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.
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.
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.
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.
•COVID-19 disease and ensuing mental health problems might be two related pandemics.•Problematic use of internet (PUI) should be regarded from a mental health perspective.•This review covers PUI ...(specifically online gaming, gambling, pornography use) during COVID-19.•Guidance for mental health professionals, patients and the general public is provided.•Research priorities, best therapeutic and preventive practices for PUI are outlined.
With the onset of the COVID-19 pandemic and the accelerated spread of the SARS-CoV-2 virus came jurisdictional limitations on mobility of citizens and distinct alterations in their daily routines. Confined to their homes, many people increased their overall internet use, with problematic use of the internet (PUI) becoming a potential reason for increased mental health concerns. Our narrative review summarizes information on the extent of PUI during the pandemic, by focusing on three types: online gaming, gambling and pornography viewing. We conclude by providing guidance for mental health professionals and those affected by PUI (with an outline of immediate research priorities and best therapeutic approaches), as well as for the general public (with an overview of safe and preventative practices).
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.
Global concern about problematic usage of the internet (PUI), and its public health and societal costs, continues to grow, sharpened in focus under the privations of the COVID-19 pandemic. This ...narrative review reports the expert opinions of members of the largest international network of researchers on PUI in the framework of the European Cooperation in Science and Technology (COST) Action (CA 16207), on the scientific progress made and the critical knowledge gaps remaining to be filled as the term of the Action reaches its conclusion.
A key advance has been achieving consensus on the clinical definition of various forms of PUI. Based on the overarching public health principles of protecting individuals and the public from harm and promoting the highest attainable standard of health, the World Health Organisation has introduced several new structured diagnoses into the ICD-11, including gambling disorder, gaming disorder, compulsive sexual behaviour disorder, and other unspecified or specified disorders due to addictive behaviours, alongside naming online activity as a diagnostic specifier. These definitions provide for the first time a sound platform for developing systematic networked research into various forms of PUI at global scale. Progress has also been made in areas such as refining and simplifying some of the available assessment instruments, clarifying the underpinning brain-based and social determinants, and building more empirically based etiological models, as a basis for therapeutic intervention, alongside public engagement initiatives.
However, important gaps in our knowledge remain to be tackled. Principal among these include a better understanding of the course and evolution of the PUI-related problems, across different age groups, genders and other specific vulnerable groups, reliable methods for early identification of individuals at risk (before PUI becomes disordered), efficacious preventative and therapeutic interventions and ethical health and social policy changes that adequately safeguard human digital rights. The paper concludes with recommendations for achievable research goals, based on longitudinal analysis of a large multinational cohort co-designed with public stakeholders.
•Research advances in Problematic Use of the Internet (PUI) and key evidence gaps.•Narrative review by experts and public stakeholders from the European COST Action.•PUI is growing; Vulnerable groups include children and young people.•Reliable methods for early detection, recognition and prevention are needed.•Longitudinal study of PUI, health and wellbeing will inform effective policy change.
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.
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