What develops during emotional development? A component process approach to identifying sources of psychopathology risk in adolescence

Adolescence is a phase of the lifespan associated with widespread changes in emotional behavior thought to reflect both changing environments and stressors, and psychological and neurobiological development. However, emotions themselves are complex phenomena that are composed of multiple subprocesses. In this paper, we argue that examining emotional development from a process-level perspective facilitates important insights into the mechanisms that underlie adolescents'' shifting emotions and intensified risk for psychopathology. Contrasting the developmental progressions for the antecedents to emotion, physiological reactivity to emotion, emotional regulation capacity, and motivation to experience particular affective states reveals complex trajectories that intersect in a unique way during adolescence. We consider the implications of these intersecting trajectories for negative outcomes such as psychopathology, as well as positive outcomes for adolescent social bonds.     

Emotor control: computations underlying bodily resource allocation,emotions, and confidence

Emotional processes are central to behavior, yet their deeply subjective nature has been a challenge for neuroscientific study as well as for psychiatric diagnosis. Here we explore the relationships between subjective feelings and their underlying brain circuits from a computational perspective. We apply recent insights from systems neuroscience—approaching subjective behavior as the result of mental computations instantiated in the brain—to the study of emotions. We develop the hypothesis that emotions are the product of neural computations whose motor role is to reallocate bodily resources mostly gated by smooth muscles. This “emotor” control system is analagous to the more familiar motor control computations that coordinate skeletal muscle movements. To illustrate this framework, we review recent research on “confidence.” Although familiar as a feeling, confidence is also an objective statistical quantity: an estimate of the probability that a hypothesis is correct. This model-based approach helped reveal the neural basis of decision confidence in mammals and provides a bridge to the subjective feeling of confidence in humans. These results have important implications for psychiatry, since disorders of confidence computations appear to contribute to a number of psychopathologies. More broadly, this computational approach to emotions resonates with the emerging view that psychiatric nosology may be best parameterized in terms of disorders of the cognitive computations underlying complex behavior.     

Typical and atypical brain development: a review of neuroimaging studies

In the course of development, the brain undergoes a remarkable process of restructuring as it adapts to the environment and becomes more efficient in processing information. A variety of brain imaging methods can be used to probe how anatomy, connectivity, and function change in the developing brain. Here we review recent discoveries regarding these brain changes in both typically developing individuals and individuals with neurodevelopmental disorders. We begin with typical development, summarizing research on changes in regional brain volume and tissue density, cortical thickness, white matter integrity, and functional connectivity. Space limits preclude the coverage of all neurodevelopmental disorders; instead, we cover a representative selection of studies examining neural correlates of autism, attention deficit/hyperactivity disorder, Fragile X, 22q11.2 deletion syndrome, Williams syndrome, Down syndrome, and Turner syndrome. Where possible, we focus on studies that identify an age by diagnosis interaction, suggesting an altered developmental trajectory. The studies we review generally cover the developmental period from infancy to early adulthood. Great progress has been made over the last 20 years in mapping how the brain matures with MR technology. With ever-improving technology, we expect this progress to accelerate, offering a deeper understanding of brain development, and more effective interventions for neurodevelopmental disorders.     

A systematic review of the neural bases of psychotherapy for anxiety and related disorders

Brain imaging studies over two decades have delineated the neural circuitry of anxiety and related disorders, particularly regions involved in fear processing and in obsessive-compulsive symptoms. The neural circuitry of fear processing involves the amygdala, anterior cingulate, and insular cortex, while cortico-striatal-thalamic circuitry plays a key role in obsessive-compulsive disorder. More recently, neuroimaging studies have examined how psychotherapy for anxiety and related disorders impacts on these neural circuits. Here we conduct a systematic review of the findings of such work, which yielded 19 functional magnetic resonance imaging studies examining the neural bases of cognitive-behavioral therapy (CBT) in 509 patients with anxiety and related disorders. We conclude that, although each of these related disorders is mediated by somewhat different neural circuitry, CBT may act in a similar way to increase prefrontal control of subcortical structures. These findings are consistent with an emphasis in cognitive-affective neuroscience on the potential therapeutic value of enhancing emotional regulation in various psychiatric conditions.     

Neural systems underlying approach and avoidance in anxiety disorders

Approach-avoidance conflict is an important psychological concept that has been used extensively to better understand cognition and emotion. This review focuses on neural systems involved in approach, avoidance, and conflict decision making, and how these systems overlap with implicated neural substrates of anxiety disorders. In particular, the role of amygdala, insula, ventral striatal, and prefrontal regions are discussed with respect to approach and avoidance behaviors. Three specific hypotheses underlying the dysfunction in anxiety disorders are proposed, including: (i) over-representation of avoidance valuation related to limbic overactivation; (ii) under- or over-representation of approach valuation related to attenuated or exaggerated striatal activation respectively; and (iii) insufficient integration and arbitration of approach and avoidance valuations related to attenuated orbitofrontal cortex activation. These dysfunctions can be examined experimentally using versions of existing decision-making paradigms, but may also require new translational and innovative approaches to probe approach-avoidance conflict and related neural systems in anxiety disorders.     

Cellular plasticity and resilience and the pathophysiology of severe mood disorders

Recent advances in the identification of the neural circuits, neurochemicals, and signal transduction mechanisms involved in the pathophysiology and treatment of mood disorders have led to much progress toward understanding the roles of genetic factors and psychosocial stressors. The monoaminergic neurotransmitter systems have received the most attention, partly because of the observation that effective antidepressant drugs exert their primary biochemical effects by regulating intrasynaptic concentrations of serotonin and norepinephrine. Furthermore, the monoaminergic systems are extensively distributed throughout the network of limbic, striatal, and prefrontal cortical neuronal circuits thought to support the behavioral and visceral manifestations of mood disorders. Increasing numbers of neuroimaging, neuropathological, and biochemical studies indicate impairments in cellular plasticity and resilience in patients who suffer from severe, recurrent mood disorders. In this paper, we describe studies identifying possible structural, functional, and cellular abnormalities associated with depressive disorders, which are potentially the cellular underpinnings of these diseases. We suggest that drugs designed to enhance cellular plasticity and resilience, and attenuate the activity of maladaptive stress-responsive systems, may be useful for the treatment of severe mood disorders.     

Affective neuroscience of the emotional BrainMind: evolutionary perspectives and implications for understanding depression

Cross-species affective neuroscience studies confirm that primary-process emotional feelings are organized within primitive subcortical regions of the brain that are anatomically, neurochemically, and functionally homologous in all mammals that have been studied. Emotional feelings (affects) are intrinsic values that inform animals how they are faring in the quest to survive. The various positive affects indicate that animals are returning to "comfort zones" that support survival, and negative affects reflect "discomfort zones" that indicate that animals are in situations that may impair survival. They are ancestral tools for living--evolutionary memories of such importance that they were coded into the genome in rough form (as primary brain processes), which are refined by basic learning mechanisms (secondary processes) as well as by higher-order cognitions/thoughts (tertiary processes). To understand why depression feels horrible, we must fathom the affective infrastructure of the mammalian brain. Advances in our understanding of the nature of primary-process emotional affects can promote the development of better preclinical models of psychiatric disorders and thereby also allow clinicians new and useful ways to understand the foundational aspects of their clients' problems. These networks are of clear importance for understanding psychiatric disorders and advancing psychiatric practice.     

Affective preclinical modeling of psychiatric disorders: taking imbalanced primal emotional feelings of animals seriously in our search for novel antidepressants

Preclinical animal models of psychiatric disorders are of critical importance for advances in development of new psychiatric medicine. Regrettably, behavior-only models have yielded no novel targeted treatments during the past half-century of vigorous deployment. This may reflect the general neglect of experiential aspects of animal emotions, since affective mental states of animals supposedly cannot be empirically monitored. This supposition is wrong—to the extent that the rewarding and punishing aspects of emotion circuit arousals reflect positive and negative affective states. During the past decade, the use of such affective neuroscience-based animal modeling has yielded three novel antidepressants (i) via the alleviation of psychic pain with low doses of buprenorphine; (ii) via the amplification of enthusiasm by direct stimulation of the medial forebrain bundle); and (iii) via the facilitation of the capacity for social joy with play facilitators such as rapastinel (GLYX13). All have progressed to successful human testing. For optimal progress, it may be useful for preclinical investigators to focus on the evolved affective foundations of psychiatrically relevant brain emotional disorders for optimal animal modeling.     

The effectiveness of anticonvulsants in psychiatric disorders

Anticonvulsant drugs are widely used in psychiatric indications. These include mainly alcohol and benzodiazepine withdrawal syndromes, panic and anxiety disorders, dementia, schizophrenia, affective disorders, bipolar affective disorders in particular, and, to some extent, personality disorders. A further area in which neurology and psychiatry overlap is pain conditions, in which some anticonvulsants, and also typical psychiatric medications such as antidepressants, are helpful. From the beginning of their psychiatric use, anticonvulsants have also been used to ameliorate specific symptoms of psychiatric disorders independently of their causality and underlying illness, eg, aggression, and, more recently, cognitive impairment, as seen in affective disorders and schizophrenia. With new anticonvulsants currently under development, it is likely that their use in psychiatry will further increase, and that psychiatrists need to learn about their differential efficacy and safety profiles to the same extent as do neurologists.     

Biological rhythms, higher brain function, and behavior: Gaps, opportunities, and challenges

Increasing evidence suggests that disrupted temporal organization impairs behavior, cognition, and affect; further, disruption of circadian clock genes impairs sleep-wake cycle and social rhythms which may be implicated in mental disorders. Despite this strong evidence, a gap in understanding the neural mechanisms of this interaction obscures whether biological rhythms disturbances are the underlying causes or merely symptoms of mental disorder. Here, we review current understanding, emerging concepts, gaps, and opportunities pertinent to (1) the neurobiology of the interactions between circadian oscillators and the neural circuits subserving higher brain function and behaviors of relevance to mental health, (2) the most promising approaches to determine how biological rhythms regulate brain function and behavior under normal and pathological conditions, (3) the gaps and challenges to advancing knowledge on the link between disrupted circadian rhythms/sleep and psychiatric disorders, and (4) the novel strategies for translation of basic science discoveries in circadian biology to clinical settings to define risk, prevent or delay onset of mental illnesses, design diagnostic tools, and propose new therapeutic strategies. The review is organized around five themes pertinent to (1) the impact of molecular clocks on physiology and behavior, (2) the interactions between circadian signals and cognitive functions, (3) the interface of circadian rhythms with sleep, (4) a clinical perspective on the relationship between circadian rhythm abnormalities and affective disorders, and (5) the pre-clinical models of circadian rhythm abnormalities and mood disorders.     

Quality of life in schizophrenic patients

In the last decades, there has been increased interest in the field of quality of life in mental disorders in general, and particularly in schizophrenia. In addition, the appearance of the atypical antipsychotic drugs (amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone) with different therapeutic and side-effect profiles, has promoted a greater interest in assessing the quality of life of schizophrenic patients. In this paper we will briefly summarize the difficulties in assessing quality of life in schizophrenic patients, as well as the results concerning their quality of life and the influence of psychopathology, especially negative and depressive symptoms, on it. We will also review data from recent clinical trials showing the impact ofantipsychotic treatments and their side effects upon quality of life.     

Anxiety and DSM-5

The DSM-5 process, and the publication of DSM-5 in 2013, have had a considerable impact on the classification of anxiety disorders. Major changes included the reorganization of the chapter structure, individual groupings of disorders within each chapter from a life span viewpoint, and the use of specifiers. The DSM-5 chapter on anxiety disorders does not include obsessive-compulsive disorder or post-traumatic stress disorder. The chapter itself now reflects a developmental approach. The text of each disorder has been enhanced with short sections on development and course, risk and prognostic factors, etc. It is expected that the reformulation of anxiety disorders in DSM-5 will lead to greater precision in a variety of ways, as illustrated in the papers in this issue of Dialogues in Clinical Neuroscience. In summary, these changes in the way we classify anxiety disorders reflect our best view on the clinical empirical data and should prove useful in the assessment of specific anxiety disorders.     

Acupuncture inhibits Notch1 and Hes1 protein expression in the basal ganglia of rats with cerebral hemorrhage

Notch pathway activation maintains neural stem cells in a proliferating state and increases nerve repair capacity. To date, studies have rarely focused on changes or damage to signal transduction pathways during cerebral hemorrhage. Here, we examined the effect of acupuncture in a rat model of cerebral hemorrhage. We examined four groups: in the control group, rats received no treatment. In the model group, cerebral hemorrhage models were established by infusing non-heparinized blood into the brain. In the acupuncture group, modeled rats had Baihui(DU20) and Qubin(GB7) acupoints treated once a day for 30 minutes. In the DAPT group, modeled rats had 0.15 μg/m L DAPT solution(10 m L) infused into the brain. Immunohistochemistry and western blot results showed that acupuncture effectively inhibits Notch1 and Hes1 protein expression in rat basal ganglia. These inhibitory effects were identical to DAPT, a Notch signaling pathway inhibitor. Our results suggest that acupuncture has a neuroprotective effect on cerebral hemorrhage by inhibiting Notch-Hes signaling pathway transduction in rat basal ganglia after cerebral hemorrhage.     

Sleep and psychiatry

Psychiatric disorders constitute 15.4% of the disease burden in established market economies. Many psychiatric disorders are associated with sleep disturbances, and the relationship is often bidirectional. This paper reviews the prevalence of various psychiatric disorders, their clinical presentation, and their association with sleep disorders. Among the psychiatric disorders reviewed are affective disorders, psychosis, anxiety disorders (including posttraumatic stress disorder), substance abuse disorders, eating disorders, and attention deficit/hyperactivity disorders. The spectrum of associated sleep disorders includes insomnia, hypersomnia, nocturnal panic, sleep paralysis, hypnagogic hallucinations, restless legs/periodic limb movements of sleep, obstructive sleep apnea, and parasomnias. The effects on sleep of various psychotropic medications utilized to treat the above psychiatric disorders are summarized.     

Epigenetic alterations in depression and antidepressant treatment

Epigenetic modifications control chromatin structure and function, and thus mediate changes in gene expression, ultimately influencing protein levels. Recent research indicates that environmental events can induce epigenetic changes and, by this, contribute to long-term changes in neural circuits and endocrine systems associated with altered risk for stress-related psychiatric disorders such as major depression. In this review, we describe recent approaches investigating epigenetic modifications associated with altered risk for major depression or response to antidepressant drugs, both on the candidate gene levels as well as the genome-wide level. In this review we focus on DNA methylation, as this is the most investigated epigenetic change in depression research.     

The maturation of affective neuroscience: celebrating the research career of Jaak Panksepp

Jaak Panksepp has been a pioneer in the burgeoning field of affective neuroscience. His visionary research has inspired numerous students, colleagues and health professionals to aspire to understand the neurobiological underpinnings of emotions and their relationship to psychiatric disorders. Bowling Green State University was honored to host a celebration of Jaak and his considerable research accomplishments, and what follows is an abbreviated biography of his career in science.     

Gonadal steroids, brain, and behavior: role of context

The nature and extent of the impact of gender and reproductive function on mood has been the subject of speculation and controversy for centuries. Over the past 50 years, however, it has become increasingly clear that not only is the brain a major target of reproductive steroid hormones, but additionally, the steroid hormones, as neuroregulators, create a context thai influences a broad range of brain activities; ie, neural actions and resultant behaviors are markedly different in the presence and absence of gonadal steroids. In turn, the actions of gonadal steroids are themselves context-dependent. Thus, even where it can be demonstrated thai gonadal steroids trigger mood disorders, the triggers are normal levels of gonadal steroids (to be contrasted with the mood disturbances accompanying endocrinopathies), and the mood disorders appear only in a subset of susceptible individuals. The context specificity and differential susceptibility to affective dysregulation seen in women with reproductive endocrine-related mood disorders are undoubtedly important underlying characteristics of a wide range of psychiatric disorders in which the triggers have not yet been identified. Consequently, reproductive endocrine-related mood disorders offer unparalleled promise for the identification of those contextual variables that permit biological stimuli to differentially translate into depression in individuals at risk.     

Rodent empathy and affective neuroscience

In the past few years, several experimental studies have suggested that empathy occurs in the social lives of rodents. Thus, rodent behavioral models can now be developed to elucidate the mechanistic substrates of empathy at levels that have heretofore been unavailable. For example, the finding that mice from certain inbred strains express behavioral and physiological responses to conspecific distress, while others do not, underscores that the genetic underpinnings of empathy are specifiable and that they could be harnessed to develop new therapies for human psychosocial impairments. However, the advent of rodent models of empathy is met at the outset with a number of theoretical and semantic problems that are similar to those previously confronted by studies of empathy in humans. The distinct underlying components of empathy must be differentiated from one another and from lay usage of the term. The primary goal of this paper is to review a set of seminal studies that are directly relevant to developing a concept of empathy in rodents. We first consider some of the psychological phenomena that have been associated with empathy, and within this context, we consider the component processes, or endophenotypes of rodent empathy. We then review a series of recent experimental studies that demonstrate the capability of rodents to detect and respond to the affective state of their social partners. We focus primarily on experiments that examine how rodents share affective experiences of fear, but we also highlight how similar types of experimental paradigms can be utilized to evaluate the possibility that rodents share positive affective experiences. Taken together, these studies were inspired by Jaak Panksepp's theory that all mammals are capable of felt affective experiences.