In response to the emerging crisis and growing calls from patients and clinicians for guidance 5, a working group of clinical experts from the International College of Obsessive Compulsive Spectrum ...Disorders (ICOCS) and the Obsessive-Compulsive and Related Disorders Research Network of the European College of Neuropsychopharmacology (OCRN) have produced this consensus statement with the aim of delivering pragmatic guidance at the earliest opportunity to clinicians for managing this complex challenge. Based on the risks associated with exposure and response prevention (ERP) in the pandemic (see below), and uncertainty as to which of the two evidence-based treatments, pharmacotherapy or cognitive behaviour therapy (CBT), represents the most efficacious first line treatment modality 11, pharmacotherapy should be the first option for adults and children with OCD with contamination, washing or cleaning symptoms during the COVID-19 pandemic. Consider A) type of medication; most patients should receive an SSRI, or if not responsive, another SSRI and as a third choice clomipramine (for which an ECG may be required in certain patient groups); Note US Food and Drug Administration "black box" warnings or advice from equivalent national regulatory authorities regarding increased risk in young people and other vulnerable patient groups. Check for adverse effects and be available for any concerns related to "activation" or newly emergent or increased suicidal ideation, which in the young can be mitigated by starting treatment at a low dose and titrating more gradually; B) dosage; if the patient is on a suboptimal dose, consider increasing it, paying attention to any contraindications; C) SSRI-resistance; consider a low dose of adjunctive antipsychotic (aripiprazole, risperidone, quetiapine, olanzapine), especially if a tic is present; D) adherence; ensure the patient is able to obtain an adequate supply and is taking the treatment regularly.
Abstract Objectives To collate data from multiple obsessive–compulsive disorder (OCD) treatment centers across seven countries and five continents, and to report findings in relation to OCD ...comorbidity, age of onset of OCD and comorbid disorders, and suicidality, in a large clinical and ethnically diverse sample, with the aim of investigating cultural variation and the utility of the psychiatric diagnostic classification of obsessive–compulsive and related disorders. Methods Researchers in the field of OCD were invited to contribute summary statistics on current and lifetime psychiatric comorbidity, age of onset of OCD and comorbid disorders and suicidality in their patients with OCD. Results Data from 3711 adult patients with primary OCD came from Brazil (n = 955), India (n = 802), Italy (n = 750), South Africa (n = 565), Japan (n = 322), Australia (n = 219), and Spain (n = 98). The most common current comorbid disorders were major depressive disorder (28.4%; n = 1055), obsessive–compulsive personality disorder (24.5%, n = 478), generalized anxiety disorder (19.3%, n = 716), specific phobia (19.2%, n = 714) and social phobia (18.5%, n = 686). Major depression was also the most commonly co-occurring lifetime diagnosis, with a rate of 50.5% (n = 1874). OCD generally had an age of onset in late adolescence (mean = 17.9 years, SD = 1.9). Social phobia, specific phobia and body dysmorphic disorder also had an early age of onset. Co-occurring major depressive disorder, generalized anxiety disorder and psychotic disorders tended to have a later age of onset than OCD. Suicidal ideation within the last month was reported by 6.4% (n = 200) of patients with OCD and 9.0% (n = 314) reported a lifetime history of suicide attempt. Conclusions In this large cross-continental study, comorbidity in OCD was common. The high rates of comorbid major depression and anxiety disorders emphasize the need for clinicians to assess and monitor for these disorders. Earlier ages of onset of OCD, specific phobia and social phobia may indicate some relatedness between these disorders, but this requires further study. Although there do not appear to be significant cultural variations in rates or patterns of comorbidity and suicidality, further research using similar recruitment strategies and controlling for demographic and clinical variables may help to determine whether any sociocultural factors protect against suicidal ideation or psychiatric comorbidity in patients with OCD.
Social anxiety disorder (SAD) is characterized by abnormal fear and anxiety in social situations. Functional magnetic resonance imaging (fMRI) is a brain imaging technique that can be used to ...demonstrate neural activation to emotionally salient stimuli. However, no attempt has yet been made to statistically collate fMRI studies of brain activation, using the activation likelihood-estimate (ALE) technique, in response to emotion recognition tasks in individuals with SAD.
A systematic search of fMRI studies of neural responses to socially emotive cues in SAD was undertaken. ALE meta-analysis, a voxel-based meta-analytic technique, was used to estimate the most significant activations during emotional recognition.
Seven studies were eligible for inclusion in the meta-analysis, constituting a total of 91 subjects with SAD, and 93 healthy controls. The most significant areas of activation during emotional vs. neutral stimuli in individuals with SAD compared to controls were: bilateral amygdala, left medial temporal lobe encompassing the entorhinal cortex, left medial aspect of the inferior temporal lobe encompassing perirhinal cortex and parahippocampus, right anterior cingulate, right globus pallidus, and distal tip of right postcentral gyrus.
The results are consistent with neuroanatomic models of the role of the amygdala in fear conditioning, and the importance of the limbic circuitry in mediating anxiety symptoms.
Abstract The monoamine oxidases (MAOA/B) and catechol-O-methyltransferase (COMT) enzymes break down regulatory components within serotonin and dopamine pathways, and polymorphisms within these genes ...are candidates for OCD susceptibility. Childhood trauma has been linked OCD psychopathology, but little attention has been paid to the interactions between genes and environment in OCD aetiology. This pilot study investigated gene-by-environment interactions between childhood trauma and polymorphisms in the MAOA , MAOB and COMT genes in OCD. Ten polymorphisms ( MAOA : 3 variants, MAOB : 4 variants, COMT : 3 variants) were genotyped in a cohort of OCD patients and controls. Early-life trauma was assessed using the Childhood Trauma Questionnaire (CTQ). Gene-by-gene (GxG) and gene-by-environment interactions (GxE) of the variants and childhood trauma were assessed using logistic regression models. Significant GxG interactions were found between rs362204 ( COMT ) and two independent polymorphisms in the MAOB gene (rs1799836 and rs6651806). Haplotype associations for OCD susceptibility were found for MAOB . Investigation of GxE interactions indicated that the sexual abuse sub-category was significantly associated with all three genes in haplotype x environment interaction analyses. Preliminary findings indicate that polymorphisms within the MAOB and COMT genes interact resulting in risk for OCD. Childhood trauma interacts with haplotypes in COMT , MAOA and MAOB , increasing risk for OCD.
•Variants within matrix metallopeptidase 9 (MMP9) and brain-derived neurotrophic factor (BDNF) are associated with risk to anxiety disorders.•The relationship between childhood trauma and risk for ...anxiety disorders diagnoses is modified by variants in synaptic plasticity genes.•The severity of childhood trauma is associated with an anxiety disorders diagnoses.
There have been important advances in our understanding of the genetic architecture of anxiety disorders. At the same time, relatively few genes have reached genome wide significance in anxiety disorders, and there is relatively little work on how exposure to an adverse environment impacts on gene expression in either animal models or human clinical populations. Here we assessed differential expression of genes of the dorsal striatum involved in synaptic transmission in an animal models of early adversity (maternal separation followed by restraint stress), and investigated whether variants in these genes were associated with risk for anxiety disorders, particularly in the presence of environmental stressors. Fifty-two male Sprague Dawley rats underwent maternal separation, and gene expression was studied using array technology. The human homologues of the differentially expressed genes were screened and analysed in a DSM-IV anxiety disorders cohort, and healthy controls (patients, n = 92; controls, n = 194), using blood. Two candidate genes (Mmp9 and Bdnf) were aberrantly expressed in the experimental rodent group relative to controls. Four single nucleotide polymorphisms (SNPs) in the human homologues of these genes were significantly associated with susceptibility for anxiety disorders (MMP9: rs3918242 and BDNF: rs6265, rs10835210 and rs11030107). Three of these (BDNF: rs6265, rs10835210, rs11030107) were found to interact significantly with childhood trauma severity resulting in increased likelihood of an anxiety disorder diagnosis. This study provides insights into the utility of rat models for identifying molecular candidates for anxiety disorders in humans.
Obsessive-compulsive disorder (OCD) is a highly disabling condition, with frequent early onset. Adult/adolescent OCD has been extensively investigated, but little is known about prevalence and ...clinical characterization of geriatric patients with OCD (G-OCD=65years). The present study aimed to assess prevalence of G-OCD and associated socio-demographic and clinical correlates in a large international sample.
Data from 416 outpatients, participating in the ICOCS network, were assessed and categorized into 2 groups, age<vs=65years, and then divided on the basis of the median age of the sample (age<vs=42years). Socio-demographic and clinical variables were compared between groups (Pearson Chi-squared and t tests).
G-OCD compared with younger patients represented a significant minority of the sample (6% vs 94%, P<.001), showing a significantly later age at onset (29.4±15.1 vs 18.7±9.2years, P<.001), a more frequent adult onset (75% vs 41.1%, P<.001) and a less frequent use of cognitive-behavioural therapy (CBT) (20.8% vs 41.8%, P<.05). Female gender was more represented in G-OCD patients, though not at a statistically significant level (75% vs 56.4%, P=.07). When the whole sample was divided on the basis of the median age, previous results were confirmed for older patients, including a significantly higher presence of women (52.1% vs 63.1%, P<.05).
G-OCD compared with younger patients represented a small minority of the sample and showed later age at onset, more frequent adult onset and lower CBT use. Age at onset may influence course and overall management of OCD, with additional investigation needed.
OCD is characterised by recurrent obsessions and compulsions that result in severe distress and increased risk for comorbidity. Recently published findings have indicated that the neuronal cadherin ...gene (
CDH2
) plays a role in the development of canine OCD, and led us to investigate the human ortholog,
CDH2
, in a human OCD cohort. Seven
CDH2
polymorphisms were selected and genotyped in a South African Caucasian cohort of 234 OCD patients and 180 healthy controls using TaqMan assays. Polymorphisms were analysed in a single-locus and haplotypic context. Of the seven polymorphisms, two reached statistical significance for OCD under additive and codominant models of inheritance (rs1120154 and rs12605662).
CDH2
SNP, rs1120154,
C
-allele carriers were found to be significantly associated with lower risk to develop OCD compared to
TT
-homozygotes (OR = 0.49; 95 % CI: 0.32–0.75;
p
< 0.001), and rs12605662
G
-allele carriers were significantly associated with reduced risk OCD compared to
TT
-homozygotes (OR = 0.46; 95 % CI: 0.30–0.71;
p
< 0.001), Furthermore, a single haplotype was found to infer an increased risk for OCD diagnosis (*
rs8087457-rs1148374
:
A-T
). Polymorphisms within the
CDH2
gene are associated with susceptibility to OCD in a South African cohort.
There is a high incidence of distressing psychological symptoms including anxiety in pregnancy. Nevertheless, predictors of distress and anxiety during pregnancy have not been well characterized. We ...determined whether temperament and character, trait anxiety, resilience, and social support predicted distress and anxiety symptoms in pregnancy.
Pregnant women (n=105) with low risk singleton pregnancies were recruited from Midwife Obstetric Units. Assessments of distress (using the K-10) and anxiety (using the Spielberger State Inventory) were undertaken in trimester 2 and 3. Measures of temperament and character, trait anxiety, resilience and social support were undertaken at the same time points. Regression analyses were used to determine predictors of distress and anxiety at each trimester.
Predictors of distress and anxiety were lower selfdirectedness, higher harm avoidance, higher trait anxiety, lower resilience, and lower social support, at each time point.
Understanding predictors of distress and anxiety in pregnancy may be useful in developing interventions for addressing such symptoms, as well as perhaps in preventing potential sequelae such as anxiety and mood disorders.
In response to emergent antibiotic resistance, new strategies are needed to enhance the effectiveness of existing antibiotics. Here, we describe a phagemid-delivered, RNA-mediated system capable of ...directly knocking down antibiotic resistance phenotypes. Small regulatory RNAs (sRNAs) were designed to specifically inhibit translation of chloramphenicol acetyltransferase and kanamycin phosphotransferase. Nonlytic phagemids coding for sRNA expression were able to infect and restore chloramphenicol and kanamycin sensitivity to populations of otherwise resistant E. coli. This modular system could easily be extended to other bacteria with resistance profiles that depend on specific transcripts.
Social anxiety disorder (SAD) is characterised by fear of social or performance situations where the individual is exposed to unfamiliar people or to possible scrutiny by others. The literature on ...dopamine ligands and dopamine genotypes in SAD is however inconsistent. In this study we measured the effects of SSRI pharmacotherapy on dopamine transporter (DAT) binding in patients with SAD, also addressing variability in DAT genotype. Adult subjects meeting DSM-IV criteria for generalised SAD were studied before and after 12 weeks of pharmacotherapy with the selective serotonin reuptake inhibitor (SSRI) escitalopram. DAT single photon emission computed tomography (SPECT) using
123
I-FP-CIT was performed at baseline, and repeated at 12 weeks. Striatal DAT binding was analysed for changes following therapy, and for correlations with clinical efficacy, in the whole group as well as for a subgroup with the A10/A10 DAT genotype. The study included 14 subjects (9 male, 5 female) with a mean (SD) age of 41 (±13) years. The subjects’ Liebowitz Social Anxiety Scale (LSAS) score was significantly decreased following pharmacotherapy. In the combined group the left caudate and left putamen showed clusters of increased DAT binding after therapy. The left caudate changes were also observed in the subgroup of 9 A10/A10 homozygotes. However no correlation was found between improved symptoms and DAT binding. The changes found in DAT binding in the caudate and putamen may be due to serotonergic activation of dopamine function by SSRI therapy. This is consistent with previous work indicating decreased DAT binding in SAD, and increased DAT binding after SSRI administration.
PDF
