Altered Uncinate Fasciculus Microstructure in Childhood Anxiety Disorders in Boys But Not Girls.

OBJECTIVE: Anxiety disorders are common, can result in lifelong suffering, and frequently begin before adolescence. Evidence from adults suggests that altered prefrontal-limbic connectivity is a pathophysiological feature of anxiety disorders. More specifically, in adults with anxiety disorders, decreased fractional anisotropy (FA), a measure of white matter integrity, has been observed in the uncinate fasciculus, the major tract that connects limbic and prefrontal regions. Because of the early onset of anxiety disorders and the increased incidence in anxiety disorders in females during their reproductive years, it is important to understand whether the reduction in uncinate fasciculus FA exists in children with anxiety disorders and the extent to which this alteration is sex related. To address these issues, the authors assessed FA in the uncinate fasciculus in unmedicated boys and girls with anxiety disorders. METHODS: FA measures were derived from diffusion tensor images that were acquired from 98 unmedicated children (ages 8-12); 52 met criteria for generalized anxiety disorder, separation anxiety disorder, social anxiety disorder, or anxiety disorder not otherwise specified, and 46 were matched control subjects. RESULTS: Tract-based results demonstrated that children with anxiety disorders have significant reductions in uncinate fasciculus FA. A significant sex-by-group interaction and post hoc testing revealed that this effect was evident only in boys. No other main effects or sex-by-group interactions were found for other white matter tracts. CONCLUSIONS: These findings provide evidence of uncinate fasciculus white matter alterations in boys with anxiety disorders. The data demonstrate that anxiety disorder-related alterations in prefrontal-limbic structural connectivity are present early in life, are not related to psychotropic medication exposure, and are sex specific. Building on these findings, future research has the potential to provide insights into the genesis and sexual dimorphism of the pathophysiology that leads to anxiety disorders, as well as to identify sex-specific early-life treatment targets.

Visual Attention to Suffering After Compassion Training Is Associated With Decreased Amygdala Responses.

Compassion meditation training is hypothesized to increase the motivational salience of cues of suffering, while also enhancing equanimous attention and decreasing emotional reactivity to suffering. However, it is currently unknown how compassion meditation impacts visual attention to suffering, and how this impacts neural activation in regions associated with motivational salience as well as aversive responses, such as the amygdala. Healthy adults were randomized to 2 weeks of compassion or reappraisal training. We measured BOLD fMRI responses before and after training while participants actively engaged in their assigned training to images depicting human suffering or non-suffering. Eye-tracking data were recorded concurrently, and we computed looking time for socially and emotionally evocative areas of the images, and calculated visual preference for suffering vs. non-suffering. Increases in visual preference for suffering due to compassion training were associated with decreases in the amygdala, a brain region involved in negative valence, arousal, and physiological responses typical of fear and anxiety states. This pattern was specifically in the compassion group, and was not found in the reappraisal group. In addition, compassion training-related increases in visual preference for suffering were also associated with decreases in regions sensitive to valence and empathic distress, spanning the anterior insula and orbitofrontal cortex (while the reappraisal group showed the opposite effect). Examining visual attention alone demonstrated that engaging in compassion in general (across both time points) resulted in visual attention preference for suffering compared to engaging in reappraisal. Collectively, these findings suggest that compassion meditation may cultivate visual preference for suffering while attenuating neural responses in regions typically associated with aversive processing of negative stimuli, which may cultivate a more equanimous and nonreactive form of attention to stimuli of suffering.

Can Quantab titrator sticks reliably predict urinary sodium?

BACKGROUND & AIMS: Urinary sodium concentration is a commonly used marker for extracellular fluid depletion which is often associated with dehydration. A point of care test for urinary sodium may reduce delays in clinical decision making by offering more timely guidance leading to improved salt and fluid management. We compared laboratory assessed urinary sodium with a potential point of care measure of urinary chloride in a variety of in- and outpatient specialities, to explore its use as an indicator of low urine sodium. METHODS: Urinary chloride concentrations were estimated using a Quantab titrator stick in samples from patients that had been sent for urinary sodium assays. We validated the results of this titrator stick with laboratory-assessed sodium concentrations by deriving correlation coefficients between these methods and using limits of agreement testing. We determined the optimal titrator stick cut-point for identifying low urinary sodium (urinary sodium <20 mmol/L) by maximising the product of the sensitivity and specificity. This level of urinary sodium was used to mirror the British Society of Gastroenterology guidance on short bowel patients Nightingale and Woodward, 2006. RESULTS: We obtained laboratory urinary sodium concentration and Quantab stick chloride measures on 127 samples. Twenty three percent had a urinary sodium below 20 mmol/L so were regarded as biochemically dehydrated. A threshold of <4.3 on the Quantab scale had a positive predictive value for low sodium of 56% (95%CI 40%-71%) and a negative predictive value of 94% (95%CI 87%-98%). CONCLUSIONS: These data suggest that the Quantab stick could be used as a point of care test to aid fluid and salt management decisions in an outpatient setting. Further work to explore the use of the titrator stick in specific patient populations at risk of salt and water depletion is justified.

Herbs and Inflammatory Bowel Disease.

Although herbal preparations are widely used by patients with inflammatory bowel disease (IBD), evidence for their efficacy is limited and they may not always be safe. Mainly small studies of varying quality have suggested that several herbal preparations could be of benefit in IBD, but larger better-designed trials are needed to establish their place in inducing and maintaining remission. Patients and health care workers need to be made more aware of the limitations and risks of using herbal products for IBD.

Fear of the unknown: uncertain anticipation reveals amygdala alterations in childhood anxiety disorders.

Children with anxiety disorders (ADs) experience persistent fear and worries that are highly debilitating, conferring risk for lifelong psychopathology. Anticipatory anxiety is a core clinical feature of childhood ADs, often leading to avoidance of uncertain and novel situations. Extensive studies in non-human animals implicate amygdala dysfunction as a critical substrate for early life anxiety. To test specific amygdala-focused hypotheses in preadolescent children with ADs, we used fMRI to characterize amygdala activation during uncertain anticipation and in response to unexpected stimuli. Forty preadolescent (age 8-12 years) children, 20 unmedicated AD patients and 20 matched controls completed an anticipation task during an fMRI scan. In the task, symbolic cues preceded fear or neutral faces, such that 'certain' cues always predicted the presentation of fear or neutral faces, whereas 'uncertain' cues were equally likely to be followed by fear or neutral faces. Both AD children and controls showed robust amygdala response to faces. In response to the uncertain cues, AD children had increased amygdala activation relative to controls. Moreover, in the AD children, faces preceded by an 'uncertain' cue elicited increased amygdala activation, as compared with the same faces following a 'certain' cue. Children with ADs experience distress both in anticipation of and during novel and surprising events. Our findings suggest that increased amygdala activation may have an important role in the generation of uncertainty-related anxiety. These findings may guide the development of neuroscientifically informed treatments aimed at relieving the suffering and preventing the lifelong disability associated with pediatric ADs.

Compassion training alters altruism and neural responses to suffering.

Compassion is a key motivator of altruistic behavior, but little is known about individuals' capacity to cultivate compassion through training. We examined whether compassion may be systematically trained by testing whether (a) short-term compassion training increases altruistic behavior and (b) individual differences in altruism are associated with training-induced changes in neural responses to suffering. In healthy adults, we found that compassion training increased altruistic redistribution of funds to a victim encountered outside of the training context. Furthermore, increased altruistic behavior after compassion training was associated with altered activation in brain regions implicated in social cognition and emotion regulation, including the inferior parietal cortex and dorsolateral prefrontal cortex (DLPFC), and in DLPFC connectivity with the nucleus accumbens. These results suggest that compassion can be cultivated with training and that greater altruistic behavior may emerge from increased engagement of neural systems implicated in understanding the suffering of other people, executive and emotional control, and reward processing.

The dysfunctional attitudes scale: psychometric properties in depressed adolescents.

The psychometric properties and factor structure of the Dysfunctional Attitudes Scale were examined in a sample of 422 male and female adolescents (ages 12-17) with current major depressive disorder. The scale demonstrated high internal consistency (alpha = .93) and correlated significantly with self-report and interview-based measures of depression. Confirmatory factor analysis indicated that a correlated 2-factor model, with scales corresponding to perfectionism and need for social approval, provided a satisfactory fit to the data. The goodness-of-fit was equivalent across sexes and age groups. The findings support the use of the Dysfunctional Attitudes Scale and its subscales in the assessment of clinically depressed adolescents.

Affective synchrony: individual differences in mixed emotions.

Most models of affect suggest either inverse or null associations between positivity and negativity. Recent work has highlighted situations that sometimes lead to mixed positive-negative affect. Focusing on the counterpart to these situational factors, the authors explore the individual-difference tendency toward mixed emotions, which they term affective synchrony. In five studies, the authors show that some individuals demonstrate affective synchrony (overlapping experience of positive and negative moods), others a-synchrony (positive and negative mood that fluctuate independently), and still others de-synchrony (positive and negative moods that function as bipolar opposites). These tendencies are stable over time within persons, vary broadly across individuals, and are associated with individual differences in cognitive representation of self and of emotions.

Comparative efficacy of cognitive behavioral therapy, fluoxetine, and their combination in depressed adolescents: initial lessons from the treatment for adolescents with depression study.

Adolescents with major depressive disorder (MDD), their families and clinicians experience significant challenges when weighing the potential risks versus benefits of available choices in the treatment of MDD. Although MDD is highly prevalent in adolescents and is associated with marked suffering, impairment and risk of suicide, the scientific data regarding the safety and efficacy of treatments for pediatric depression are limited. Controlled clinical trials have provided support for the use of psychotherapy and fluoxetine for the treatment of pediatric depression, but until recently no information on the comparative efficacy of these recommended interventions alone or in combination was available. The Treatment for Adolescents with Depression Study provides a very important therapeutic advance in the field by convincingly showing that combination treatment with cognitive behavioral therapy and fluoxetine has the best benefit to risk ratio for adolescents with moderate to severe depression, and is superior to monotherapy. Moreover, the study results confirm that fluoxetine alone is effective in the treatment of depressed adolescents.