Specificity of regional brain activity in anxiety types during emotion processing

The present study tested the hypothesis that anxious apprehension involves more left- than right-hemisphere activity and that anxious arousal is associated with the opposite pattern. Behavioral and fMRI responses to threat stimuli in an emotional Stroop task were examined in nonpatient groups reporting anxious apprehension, anxious arousal, or neither. Reaction times were longer for negative than for neutral words. As predicted, brain activation distinguished anxious groups in a left inferior frontal region associated with speech production and in a right-hemisphere inferior temporal area. Addressing a second hypothesis about left-frontal involvement in emotion, distinct left frontal regions were associated with anxious apprehension versus processing of positive information. Results support the proposed distinction between the two types of anxiety and resolve an inconsistency about the role of left-frontal activation in emotion and psychopathology.     

A medical issue affecting the diagnosis of mood,attention and autistic disorders: a closer look at celiac disease and gluten sensitivity

Abstract

Objective: The purpose of this article is to highlight important medical advances around the presentation of celiac disease and gluten sensitivity, and their implications as potential differential diagnoses for mood, attention and autistic disorders. Celiac disease is an autoimmune disorder associated with gluten consumption. An overview of the recent scientific literature relevant to psychologists is provided along with a discussion of implications for therapy. Conclusion: Psychologists can significantly contribute to the reduction of serious psycho-socio-medical problems affecting a segment of the population by ruling out celiac disease and gluten sensitivity before initiating treatment of mood, attention, and autistic disorders. While not all people suffering from these psychological disorders will improve on a gluten-free diet, the dramatic remission displayed by a subgroup of people under a gluten-free diet makes the consideration important in new treatment protocols by psychologists and health professionals.     

The use of virtual reality in assessment and treatment of anxiety and related disorders

In recent years the development of new virtual environments has been qualitatively high and fast at the same time, but the dissemination of virtual reality (VR) in clinical practice is still scarce. The aim of this review is to give an insight into the state of the art of the use of VR as an assessment tool and treatment intervention in anxiety and related disorders as posttraumatic stress disorder and obsessive–compulsive disorders. Besides an overview into the efficacy of VR, a summary will be given on assumed working mechanisms in virtual reality exposure therapy and how this aligns with current theoretical models. Further, it will be discussed how VR is accepted by patients and research into the reluctance of therapist to use this technology during treatment with focus on the therapeutic alliance and how it may be influenced by the use of VR. Finally, we discuss clinical and future issues as, for example, dissemination into clinical practice and what VR has to offer therapists in future. This not only in adult population but as well in younger patients, as young adolescents VR has a great potential as it connects easily with its playful elements to this population and might be a low threshold step to offer treatment or preventive interventions.     

On the specificity of positive emotional dysfunction in psychopathology: Evidence from the mood and anxiety disorders and schizophrenia/schizotypy

We review recent research to establish that the associations between positive emotional experience and major forms of psychopathology show considerable specificity. Although indicators of low positive affect are consistently related to both social anxiety/social phobia and schizophrenia/schizotypy, they are more strongly linked to depression, thereby displaying relative specificity. Moreover, low positive affect actually shows greater specificity than the diagnostic criteria for depression and is most strongly related to those symptoms (anhedonia, dysphoria, lassitude, suicidality) that are specific to the disorder. With regard to social phobia, findings suggest that low positive affect is more strongly related to the generalized subtype than to the non-generalized performance subtype. Analyses of schizophrenia/schizotypy indicate that although low positive affect is consistently associated with the negative symptoms (e.g., constricted affect, social aloofness), it is only weakly related to positive symptoms (e.g., magical thinking, perceptual aberrations, suspiciousness). Other data suggest that schizophrenia is associated with an anticipatory pleasure deficit, such that individuals with the disorder engage in rewarding activities less frequently because they do not expect to derive pleasure from them. Finally, we summarize evidence indicating that elevated positive affect is both a risk factor for bipolar disorder and a concomitant of manic symptoms.     

A study in male and female 5-HT transporter knockout rats: an animal model for anxiety and depression disorders

Human studies have shown that a reduction of 5-HT transporter (SERT) increases the vulnerability for anxiety and depression. Moreover, women are more vulnerable to develop depression and anxiety disorders than men. For that reason we hypothesized that homozygous 5-HT transporter knockout rat (SERT(-/-)) models, especially female, are valuable and reliable animal models for humans with an increased vulnerability for anxiety- and depression-related disorders. As rats are extensively used in neuroscience research, we used the unique 5-HT transporter knockout rat, that was recently generated using N-ethyl-N-nitrosurea (ENU) -driven mutagenesis, to test this hypothesis. Behavioral testing revealed that male and female SERT(-/-) rats spent less time in the center of the open field and spent less time on the open arm of the elevated plus maze compared with wild-type 5-HT transporter knockout rats (SERT(+/+)). In the novelty suppressed feeding test, only male SERT(-/-) rats showed a higher latency before starting to eat in a bright novel arena compared with SERT(+/+) controls. Both male and female SERT(-/-) rats showed a higher escape latency from their home cage than SERT(+/+) littermates. Moreover, SERT(-/-) rats were less mobile in the forced swim test, and sucrose consumption was reduced in SERT(-/-) rats relative to SERT(+/+) rats. Both effects were sex-independent. Neurochemically, basal extracellular 5-HT levels were elevated to a similar extent in male and female SERT(-/-) rats, which was not influenced by the selective 5-HT reuptake inhibitor citalopram. 5-HT immunostaining revealed no difference between SERT(+/+) and SERT(-/-) rats in the dorsal raphe nuclei, in both males and females. These findings demonstrate that SERT(-/-) rats show anxiety and depression-related behavior, independent of sex. Genetic inactivation of the SERT has apparently such a great impact on behavior, that hardly any differences are found between male and female rats. This knockout rat model may provide a valuable model to study anxiety- and depression-related disorders in male and female rats.     

Heart rate variability and its neural correlates during emotional face processing in social anxiety disorder

The monitoring and regulation of one's own physiological reactions and cardioregulatory abnormalities are central to the aetiology and maintenance of social anxiety disorder (SAD). We therefore explored the neural correspondences of these heart rate alterations.     

Meaning-making as a mediator of anxiety and depression reduction during cognitive behavioral therapy intervention in participants with adjustment disorders

There is a consensus among researchers about the link between low meaning in life and anxiety and depressive symptoms. One unanswered question is whether meaning-making is a mediator of the change in anxiety and depression symptoms in participants with adjustment disorders during cognitive behavioural therapy (CBT) treatment. The aims of this study were (a) to analyse whether there was meaning-making during the application of the CBT, (b) to analyse whether meaning-making was a mediator of anxiety psychopathology and (c) to analyse whether meaning-making was a mediator of depressive symptoms. The sample was composed of 115 patients who satisfied the full Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for adjustment disorder as their primary diagnosis and completed CBT treatment in a primary care mental health service: 74.78% women, n = 86, and 25.22% men, n = 29, with a mean age of 41.89 (standard deviation [SD] = 10.39) years. The diagnosis was established using the Structured Clinical Interview for DSM-5 (SCID-5), and participants filled out the Beck Anxiety Inventory, the Beck Depression Inventory and Purpose in Life questionnaires. The therapists were clinical psychologists with experience in clinical assessment. A repeated-measures analysis of variance (ANOVA) and two mediation analyses using the bootstrap method were performed. The results indicated that (a) There was meaning-making during the CBT because the treated sample showed a statistically significant improvement in meaning in life, and (b) meaning-making during the CBT was a partial mediator between anxiety symptoms and depressive symptoms before and after the treatment. The present study suggests that meaning in life could be an important variable in the psychopathology of adjustment disorders.     

Cognitive processes during fear acquisition and extinction in animals and humans: implications for exposure therapy of anxiety disorders

Anxiety disorders are highly prevalent. Fear conditioning and extinction learning in animals often serve as simple models of fear acquisition and exposure therapy of anxiety disorders in humans. This article reviews the empirical and theoretical literature on cognitive processes in fear acquisition, extinction, and exposure therapy. It is concluded that exposure therapy is a form of cognitive intervention that specifically changes the expectancy of harm. Implications for therapy research are discussed.     

Social stress during adolescence in Wistar rats induces social anxiety in adulthood without affecting brain monoaminergic content and activity

Adolescence has been described as an important period to acquire social competences required for adult life. It has been suggested that early stress experiences could affect the development of the brain at different levels. These changes in the brain during adolescence may be related with the development of psychopathologies such as depression and social anxiety in adulthood. In the first experiment, we examined long-term effects of repeated social stress during adolescence on adult social approach-avoidance behavior. For that purpose, adolescent male Wistar rats were exposed twice at postnatal day (Pnd) 45 and Pnd48 to the resident-intruder paradigm followed by three times psychosocial threat with the same resident. Three weeks after the last psychosocial threat experience the animals were behaviorally tested in a social approach-avoidance test. Socially stressed animals spent less time in the interaction zone with an unfamiliar male adult rat. These data suggest that animals exposed to social stress during adolescence show a higher level of social anxiety in adulthood. In the second experiment, we investigated whether these long-term effects of social stress during adolescence on behavior draw a parallel with changes in brain monoamine content, biosynthesis and turnover. Using the same experimental design as in the first experiment, HPLC analysis of various brain regions showed that there were no differences in monoamine content, monoamine biosynthesis and monoamines activity in the prefrontal cortex, hippocampus, hypothalamus and striatum in adulthood. These results indicate that long-lasting changes in social behavior following social stress during adolescence are not accompanied by changes in brain monoamine content, biosynthesis and turnover.     

Identification of sites of sympathetic outflow at rest and during emotional arousal: Concurrent recordings of sympathetic nerve activity and fMRI of the brain

The sympathetic nervous system subserves many of the autonomic responses to mental stress and emotional processing. While peripheral markers of sympathetic activity can be obtained indirectly – by measuring heart rate, blood pressure, sweat release and skin blood flow – these effector-organ responses are slower compared to the directly recorded sympathetic nerve activity. Microneurography, in which a tungsten microelectrode is inserted percutaneously into a peripheral nerve in awake human subjects, allows one to record sympathetic nerve activity to either muscle or skin. Muscle sympathetic nerve activity (MSNA) is involved in the beat-to-beat control of blood pressure, and is elevated during mental stress; chronic stress can lead to high blood pressure. The primary role of skin sympathetic nerve activity (SSNA) is to regulate body temperature by controlling sweat release and skin blood flow, but it has also been commandeered for emotional expression. In this review we discuss our recent work in which we have performed concurrent microelectrode recordings of MSNA or SSNA and fMRI of the brain, with a view to identifying areas in the brain responsible for generating the increases in sympathetic outflow at rest and during emotional engagement. Spontaneous bursts of MSNA at rest were positively correlated to activity in the left dorsomedial hypothalamus and left insula, and bilaterally in the ventromedial hypothalamus, dorsolateral prefrontal cortex, posterior cingulate cortex and precuneus. Spontaneous bursts of SSNA at rest were positively correlated with activity in the left ventromedial nucleus of the thalamus, the left posterior and right anterior insula, the right orbitofrontal and frontal cortices and bilaterally in the mid-cingulate cortex and precuneus. Increases in SSNA occurred when subjects viewed emotionally charged images, resulting in increases in activity in the central and lateral amygdala, dorsolateral pons, thalamus, nucleus accumbens, and cerebellar cortex; surprisingly, there was no activation of the insula in response to these emotional stimuli. We have shown that concurrent microelectrode recordings of sympathetic outflow to either muscle or skin and fMRI of the brain can be used to identify areas of the brain involved in the generation of sympathetic nerve activity. We propose that this approach can be extended to examine specific disorders of emotional expression to increase our understanding of the underlying neural processes.     

The key role of insomnia and sleep loss in the dysregulation of multiple systems involved in mood disorders: A proposed model

Mood disorders are amongst the most prevalent and severe disorders worldwide, with a tendency to be recurrent and disabling. Although multiple mechanisms have been hypothesized to be involved in their pathogenesis, just a few integrative theoretical frameworks have been proposed and have yet to integrate comprehensively all available findings. As such, a comprehensive framework would be quite useful from a clinical and therapeutic point of view in order to identify elements to evaluate and target in the clinical practice. Because conditions of sleep loss, which include reduced sleep duration and insomnia, are constant alterations in mood disorders, the aim of this paper was to review the literature on their potential role in the pathogenesis of mood disorders and to propose a novel theoretical model. According to this hypothesis, sleep should be considered the main regulator of several systems and processes whose dysregulation is involved in the pathogenesis of mood disorders. The model may help explain why sleep disturbances are so strikingly linked to mood disorders, and underscores the need to evaluate, assess and target sleep disturbances in clinical practice, as a priority, in order to prevent and treat mood disorders.     

Self-help treatment of anxiety disorders: a meta-analysis and meta-regression of effects and potential moderators

Self-help treatments have the potential to increase the availability and affordability of evidence-based treatments for anxiety disorders. Although promising, previous research results are heterogeneous, indicating a need to identify factors that moderate treatment outcome. The present article reviews the literature on self-help treatment for anxiety disorders among adults, with a total sample of 56 articles with 82 comparisons. When self-help treatment was compared to wait-list or placebo, a meta-analysis indicated a moderate to large effect size (g=0.78). When self-help treatment was compared to face-to-face treatment, results indicated a small effect that favored the latter (g=-0.20). When self-help was compared to wait-list or placebo, subgroup analyses indicated that self-help treatment format, primary anxiety diagnosis and procedures for recruitment of subjects were related to treatment outcome in bivariate analyses, but only recruitment procedures remained significant in a multiple meta-regression analysis. When self-help was compared to face-to-face treatment, a multiple meta-regression indicated that the type of comparison group, treatment format and gender were significantly related to outcome. We conclude that self-help is effective in the treatment of anxiety disorders, and should be offered as part of stepped care treatment models in community services. Implications of the results and future directions are discussed.     

Overlapping prefrontal systems involved in cognitive and emotional processing in euthymic bipolar disorder and following sleep deprivation: A review of functional neuroimaging studies

Prefrontal cortex (PFC) mediated cognitive and emotional processing deficits in bipolar disorder lead to functional limitations even during periods of mood stability. Alterations of sleep and circadian functioning are well-documented in bipolar disorder, but there is little research directly examining the mechanistic role of sleep and/or circadian rhythms in the observed cognitive and emotional processing deficits. We systematically review the cognitive and emotional processing deficits reliant upon PFC functioning of euthymic patients with bipolar disorder and in healthy individuals deprived of sleep. The evidence from two parallel lines of investigation suggests that sleep and circadian rhythms may be involved in the cognitive and emotional processing deficits seen in bipolar disorder through overlapping neurobiological systems. We discuss current models of bipolar highlighting the PFC-limbic connections and discuss inclusion of sleep-related mechanisms. Sleep and circadian dysfunction is a core feature of bipolar disorder and models of neurobiological abnormalities should incorporate chronobiological measures. Further research into the role of sleep and circadian rhythms in cognition and emotional processing in bipolar disorder is warranted.     

Seeing the invisible: the scope and limits of unconscious processing in binocular rivalry

When an image is presented to one eye and a very different image is presented to the corresponding location of the other eye, the two images compete for conscious representations, such that only one image is visible at a time while the other is suppressed. Called binocular rivalry, this phenomenon and its deviants have been extensively exploited to study the mechanism and neural correlates of consciousness. In this paper, we propose a framework - the unconscious binding hypothesis - to distinguish unconscious processing from conscious processing. According to this framework, the unconscious mind not only encodes individual features but also temporally binds distributed features to give rise to cortical representations; unlike conscious binding, however, unconscious binding is fragile. Under this framework, we review evidence from psychophysical and neuroimaging studies and come to two important conclusions. First, processing of invisible features depends on the "level" of the features as defined by their neural mechanisms. For low-level simple features, prolonged exposure to visual patterns (e.g. tilt) and simple translational motion can alter the appearance of subsequent visible features (i.e. adaptation). For invisible high-level features, complex spiral motion cannot produce adaptation, nor can objects/words enhance subsequent processing of related stimuli (i.e. priming). Yet images of tools can activate the dorsal pathway. Second, processing of invisible features has functional significance. Although invisible central cues cannot orient attention, invisible erotic pictures in the periphery can nevertheless guide attention, likely through emotional arousal; reciprocally, the processing of invisible information can be modulated by attention.