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Showing papers in "Dialogues in Clinical Neuroscience in 2016"


Journal ArticleDOI
TL;DR: Considering sex as a biological variable in dementia research promises to advance the understanding of the pathophysiology and treatment of these conditions.
Abstract: Suffering related to dementia is multifaceted because cognitive and physical functioning slowly deteriorates. Advanced age and sex, two of the most prominent risk factors for dementia, are not modifiable. Lifestyle factors such as smoking, excessive alcohol use, and poor diet modulate susceptibility to dementia in both males and females. The degree to which the resulting health conditions (eg, obesity, type 2 diabetes, and cardiovascular disease) impact dementia risk varies by sex. Depending on the subtype of dementia, the ratio of male to female prevalence differs. For example, females are at greater risk of developing Alzheimer disease dementia, whereas males are at greater risk of developing vascular dementia. This review examines sex and gender differences in the development of dementia with the goal of highlighting factors that require further investigation. Considering sex as a biological variable in dementia research promises to advance our understanding of the pathophysiology and treatment of these conditions.

346 citations


Journal ArticleDOI
TL;DR: Dopamine neurons in the midbrain of humans, monkeys, and rodents signal a reward prediction error, and the important concept of reward prediction errors is implemented in neuronal hardware.
Abstract: Reward prediction errors consist of the differences between received and predicted rewards. They are crucial for basic forms of learning about rewards and make us strive for more rewards-an evolutionary beneficial trait. Most dopamine neurons in the midbrain of humans, monkeys, and rodents signal a reward prediction error; they are activated by more reward than predicted (positive prediction error), remain at baseline activity for fully predicted rewards, and show depressed activity with less reward than predicted (negative prediction error). The dopamine signal increases nonlinearly with reward value and codes formal economic utility. Drugs of addiction generate, hijack, and amplify the dopamine reward signal and induce exaggerated, uncontrolled dopamine effects on neuronal plasticity. The striatum, amygdala, and frontal cortex also show reward prediction error coding, but only in subpopulations of neurons. Thus, the important concept of reward prediction errors is implemented in neuronal hardware.

311 citations


Journal ArticleDOI
TL;DR: In rodents, short-term estradiol intake in female rats enhances acquisition and escalation of drug taking, motivation for drugs of abuse, and relapse-like behaviors, and there is a sex difference in the dopamine response in the nucleus accumbens.
Abstract: Women exhibit more rapid escalation from casual drug taking to addiction, exhibit a greater withdrawal response with abstinence, and tend to exhibit greater vulnerability than men in terms of treatment outcome. In rodents, short-term estradiol intake in female rats enhances acquisition and escalation of drug taking, motivation for drugs of abuse, and relapse-like behaviors. There is also a sex difference in the dopamine response in the nucleus accumbens. Ovariectomized female rats exhibit a smaller initial dopamine increase after cocaine treatment than castrated males. Estradiol treatment of ovariectomized female rats enhances stimulated dopamine release in the dorsolateral striatum, but not in the nucleus accumbens, resulting in a sex difference in the balance between these two dopaminergic projections. In the situation where drug-taking behavior becomes habitual, dopamine release has been reported to be enhanced in the dorsolateral striatum and attenuated in the nucleus accumbens. The sex difference in the balance between these neural systems is proposed to underlie sex differences in addiction.

192 citations


Journal ArticleDOI
TL;DR: The history and current research on sex effects of antidepressant treatment is reviewed, finding that females respond better to serotonergic antidepressants than males and postmenopausal females have a diminished response to antidepressants compared with younger females.
Abstract: Although a number of studies have observed that females respond better to serotonergic antidepressants than males and that postmenopausal females have a diminished response to antidepressants compared with younger females, there are also studies that conflict with both of these findings, making any generalizations regarding sex differences difficult to make. Sex variance in antidepressant efficacy and pharmacokinetics profiles have been attributed to sex-based physiological differences, behavioral differences, related disorders, and sex-specific conditions, including pregnancy and menopause. This paper will review the history and current research on sex effects of antidepressant treatment.

174 citations


Journal ArticleDOI
TL;DR: Sex differences, and responses to sex hormones in brain regions and upon functions not previously regarded as subject to such differences, indicate that the authors are entering a new era in their ability to understand and appreciate the diversity of gender-related behaviors and brain functions.
Abstract: Contrary to popular belief, sex hormones act throughout the entire brain of both males and females via both genomic and nongenomic receptors. Many neural and behavioral functions are affected by estrogens, including mood, cognitive function, blood pressure regulation, motor coordination, pain, and opioid sensitivity. Subtle sex differences exist for many of these functions that are developmentally programmed by hormones and by not yet precisely defined genetic factors, including the mitochondrial genome. These sex differences, and responses to sex hormones in brain regions and upon functions not previously regarded as subject to such differences, indicate that we are entering a new era in our ability to understand and appreciate the diversity of gender-related behaviors and brain functions.

145 citations


Journal Article
TL;DR: Through a genome-wide screen after maternal stress in mice, the X-linked gene O-linked N-acetylglucosamine transferase (OGT) is identified and its causality in neurodevelopmental programming producing a male-specific stress phenotype is demonstrated.
Abstract: Prenatal insults, such as maternal stress, are associated with an increased neurodevelopmental disease risk and impact males significantly more than females, including increased rates of autism, mental retardation, stuttering, dyslexia, and attention deficit/hyperactivity disorder (ADHD). Sex differences in the placenta, which begin with sex chromosomes, are likely to produce sex-specific transplacental signals to the developing brain. Our studies and others have identified X-linked genes that are expressed at higher levels in the female placenta. Through a genome-wide screen after maternal stress in mice, we identified the X-linked gene O-linked N-acetylglucosamine transferase (OGT) and demonstrated its causality in neurodevelopmental programming producing a male-specific stress phenotype. Elucidating the sex-specific molecular mechanisms involved in transplacental signals that impact brain development is key to understanding the sex bias in neurodevelopmental disorders and is expected to yield novel insight into disease risk and resilience.

144 citations


Journal ArticleDOI
TL;DR: As a single-gene disorder, HD has the distinction of having the potential of treatment that is aimed directly at the known pathogenic mechanism by gene silencing, providing hope for neuroprotection and ultimately, prevention.
Abstract: Huntington disease (HD) is an autosomal dominant, neurodegenerative disorder with a primary etiology of striatal pathology. The Huntingtin gene (HTT) has a unique feature of a DNA trinucleotide (triplet) repeat, with repeat length ranging from 10 to 35 in the normal population. Repeat lengths between 36 and 39 cause HD at reduced penetrance (some will get the disease, others won't) and when expanded to 40 or more repeats (mHTT), causes HD at full penetrance (every person with this length or beyond will definitely develop the disease). The symptoms of HD may be motor, cognitive, and psychiatric, and are consistent with the pathophysiology of frontostriatal circuitry malfunction. Expressed ubiquitously and throughout the entire life cycle (development through adulthood), mHTT causes initial dysfunction and eventual death of a specific cell population within the striatum. Although all areas of the brain are eventually affected, the primary pathology of the disease is regionally specific. As a single-gene disorder, HD has the distinction of having the potential of treatment that is aimed directly at the known pathogenic mechanism by gene silencing, providing hope for neuroprotection and ultimately, prevention.

105 citations


Journal ArticleDOI
TL;DR: This work has shown that non-neuronal cells and inflammatory mediators are found in greater number and at higher levels in parts of male brains, which is speculated to increase male vulnerability to developmental neuropsychiatric disorders that are triggered by inflammation.
Abstract: Brain development diverges in males and females in response to androgen production by the fetal testis. This sexual differentiation of the brain occurs during a sensitive window and induces enduring neuroanatomical and physiological changes that profoundly impact behavior. What we know about the contribution of sex chromosomes is still emerging, highlighting the need to integrate multiple factors into understanding sex differences, including the importance of context. The cellular mechanisms are best modeled in rodents and have provided both unifying principles and surprising specifics. Markedly distinct signaling pathways direct differentiation in specific brain regions, resulting in mosaicism of relative maleness, femaleness, and sameness through-out the brain, while canalization both exaggerates and constrains sex differences. Non-neuronal cells and inflammatory mediators are found in greater number and at higher levels in parts of male brains. This higher baseline of inflammation is speculated to increase male vulnerability to developmental neuropsychiatric disorders that are triggered by inflammation.

81 citations


Journal Article
TL;DR: Recent evidence that functional connectivity profiles are both reliable within subjects and unique across subjects, and that features of these profiles relate to behavioral phenotypes are reviewed, suggest the potential to discover reliable correlates of present and future illness and/or response to treatment in the strength of an individual's functional brain connections.
Abstract: Functional brain connectivity measured with functional magnetic resonance imaging (fMRI) is a popular technique for investigating neural organization in both healthy subjects and patients with mental illness. Despite a rapidly growing body of literature, however, functional connectivity research has yet to deliver biomarkers that can aid psychiatric diagnosis or prognosis at the single-subject level. One impediment to developing such practical tools has been uncertainty regarding the ratio of intra- to interindividual variability in functional connectivity; in other words, how much variance is state- versus trait-related. Here, we review recent evidence that functional connectivity profiles are both reliable within subjects and unique across subjects, and that features of these profiles relate to behavioral phenotypes. Together, these results suggest the potential to discover reliable correlates of present and future illness and/or response to treatment in the strength of an individual's functional brain connections. Ultimately, this work could help develop personalized approaches to psychiatric illness.

72 citations


Journal ArticleDOI
TL;DR: This review summarizes the current body of evidence and highlights pros and cons of Internet interventions, also outlines how they could be implemented in mental health care systems and points out unresolved questions.
Abstract: A wide range of Internet interventions, mostly grounded in methods of cognitive behavioral therapy, have been developed and tested for several mental disorders. The evidence to date shows that these interventions are effective in reducing symptoms of depression. Metaanalyses report small-to-medium effect sizes when Internet interventions are delivered as stand-alone self-help interventions (d=0.25-0.36), and medium-to-large effect sizes when delivered as therapist-guided interventions (d=0.58-0.78), both compared with usual care. Only a minority of people suffering from depression receive adequate treatment, and Internet interventions might help bridge the large treatment gap. This review summarizes the current body of evidence and highlights pros and cons of Internet interventions. It also outlines how they could be implemented in mental health care systems and points out unresolved questions, as well as future directions, in this research field.

71 citations


Journal ArticleDOI
TL;DR: Mobile technology (mobile applications on smartphones, activity bracelets) has the potential to overcome problems with traditional assessment and provide information about patient symptoms, behavior, and functioning in real time.
Abstract: Assessment and outcome monitoring are critical for the effective detection and treatment of mental illness. Traditional methods of capturing social, functional, and behavioral data are limited to the information that patients report back to their health care provider at selected points in time. As a result, these data are not accurate accounts of day-to-day functioning, as they are often influenced by biases in self-report. Mobile technology (mobile applications on smartphones, activity bracelets) has the potential to overcome such problems with traditional assessment and provide information about patient symptoms, behavior, and functioning in real time. Although the use of sensors and apps are widespread, several questions remain in the field regarding the reliability of off-the-shelf apps and sensors, use of these tools by consumers, and provider use of these data in clinical decision-making.

Journal ArticleDOI
TL;DR: Clinical GS faces a pivotal moment, as the vast potential of new quantities and types of data enable further clinical innovation and complicated implementation questions continue to be resolved.
Abstract: The development of massively parallel sequencing (or next-generation sequencing) has facilitated a rapid implementation of genomic sequencing in clinical medicine. Genomic sequencing (GS) is now an essential tool for evaluating rare disorders, identifying therapeutic targets in neoplasms, and screening for prenatal aneuploidy. Emerging applications, such as GS for preconception carrier screening and predisposition screening in healthy individuals, are being explored in research settings and utilized by members of the public eager to incorporate genomic information into their health management. The rapid pace of adoption has created challenges for all stakeholders in clinical GS, from standardizing variant interpretation approaches in clinical molecular laboratories to ensuring that nongeneticist clinicians are prepared for new types of clinical information. Clinical GS faces a pivotal moment, as the vast potential of new quantities and types of data enable further clinical innovation and complicated implementation questions continue to be resolved.

Journal Article
TL;DR: In several European regions, the four-level intervention concept of the European Alliance Against Depression (EAAD), simultaneously targeting depression and suicidal behavior, has been found to have preventive effects on suicidal behavior.
Abstract: More than 800 000 people die every year from suicide, and about 20 times more attempt suicide. In most countries, suicide risk is highest in older males, and risk of attempted suicide is highest in younger females. The higher lethal level of suicidal acts in males is explained by the preference for more lethal methods, as well as other factors. In the vast majority of cases, suicidal behavior occurs in the context of psychiatric disorders, depression being the most important one. Improving the treatment of depression, restricting access to lethal means, and avoiding the Werther effect (imitation suicide) are central aspects of suicide prevention programs. In several European regions, the four-level intervention concept of the European Alliance Against Depression (www.EAAD.net), simultaneously targeting depression and suicidal behavior, has been found to have preventive effects on suicidal behavior. It has already been implemented in more than 100 regions in Europe.

Journal Article
TL;DR: It is proposed that there are shared biologic substrates at the anatomical, molecular, and/or genetic levels that produce the comorbid risk for MDD-MetS through sex-dependent fetal origins.
Abstract: Major depressive disorder (MDD) is the number one cause of disability worldwide and is comorbid with many chronic diseases, including obesity/metabolic syndrome (MetS). Women have twice as much risk for MDD and comorbidity with obesity/MetS as men, although pathways for understanding this association remain unclear. On the basis of clinical and preclinical studies, we argue that prenatal maternal stress (ie, excess glucocorticoid expression and associated immune responses) that occurs during the sexual differentiation of the fetal brain has sex-dependent effects on brain development within highly sexually dimorphic regions that regulate mood, stress, metabolic function, the autonomic nervous system, and the vasculature. Furthermore, these effects have lifelong consequences for shared sex-dependent risk of MDD and obesity/MetS. Thus, we propose that there are shared biologic substrates at the anatomical, molecular, and/or genetic levels that produce the comorbid risk for MDD-MetS through sex-dependent fetal origins.

Journal ArticleDOI
TL;DR: It is posited that because intrusive thinking is a shared endophenotype in many disorders, N-acetylcysteine has positive effects in clinical trials for a variety of neuropsychiatric disorders, including drug addiction, gambling, trichotillomania, and depression.
Abstract: Intrusive thinking triggers clinical symptoms in many neuropsychiatric disorders. Using drug addiction as an exemplar disorder sustained in part by intrusive thinking, we explore studies demonstrating that impairments in corticostriatal circuitry strongly contribute to intrusive thinking. Neuroimaging studies have long implicated this projection in cue-induced craving to use drugs, and preclinical models show that marked changes are produced at corticostriatal synapses in the nucleus accumbens during a relapse episode. We delineate an accumbens microcircuit that mediates cue-induced drug seeking becoming an intrusive event. This microcircuit harbors many potential therapeutic targets. We focus on preclinical and clinical studies, showing that administering N-acetylcysteine restores uptake of synaptic glutamate by astroglial glutamate transporters and thereby inhibits intrusive thinking. We posit that because intrusive thinking is a shared endophenotype in many disorders, N-acetylcysteine has positive effects in clinical trials for a variety of neuropsychiatric disorders, including drug addiction, gambling, trichotillomania, and depression.

Journal ArticleDOI
TL;DR: The causes and consequences of this striata! dopamine alteration are discussed, and a series of recent studies that are exemplary for a particular research approach are presented: a combination of theory-driven reinforcement learning and decision-making tasks in combination with computational modeling and functional neuroimaging.
Abstract: Elevated striatal dopamine function is one of the best-established findings in schizophrenia. In this review, we discuss causes and consequences of this striata! dopamine alteration. We first summarize earlier findings regarding striatal reward processing and anticipation using functional neuroimaging. Secondly, we present a series of recent studies that are exemplary for a particular research approach: a combination of theory-driven reinforcement learning and decision-making tasks in combination with computational modeling and functional neuroimaging. We discuss why this approach represents a promising tool to understand underlying mechanisms of symptom dimensions by dissecting the contribution of multiple behavioral control systems working in parallel. We also discuss how it can advance our understanding of the neurobiological implementation of such functions. Thirdly, we review evidence regarding the topography of dopamine dysfunction within the striatum. Finally, we present conclusions and outline important aspects to be considered in future studies.

Journal ArticleDOI
TL;DR: P perturbations in the PACAP-PAC1R pathway are regulated by estrogen and are involved in abnormal fear responses underlying PTSD, suggesting a window into understanding mechanisms of sex differences in the stress response.
Abstract: Trauma-related disorders, such as posttraumatic stress disorder (PTSD) are remarkably common and debilitating, and are often characterized by dysregulated threat responses. Across numerous epidemiological studies, females have been found to have an approximately twofold increased risk for PTSD and other stress-related disorders. Understanding the biological mechanisms of this differential risk is of critical importance. Recent data suggest that the pituitary adenylate cyclase-activating polypeptide (PACAP) pathway is a critical regulator of the stress response across species. Moreover, increasing evidence suggests that this pathway is regulated by both stress and estrogen modulation and may provide an important window into understanding mechanisms of sex differences in the stress response. We have recently shown that PACAP and its receptor (PAC1R) are critical mediators of abnormal processes after psychological trauma. Notably, in heavily traumatized human subjects, there appears to be a robust sex-specific association of PACAP blood levels and PAC1R gene variants with fear physiology, PTSD diagnosis, and symptoms, specifically in females. The sex-specific association occurs within a single-nucleotide polymorphism (rs2267735) that resides in a putative estrogen response element involved in PAC1R gene regulation. Complementing these human data, the PAC1R messenger RNA is induced with fear conditioning or estrogen replacement in rodent models. These data suggest that perturbations in the PACAP-PAC1R pathway are regulated by estrogen and are involved in abnormal fear responses underlying PTSD.

Journal Article
TL;DR: The potential of technological innovations for overcoming the challenges involved in both functional assessment and intervention in people with SMI are described and promising data regarding the acceptability, adherence, and efficacy of EMA-based mobile technologies are reviewed.
Abstract: The functional impairment associated with serious mental illness (SMI) places an immense burden on individuals and society, and disability often persists even after efficacious treatment of psychopathologic symptoms. Traditional methods of measuring functioning have limitations, and numerous obstacles reduce the reach and impact of evidence-based interventions developed to improve functioning in SMI. This review describes the potential of technological innovations for overcoming the challenges involved in both functional assessment and intervention in people with SMI. Ecological momentary assessment (EMA), which involves the repeated sampling of naturalistic behaviors and experiences while individuals carry out their daily lives, has provided a new window through which the determinants of day-to-day function in SMI can be observed. EMA has several advantages over traditional assessment methods and has in recent years evolved to use mobile-based platforms, such as text messaging and smartphone applications, for both assessment and promotion of self-management in people with SMI. We will review promising data regarding the acceptability, adherence, and efficacy of EMA-based mobile technologies; explore ways in which these technologies can extend the reach and impact of evidence-based psychosocial rehabilitative interventions in SMI; and outline future directions for research in this important area.

Journal ArticleDOI
TL;DR: This review focuses on pharmacokinetic and pharmacodynamic gene variants that are currently available in commercial genetic testing panels and associations with clinical efficacy and adverse effects, as well as other clinical implications, in antipsychotic pharmacotherapy are discussed.
Abstract: Optimizing antipsychotic pharmacotherapy is often challenging due to significant variability in effectiveness and tolerability. Genetic factors influencing pharmacokinetics and pharmacodynamics may contribute to some of this variability. Research studies have characterized these pharmacogenetic relationships, and some genetic markers are now available as clinical tests. These advances in pharmacogenetics research and test availability have great potential to improve clinical outcomes and quality of life in psychiatric patients. For clinicians considering using pharmacogenetics, it is important to understand the clinical implications and also the limitations of markers included in currently available tests. This review focuses on pharmacokinetic and pharmacodynamic gene variants that are currently available in commercial genetic testing panels. Associations of these variants with clinical efficacy and adverse effects, as well as other clinical implications, in antipsychotic pharmacotherapy are discussed.

Journal ArticleDOI
TL;DR: Factors influencing the relationships between brain development and function and sex or gender may help to understand the differences between males and females in terms of risk or resilience factors in brain diseases.
Abstract: The prevalence, age of onset, and clinical symptoms of many neuropsychiatric diseases substantially differ between males and females. Factors influencing the relationships between brain development and function and sex or gender may help us understand the differences between males and females in terms of risk or resilience factors in brain diseases.

Journal ArticleDOI
TL;DR: Case studies of neurological disorders affecting men and women, including multiple sclerosis and migraine, show strong sex differences in incidence and disease manifestation, to demonstrate the need for more such studies.
Abstract: Beginning in the late 1980s and early 1990s, scientists and the public alike recognized that, for too long, women had been underrepresented in clinical trials. While much progress was made in the following decades, preclinical research still often ignores sex as a fundamental biological variable. Many neurological disorders, including multiple sclerosis and migraine, show strong sex differences in incidence and disease manifestation. In this commentary, we highlight case studies of neurological disorders affecting men and women to demonstrate the need for more such studies. Research conducted in these areas so far has shed light on the underlying mechanisms of the disease and offers the promise to help develop more personalized treatments for both men and women.

Journal Article
TL;DR: The potential role of big data approaches in improving health care systems is described and the most common challenges facing the utilization of health care big data are reviewed.
Abstract: Health care systems generate a huge volume of different types of data. Due to the complexity and challenges inherent in studying medical information, it is not yet possible to create a comprehensive model capable of considering all the aspects of health care systems. There are different points of view regarding what the most efficient approaches toward utilization of this data would be. In this paper, we describe the potential role of big data approaches in improving health care systems and review the most common challenges facing the utilization of health care big data.

Journal ArticleDOI
TL;DR: This review discusses how testosterone acts in the central nervous system, and especially the hypothalamus, to promote metabolic homeostasis or dysfunction in a sexually dimorphic manner and how the metabolic effect of testosterone is centrally mediated via the androgen receptor.
Abstract: One of the most sexually dimorphic aspects of metabolic regulation is the bidirectional modulation of glucose and energy homeostasis by testosterone in males and females. Testosterone deficiency predisposes men to metabolic dysfunction, with excess adiposity, insulin resistance, and type 2 diabetes, whereas androgen excess predisposes women to insulin resistance, adiposity, and type 2 diabetes. This review discusses how testosterone acts in the central nervous system, and especially the hypothalamus, to promote metabolic homeostasis or dysfunction in a sexually dimorphic manner. We compare the organizational actions of testosterone, which program the hypothalamic control of metabolic homeostasis during development, and the activational actions of testosterone, which affect metabolic function after puberty. We also discuss how the metabolic effect of testosterone is centrally mediated via the androgen receptor.

Journal ArticleDOI
TL;DR: How sex differences at the molecular level of cell signaling and protein trafficking are amplified to create a state of vulnerability that under the right conditions can result in symptoms of neuropsychiatry disease is discussed.
Abstract: The recognition that there are fundamental biological sex differences that extend beyond those that define sexual behavior and reproductive function has inspired the drive toward inclusion of both sexes in research design. This is supported by an underlying clinical rationale that studying both sexes is necessary to elucidate pathophysiology and develop treatments for the entire population. However, at a more basic level, sex differences, like genetic differences, can be exploited to better understand biology. Here, we discuss how sex differences at the molecular level of cell signaling and protein trafficking are amplified to create a state of vulnerability that under the right conditions can result in symptoms of neuropsychiatry disease. Although this dialogue focuses on the specific example of corticotropin-releasing factor, the potential for analogous sex differences in signaling and/or trafficking of receptors for other neuromodulators has broad biological and therapeutic implications.

Journal ArticleDOI
TL;DR: Two tools are gaining popularity for personalized medicine research on neuropsychiatric disorders: human induced pluripotent stem cell-derived neurons and human lymphoblastoid cell lines.
Abstract: The development and clinical implementation of personalized medicine crucially depends on the availability of high-quality human biosamples; animal models, although capable of modeling complex human diseases, cannot reflect the large variation in the human genome, epigenome, transcriptome, proteome, and metabolome Although the biosamples available from public biobanks that store human tissues and cells may represent the large human diversity for most diseases, these samples are not always sufficient for developing biomarkers for patient-tailored therapies for neuropsychiatric disorders Postmortem human tissues are available from many biobanks; nevertheless, collections of neuronal human cells from large patient cohorts representing the human diversity remain scarce Two tools are gaining popularity for personalized medicine research on neuropsychiatric disorders: human induced pluripotent stem cell-derived neurons and human lymphoblastoid cell lines This review examines and contrasts the advantages and limitations of each tool for personalized medicine research

Journal ArticleDOI
TL;DR: A conceptual review of mobile technologies' application to addiction research and treatment is presented while using illustrations of research applications that are capable of overcoming specific methodological barriers.
Abstract: Mobile technologies are revolutionizing the field of mental health, and particular progress has been made in their application to addiction research and treatment. The use of smartphones and other mobile devices has been shown to be feasible with individuals addicted to any of a wide range of substances, with few biases being observed concerning the repeated monitoring of daily life experiences, craving, or substance use. From a methodological point of view, the use of mobile technologies overcomes longstanding limitations of traditional clinical research protocols, including the more accurate assessment of temporal relationships among variables, as well as the reduction in both contextual constraints and discipline-specific methodological isolation. The present article presents a conceptual review of these advances while using illustrations of research applications that are capable of overcoming specific methodological barriers. Finally, a brief review of both the benefits and risks of mobile technology use for the treatment of patients will be addressed.

Journal ArticleDOI
TL;DR: It is shown that activation of the ventral striatum is low in patients with schizophrenia, and that this low activation is related to primary and secondary negative symptoms induced by neuroleptics, also known as antipsychotics.
Abstract: The mesolimbic dopaminergic reward system is responsible for the negative affective symptomatology of schizophrenia, which may be related to a low dopamine tonus within the ventral striatum. The monetary incentive delay (MID) task can be used to study the response of the ventral striatum to incentive stimuli. We show that activation of the ventral striatum is low in patients with schizophrenia, and that this low activation is related to primary and secondary negative symptoms induced by neuroleptics, also known as antipsychotics. Switching from first-(typical) to second-generation (atypical) antipsychotics increased activation of the ventral striatum due to less blocking of dopamine D2 receptors. This and similar studies show that functional magnetic resonance imaging (fMRI) tasks are suitable to investigate important aspects of antipsychotic mechanisms.

Journal ArticleDOI
TL;DR: This paper reviews behavioral tailoring strategies that aim to improve medication adherence and other functional outcomes among individuals with serious mental illness and concludes that most require further empirical testing.
Abstract: Nonadherence to psychopharmacological treatments poses a significant challenge to treatment success in individuals with serious mental illness, with upwards of 60% of people not taking their psychiatric medications as prescribed. Nonadherence is associated with adverse outcomes, including exacerbation of psychiatric symptoms, impaired functioning, increased hospitalizations and emergency room use, and increased health care costs. Whereas interventions using psychoeducation or cognitive approaches, such as motivational interviewing, have largely proven ineffective in improving adherence, approaches employing behavioral tailoring that incorporate medication taking into the daily routine and/or use environmental supports have shown promise. Recently, adherence-enhancing behavioral tailoring interventions that utilize novel technologies, such as electronic monitors and mobile phones, have been developed. Although interventions utilizing these platforms have the potential for widespread dissemination to a broad range of individuals, most require further empirical testing. This paper reviews selected behavioral tailoring strategies that aim to improve medication adherence and other functional outcomes among individuals with serious mental illness.

Journal Article
TL;DR: This work focuses on how optogenetics has been used over the last decade to probe striatal circuits that are involved in Parkinson disease, a neurodegenerative condition involving motor and cognitive abnormalities resulting from degeneration of midbrain dopaminergic neurons.
Abstract: Optogenetics refers to the ability to control cells that have been genetically modified to express light-sensitive ion channels. The introduction of optogenetic approaches has facilitated the dissection of neural circuits. Optogenetics allows for the precise stimulation and inhibition of specific sets of neurons and their projections with fine temporal specificity. These techniques are ideally suited to investigating neural circuitry underlying motor and cognitive dysfunction in animal models of human disease. Here, we focus on how optogenetics has been used over the last decade to probe striatal circuits that are involved in Parkinson disease, a neurodegenerative condition involving motor and cognitive abnormalities resulting from degeneration of midbrain dopaminergic neurons. The precise mechanisms underlying the striatal contribution to both cognitive and motor dysfunction in Parkinson disease are unknown. Although optogenetic approaches are somewhat removed from clinical use, insight from these studies can help identify novel therapeutic targets and may inspire new treatments for Parkinson disease. Elucidating how neuronal and behavioral functions are influenced and potentially rescued by optogenetic manipulation in animal models could prove to be translatable to humans. These insights can be used to guide future brain-stimulation approaches for motor and cognitive abnormalities in Parkinson disease and other neuropsychiatric diseases.

Journal ArticleDOI
TL;DR: There is a need to improve the ecological value of experimental tasks that assess decision making in various contexts and with rewards to help translate laboratory learnings into real-life benefits and strengthen the degree of integration of both cognitive and neural substrates.
Abstract: Decision making has been extensively studied in the context of economics and from a group perspective, but still little is known on individual decision making. Here we discuss the different cognitive processes involved in decision making and its associated neural substrates. The putative conductors in decision making appear to be the prefrontal cortex and the striatum. Impaired decision-making skills in various clinical populations have been associated with activity in the prefrontal cortex and in the striatum. We highlight the importance of strengthening the degree of integration of both cognitive and neural substrates in order to further our understanding of decision-making skills. In terms of cognitive paradigms, there is a need to improve the ecological value of experimental tasks that assess decision making in various contexts and with rewards; this would help translate laboratory learnings into real-life benefits. In terms of neural substrates, the use of neuroimaging techniques helps characterize the neural networks associated with decision making; more recently, ways to modulate brain activity, such as in the prefrontal cortex and connected regions (eg, striatum), with noninvasive brain stimulation have also shed light on the neural and cognitive substrates of decision making. Together, these cognitive and neural approaches might be useful for patients with impaired decision-making skills. The drive behind this line of work is that decision-making abilities underlie important aspects of wellness, health, security, and financial and social choices in our daily lives.