Showing papers in "Frontiers in Psychiatry in 2016"
TL;DR: The present review reveals the coexistence relationship between problematic cell-phone use and substance use such as tobacco and alcohol and defines a distinct user profile that differentiates it from Internet addiction.
Abstract: We present a review of the studies that have been published about addiction to cell phones. We analyse the concept of cell phone addiction as well as its prevalence, study methodologies, psychological features and associated psychiatric comorbidities. Research in this field has generally evolved from a global view of the cell phone as a device to its analysis via applications and contents. The diversity of criteria and methodological approaches that have been used is notable, as is a certain lack of conceptual delimitation that has resulted in a broad spread of prevalent data. There is a consensus about the existence of cell phone addiction, but the delimitation and criteria used by various researchers vary. Cell phone addiction shows a distinct user profile that differentiates it from Internet addiction. Without evidence pointing to the influence of cultural level and socioeconomic status, the pattern of abuse is greatest among young people, primarily females. Intercultural and geographical differences have not been sufficiently studied. The problematic use of cell phones has been associated with personality variables such as extraversion, neuroticism, self-esteem, impulsivity, self-identity and self-image. Similarly, sleep disturbance, anxiety, stress, and, to a lesser extent, depression, which are also associated with Internet abuse, have been associated with problematic cell phone use. In addition, the present review reveals the coexistence relationship between problematic cell phone use and substance use such as tobacco and alcohol.
426 citations
TL;DR: This review provides an outline of the association between major depressive disorder (MDD) and coronary heart disease (CHD), and the activation of stress pathways have been implicated as a neurochemical mechanism that links MDD and CHD.
Abstract: This review provides an outline of the association between major depressive disorder (MDD) and coronary heart disease (CHD). Much is known about the two individual clinical conditions; however, it is not until recently, biological mechanisms have been uncovered that link both MDD and CHD. The activation of stress pathways have been implicated as a neurochemical mechanism that links MDD and CHD. Depression is known to be associated with poorer outcomes of CHD. Psychological factors, such as major depression and stress, are now known as risk factors for developing CHD, which is as important and is independent of classic risk factors, such as hypertension, diabetes mellitus, and cigarette smoking. Both conditions have great socioeconomic importance given that depression and CHD are likely to be two of the three leading causes of global burden of disease. Better understanding of the common causal pathways will help us delineate more appropriate treatments.
259 citations
TL;DR: The paper focuses on the two leading virtual technologies – augmented reality (AR) and virtual reality (VR) – exploring their current uses in behavioral health and the outcomes of the 28 available systematic reviews and meta-analyses.
Abstract: During our life we undergo many personal changes: we change our house, our school, our work and even our friends and partners. However, our daily experience shows clearly that in some situations subjects are unable to change even if they want to. The recent advances in psychology and neuroscience are now providing a better view of personal change, the change affecting our assumptive world: a) the focus of personal change is reducing the distance between self and reality (conflict); b) this reduction is achieved through (1) an intense focus on the particular experience creating the conflict or (2) an internal or external reorganization of this experience; c) personal change requires a progression through a series of different stages; d) clinical psychology is often used to facilitate personal change when subjects are unable to move forward. Starting from these premises, the aim of this paper is to review the potential of virtuality for enhancing the processes of personal and clinical change. First, the paper will focus on the two leading virtual technologies – Augmented Reality (AR) and Virtual Reality (VR) – exploring their current uses in behavioral health and the outcomes of the 28 available systematic reviews and meta-analyses. Then the paper discusses the added value provided by VR and AR in transforming our external experience, by focusing on the high level of self-reflectiveness and personal efficacy induced by their emotional engagement and sense of presence. Finally, it outlines the potential future use of virtuality for transforming our inner experience by structuring, altering and/or replacing our bodily self-consciousness. The final outcome may be a new generation of transformative experiences that provide knowledge that is epistemically inaccessible to the individual until he or she has that experience, while at the same time transforming the individual’s worldview.
243 citations
TL;DR: It is concluded that interoception represents a viable avenue for clinical and translational research in psychiatry, with a well-established conceptual framework, a neural basis, measurable biomarkers, interdisciplinary appeal, and transdiagnostic targets for understanding and improving mental health outcomes.
Abstract: Disrupted interoception is a prominent feature of the diagnostic classification of several psychiatric disorders. However, progress in understanding the interoceptive basis of these disorders has been incremental and the application of interoception in clinical treatment is currently limited to panic disorder. To examine the degree to which the scientific community has recognized interoception as a construct of interest, we identified and individually screened all articles published in the English language on interoception and associated root terms in Pubmed, Psychinfo and ISI Web of Knowledge. This search revealed that interoception is a multifaceted process that is being increasingly studied within the fields of psychiatry, psychology, neuroscience and biomedical science. To illustrate the multifaceted nature of interoception we provide a focused review of one of the most commonly studied interoceptive channels, the cardiovascular system, and give a detailed comparison of the most popular methods used to study cardiac interoception. We subsequently review evidence of interoceptive dysfunction in panic disorder, depression, somatic symptom disorders, anorexia nervosa, and bulimia nervosa. For each disorder, we suggest how interoceptive predictions constructed by the brain may erroneously bias individuals to express key symptoms and behaviors, and outline questions that are suitable for the development of neuroscience-based mental health interventions. We conclude that interoception represents a viable avenue for clinical and translational research in psychiatry, with a well-established conceptual framework, a neural basis, measurable biomarkers, interdisciplinary appeal, and transdiagnostic targets for understanding and improving mental health outcomes.
213 citations
TL;DR: The findings indicate a significant electrophysiological and behavioral impact of the pretrial state of the hippocampus that suggests an important role for this MTL system in associative learning and a significant deleterious impact in the absence of theta.
Abstract: Typical information processing is thought to depend on the integrity of neurobiological oscillations that may underlie coordination and timing of cells and assemblies within and between structures. The 3-7 Hz bandwidth of hippocampal theta rhythm is associated with cognitive processes essential to learning and depends on the integrity of cholinergic, GABAergic, and glutamatergic forebrain systems. Since several significant psychiatric disorders appear to result from dysfunction of medial temporal lobe (MTL) neurochemical systems, preclinical studies on animal models may be an important step in defining and treating such syndromes. Many studies have shown that the amount of hippocampal theta in the rabbit strongly predicts the acquisition rate of classical eyeblink conditioning and that impairment of this system substantially slows the rate of learning and attainment of asymptotic performance. Our lab has developed a brain-computer interface that makes eyeblink training trials contingent upon the explicit presence or absence of hippocampal theta. The behavioral benefit of theta-contingent training has been demonstrated in both delay and trace forms of the paradigm with a two- to fourfold increase in learning speed over non-theta states. The non-theta behavioral impairment is accompanied by disruption of the amplitude and synchrony of hippocampal local field potentials, multiple-unit excitation, and single-unit response patterns dependent on theta state. Our findings indicate a significant electrophysiological and behavioral impact of the pretrial state of the hippocampus that suggests an important role for this MTL system in associative learning and a significant deleterious impact in the absence of theta. Here, we focus on the impairments in the non-theta state, integrate them into current models of psychiatric disorders, and suggest how improvement in our understanding of neurobiological oscillations is critical for theories and treatment of psychiatric pathology.
180 citations
TL;DR: Mental pain is a core clinical factor for understanding suicide, both in the context of mood disorders and independently from depression, even in the absence of a diagnosed mental disorder.
Abstract: Background: Mental pain, defined as a subjective experience characterized by perception of strong negative feelings and changes in the self and its function, is no less real than other types of grief. Mental pain has been considered to be a distinct entity from depression. We have performed a systematic review analyzing the relationship between mental pain and suicide by providing a qualitative data synthesis of the studies. Methods: We have conducted, in accordance with PRISMA guidelines, a systematic search for literature in PubMed, Web Of Science, and Scopus. Search terms were ‘mental pain’ “OR” ‘psychological pain’ OR ‘psychache’ combined with the Boolean “AND” operator with ‘suicid*’. In addition, a manual search of the literature, only including the term ‘psychache’, was performed on Google Scholar for further studies not yet identified. Results: Initial search identified 1450 citations. A total of 42 research reports met the predefined inclusion criteria and were analyzed. Mental pain was found to be a significant predictive factor of suicide risk, even in the absence of a diagnosed mental disorder. Specifically, mental pain is a stronger factor of vulnerability of suicidal ideation than depression. Conclusions: Mental pain is a core clinical factor for understanding suicide, both in the context of mood disorders and independently from depression. Health care professionals need to be aware of the higher suicidal risk in patients reporting mental pain. In this regard, psychological assessment should include a clinimetric evaluation of mental pain in order to further detect its contribution to suicidal tendency.
172 citations
TL;DR: A simple model is derived of how the different factors, such as sample heterogeneity and study setup determine this ML effect size, and explain the variation in prediction accuracies found from the literature, both in cross-validation and independent sample testing are explained.
Abstract: Recently it was suggested that much larger cohorts are needed to prove the diagnostic value of neuroimaging biomarkers in psychiatry. While within a sample increase of diagnostic accuracy of schizophrenia with number of subjects (N) has been shown, the relationship between N and accuracy is completely different between studies. Using data from a meta-analysis of machine learning in imaging schizophrenia, we found that while low-N studies can reach 90% and higher accuracy, above N/2=50 the maximum accuracy achieved steadily drops to below 70% for N/2>150. We investigate the role N plays in the wide variability in accuracy results (63-97%). We hypothesize that the underlying cause of the decrease in accuracy with increasing N is sample heterogeneity. While smaller studies more easily include a homogeneous group of subjects (strict inclusion criteria are easily met; subjects live close to study site), larger studies inevitably need to relax the criteria / recruit from large geographic areas. A schizophrenia prediction model based on a heterogeneous group of patients with presumably a heterogeneous pattern of structural or functional brain changes will not be able to capture the whole variety of changes, thus being limited to patterns shared by most patients. In addition to heterogeneity, we investigate other factors influencing accuracy and introduce a machine learning effect size. We derive a simple model of how the different factors such as sample heterogeneity determine this effect size, and explain the variation in prediction accuracies found from the literature, both in cross-validation and independent sample testing. From this we argue that smaller-N studies may reach high prediction accuracy at the cost of lower generalizability to other samples. Higher-N studies, on the other hand, will have more generalization power, but at the cost of lower accuracy. In conclusion, when comparing results from different machine learning studies, the sample sizes should be taken into account. To assess the generalizability of the models, validation of the prediction models should be tested in independent samples. The prediction of more complex measures such as outcome, which are expected to have an underlying pattern of more subtle brain abnormalities, will require large (multicenter) studies.
170 citations
TL;DR: It is suggested it is time for researchers, clinicians, developers, and end-users to collaborate on these aspects in order to maximize the impact of e-therapies and serious gaming.
Abstract: Internet interventions for mental health, including serious games, online programs, and apps, hold promise for increasing access to evidence-based treatments and prevention. Many such interventions have been shown to be effective and acceptable in trials; however, uptake and adherence outside of trials is seldom reported, and where it is, adherence at least, generally appears to be underwhelming. In response, an international Collaboration On Maximizing the impact of E-Therapy and Serious Gaming (COMETS) was formed. In this perspectives' paper, we call for a paradigm shift to increase the impact of internet interventions toward the ultimate goal of improved population mental health. We propose four pillars for change: (1) increased focus on user-centered approaches, including both user-centered design of programs and greater individualization within programs, with the latter perhaps utilizing increased modularization; (2) Increased emphasis on engagement utilizing processes such as gaming, gamification, telepresence, and persuasive technology; (3) Increased collaboration in program development, testing, and data sharing, across both sectors and regions, in order to achieve higher quality, more sustainable outcomes with greater reach; and (4) Rapid testing and implementation, including the measurement of reach, engagement, and effectiveness, and timely implementation. We suggest it is time for researchers, clinicians, developers, and end-users to collaborate on these aspects in order to maximize the impact of e-therapies and serious gaming.
127 citations
TL;DR: A systematic meta-analysis over all studies available to date relating EEG microstates to schizophrenia showed medium size effects for two classes of microstates, namely, a class labeled C that was found to be more frequent in schizophrenia and a class named D that was finding to be shortened.
Abstract: Schizophrenia patients show abnormalities in a broad range of task demands. Therefore, an explanation common to all these abnormalities has to be sought independently of any particular task, ideally in the brain dynamics before a task takes place or during resting state. For the neurobiological investigation of such baseline states, EEG microstate analysis is particularly well suited, because it identifies subsecond global states of stable connectivity patterns directly related to the recruitment of different types of information processing modes (e.g., integration of top-down and bottom-up information). Meanwhile, there is an accumulation of evidence that particular microstate networks are selectively affected in schizophrenia. To obtain an overall estimate of the effect size of these microstate abnormalities, we present a systematic meta-analysis over all studies available to date relating EEG microstates to schizophrenia. Results showed medium size effects for two classes of microstates, namely, a class labeled C that was found to be more frequent in schizophrenia and a class labeled D that was found to be shortened. These abnormalities may correspond to core symptoms of schizophrenia, e.g., insufficient reality testing and self-monitoring as during auditory verbal hallucinations. As interventional studies have shown that these microstate features may be systematically affected using antipsychotic drugs or neurofeedback interventions, these findings may help introducing novel diagnostic and treatment options.
119 citations
TL;DR: Improved community and professional awareness about TS and related comorbidities and other psychopathologies as well as the provision of multidisciplinary services to meet the complex needs of this clinical population are critical.
Abstract: Tourette syndrome (TS) is more than having motor and vocal tics, and this review will examine the varied comorbidities as well as the social impact and quality of life (QoL) in individuals with TS. The relationship between any individual and his/her environment is complex, and this is further exaggerated in the case of a person with TS. For example, tics may play a significant role in shaping the person's experiences, perceptions, and interactions with the environment. Furthermore, associated clinical features, comorbidities, and coexisting psychopathologies may compound or alter this relationship. In this regard, the common comorbidities include attention-deficit hyperactivity disorder and disruptive behaviors, obsessive compulsive disorder, and autism spectrum disorder, and coexistent problems include anxiety, depression, and low self-esteem, which can all lead to poorer psychosocial functioning and QoL. Thus, the symptoms of TS and the associated comorbid conditions may interact to result in a vicious cycle or a downward spiraling of negative experiences and poor QoL. The stigma and social maladjustment in TS and the social exclusion, bullying, and discrimination are considered to be caused in large part by misperceptions of the disorder by teachers, peers, and the wider community. Improved community and professional awareness about TS and related comorbidities and other psychopathologies as well as the provision of multidisciplinary services to meet the complex needs of this clinical population are critical. Future research to inform the risk and resilience factors for successful long-term outcomes is also warranted.
118 citations
TL;DR: The aim of this paper is to review recent genetic association studies in SBs including case–control studies, family-based association studies, and genome-wide association studies (GWAS) to understand the lack of reproducibility and the disappointing results.
Abstract: Suicidal behaviours, which range from suicidal ideation to suicide attempts and completed suicide, represent a fatal dimension of mental ill-health. The involvement of genetic risk factors in suicidal behaviour is supported by family, twin, and adoption studies. The aim of this paper is to review recent genetic association studies in suicidal behaviours including (i) case-control studies, (ii) family-based association studies and (iii) genome-wide association studies (GWAS). Various studies on genetic associations have tended to suggest that a number of genes (e.g., tryptophan hydroxylase, serotonin receptors and transporters or brain-derived neurotrophic factors) are linked to suicidal behaviours, but these findings are not consistently supported by the results obtained. Although the candidate-gene approach is useful, it is hampered by the present state of knowledge concerning the pathophysiology of diseases. Interpretations of GWAS results are mostly hindered by a lack of annotation describing the functions of most variation throughout the genome. Association studies have addressed a wide range of SNPs in numerous genes. We have included 104 such studies, of which 10 are family-based association studies and 11 are GWAS studies. Numerous meta-analyses of case-control studies have shown significant associations of suicidal behaviour with variants in the serotonin transporter gene (5-HTT or SLC6A4) and the tryptophane hydroxylase1 gene (TPH1), but others report contradictory results. The gene encoding brain-derived neurotrophic factor (BDNF) and its receptor (NTRK2) are also promising candidates. Only two of the GWAS studies showed any significant associations. Several pathways are mentioned in an attempt to understand the lack of reproducibility and the disappointing results. Consequently, we review and discuss here the following aspects: (i) sample characteristics and confounding factors; (ii) statistical limits; (iii) gene-gene interactions; (iv) gene, environment and by time interactions; and (v) technological and theoretical limits. Keywords: association study, genetics of suicide, suicidal behaviour, single nucleotide polymorphism
TL;DR: A narrative review summarizes available evidences on suicide in the early stage of schizophrenia and deals with issues to be further studied and discussed.
Abstract: Suicide is a relevant leading cause of death among patients affected by schizophrenia. Even if suicidal ideation may be present in different stages of disease, some differences have been described between the risk of suicide in patients experiencing first-episode of psychosis and those with long-term schizophrenia. It is particularly higher during the first year of illness and reaches a steady decline over the following years. Suicidal ideation and attempts may also be common among subjects with subthreshold psychotic experiences. Factors associated with the risk of suicide in the early phase of schizophrenia are previous suicidal attempts and social aspects: the lack of social support and stable relationships, social drift after the first- episode, social impairment. Also, several psychotic symptoms (suspiciousness, paranoid delusions, mental disintegration and agitation, negative symptoms, depression and hopelessness, command hallucinations) and substance abuse are associated to higher risk of suicide. It has been described that perfectionism and good levels of insight among individuals who have recently developed psychotic symptoms are significantly associated to higher numbers of suicidal attempts. Moreover, recent evidences show that prefrontal- cortex- based circuit dysfunction may be related to suicide in the early stage of schizophrenia. This narrative review summarizes available evidences on suicide in the early stage of schizophrenia and deals with issues to be further studied and discussed.
TL;DR: A focused review about epidemiological data, risk factors, and an overview about the main clinical correlates associated with the suicidal behavior during the pregnancy and postpartum period are provided.
Abstract: Perinatal period may pose a great challenge for the clinical management and treatment of psychiatric disorders in women. In fact, several mental illnesses can arise during pregnancy and/or following childbirth. Suicide and infanticide have been considered relatively rare events during the perinatal period. However, in some mental disorders (i.e. postpartum depression, bipolar disorder, postpartum psychosis, etc.) have been reported a higher risk of suicidal ideation, suicide attempt or suicide. Therefore, a complete screening of mothers’ mental health should also take into account thoughts of suicide and thoughts about harming infants as well. Clinicians should carefully monitor and early identify related clinical manifestations, potential risk factors and alarm symptoms related to suicide. The present paper aims at providing a focused review about epidemiological data, risk and protective factors and an overview about the main clinical correlates associated with the suicidal behaviour during the pregnancy and postpartum period.
TL;DR: Non-tobacco-based routes are associated with increased motivation to change tobacco use, and interventions addressing tobacco and cannabis need to accommodate this finding and encourage non-Tobacco routes.
Abstract: Cannabis and tobacco are common drugs of abuse worldwide and are often used in combination through a variety of routes of administration. Here we aimed to provide an overview of how cannabis and tobacco routes varied across countries and assess the impact of tobacco based routes of administration on motivation to use less cannabis, and less tobacco, in separate models. A cross-sectional online survey (Global Drugs Survey 2014) was completed by 33687 respondents (mean age = 27.9; %female = 25.9) who smoked cannabis at least once in the last 12 months. Most common route of administration, frequency of cannabis/tobacco use, and questions about motivation to use less cannabis/tobacco were recorded. Tobacco based routes of administration were used by 65.6% of respondents. These were most common in Europe (77.2-90.9%) and Australasia (20.7-51.6%) and uncommon in the Americas (4.4-16.0%). Vaporizer use was most common in Canada (13.2%) and the United States (11.2%). Non-tobacco based routes of administration were associated with a 10.7% increase in odds for ‘desire to use less’ tobacco (OR: 1.107, 95% CI: 1.003, 1.221), 80.6% increase in odds for ‘like help to use less tobacco’ (OR: 1.806, 95% CI: 1.556, 2.095) and a 103.9% increase in the odds for ‘planning to seek help to use less tobacco’ (OR: 2.039, 95% CI: 1.638, 2.539) in comparison to tobacco based routes of administration. Associations between route of administration and intentions to use less cannabis were inconsistent. Results support considerable global variation in cannabis and tobacco routes of administration. Tobacco routes are common, especially ‘joints with tobacco’, especially in Europe, but not in the Americas. Non-tobacco based routes are associated with increased motivation to change tobacco use. Interventions addressing tobacco and cannabis need to accommodate this finding and encourage non-tobacco routes.
TL;DR: Current understanding of the structure and function relationship of dendritic spines is reviewed, focusing on the controversy of electrical compartmentalization and the potential role of spine structural changes in synaptic plasticity.
Abstract: Neurons are perpetually receiving vast amounts of information in the form of synaptic input from surrounding cells. The majority of input occurs at thousands of dendritic spines, which mediate excitatory synaptic transmission in the brain, and is integrated by the dendritic and somatic compartments of the postsynaptic neuron. The functional role of dendritic spines in shaping biochemical and electrical signals transmitted via synapses has long been intensely studied. Yet, many basic questions remain unanswered, in particular regarding the impact of their nanoscale morphology on electrical signals. Here, we review our current understanding of the structure and function relationship of dendritic spines, focusing on the controversy of electrical compartmentalization and the potential role of spine structural changes in synaptic plasticity.
TL;DR: The hypothesis that anatomically distinct memory systems differentially contribute to the development of drug addiction and relapse is revisited as it was originally proposed 20 years ago and highlights several recent developments.
Abstract: The view that anatomically distinct memory systems differentially contribute to the development of drug addiction and relapse has received extensive support. The present brief review revisits this hypothesis as it was originally proposed twenty years ago (White, 1996) and highlights several recent developments. Extensive research employing a variety of animal learning paradigms indicates that dissociable neural systems mediate distinct types of learning and memory. Each memory system potentially contributes unique components to the learned behavior supporting drug addiction and relapse. In particular, the shift from recreational drug use to compulsive drug abuse may reflect a neuroanatomical shift from cognitive control of behavior mediated by the hippocampus/dorsomedial striatum toward habitual control of behavior mediated by the dorsolateral striatum (DLS). In addition, stress/anxiety may constitute a cofactor that facilitates DLS-dependent memory, and this may serve as a neurobehavioral mechanism underlying the increased drug use and relapse in humans following stressful life events. Evidence supporting the multiple systems view of drug addiction comes predominantly from studies of learning and memory that have employed as reinforcers addictive substances often considered within the context of drug addiction research, including cocaine, alcohol, and amphetamines. In addition, recent evidence suggests that the memory systems approach may also be helpful for understanding topical sources of addiction that reflect emerging health concerns, including marijuana use, high-fat diet, and video game playing.
TL;DR: It is suggested that both non-suicidal self-injury (NSSI) and suicidal behavior (SB) can be conceptualized as addictions.
Abstract: Introduction: Behavioral addictions such as gambling, sun-tanning, shopping, internet use, work, exercise, or even love and sex are frequent, and share many characteristics and common neurobiological and genetic underpinnings with substance addictions (i.e., tolerance, withdrawal, and relapse). Recent literature suggests that both non-suicidal self-injury (NSSI) and suicidal behavior (SB) can also be conceptualized as addictions. The major aim of this mini review is to review the literature and explore the neurobiological and psychological mechanisms underlying the addiction to self-harming behaviors. Method: This is a narrative review. The authors performed literature searches on PubMed and Google for suicidal behavior, self-harming, addiction, and “major repeaters”. Given the scarce literature on the topic, a subset of the most closely related studies was selected. The authors also focused on three empirical studies testing the hypothesis that major repeaters (individuals with ≥5 lifetime suicide attempts) represent a distinctive suicidal phenotype, and are the individuals at risk of developing an addiction to SB. Results: The authors reviewed the concept of behavioral addictions and major repeaters, current empirical evidence testing concerning whether or not NSSI and SB can be understood as “addictions”, and the putative mechanisms underlying them. Conclusion: Our review suggests that both NSSI and SB can be conceptualized as addictions. This is relevant because if some individual’s self-harming behaviors are better conceptualized as an addiction, treatment approaches could be tailored to this addiction.
TL;DR: In this paper, the authors describe potential classification pipelines for Autism Spectrum Disorder, as an example of a psychiatric disorder, using resting-state fMRI data derived from a multi-site data repository (ABIDE), and compare several popular ML classifiers such as support vector machines, neural networks and regression approaches.
Abstract: Most psychiatric disorders are associated with subtle alterations in brain function and are subject to large inter-individual differences. Typically the diagnosis of these disorders requires time-consuming behavioral assessments administered by a multi-disciplinary team with extensive experience. Whilst the application of machine learning classification methods (ML classifiers) to neuroimaging data has the potential to speed and simplify diagnosis of psychiatric disorders, the methods, assumptions, and analytical steps are not currently opaque and accessible to researchers and clinicians outside the field. In this paper, we describe potential classification pipelines for Autism Spectrum Disorder, as an example of a psychiatric disorder. The analyses are based on resting-state fMRI data derived from a multi-site data repository (ABIDE). We compare several popular ML classifiers such as support vector machines, neural networks and regression approaches, among others. In a tutorial style, written to be equally accessible for researchers and clinicians, we explain the rationale of each classification approach, clarify the underlying assumptions, and discuss possible pitfalls and challenges. We also provide the data as well as the MATLAB code we used to achieve our results. We show that out-of-the-box ML classifiers can yield classification accuracies of about 60-70%. Finally, we discuss how classification accuracy can be further improved, and we mention methodological developments that are needed to pave the way for the use of ML classifiers in clinical practice.
TL;DR: The review suggests that improving the care of patients will necessarily depend on the better characterization of drug-induced cognitive phenotypes because they might inform the development of better pharmacological and behavioral interventions, with the goal of improving cognitive functions in these subsets of drug users.
Abstract: Heavy use of drugs impacts of the daily activities of individuals in these activities. Several groups of investigators have indeed documented changes in cognitive performance by individuals who have a long history of chronic drug use. In the case of marijuana, a wealth of information suggests that heavy long-term use of the drug may have neurobehavioral consequences in some individuals. In humans, heavy cocaine use is accompanied by neuropathological changes that might serve as substrates for cognitive dysfunctions. Similarly, methamphetamine users suffer from cognitive abnormalities that may be consequent to alterations in structures and functions. Here, we detail the evidence for these neuropsychological consequences. The review suggests that improving the care of our patients will necessarily depend on the better characterization of drug-induced cognitive phenotypes because they might inform the development of better pharmacological and behavioral interventions, with the goal of improving cognitive functions in these subsets of drug users.
TL;DR: Brain-derived neurotrophic factor, a molecule involved in hippocampal neurogenesis and altered in ASD, is targeted by 6 of the 27 miRNAs of interest, which represents one intriguing mechanism by which perturbations in miRNA signaling might influence central nervous system development in children with ASD.
Abstract: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by a wide spectrum of deficits in social interaction, communication, and behavior. There is a significant genetic component to ASD, yet no single gene variant accounts for >1% of incidence. Posttranscriptional mechanisms such as microRNAs (miRNAs) regulate gene expression without altering the genetic code. They are abundant in the developing brain and are dysregulated in children with ASD. Patterns of miRNA expression are altered in the brain, blood, saliva, and olfactory precursor cells of ASD subjects. The ability of miRNAs to regulate broad molecular pathways in response to environmental stimuli makes them an intriguing player in ASD, a disorder characterized by genetic predisposition with ill-defined environmental triggers. In addition, the availability and extracellular stability of miRNAs make them an ideal candidate for biomarker discovery. Here, we discuss 27 miRNAs with overlap across ASD studies, including 3 miRNAs identified in 3 or more studies (miR-23a, miR-146a, and miR-106b). Together, these 27 miRNAs have 1245 high-confidence mRNA targets, a significant number of which are expressed in the brain. Furthermore, these mRNA targets demonstrate over-representation of autism-related genes with enrichment of neurotrophic signaling molecules. Brain-derived neurotrophic factor, a molecule involved in hippocampal neurogenesis and altered in ASD, is targeted by 6 of the 27 miRNAs of interest. This neurotrophic pathway represents one intriguing mechanism by which perturbations in miRNA signaling might influence central nervous system development in children with ASD.
TL;DR: How the development of computational diagnostics applicable to behavioral and functional neuroimaging data in routine clinical practice could not only fundamentally alter the concept of ASD but eventually also transform the clinical management of this disorder is outlined.
Abstract: Diagnosis and individualised treatment of autism spectrum disorder (ASD) represent major problems for contemporary psychiatry. Tackling these problems requires guidance by a pathophysiological theory. In this paper, we consider recent theories that re-conceptualise ASD from a “Bayesian brain” perspective, which posit that the core abnormality of ASD resides in perceptual aberrations due to a dysbalance in the precision of prediction errors (sensory noise) relative to the precision of predictions (prior beliefs). This results in percepts that are dominated by sensory inputs and less guided by top-down regularisation and shifts the perceptual focus to detailed aspects of the environment with difficulties in extracting meaning. While these Bayesian theories have inspired ongoing empirical studies, their clinical implications have not yet been carved out. Here, we consider how this Bayesian perspective on disease mechanisms in ASD might contribute to improving clinical care for affected individuals. Specifically, we describe a computational strategy, based on generative (e.g., hierarchical Bayesian) models of behavioural and functional neuroimaging data, for establishing diagnostic tests. These tests could provide estimates of specific cognitive processes underlying ASD and delineate pathophysiological mechanisms with concrete treatment targets. Written with a clinical audience in mind, this article outlines how the development of computational diagnostics applicable to behavioural and functional neuroimaging data in routine clinical practice could not only fundamentally alter our concept of ASD but eventually also transform the clinical management of this disorder.
TL;DR: Results show that unimodal studies do not indicate GABA as a biomarker for the psychiatric disorders considered, and multimodal approaches seem promising for moving from GABA MRS unimmodal-descriptive to causal level, and for integrating GABA results into a more comprehensive interpretation of mental disorder pathophysiology.
Abstract: Third-generation neuroimaging research has been enriched by advances in magnetic resonance spectroscopy (MRS) measuring the concentration of important neurotrasmitters, such as the inhibitory amino acid GABA. Here, we performed a systematic mini-review on brain MRS studies measuring GABA concentration in patients affected by schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). We wondered whether multimodal investigations could overcome intrinsic technical limits of MRS giving a broader view of mental disorders pathogenesis. In SZ, unimodal studies gave mixed results, as increased, decreased, or unaltered GABA levels were reported depending on region, disease phase, and treatment. Conversely, multimodal results showed reduced level of glutamate, but not of GABA, in patients mirrored by in vitro biochemical findings revealing hippocampal reduction in glutamate signaling in SZ, and no deficits in GABA synthesis. Moreover, a mouse model confirmed the unique pathological characteristic of glutamate function in SZ. Unimodal studies in BD revealed again, inconsistent results, while no multimodal investigations including MRS on GABA exist. In MDD, unimodal studies could not differentiate patients from controls nor characterize high-risk subjects and remitted patients. However, a multimodal study combining functional magnetic resonance imaging and MRS revealed that cingulate cortex activity is related to glutamate, N-acetylaspartate levels and anhedonia in patients, and to GABA concentration in healthy subjects, improving the distinction between MDD and physiology. Overall, our results show that unimodal studies do not indicate GABA as a biomarker for the psychiatric disorders considered. Conversely, multimodal studies can widen the understanding of the link between psychopathology, genetics, neuroanatomy, and functional-biochemical brain activity in mental disorders. Although scarce, multimodal approaches seem promising for moving from GABA MRS unimodal-descriptive to causal level, and for integrating GABA results into a more comprehensive interpretation of mental disorder pathophysiology.
TL;DR: Hikikomori is a Japanese condition that mainly affects adolescents or young adults who live isolated from the world, cloistered within their parents’ homes, locked in their bedrooms for days, months, or even years on end, and refusing to communicate even with their family.
Abstract: Computers, video games, and technological devices are part of young people's everyday lives. Hikikomori is a Japanese word describing a condition that mainly affects adolescents or young adults who live isolated from the world, cloistered within their parents' homes, locked in their bedrooms for days, months, or even years on end, and refusing to communicate even with their family. These patients use the Internet profusely, and only venture out to deal with their most imperative bodily needs. Although first described in Japan, cases have been described from around the world. This is the first published report from Canada. The disorder shares characteristics with prodromal psychosis, negative symptoms of schizophrenia, or Internet addiction, which are common differential or comorbid diagnoses. However, certain cases are not accompanied by a mental disorder. Psychotherapy is the treatment of choice although many cases are reluctant to present. The exact place of hikikomori in psychiatric nosology has yet to be determined. We searched Medline up to 12th May, 2015 supplemented by a hand search of the bibliographies of all retrieved articles. We used the following search terms: Hikikomori OR (prolonged AND social AND withdrawal). We found 97 potential papers. Of these 42 were in Japanese, and 1 in Korean. However, many of these were cited by subsequent English language papers that were included in the review. Following scrutiny of the titles and abstracts, 29 were judged to be relevant. Further research is needed to distinguish between primary and secondary hikikomori and establish whether this is a new diagnostic entity, or particular cultural or societal manifestations of established diagnoses.
TL;DR: The status of selected research issues from the exercise depression literature are described and insights into research areas that are currently lacking are offered.
Abstract: Research exploring links between exercise and depression now span several decades, yet several clinically relevant research questions remain unanswered. This opinion article briefly describes the status of selected research issues from the exercise depression literature and offer insights into research areas that are currently lacking. We draw particular attention to the potential of research exploring links between sedentary behavior and depression.
TL;DR: Factors contributing to behavioral dyscontrol are an important target for advancing knowledge on the etiology of drug abuse, intervening with the drug addiction process and developing novel treatments.
Abstract: The purpose of this review is to discuss recent findings related to sex differences in behavioral dyscontrol that lead to drug addiction, and clinical implications for humans are discussed. This review includes research conducted in animals and humans that reveals fundamental aspects of behavioral dyscontrol. The importance of sex differences in aspects of behavioral dyscontrol, such as impulsivity and compulsivity, is discussed as major determinants of drug addiction. Behavioral dyscontrol during adolescence is also an important consideration, as this is the time of onset for drug addiction. These vulnerability factors additively increase drug-abuse vulnerability, and they are integral aspects of addiction that covary and interact with sex differences. Sex differences in treatments for drug addiction are also reviewed in terms of their ability to modify the behavioral dyscontrol that underlies addictive behavior. Customized treatments to reduce behavioral dyscontrol are discussed, such as (1) using natural consequences such as non-drug rewards (e.g., exercise) to maintain abstinence, or using punishment as a consequence for drug use, (2) targeting factors that underlie behavioral dyscontrol, such as impulsivity or anxiety, by repurposing medications to relieve these underlying conditions, and (3) combining two or more novel behavioral or pharmacological treatments to produce additive reductions in drug seeking. Recent published work has indicated that factors contributing to behavioral dyscontrol are an important target for advancing our knowledge on the etiology of drug abuse, intervening with the drug addiction process and developing novel treatments.
TL;DR: Bilateral rTMS of PFC at 10 Hz did not show a significant effect on cocaine intake compared to sham, but a long-term reduction in cocaine intake in active TMS-treated patients was observed when the time as factor was considered.
Abstract: Background: Chronic cocaine consumption is associated to a decrease in mesolimbic dopamine transmission that maintains drug intake. Transcranial Magnetic Stimulation (TMS) is gaining reliability a useful therapeutic tool in drug addiction since it can modulate cortico-limbic activity resulting in reduction of drug craving. Aims: In the present study we investigated the therapeutic effect of bilateral TMS of prefrontal cortex (PFC) in reducing cocaine intake, in a sample of treatment-seeking patients with current cocaine use disorder (DSM-V). Methods: 10 cocaine addicts (DSM-V) were randomly assigned to the active or sham stimulation protocol in a double-blind experimental design. Twelve repetitive TMS (rTMS) sessions were administered 3 times a week for 4 weeks at 100% of motor threshold, over bilateral PFC. Cocaine intake (ng/mg) was assessed by hair analysis at baseline (before treatment, T0), after one month (end of treatment, T1), 3 (T2) and 6 (T3) months later. All subjects received psychological support weekly. Results: The two-way ANOVA for repeated measures did not show a significant effect of the interaction between time and treatment (F4,32= 0.35; p=.87). Despite that result indicated no difference in the effect of the two conditions (active vs sham) along time, a decreasing trend in cocaine consumption in active TMS group (F3,23=3.42; p=.04) vs sham (F3,15=1.88; p=.20) was observed when we performed exploratory analysis with time as factor . Indeed, Post-hoc comparisons showed a significant reduction in the amount of cocaine detected from the onset to three months later (T0-T2; p=.02) and to the end of treatment (T0-T3; p=.01) in addicts from the active group. Conclusions: Bilateral rTMS of PFC at 10 Hz did not show a significant effect on cocaine intake compared to sham. However, a long-term reduction in cocaine intake in active TMS treated patients was observed when we considered the time as factor. Further studies are required to confirm these encouraging but preliminary findings, in order to consolidate rTMS as a valid tool to treat cocaine addiction.
TL;DR: The emerging evidence of an association between BSs and aberrant brain activation, connectivity patterns, and metabolism is reviewed, and promising routes for the use of BSs in aetiopathological research on psychosis are outlined.
Abstract: In its initial formulation, the concept of basic symptoms (BSs) integrated findings on the early symptomatic course of schizophrenia and first in vivo evidence of accompanying brain aberrations. It argued that the subtle subclinical disturbances in mental processes described as BSs were the most direct self-experienced expression of the underlying neurobiological aberrations of the disease. Other characteristic symptoms of psychosis (e.g., delusions and hallucinations) were conceptualized as secondary phenomena, resulting from dysfunctional beliefs and suboptimal coping styles with emerging BSs and/or concomitant stressors. While BSs can occur in many mental disorders, in particular affective disorders, a subset of perceptive and cognitive BSs appear to be specific to psychosis and are currently employed in two alternative risk criteria. However, despite their clinical recognition in the early detection of psychosis, neurobiological research on the aetiopathology of psychosis with neuroimaging methods has only just begun to consider the neural correlate of BSs. This perspective paper reviews the emerging evidence of an association between BSs and aberrant brain activation, connectivity patterns, and metabolism, and outlines promising routes for the use of BSs in aetiopathological research on psychosis.
TL;DR: It is demonstrated that long-term administration of intranasal OXT is tolerable in a representative cohort of ASD individuals with ID and suggests that future multicenter trials of OXT are warranted and should include measurements of reciprocal social interactions based on daily life under closer surveillance for epilepsy.
Abstract: Approximately half of autism spectrum disorder (ASD) individual suffer from comorbid intellectual disabilities (ID). Oxytocin (OXT) receptors are highly expressed in temporal lobe structures and are likely to play a modulatory role in excitatory/inhibitory balance, at least based on animal model findings. Thus, it is feasible that in the highly representative group of Kanner type ASD subjects OXT could have a beneficial effect on social communication and social interaction. The aim of this pilot study was to investigate the feasibility and adverse events, such as epilepsy, of the long-term administration of intranasal OXT for adolescent and adult ASD subjects with ID because such patients frequently have seizures. We also addressed the question on how to scale the OXT effects to the core symptoms of social deficits because of the relative difficulty in obtaining objective measurements. Twenty-nine males (aged 15-40 years old) participated in a randomized, double-blind, placebo-controlled crossover study (each for 8 weeks) with OXT (16 international units per day). Except for seizures experienced by one participant, other serious adverse events did not occur. The primary and secondary outcomes measured using the Childhood Autism Rating Scale and several standard scales, respectively, revealed no difference between the OXT and placebo groups. Instead, in an exploratory analysis, the social interactions observed in the play sessions or in daily-life were significantly more frequent in the initial half period in the OXT-first arm of the crossover trial. There were also significant correlations between the plasma OXT concentration and subscale scores for irritability on the Aberrant Behavior Checklist. In conclusion, this pilot study demonstrates that long-term administration of intranasal OXT is tolerable in a representative cohort of ASD individuals with ID and suggests that future multicenter trials of OXT are warranted and should include measurements of reciprocal social interactions based on daily life under closer surveillance for epilepsy. Trial registration: UMIN000007250.
TL;DR: Significant advances and current challenges for precision medicine, which aims to combine new pathophysiologically based treatments with objective tests (stratification biomarkers) to predict which treatment may be beneficial for a particular person, are discussed.
Abstract: The tremendous clinical and etiological variability between individuals with Autism Spectrum Disorder (ASD) has made precision medicine the most promising treatment approach. It aims to combine new pathophysiologically based treatments with objective tests (stratification biomarkers) to predict which treatment may be beneficial for a particular person. Here we discuss significant advances and current challenges for this approach: Rare monogenic forms of ASD have provided a major breakthrough for the identification of treatment targets by providing a means to trace causal links from a gene to specific molecular alterations and biological pathways. To estimate whether treatment targets thus identified may be useful for larger patient groups we need a better understanding of whether different etiologies (i.e., genetic and environmental risk factors acting at different critical time points) lead to convergent or divergent molecular mechanisms, and how they map onto differences in circuit-level brain and cognitive development, and behavioural symptom profiles. Several recently failed clinical trials with syndromic forms of ASD provide valuable insights into conceptual and methodological issues linked to limitations in the translatability from animal models to humans, placebo effects, and a need for mechanistically plausible, objective outcome measures. To identify stratification biomarkers markers that enrich participant selection in clinical trials, large-scale multi-modal longitudinal observational studies are underway. Addressing these different factors in the next generation of research studies requires a translatable developmental perspective and multidisciplinary, collaborative efforts, with a commitment to sharing protocols and data, to increase transparency and reproducibility.
TL;DR: Preliminary results support feasibility of this novel neurofeedback intervention for PTSD and indicate that larger, well-controlled studies of efficacy are warranted.
Abstract: Many patients with post-traumatic stress disorder (PTSD), especially war veterans, do not respond to available treatments. Here we describe a novel neurofeedback (NF) intervention using real-time functional magnetic resonance imaging (rt-fMRI) for treating and studying PTSD. The intervention involves training participants to control amygdala activity after exposure to personalized trauma scripts. Three combat veterans with chronic PTSD participated in this feasibility study. All three participants tolerated well the NF training. Moreover, two participants, despite the chronicity of their symptoms, showed clinically meaningful improvements, while one participant showed a smaller symptom reduction. Examination of changes in resting state functional connectivity patterns revealed a normalization of brain connectivity consistent with clinical improvement. These preliminary results support feasibility of this novel intervention for PTSD and indicate that larger, well controlled studies of efficacy are warranted