Glucocorticoid-based pharmacotherapies preventing PTSD

Altres ajuts: Swiss National Science Foundation (SNSF) [NCCR Synapsy grant: 51NF40-158776 and − 185897]Posttraumatic stress disorder (PTSD) is a highly disabling psychiatric condition that may arise after exposure to acute and severe trauma. It is a highly prevalent mental disorder worldwide, and the current treatment options for these patients remain limited due to low effectiveness. The time window right after traumatic events provides clinicians with a unique opportunity for preventive interventions against potential deleterious alterations in brain function that lead to PTSD. Some studies pointed out that PTSD patients present an abnormal function of the hypothalamic-pituitary-adrenal axis that may contribute to a vulnerability toward PTSD. Moreover, glucocorticoids have arisen as a promising option for preventing the disorder's development when administered in the aftermath of trauma. The present work compiles the recent findings of glucocorticoid administration for the prevention of a PTSD phenotype, from human studies to animal models of PTSD. Overall, glucocorticoid-based therapies for preventing PTSD demonstrated moderate evidence in terms of efficacy in both clinical and preclinical studies. Although clinical studies point out that glucocorticoids may not be effective for all patients' subpopulations, those with adequate traits might greatly benefit from them. Preclinical studies provide precise insight into the mechanisms mediating this preventive effect, showing glucocorticoid-based prevention to reduce long-lasting behavioral and neurobiological abnormalities caused by traumatic stress. However, further research is needed to delineate the precise mechanisms and the extent to which these interventions can translate into lower PTSD rates and morbidity

Brain Structural Correlates of Emotion Recognition in Psychopaths

Individuals with psychopathy present deficits in the recognition of facial emotional expressions. However, the nature and extent of these alterations are not fully understood. Furthermore, available data on the functional neural correlates of emotional face recognition deficits in adult psychopaths have provided mixed results. In this context, emotional face morphing tasks may be suitable for clarifying mild and emotion-specific impairments in psychopaths. Likewise, studies exploring corresponding anatomical correlates may be useful for disentangling available neurofunctional evidence based on the alleged neurodevelopmental roots of psychopathic traits.We used Voxel-Based Morphometry and a morphed emotional face expression recognition task to evaluate the relationship between regional gray matter (GM) volumes and facial emotion recognition deficits in male psychopaths. In comparison to male healthy controls, psychopaths showed deficits in the recognition of sad, happy and fear emotional expressions. In subsequent brain imaging analyses psychopaths with better recognition of facial emotional expressions showed higher volume in the prefrontal cortex (orbitofrontal, inferior frontal and dorsomedial prefrontal cortices), somatosensory cortex, anterior insula, cingulate cortex and the posterior lobe of the cerebellum. Amygdala and temporal lobe volumes contributed to better emotional face recognition in controls only. These findings provide evidence suggesting that variability in brain morphometry plays a role in accounting for psychopaths' impaired ability to recognize emotional face expressions, and may have implications for comprehensively characterizing the empathy and social cognition dysfunctions typically observed in this population of subjects

Removing and reimplanting deep brain stimulation therapy devices in resistant OCD (when the patient does not respond): case report

Background: Deep brain stimulation (DBS) is emerging as a promising tool in the treatment of refractory obsessive-compulsive disorder (OCD) but the search for the best target still continues. This issue is especially relevant when particularly resistant profiles are observed in some patients, which have been ascribed to individual responses to DBS according to differential patterns of connectivity. As patients have been implanted, new dilemmas have emerged, such as what to do when the patient does not respond to surgery. Case presentation: Here we describe a 22-year-old male with extremely severe OCD who did not respond to treatment with DBS in the nucleus accumbens, but who did respond after explanting and reimplanting leads targeting the ventral capsule-ventral striatum region. Information regarding the position of the electrodes for both surgeries is provided and possible brain structures affected during stimulation are reviewed. To our knowledge this case is the first in the literature reporting the removal and reimplantation of DBS leads for therapeutical benefits in a patient affected by a mental disorder. Conclusion: The capability for explantation and reimplantation of leads should be considered as part of the DBS therapy reversibility profile in resistant mental disorders, as it allows application in cases of non-response to the first surgery

An fMRI study of cognitive reappraisal in major depressive disorder and borderline personality disorder

Background: One common denominator to the clinical phenotypes of borderline personality disorder (BPD) and major depressive disorder (MDD) is emotion regulation impairment. Although these two conditions have been extensively studied separately, it remains unclear whether their emotion regulation impairments are underpinned by shared or distinct neurobiological alterations. Methods: We contrasted the neural correlates of negative emotion regulation across an adult sample of BPD patients (n = 19), MDD patients (n = 20), and healthy controls (HCs; n = 19). Emotion regulation was assessed using an established functional magnetic resonance imaging cognitive reappraisal paradigm. We assessed both task-related activations and modulations of interregional connectivity. Results: When compared to HCs, patients with BPD and MDD displayed homologous decreased activation in the right ventrolateral prefrontal cortex (vlPFC) during cognitive reappraisal. In addition, the MDD group presented decreased activations in other prefrontal areas (i.e., left dorsolateral and bilateral orbitofrontal cortices), while the BPD group was characterized by a more extended pattern of alteration in the connectivity between the vlPFC and cortices of the visual ventral stream during reappraisal. Conclusions: This study identified, for the first time, a shared neurobiological contributor to emotion regulation deficits in MDD and BPD characterized by decreased vlPFC activity, although we also observed disorder-specific alterations. In MDD, results suggest a primary deficit in the strength of prefrontal activations, while BPD is better defined by connectivity disruptions between the vlPFC and temporal emotion processing regions. These findings substantiate, in neurobiological terms, the different profiles of emotion regulation alterations observed in these disorders

Neural response to the observable self in social anxiety disorder

Background: Distorted images of the observable self are considered crucial in the development and maintenance of social anxiety. We generated an experimental situation in which participants viewed themselves from an observer's perspective when exposed to scrutiny and evaluation by others. Method: Twenty patients with social anxiety disorder (SAD) and 20 control subjects were assessed using functional magnetic resonance imaging (fMRI) during the public exposure of pre-recorded videos in which they were each shown performing a verbal task. The examiners acted as the audience in the experiment and rated performance. Whole-brain functional maps were computed using Statistical Parametric Mapping. Results: Robust activation was observed in regions related to self-face recognition, emotional response and general arousal in both study groups. Patients showed significantly greater activation only in the primary visual cortex. By contrast, they showed significant deactivation or smaller activation in dorsal frontoparietal and anterior cingulate cortices relevant to the cognitive control of negative emotion. Task-related anxiety ratings revealed a pattern of negative correlation with activation in this frontoparietal/cingulate network. Importantly, the relationship between social anxiety scores and neural response showed an inverted-U function with positive correlations in the lower score range and negative correlations in the higher range. Conclusions: Our findings suggest that exposure to scrutiny and evaluation in SAD may be associated with changes in cortical systems mediating the cognitive components of anxiety. Disorder severity seems to be relevant in shaping the neural response pattern, which is distinctively characterized by a reduced cortical response in the most severe cases

Altered functional connectivity of the subthalamus and the bed nucleus of the stria terminalis in obsessive-compulsive disorder

Background: the assessment of inter-regional functional connectivity (FC) has allowed for the description of the putative mechanism of action of treatments such as deep brain stimulation (DBS) of the nucleus accumbens in patients with obsessive-compulsive disorder (OCD). Nevertheless, the possible FC alterations of other clinically-effective DBS targets have not been explored. Here we evaluated the FC patterns of the subthalamic nucleus (STN) and the bed nucleus of the stria terminalis (BNST) in patients with OCD, as well as their association with symptom severity. Methods: eighty-six patients with OCD and 104 healthy participants were recruited. A resting-state image was acquired for each participant and a seed-based analysis focused on our two regions of interest was performed using statistical parametric mapping software (SPM8). Between-group differences in FC patterns were assessed with two-sample t test models, while the association between symptom severity and FC patterns was assessed with multiple regression analyses. Results: in comparison with controls, patients with OCD showed: (1) increased FC between the left STN and the right pre-motor cortex, (2) decreased FC between the right STN and the lenticular nuclei, and (3) increased FC between the left BNST and the right frontopolar cortex. Multiple regression analyses revealed a negative association between clinical severity and FC between the right STN and lenticular nucleus. Conclusions: this study provides a neurobiological framework to understand the mechanism of action of DBS on the STN and the BNST, which seems to involve brain circuits related with motor response inhibition and anxiety control, respectively

If you feel you can’t, you won’t: the role of subjective and objective cognitive competence on psychosocial functioning in depression

BackgroundThe purpose of this exploratory study is to examine the role of sociodemographic, clinical, and cognitive - both objective and subjective - factors in overall and in specific domains of psychosocial functioning, in patients with depression at different clinical states of the disease (remitted and non-remitted).MethodsA sample of 325 patients with major depressive disorder, 117 in remission and 208 in non-remission, were assessed with a semi-structured interview collecting sociodemographic, clinical, cognitive (with neuropsychological tests and the Perceived Deficit Questionnaire), and functional (Functioning Assessment Short Test) characteristics. Backward regression models were conducted to determine associations of global and specific areas of functioning with independent factors, for both clinical states.ResultsResidual depressive symptomatology and self-appraisal of executive competence were significantly associated with psychosocial functioning in remitted patients, in overall and some subdomains of functioning, particularly cognitive and interpersonal areas. While depressive symptoms, executive deficits and self-appraisal of executive function were significantly related to functional outcomes in non-remitted patients, both in overall functioning and in most of subdomains.DiscussionThis study evidences the strong association of one's appraisal of executive competence with psychosocial functioning, together with depressive symptoms, both in remitted and non-remitted patients with depression. Therefore, to achieve full recovery, clinical management of patients should tackle not only the relief of core depressive symptoms, but also the cognitive ones, both those that are objectified with neuropsychological tests and those that are reported by the patients themselves

Brain structural alterations in obsessive-compulsive disorder patients with autogenous and reactive obsessions

Obsessive-compulsive disorder (OCD) is a clinically heterogeneous condition. Although structural brain alterations have been consistently reported in OCD, their interaction with particular clinical subtypes deserves further examination. Among other approaches, a two-group classification in patients with autogenous and reactive obsessions has been proposed. The purpose of the present study was to assess, by means of a voxel-based morphometry analysis, the putative brain structural correlates of this classification scheme in OCD patients. Ninety-five OCD patients and 95 healthy controls were recruited. Patients were divided into autogenous (n = 30) and reactive (n = 65) sub-groups. A structural magnetic resonance image was acquired for each participant and pre-processed with SPM8 software to obtain a volume-modulated gray matter map. Whole-brain and voxel-wise comparisons between the study groups were then performed. In comparison to the autogenous group, reactive patients showed larger gray matter volumes in the right Rolandic operculum. When compared to healthy controls, reactive patients showed larger volumes in the putamen (bilaterally), while autogenous patients showed a smaller left anterior temporal lobe. Also in comparison to healthy controls, the right middle temporal gyrus was smaller in both patient subgroups. Our results suggest that autogenous and reactive obsessions depend on partially dissimilar neural substrates. Our findings provide some neurobiological support for this classification scheme and contribute to unraveling the neurobiological basis of clinical heterogeneity in OCD

Altered corticostriatal functional connectivity in obsessive-compulsive disorder

Context: neurobiological models of obsessive-compulsive disorder (OCD) emphasize disturbances in the function and connectivity of brain corticostriatal networks, or 'loops.' Although neuroimaging studies of patients have supported this network model of OCD, very few have applied measurements that are sensitive to brain connectivity features. Objective: using resting-state functional magnetic resonance imaging, we tested the hypothesis that OCD is associated with disturbances in the functional connectivity of primarily ventral corticostriatal regions, measured from coherent spontaneous fluctuations in the blood oxygenation level-dependent (BOLD) signal. Design: case-control cross-sectional study. Setting: hospital referral OCD unit and magnetic resonance imaging facility. Participants: a total of 21 patients with OCD (10 men, 11 women) and 21 healthy control subjects matched for age, sex, and estimated intelligence. Main outcome measures: voxelwise statistical parametric maps testing the strength of functional connectivity of 4 striatal seed regions of interest (dorsal caudate nucleus, ventral caudate/nucleus accumbens, dorsal putamen, and ventral putamen) with remaining brain areas. Results: for both groups, there was a clear distinction in the pattern of cortical connectivity of dorsal and ventral striatal regions, consistent with the notion of segregated motor, associative, and limbic corticostriatal networks. Between groups, patients with OCD had significantly increased functional connectivity along a ventral corticostriatal axis, implicating the orbitofrontal cortex and surrounding areas. The specific strength of connectivity between the ventral caudate/nucleus accumbens and the anterior orbitofrontal cortex predicted patients' overall symptom severity (r(2) = 0.57; P < .001). Additionally, patients with OCD showed evidence of reduced functional connectivity of the dorsal striatum and lateral prefrontal cortex, and of the ventral striatum with the region of the midbrain ventral tegmental area. Conclusions: this study directly supports the hypothesis that OCD is associated with functional alterations of brain corticostriatal networks. Specifically, our findings emphasize abnormal and heightened functional connectivity of ventrolimbic corticostriatal regions in patients with OCD

Group and sex differences in social cognition in bipolar disorder, schizophrenia/schizoaffective disorder and healthy people

Background: Impairment of social cognition is documented in bipolar disorder (BD) and schizophrenia/schizoaffective disorder (SCH). In healthy individuals, women perform better than men in some of its sub-domains. However, in BD and SCH the results are mixed. Our aim was to compare emotion recognition, affective Theory of Mind (ToM) and first- and second-order cognitive ToM in BD, SCH and healthy subjects, and to investigate sex-related differences. Methods: 120 patients (BD = 60, SCH = 60) and 40 healthy subjects were recruited. Emotion recognition was assessed by the Pictures of Facial Affect (POFA) test, affective ToM by the Reading the Mind in the Eyes Test (RMET) and cognitive ToM by several false-belief stories. Group and sex differences were analyzed using parametric (POFA, RMET) and non-parametric (false-belief stories) tests. The impact of age, intelligence quotient (IQ) and clinical variables on patient performance was examined using a series of linear/logistic regressions. Results: Both groups of patients performed worse than healthy subjects on POFA, RMET and second-order false-belief (p < 0.001), but no differences were found between them. Instead, their deficits were related to older age and/or lower IQ (p < 0.01). Subthreshold depression was associated with a 6-fold increased risk of first-order false-belief failure (p < 0.001). Sex differences were only found in healthy subjects, with women outperforming men on POFA and RMET (p ≤ 0.012), but not on first/second-order false-belief. Limitations: The cross-sectional design does not allow for causal inferences. Conclusion: BD and SCH patients had deficits in emotion recognition, affective ToM, and second-order cognitive ToM, but their performance was comparable to each other, highlighting that the differences between them may be subtler than previously thought. First-order cognitive ToM remained intact, but subthreshold depression altered their normal functioning. Our results suggest that the advantage of healthy women in the emotional and affective aspects of social cognition would not be maintained in BD and SCH