Tremendous progress has been made in basic neuroscience in recent decades. One area that has been especially successful is research on how the brain detects and responds to threats. Such studies have ...demonstrated comparable patterns of brain-behavior relationships underlying threat processing across a range of mammalian species, including humans. This would seem to be an ideal body of information for advancing our understanding of disorders in which altered threat processing is a key factor, namely, fear and anxiety disorders. But research on threat processing has not led to significant improvements in clinical practice. The authors propose that in order to take advantage of this progress for clinical gain, a conceptual reframing is needed. Key to this conceptual change is recognition of a distinction between circuits underlying two classes of responses elicited by threats: 1) behavioral responses and accompanying physiological changes in the brain and body and 2) conscious feeling states reflected in self-reports of fear and anxiety. This distinction leads to a "two systems" view of fear and anxiety. The authors argue that failure to recognize and consistently emphasize this distinction has impeded progress in understanding fear and anxiety disorders and hindered attempts to develop more effective pharmaceutical and psychological treatments. The two-system view suggests a new way forward.
Summary Unipolar depressive disorder in adolescence is common worldwide but often unrecognised. The incidence, notably in girls, rises sharply after puberty and, by the end of adolescence, the 1 year ...prevalence rate exceeds 4%. The burden is highest in low-income and middle-income countries. Depression is associated with substantial present and future morbidity, and heightens suicide risk. The strongest risk factors for depression in adolescents are a family history of depression and exposure to psychosocial stress. Inherited risks, developmental factors, sex hormones, and psychosocial adversity interact to increase risk through hormonal factors and associated perturbed neural pathways. Although many similarities between depression in adolescence and depression in adulthood exist, in adolescents the use of antidepressants is of concern and opinions about clinical management are divided. Effective treatments are available, but choices are dependent on depression severity and available resources. Prevention strategies targeted at high-risk groups are promising.
Anxiety disorders Penninx, Brenda WJH; Pine, Daniel S; Holmes, Emily A ...
Lancet,
03/2021, Letnik:
397, Številka:
10277
Journal Article
Recenzirano
Odprti dostop
Anxiety disorders form the most common group of mental disorders and generally start before or in early adulthood. Core features include excessive fear and anxiety or avoidance of perceived threats ...that are persistent and impairing. Anxiety disorders involve dysfunction in brain circuits that respond to danger. Risk for anxiety disorders is influenced by genetic factors, environmental factors, and their epigenetic relations. Anxiety disorders are often comorbid with one another and with other mental disorders, especially depression, as well as with somatic disorders. Such comorbidity generally signifies more severe symptoms, greater clinical burden, and greater treatment difficulty. Reducing the large burden of disease from anxiety disorders in individuals and worldwide can be best achieved by timely, accurate disease detection and adequate treatment administration, scaling up of treatments when needed. Evidence-based psychotherapy (particularly cognitive behavioural therapy) and psychoactive medications (particularly serotonergic compounds) are both effective, facilitating patients' choices in therapeutic decisions. Although promising, no enduring preventive measures are available, and, along with frequent therapy resistance, clinical needs remain unaddressed. Ongoing research efforts tackle these problems, and future efforts should seek individualised, more effective approaches for treatment with precision medicine.
Irritability in Youths: A Translational Model Brotman, Melissa A; Kircanski, Katharina; Stringaris, Argyris ...
The American journal of psychiatry,
06/2017, Letnik:
174, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Although irritability is among the most common reasons that children and adolescents are brought for psychiatric care, there are few effective treatments. Developmentally sensitive pathophysiological ...models are needed to guide treatment development. In this review, the authors present a mechanistic model of irritability that integrates clinical and translational neuroscience research. Two complementary conceptualizations of pathological irritability are proposed: 1) aberrant emotional and behavioral responding to frustrative nonreward, mediated by reward-system dysfunction; and 2) aberrant approach responding to threat, mediated by threat-system dysfunction. The authors review the pathophysiological literature, including animal studies, as well as experimental psychology and clinical studies. Data suggest that, relative to healthy children, irritable children have deficient reward learning and elevated sensitivity to reward receipt and omission. These deficits are associated with dysfunction in the prefrontal cortex, striatum, and amygdala. Youths with irritability also show maladaptive orienting to, interpreting, and labeling of potential threats, associated with prefrontal cortical and amygdalar dysfunction. Abnormalities in reward and threat processing potentiate one another. Future work should test pathophysiological hypotheses and novel interventions targeting reward- and threat-related dysfunction to improve treatment for severe irritability in youths.
A role for aberrant reward processing in the pathogenesis of depression has long been proposed. However, no review has yet examined its role in depression by integrating conceptual and quantitative ...findings across functional MRI (fMRI) and EEG methodologies. The authors quantified these effects, with an emphasis on development.
A total of 38 fMRI and 12 EEG studies were entered into fMRI and EEG meta-analyses. fMRI studies primarily examined reward anticipation and reward feedback. These were analyzed using the activation likelihood estimation method. EEG studies involved mainly the feedback-related negativity (FRN) event-related potential, and these studies were analyzed using random-effects meta-analysis of the association between FRN and depression.
Analysis of fMRI studies revealed significantly reduced striatal activation in depressed compared with healthy individuals during reward feedback. When region-of-interest analyses were included, reduced activation was also observed in reward anticipation, an effect that was stronger in individuals under age 18. FRN was also significantly reduced in depression, with pronounced effects in individuals under age 18. In longitudinal studies, reduced striatal activation in fMRI and blunted FRN in EEG were found to precede the onset of depression in adolescents.
Taken together, the findings show consistent neural aberrations during reward processing in depression, namely, reduced striatal signal during feedback and blunted FRN. These aberrations may underlie the pathogenesis of depression and have important implications for development of new treatments.
Conduct disorder and callous-unemotional traits in youth Blair, R James R; Leibenluft, Ellen; Pine, Daniel S
New England journal of medicine/The New England journal of medicine,
12/2014, Letnik:
371, Številka:
23
Journal Article
Despite extensive research, symptom structure of posttraumatic stress disorder (PTSD) is highly debated. The network approach to psychopathology offers a novel method for understanding and ...conceptualizing PTSD. However, extant studies have mainly used small samples and self-report measures among sub-clinical populations, while also overlooking co-morbid depressive symptoms.
PTSD symptom network topology was estimated in a sample of 1489 treatment-seeking veteran patients based on a clinician-rated PTSD measure. Next, clinician-rated depressive symptoms were incorporated into the network to assess their influence on PTSD network structure. The PTSD-symptom network was then contrasted with the network of 306 trauma-exposed (TE) treatment-seeking patients not meeting full criteria for PTSD to assess corresponding network differences. Finally, a directed acyclic graph (DAG) was computed to estimate potential directionality among symptoms, including depressive symptoms and daily functioning.
The PTSD symptom network evidenced robust reliability. Flashbacks and getting emotionally upset by trauma reminders emerged as the most central nodes in the PTSD network, regardless of the inclusion of depressive symptoms. Distinct clustering emerged for PTSD and depressive symptoms within the comorbidity network. DAG analysis suggested a key triggering role for re-experiencing symptoms. Network topology in the PTSD sample was significantly distinct from that of the TE sample.
Flashbacks and psychological reactions to trauma reminders, along with their strong connections to other re-experiencing symptoms, have a pivotal role in the clinical presentation of combat-related PTSD among veterans. Depressive and posttraumatic symptoms constitute two separate diagnostic entities, but with meaningful between-disorder connections, suggesting two mutually-influential systems.
This review summarizes findings on the epidemiology and etiology of anxiety disorders among children and adolescents including separation anxiety disorder, specific phobia, social phobia, ...agoraphobia, panic disorder, and generalized anxiety disorder, also highlighting critical aspects of diagnosis, assessment, and treatment. Childhood and adolescence is the core risk phase for the development of anxiety symptoms and syndromes, ranging from transient mild symptoms to full-blown anxiety disorders. This article critically reviews epidemiological evidence covering prevalence, incidence, course, and risk factors. The core challenge in this age span is the derivation of developmentally more sensitive assessment methods. Identification of characteristics that could serve as solid predictors for onset, course, and outcome will require prospective designs that assess a wide range of putative vulnerability and risk factors. This type of information is important for improved early recognition and differential diagnosis as well as prevention and treatment in this age span.
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