines the wide range of therapeutic modalities practiced in India, such as faith healing, psychotherapy, ayurveda, psychopharmacology, Unani medicine, homeopathy, yoga, meditation, and mindfulness. We conclude by emphasizing the significance of cultural factors in making relevant diagnoses and offering effective and holistic treatments to individuals with anxiety disorders.

Journal ArticleDOI
TL;DR: This review brings together findings from multiple species in order to better understand how the mechanisms of the neuroimmune response to stress contribute to stress-related psychopathologies, such as major depressive disorder, schizophrenia, and bipolar disorder.
Abstract: The relationship between stress challenges and adverse health outcomes, particularly for the development of affective disorders, is now well established. The highly conserved neuroimmune mechanisms through which responses to stressors are transcribed into effects on males and females have recently garnered much attention from researchers and clinicians alike. The use of animal models, from mice to guinea pigs to primates, has greatly increased our understanding of these mechanisms on the molecular, cellular, and behavioral levels, and research in humans has identified particular brain regions and connections of interest, as well as associations between stress-induced inflammation and psychiatric disorders. This review brings together findings from multiple species in order to better understand how the mechanisms of the neuroimmune response to stress contribute to stress-related psychopathologies, such as major depressive disorder, schizophrenia, and bipolar disorder.

Journal ArticleDOI
TL;DR: The neural basis behind the SM is considered, since there has been little consideration of the brain basis of systemizing and directions for future work in this field are discussed.
Abstract: In 2003, we proposed the hypersystemizing theory of autism. The theory proposes that the human mind possesses a systemizing mechanism (SM) that helps identify lawful regularities (often causal) that govern the input-operation-output workings of a system. The SM can be tuned to different levels, from low to high, with a normal distribution of individual differences in how strongly people search for such input-operation-out-put regularities in any data that is systemizable. Evidence suggests that people with autism are on average hypersystemizers, scoring higher than average on the systemizing quotient and on performance tests of systemizing. In this article, we consider the neural basis behind the SM, since there has been little consideration of the brain basis of systemizing. Finally, we discuss directions for future work in this field.

Journal Article
Marc N. Potenza1
TL;DR: Gambling and gambling disorder and compulsive sexual behaviors will be considered, particularly with respect to how behavioral addictions may be considered in the forthcoming 11th edition of the International Classification of Diseases (ICD-11).
Abstract: Over the past several decades, non-substance-use behaviors like gambling, gaming, and sex have received greater consideration as possible foci of addictions. In this article, I will review the recent history and current status of non-substance or behavioral addictions. A main focus will involve gambling and gambling disorder, given that the latter is currently the sole non-substance addictive disorder described in the main text of the current (fifth) edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Internet gaming disorder, currently in the DSM-5 section addressing conditions that may need additional research, will also be considered, as will the concept of Internet addiction. Compulsive sexual behaviors (including problematic pornography use) will be considered, particularly with respect to how behavioral addictions may be considered in the forthcoming 11th edition of the International Classification of Diseases (ICD-11).

Journal ArticleDOI
TL;DR: There is still “low-hanging fruit” to be gained in educating on the proper use of nicotine replacement medications, how smoking cessation can change blood levels of specific medications and caffeine, and how to connect with quitlines and mobile technology options.
Abstract: Tobacco use remains a global problem, and options for consumers have increased with the development and marketing of e-cigarettes and other new nicotine and tobacco products, such as "heat-not-burn" tobacco and dissolvable tobacco. The increased access to these new products is juxtaposed with expanding public health and clinical intervention options, including mobile technologies and social media. The persistent high rate of tobacco-use disorders among those with psychiatric disorders has gathered increased global attention, including successful approaches to individual treatment and organizational-level interventions. Best outcomes occur when medications are integrated with behavioral therapies and community-based interventions. Addressing tobacco in mental health settings requires training and technical assistance to remove old cultural barriers that restricted interventions. There is still "low-hanging fruit" to be gained in educating on the proper use of nicotine replacement medications, how smoking cessation can change blood levels of specific medications and caffeine, and how to connect with quitlines and mobile technology options. Future innovations are likely to be related to pharmacogenomics and new technologies that are human-, home-, and community-facing.

Journal ArticleDOI
Michael Soyka1
TL;DR: BUP differs significantly from MET in its pharmacology, side effects, and safety issues, but the risk of respiratory depression is lower than with MET, so decisions regarding the use of BUP or MET in opioid-dependent people are supported.
Abstract: Opioid maintenance treatment is the first-line approach in opioid dependence. Both the full opioid agonist methadone (MET) and the partial agonist buprenorphine (BUP) are licensed for the treatment of opioid dependence. BUP differs significantly from MET in its pharmacology, side effects, and safety issues. For example, the risk of respiratory depression is lower than with MET. The risk of diversion and injection of BUP have been reduced by also making it available as a tablet containing the opioid antagonist naloxone. This review summarizes the clinical effects of BUP and examines possible factors that can support decisions regarding the use of BUP or MET in opioid-dependent people.