A 12-week, double-blind, parallel, multi-center randomized controlled trial in 316 adult patients with major depressive disorder (MDD) was conducted to evaluate the effectiveness of pharmacogenetic ...(PGx) testing for drug therapy guidance.
Patients with a CGI-S ≥ 4 and requiring antidepressant medication de novo or changes in their medication regime were recruited at 18 Spanish public hospitals, genotyped with a commercial PGx panel (Neuropharmagen®), and randomized to PGx-guided treatment (n = 155) or treatment as usual (TAU, control group, n = 161), using a computer-generated random list that locked or unlocked psychiatrist access to the results of the PGx panel depending on group allocation. The primary endpoint was the proportion of patients achieving a sustained response (Patient Global Impression of Improvement, PGI-I ≤ 2) within the 12-week follow-up. Patients and interviewers collecting the PGI-I ratings were blinded to group allocation. Between-group differences were evaluated using χ2-test or t-test, as per data type.
Two hundred eighty patients were available for analysis at the end of the 12-week follow-up (PGx n = 136, TAU n = 144). A difference in sustained response within the study period (primary outcome) was not observed (38.5% vs 34.4%, p = 0.4735; OR = 1.19 95%CI 0.74-1.92), but the PGx-guided treatment group had a higher responder rate compared to TAU at 12 weeks (47.8% vs 36.1%, p = 0.0476; OR = 1.62 95%CI 1.00-2.61), and this difference increased after removing subjects in the PGx-guided group when clinicians explicitly reported not to follow the test recommendations (51.3% vs 36.1%, p = 0.0135; OR = 1.86 95%CI 1.13-3.05). Effects were more consistent in patients with 1-3 failed drug trials. In subjects reporting side effects burden at baseline, odds of achieving a better tolerability (Frequency, Intensity and Burden of Side Effects Rating Burden subscore ≤2) were higher in the PGx-guided group than in controls at 6 weeks and maintained at 12 weeks (68.5% vs 51.4%, p = 0.0260; OR = 2.06 95%CI 1.09-3.89).
PGx-guided treatment resulted in significant improvement of MDD patient's response at 12 weeks, dependent on the number of previously failed medication trials, but not on sustained response during the study period. Burden of side effects was also significantly reduced.
European Clinical Trials Database 2013-002228-18 , registration date September 16, 2013; ClinicalTrials.gov NCT02529462 , retrospectively registered: August 19, 2015.
Emotion regulation by means of cognitive reappraisal has been widely studied with functional magnetic resonance imaging (fMRI). To date, several meta-analyses of studies using cognitive reappraisal ...tasks in healthy volunteers have been carried out, but no meta-analyses have yet been performed on the fMRI data of clinical populations with identified alterations in emotion regulation capacity.
We provide a comprehensive meta-analysis of cognitive reappraisal fMRI studies in populations of patients with mood or anxiety disorders, yielding a pooled sample of 247 patients and 262 controls from thirteen independent studies. As a distinguishing feature of this meta-analysis, original statistical brain maps were obtained from six of these studies.
Our primary results demonstrated that patients with mood and anxiety disorders recruited the regulatory fronto-parietal network involved in cognitive reappraisal to a lesser extent in comparison to healthy controls. Conversely, they presented increased activation in regions that may be associated with the emotional experience (i.e., insula, cerebellum, precentral and inferior occipital gyri) and in regions whose activation may be the consequence of compensatory mechanisms (i.e., supramarginal gyri and superior parietal lobule). Moreover, activations in the left ventrolateral prefrontal cortex and the left superior temporal gyrus were associated with reinterpretation emotion regulation strategies, whereas medial frontal and parietal activations were associated with the deployment of distancing strategies.
The regions revealed by this meta-analysis conform to a pattern of dysfunctional brain activation during cognitive reappraisal common to mood and anxiety disorders. As such, this neural pattern may reflect a transdiagnostic feature of these disorders.
•Patient groups exhibit both abnormal decreases and increases of brain activity.•The fronto-parietal network is hypoactivated during reappraisal in patient groups.•Hyperactivations may relate to both emotion experience and compensatory mechanisms.•Hypoactivations are observed both with disorder-specific and unspecific stimuli.•The cognitive reappraisal strategy employed has a significant effect on findings.
In the present study, we investigated the association between Non-Suicidal Self-Injury (NSSI) and the UPPS-P impulsivity facets in eating disorder patients and healthy controls. The prevalence of ...NSSI in eating disorder (ED) patients ranged from 17% in restrictive anorexia nervosa (AN-R) patients to 43% in patients with bulimia nervosa (BN). In healthy controls (HC), the prevalence of NSSI was 19%. Eating disorder patients from the binge eating/purging type showed significantly more NSSI compared to restrictive ED and HC participants. Binge-eating/purging ED patients also scored significantly higher on Negative/Positive Urgency, Lack of Premeditation and Lack of Perseverance compared to HC and restrictive ED patients. Comparable findings were found between ED patients and HC with and without NSSI; ED patients and HC with NSSI scored significantly higher in four of the five UPPS-P dimensions compared to participants without NSSI; Sensation Seeking was the exception. Finally, the presence of NSSI in HC/ED patients was particularly predicted by low levels of Perseverance. Therefore, the treatment of ED patients with NSSI certainly needs to focus on the training of effortful control.
Deep brain stimulation (DBS) has been proposed as an alternative to ablative neurosurgery for severe treatment-resistant Obsessive-Compulsive Disorder (OCD), although with partially discrepant ...results probably related to differences in anatomical targetting and stimulation conditions. We sought to determine the efficacy and tolerability of DBS in OCD and the existence of clinical predictors of response using meta-analysis.
We searched the literature on DBS for OCD from 1999 through January 2014 using PubMed/MEDLINE and PsycINFO. We performed fixed and random-effect meta-analysis with score changes (pre-post DBS) on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) as the primary-outcome measure, and the number of responders to treatment, quality of life and acceptability as secondary measures.
Thirty-one studies involving 116 subjects were identified. Eighty-three subjects were implanted in striatal areas--anterior limb of the internal capsule, ventral capsule and ventral striatum, nucleus accumbens and ventral caudate--27 in the subthalamic nucleus and six in the inferior thalamic peduncle. Global percentage of Y-BOCS reduction was estimated at 45.1% and global percentage of responders at 60.0%. Better response was associated with older age at OCD onset and presence of sexual/religious obsessions and compulsions. No significant differences were detected in efficacy between targets. Five patients dropped out, but adverse effects were generally reported as mild, transient and reversible.
Our analysis confirms that DBS constitutes a valid alternative to lesional surgery for severe, therapy-refractory OCD patients. Well-controlled, randomized studies with larger samples are needed to establish the optimal targeting and stimulation conditions and to extend the analysis of clinical predictors of outcome.
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.
Patients with anorexia nervosa (AN) display impaired social interactions, implicated in the development and prognosis of the disorder. Importantly, social behavior is modulated by reward-based ...processes, and dysfunctional at-brain-level reward responses have been involved in AN neurobiological models. However, no prior evidence exists of whether these neural alterations would be equally present in social contexts. In this study, we conducted a cross-sectional social-judgment functional magnetic resonance imaging (fMRI) study of 20 restrictive-subtype AN patients and 20 matched healthy controls. Brain activity during acceptance and rejection was investigated and correlated with severity measures (Eating Disorder Inventory -EDI-2) and with personality traits of interest known to modulate social behavior (The Sensitivity to Punishment and Sensitivity to Reward Questionnaire). Patients showed hypoactivation of the dorsomedial prefrontal cortex (DMPFC) during social acceptance and hyperactivation of visual areas during social rejection. Ventral striatum activation during rejection was positively correlated in patients with clinical severity scores. During acceptance, activation of the frontal opercula-anterior insula and dorsomedial/dorsolateral prefrontal cortices was differentially associated with reward sensitivity between groups. These results suggest an abnormal motivational drive for social stimuli, and involve overlapping social cognition and reward systems leading to a disruption of adaptive responses in the processing of social reward. The specific association of reward-related regions with clinical and psychometric measures suggests the putative involvement of reward structures in the maintenance of pathological behaviors in AN.
Compulsive hoarding is a debilitating problem that is often associated with obsessive-compulsive disorder (OCD) and obsessive-compulsive personality disorder. However, the precise nosology of ...compulsive hoarding has yet to be determined.
Participants were 25 patients with severe compulsive hoarding with OCD and 27 patients with severe compulsive hoarding without OCD. Both groups were carefully characterized and compared on the following sociodemographic and clinical variables: precise phenomenology of hoarding behavior, severity of other OCD symptoms, axis I and axis II psychopathology, and adaptive functioning. For comparison purposes, the following individuals were also recruited: 71 patients with OCD without hoarding, 19 patients with anxiety disorder, and 21 community participants.
Overall, the phenomenology of hoarding behavior was similar in the two hoarding groups. The majority of participants in both groups reported hoarding common items as a result of their emotional and/or intrinsic value. However, approximately one-fourth of participants in the compulsive hoarding with OCD group showed a different psychopathological profile, which was characterized by the hoarding of bizarre items and the presence of other obsessions and compulsions related to their hoarding, such as fear of catastrophic consequences, the need to perform checking rituals, and the need to perform mental compulsions before discarding any item. These patients had a more severe and disabling form of the disorder. The strong relationship between compulsive hoarding and obsessive-compulsive personality disorder was explained entirely by the overlapping item content.
In most individuals, compulsive hoarding appears to be a syndrome separate from OCD, which is associated with substantial levels of disability and social isolation. However, in other individuals, compulsive hoarding may be considered a symptom of OCD and has unique clinical features. These findings have implications for the classification of OCD and compulsive hoarding in the next edition of DSM.
Mental health problems are very common and often lead to prolonged sickness absence, having serious economic repercussions for most European countries. Periods of economic crisis are important social ...phenomena that are assumed to increase sickness absence due to mental disorders, although research on this topic remains scarce. The aim of this study was to gather data on long-term sickness absence (and relapse) due to mental disorders in Spain during a period of considerable socio-economic crisis.
Relationships were analyzed (using chi-squared tests and multivariate modelling via binary logistic regression) between clinical, social/employment-related and demographic factors associated and long-term sickness absence (>60 consecutive days) due to mental disorders in a cohort of 7112 Spanish patients during the period 2008-2012.
Older age, severe mental disorders, being self-employed, having a non-permanent contract, and working in the real estate and construction sector were associated with an increased probability of long-term sickness absence (gender had a mediating role with respect to some of these variables). Relapses were associated with short-term sick leave (return to work due to 'improvement') and with working in the transport sector and public administration.
Aside from medical factors, other social/employment-related and demographic factors have a significant influence on the duration of sickness absence due to mental disorders.
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