•We explored the role of the HPA axis in the comorbidity between MDD and OCD.•Cortisol awakening response (CAR), cortisol diurnal slope, and DST were analyzed.•Multivariate analyses were adjusted for ...depressive and anxiety symptoms.•OCD patients with comorbid MDD showed a more flattened diurnal cortisol slope.•Trait anxiety influenced the relationship between OCD and HPA axis (CAR and DST).
Major depressive disorder (MDD) is the most common psychiatric comorbidity in patients with obsessive–compulsive disorder (OCD). Hypothalamic-pituitary-adrenal (HPA) axis abnormalities have been described in both disorders and might play a role in the association between them. We aimed to study the role of HPA axis activity in the comorbidity between OCD and MDD, while controlling for psychopathological dimensions such as anxiety and depressive symptoms. We studied 324 participants belonging to four diagnostic groups: 1) MDD (n = 101), 2) OCD with comorbid MDD (n = 33), 3) OCD without MDD (n = 52), and 4) healthy subjects (n = 138). State anxiety, trait anxiety and depressive symptoms were assessed. Three HPA axis measures were analyzed in saliva: cortisol awakening response (CAR), diurnal cortisol slope (calculated using two formulas: 1 awakening to 11 p.m. AWE diurnal slope; 2 considering fixed time points FTP diurnal slope from 10 a.m. to 11 p.m.), and dexamethasone suppression test ratio after 0.25 mg of dexamethasone (DSTR). Multiple linear regression analyses were conducted to explore the contribution of clinical diagnosis and symptom dimensions to each HPA axis measure. A more flattened FTP diurnal cortisol slope was observed for OCD patients with comorbid MDD. Regarding the CAR and DSTR, a significant interaction was found between trait anxiety and OCD, as OCD patients with greater trait anxiety showed an increased CAR and reduced cortisol suppression after dexamethasone administration. Our results suggest that trait anxiety plays an important role in the relationship between HPA axis measures and OCD/MDD comorbidity.
: The COVID-19 pandemic has the potential to worsen mental health problems in the general population, including increasing engagement in addictive behaviors. Here, we describe observations suggesting ...that the current crisis and its sequelae may worsen problem gambling. The current pandemic may impact financial and psychological well-being due to social isolation during spatial distancing, and these stressors in conjunction with substantial changes in gambling markets (land-based, online) during the pandemic may significantly influence gambling behaviors. This situation calls for rapid research initiatives in this area and preventive and regulatory measures by multiple stakeholders.
Abstract
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.
Neuroimaging research has demonstrated the involvement of a well-defined brain network in the mediation of moral judgment in normal population, and has suggested the inappropriate network use in ...criminal psychopathy. We used functional magnetic resonance imaging (fMRI) to prove that alterations in the brain network subserving moral judgment in criminal psychopaths are not limited to the inadequate network use during moral judgment, but that a primary network breakdown would exist with dysfunctional alterations outside moral dilemma situations. A total of 22 criminal psychopathic men and 22 control subjects were assessed and fMRI maps were generated to identify (i) brain response to moral dilemmas, (ii) task-induced deactivation of the network during a conventional cognitive task and (iii) the strength of functional connectivity within the network during resting-state. The obtained functional brain maps indeed confirmed that the network subserving moral judgment is underactive in psychopathic individuals during moral dilemma situations, but the data also provided evidence of a baseline network alteration outside moral contexts with a functional disconnection between emotional and cognitive elements that jointly construct moral judgment. The finding may have significant social implications if considering psychopathic behavior to be a result of a primary breakdown in basic brain systems.
Deep brain stimulation (DBS) has been proposed for severe, chronic, treatment-refractory obsessive-compulsive disorder (OCD) patients. Although serious adverse events can occur, only a few studies ...report on the safety profile of DBS for psychiatric disorders. In a prospective, open-label, interventional multi-center study, we examined the safety and efficacy of electrical stimulation in 30 patients with DBS electrodes bilaterally implanted in the anterior limb of the internal capsule. Safety, efficacy, and functionality assessments were performed at 3, 6, and 12 months post implant. An independent Clinical Events Committee classified and coded all adverse events (AEs) according to EN ISO14155:2011. All patients experienced AEs (195 in total), with the majority of these being mild (52% of all AEs) or moderate (37%). Median time to resolution was 22 days for all AEs and the etiology with the highest AE incidence was 'programming/stimulation' (in 26 patients), followed by 'New illness, injury, condition' (13 patients) and 'pre-existing condition, worsening or exacerbation' (11 patients). Sixteen patients reported a total of 36 serious AEs (eight of them in one single patient), mainly transient anxiety and affective symptoms worsening (20 SAEs). Regarding efficacy measures, Y-BOCS reduction was 42% at 12 months and the responder rate was 60%. Improvements in GAF, CGI, and EuroQol-5D index scores were also observed. In sum, although some severe AEs occurred, most AEs were mild or moderate, transient and related to programming/stimulation and tended to resolve by adjustment of stimulation. In a severely treatment-resistant population, this open-label study supports that the potential benefits outweigh the potential risks of DBS.
Major depressive disorder (MDD) and obsessive-compulsive disorder (OCD) have both been linked to abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis. Polymorphisms in the genes involved in ...HPA axis activity, such as FKBP5, and their interactions with childhood trauma have been associated with stress-related mental disorders. Our goal was to study the role of FKBP5 genetic variants in HPA axis negative feedback regulation as a possible risk factor for different mental disorders such as MDD and OCD, while controlling for childhood trauma, anxiety and depressive symptoms. The sample included 266 participants divided into three groups: 1) MDD (n = 89 n = 73 melancholic; n = 3 atypical), 2) OCD (n = 51; 39% with comorbid MDD n = 13 melancholic; n = 7 atypical) and 3) healthy controls (n = 126). Childhood trauma, trait anxiety and depressive symptoms were assessed. HPA negative feedback was analyzed using the dexamethasone suppression test ratio (DSTR) after administration of 0.25 mg of dexamethasone. Twelve SNPs in the FKBP5 gene were selected for genotyping. Multiple linear regressions, after adjusting for the covariates considered, showed a reduced DSTR in individuals with the rs9470079-A variant that was significant after correction for multiple testing. Childhood trauma did not moderate the association between the rs9470079 and DSTR. Our results support the evidence that FKBP5 genetic variation could lead to abnormal HPA axis negative feedback independent of diagnosis. Therefore, this association can be identified as a transdiagnostic feature, offering an interesting opportunity to identify patients with higher stress vulnerability. Further studies focusing on the influence of FKBP5 on measurable biological endophenotypes are needed.
Abstract Background Impulsivity is understood to be a multidimensional construct involving aspects such as impulsive choice and impulsive traits. Delay discounting, the tendency to place greater ...value in immediate rewards over larger, long-term rewards, has been associated with maladaptive choices in gambling disorder (GD). Delay discounting is known to evolve with age; though no study to date has evaluated the interactions between impulsivity, GD severity and age in treatment-seeking patients. Objectives We aimed to examine whether associations between delay discounting and impulsivity traits differed between younger and older-aged GD patients. Secondly, we sought to untangle the mediating role of impulsivity in determining gambling behavior in these two age groups. Methods GD patients ( N = 335) were evaluated using the UPPS-P Impulsive Behavior Scale and a delay discounting task. Structural Equation Modeling (SEM) was used to explore associations between impulsivity measures and gambling severity in young (18–30 years) and old (31–70) GD patients. Results No differences in delay discounting were found between young and old GD patients. Significant correlations between delay discounting and urgency levels (the tendency to act rashly under emotional states) were identified only in the young GD group. Path analyses also revealed both positive and negative urgency to be a mediator of GD severity levels in young GD patients. Discussion and conclusions Significant associations between impulsive choice and positive urgency are only present in young gamblers, suggesting that positive urgency influence choice behavior to a greater degree at younger ages. Implications for targeted interventions are discussed.
Brain structural covariance networks reflect covariation in morphology of different brain areas and are thought to reflect common trajectories in brain development and maturation. Large-scale ...investigation of structural covariance networks in obsessive-compulsive disorder (OCD) may provide clues to the pathophysiology of this neurodevelopmental disorder. Using T1-weighted MRI scans acquired from 1616 individuals with OCD and 1463 healthy controls across 37 datasets participating in the ENIGMA-OCD Working Group, we calculated intra-individual brain structural covariance networks (using the bilaterally-averaged values of 33 cortical surface areas, 33 cortical thickness values, and six subcortical volumes), in which edge weights were proportional to the similarity between two brain morphological features in terms of deviation from healthy controls (i.e. z-score transformed). Global networks were characterized using measures of network segregation (clustering and modularity), network integration (global efficiency), and their balance (small-worldness), and their community membership was assessed. Hub profiling of regional networks was undertaken using measures of betweenness, closeness, and eigenvector centrality. Individually calculated network measures were integrated across the 37 datasets using a meta-analytical approach. These network measures were summated across the network density range of K = 0.10-0.25 per participant, and were integrated across the 37 datasets using a meta-analytical approach. Compared with healthy controls, at a global level, the structural covariance networks of OCD showed lower clustering (P < 0.0001), lower modularity (P < 0.0001), and lower small-worldness (P = 0.017). Detection of community membership emphasized lower network segregation in OCD compared to healthy controls. At the regional level, there were lower (rank-transformed) centrality values in OCD for volume of caudate nucleus and thalamus, and surface area of paracentral cortex, indicative of altered distribution of brain hubs. Centrality of cingulate and orbito-frontal as well as other brain areas was associated with OCD illness duration, suggesting greater involvement of these brain areas with illness chronicity. In summary, the findings of this study, the largest brain structural covariance study of OCD to date, point to a less segregated organization of structural covariance networks in OCD, and reorganization of brain hubs. The segregation findings suggest a possible signature of altered brain morphometry in OCD, while the hub findings point to OCD-related alterations in trajectories of brain development and maturation, particularly in cingulate and orbitofrontal regions.
Compulsive buying behavior (CBB) has begun to be recognized as a condition worthy of attention by clinicians and researchers. Studies on the commonalities between CBB and other behavioral addictions ...such as gambling disorder (GD) exist in the literature, but additional research is needed to assess the frequency and clinical relevance of the comorbidity of CBB and GD. The aim of the study was to estimate the point-prevalence of CBB+GD in a clinical setting. Data corresponded to n = 3221 treatment-seeking patients who met criteria for CBB or GD at a public hospital unit specialized in treating behavioral addictions. Three groups were compared: only-CBB (n = 127), only-GD (n = 3118) and comorbid CBB+GD (n = 24). Prevalence for the co-occurrence of CBB+GD was 0.75%. In the stratum of patients with GD, GD+CBB comorbidity obtained relatively low point prevalence (0.77%), while in the subsample of CBB patients the estimated prevalence of comorbid GD was relatively high (18.9%). CBB+GD comorbidity was characterized by lower prevalence of single patients, higher risk of other behavioral addictions (sex, gaming or internet), older age and age of onset. CBB+GD registered a higher proportion of women compared to only-GD (37.5 vs. 10.0%) but a higher proportion of men compared to only-CBB (62.5 vs. 24.4%). Compared to only-GD patients, the simultaneous presence of CBB+GD was associated with increased psychopathology and dysfunctional levels of harm avoidance. This study provides empirical evidence to better understand CBB, GD and their co-occurrence. Future research should help delineate the processes through which people acquire and develop this comorbidity.
This is the third version of the guideline of the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and ...Posttraumatic Stress Disorders which was published in 2002 and revised in 2008.
A consensus panel of 34 international experts representing 22 countries developed recommendations based on efficacy and acceptability of the treatments. In this version, not only medications but also psychotherapies and other non-pharmacological interventions were evaluated, applying the same rigorous methods that are standard for the assessment of medication treatments.
The present paper (Part II) contains recommendations based on published randomised controlled trials (RCTs) for the treatment of OCD (n = 291) and PTSD (n = 234) in children, adolescents, and adults. The accompanying paper (Part I) contains the recommendations for the treatment of anxiety disorders.
For OCD, first-line treatments are selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioural therapy (CBT). Internet-CBT was also superior to active controls. Several second-line medications are available, including clomipramine. For treatment-resistant cases, several options are available, including augmentation of SSRI treatment with antipsychotics and other drugs.
Other non-pharmacological treatments, including repetitive transcranial magnetic stimulation (rTMS), deep brain stimulation (DBS) and others were also evaluated.
For PTSD, SSRIs and the SNRI venlafaxine are first-line treatments. CBT is the psychotherapy modality with the best body of evidence. For treatment-unresponsive patients, augmentation of SSRI treatment with antipsychotics may be an option.
OCD and PTSD can be effectively treated with CBT and medications.
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