The gut microbiome and inflammation in obsessive-compulsive disorder patients compared to age- and sex-matched controls: a pilot study.

OBJECTIVE: To compare the gut microbiome profile (by way of taxon analysis and indices of ß- and α-diversity) and inflammatory markers (C-reactive protein [CRP], interleukin-6[IL-6] and tumour necrosis factor-α [TNF-α]) of obsessive-compulsive disorder (OCD) outpatients and non-psychiatric community controls. METHODS: We collected morning stool and blood samples from 21 non-depressed, medication-free OCD patients and 22 age- and sex-matched non-psychiatric community controls. Microbiota analysis was performed using Illumina sequencing of the V3 region of 16S rRNA; serum CRP samples were analysed using immunoturbidimetry and plasma IL-6/TNF-α were examined by high-sensitivity ELISA. Multiple comparisons were corrected for using the false discovery rate (α = 0.05). RESULTS: Compared to controls, the OCD group presented lower species richness/evenness (α-diversity, Inverse Simpson) and lower relative abundance of three butyrate producing genera (Oscillospira, Odoribacter and Anaerostipes). Compared to controls, mean CRP, but not IL-6 and TNF-α, was elevated OCD patients. CRP revealed moderate to strong associations with psychiatric symptomatology. CONCLUSION: To our knowledge, this is the first investigation of the gut microbiome in OCD. In addition, our findings lend further support for the potential association of inflammation and OCD. These results suggest the gut microbiome may be a potential pathway of interest for future OCD research.

Manifesto for a European research network into Problematic Usage of the Internet.

The Internet is now all-pervasive across much of the globe. While it has positive uses (e.g. prompt access to information, rapid news dissemination), many individuals develop Problematic Use of the Internet (PUI), an umbrella term incorporating a range of repetitive impairing behaviours. The Internet can act as a conduit for, and may contribute to, functionally impairing behaviours including excessive and compulsive video gaming, compulsive sexual behaviour, buying, gambling, streaming or social networks use. There is growing public and National health authority concern about the health and societal costs of PUI across the lifespan. Gaming Disorder is being considered for inclusion as a mental disorder in diagnostic classification systems, and was listed in the ICD-11 version released for consideration by Member States (http://www.who.int/classifications/icd/revision/timeline/en/). More research is needed into disorder definitions, validation of clinical tools, prevalence, clinical parameters, brain-based biology, socio-health-economic impact, and empirically validated intervention and policy approaches. Potential cultural differences in the magnitudes and natures of types and patterns of PUI need to be better understood, to inform optimal health policy and service development. To this end, the EU under Horizon 2020 has launched a new four-year European Cooperation in Science and Technology (COST) Action Programme (CA 16207), bringing together scientists and clinicians from across the fields of impulsive, compulsive, and addictive disorders, to advance networked interdisciplinary research into PUI across Europe and beyond, ultimately seeking to inform regulatory policies and clinical practice. This paper describes nine critical and achievable research priorities identified by the Network, needed in order to advance understanding of PUI, with a view towards identifying vulnerable individuals for early intervention. The network shall enable collaborative research networks, shared multinational databases, multicentre studies and joint publications.

Obsessive-compulsive disorder in the elderly: A report from the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS).

INTRODUCTION: 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. METHODS: Data from 416 outpatients, participating in the ICOCS network, were assessed and categorized into 2 groups, age

Paroxetine-induced increase in LDL cholesterol levels.

Paroxetine is widely prescribed because it has the indication for multiple psychiatric disorders. Our objective was to assess the effect of short-term administration of paroxetine on low-density lipoprotein cholesterol (LDL-C) levels in both healthy controls (HCs) and in patients with panic disorder (PD). Blood samples for measurement of LDL-C were collected atbaseline, after 8 weeks of paroxetine administration and post-discontinuation in 24 male HCs and nine male patients suffering from PD, for a total of 33 subjects. Paroxetine treatment, both in HCs and PD patients, induced a mean 9% increase per subject in LDL-C that normalized post-discontinuation, suggesting causality. The National Cholesterol Education Program (NCEP) guidelines suggest that this paroxetine-induced increase in LDL-C is clinically significant but would not warrant therapeutic intervention in this population selected to be at low cardiovascular risk. However, the increase in LDL-C levels raised above the threshold of 2.7 mmol/L (100 mg/dL) in 36% of our low-risk subjects. The LDL-C increase in this subgroup would be associated with a minor increase in coronary heart disease (CHD) risk. A similar 9% paroxetine-induced increase in LDL-C observed in the large number of psychiatric patients suffering from comorbid established CHD would be detrimental from a cardiovascular perspective and would oppose the new NCEP therapeutic goals of decreasing LDL-C levels by 30-40% in high and moderately high-risk patients. It is possible that longer treatment duration and use of higher doses of paroxetine would lead to a greater increase in LDL-C.

Pharmacotherapy of social anxiety disorder at the turn of the millennium.

Over the past 21 years since the birth of SP into the diagnostic nomenclature, there have been significant gains in knowledge about effective pharmacologic and psychotherapeutic treatments. The SSRIs have emerged as the first-line pharmacologic treatment, although good evidence shows efficacy of benzodiazepines; MAOIs; and anticonvulsant agents, such as gabapentin and pregabalin. There is also emerging evidence about the efficacy of the novel antidepressant venlafaxine and also optimism for the potential utility of nefazodone and possibly bupropion. However, there are many areas requiring further investigation. There has been a great deal of excitement about the publication of the RUPP Anxiety Study, demonstrating efficacy for fluvoxamine in socially phobic youth. Given that SP starts in childhood and adolescence, more data are needed to support the use of pharmacotherapy in this age group because early intervention may prevent the sequelae of chronic SP. There needs to be more investigation into what is required for social phobic individuals who obtain a good response to pharmacotherapy to move into full-remission status. Additional research is needed regarding the evaluation of the comparative efficacy of different drug classes and to develop an improved capability of predicting treatment response to a particular type of treatment. In addition, more research is needed regarding treatment resistance. In most of the anxiety disorders that have been studied, combining CBT with psychopharmacologic treatment has shown little advantage over either treatment alone. These findings may be due to methodologic problems. Research is needed on how to sequence treatments to maximize the benefits of combining the two types of effective treatments together. Finally, many clinicians are seeing an emerging trend of individuals who have had untreated SP all of their lives and are now presenting for treatment in their "golden years." The current established treatments need to be evaluated further in this geriatric population.

Prevention of relapse in generalized social phobia: results of a 24-week study in responders to 20 weeks of sertraline treatment.

The aim of this study was to evaluate the efficacy, tolerability, and effects on quality of life of sertraline, a selective serotonin reuptake inhibitor, in the prevention of relapse of generalized social phobia. Fifty adult outpatients with generalized social phobia who were rated much or very much improved on the Clinical Global Impression Scale of Improvement (CGI-I) after 20 weeks of sertraline treatment (50-200 mg/day) were randomly assigned in a one-to-one ratio to either continue double-blind treatment with sertraline or immediately switch to placebo for another 24 weeks. The initial 20-week study was placebo-controlled, and 15 responders to placebo also continued to receive double-blind placebo treatment in the continuation study. Eighty-eight percent of patients in the sertraline-continuation group and only 40% of patients in the placebo-switch and placebo-responder groups completed the study. In intent-to-treat endpoint analyses, 1 (4%) of 25 patients in the sertraline-continuation group and 9 (36%) of 25 patients in the placebo-switch group had relapsed at study endpoint (chi2 = 8.0, Fisher exact test, p = 0.01). The relative risk (hazards ratio) for relapse associated with placebo-switch relative to sertraline-continuation treatment was 10.2 (95% confidence interval, 1.3-80.7). Mean CGI-Severity, Marks Fear Questionnaire (MFQ) Social Phobia subscale, and Duke Brief Social Phobia Scale (BSPS) total scores were reduced by 0.07, 0.34, and 1.86 in the Sertraline-Continuation group and increased by 0.88, 4.09, and 5.99 in the Placebo-Switch group (all F > 5.3, p < 0.03), respectively. CGI-Severity, MFQ Social Phobia subscale, and BSPS scores also increased in the Placebo-Responder group. Discontinuations because of lack of efficacy were 4% in the sertraline-continuation group, 28% in the placebo-switch group (chi2 = 5.36, Fisher exact test, p = 0.049), relative to sertraline, and 27% in the placebo-responder group. Sertraline was effective in preventing relapse of generalized social phobia. Future research should assess whether improvements may be maintained or further increased by longer periods of treatment or through the addition of cognitive-behavioral techniques.

The neurobiology of social phobia: from pharmacotherapy to brain imaging.

Social phobia is a common psychiatric disorder that is often associated with significant psychiatric comorbidity and disability. There is currently considerable evidence for the efficacy of pharmacotherapy, especially the selective serotonin reuptake inhibitors, in the treatment of this disorder. In addition, researchers have recently begun to explore the underlying neurobiology of social phobia with results that will likely have important implications for future treatments. This article provides a review of the results to date of controlled medication trials. A review of chemical and neuroendocrine challenges, neurotransmitter functioning, and neuroimaging studies in social phobia is provided, followed by a discussion of the implications of these findings for future treatment and research.

Drugs in development for social anxiety disorder: more to social anxiety than meets the SSRI.

Individuals with social phobia (SP) fear and avoid a wide variety of social and performance situations in which they are exposed to unfamiliar persons or to possible scrutiny by others. The lifetime prevalence of SP is estimated to be as high as 13%. It is frequently co-morbid with and usually precedes the onset of other psychiatric illnesses and is associated with significant occupational and social impairment, including academic and vocational underachievement. Fortunately, there are effective treatments for this common and debilitating condition. There is currently considerable evidence for the efficacy of pharmacotherapy and especially the monoamine oxidase inhibitors (MAOIs) and selective serotonin re-uptake inhibitors (SSRIs) in the treatment of this disorder. However, SSRIs are generally preferred as the first-line treatment of choice due to the advantages of SSRIs over MAOIs in terms of safety and tolerability. Despite encouraging results, current treatments most often produce partial symptomatic improvement, rather than high end-state functioning. While current first line treatments for social phobia target the serotonergic system, it is important to remember that different social fears are likely to have different developmental roots and may be based on quite different neurobiological systems. In this article we provide a review of current pharmacotherapeutic options for SP, current knowledge of the neurobiology of SP, and a review of new and promising directions in pharmacological research. It is increasingly clear that serotonin (5-HT) is unlikely to be the whole story in SP and that other brain chemical systems, especially the dopaminergic, noradrenaline-corticotropin releasing hormone and gamma-aminobutyric acid (GABA) dependent systems, most probably have an important role to play in a substantial percentage of cases. A number of new and novel agents, including the substance P antagonists, GABA agonists and CRF antagonists show considerable promise in the treatment of SP. However, in order to enhance the understanding of the neurobiology and treatment response of SP, we need to develop more sophisticated theory-driven typologies of SP.

Serotonergic agents in the treatment of social phobia in children and adolescents: a case series.

Serotonergic agents have become the treatment of choice for adult patients with social phobia. However, there are few reports of the use of these agents in the treatment of children and adolescents with this disorder. The pharmacological treatment of social anxiety in children and adolescents is briefly reviewed, and a consecutive series of child and adolescent patients who were treated with a variety of serotonin acting agents is described. Seven patients, aged 7 to 18 years, with a Primary DSM-IV diagnosis of generalized social phobia were treated with paroxetine, sertraline, or nefazodone for up to 7 months. Response to treatment was evaluated by retrospective chart review by the treating clinicians. All of the patients appeared to have a very positive clinical response to the serotonergic agents. No adverse events were reported and side effects were well tolerated. Results suggest that serotonergic agents may be an effective and safe treatment for children and adolescents with social phobia.

Childhood attention deficit/hyperactivity disorder in adults with anxiety disorders.

BACKGROUND: Previous research has reported co-morbidity between attention deficit hyperactivity disorder (ADHD) and anxiety disorders. Interpretation of these findings is complicated by symptom overlap in the clinical presentation of the disorders. We estimate the prevalence of ADHD in both the current and childhood histories of adults with anxiety disorders, while taking symptom overlap into account. We also evaluate the utility of the Wender Utah Rating Scale (WURS) for retrospective reporting of ADHD. METHODS: Consecutive admissions (N = 149) to an anxiety disorders clinic were given a diagnostic and psychometric assessment. The WURS was administered to obtain a retrospective diagnosis of childhood ADHD. Twenty-nine of the 35 people surpassing the cut-off score on the WURS were given a structured interview of adult ADHD symptoms. RESULTS: The WURS contains many 'internalizing' items that may inflate retrospective accounts of ADHD. After taking this into account, there is still a significantly higher prevalence of ADHD in the retrospective reports of adults with anxiety disorders (15%) than would be expected by chance (4%). Furthermore, of those who meet retrospective criteria for ADHD, 45% (13 of 29) continue to meet diagnostic criteria for ADHD as adults. CONCLUSIONS: The WURS may require considerable revision for use with clinical populations. In spite of these difficulties with retrospective assessment, available evidence indicates that ADHD is more prevalent in the histories of anxiety disordered patients than would be expected from base rates.

Nefazodone in social phobia.

BACKGROUND: A variety of drug treatments have been shown to be effective in the treatment of social phobia. This study attempted to assess the efficacy of nefazodone, a new novel serotonergic drug, in the treatment of social phobia. METHOD: Nefazodone was administered to 23 patients who had a primary DSM-IV diagnosis of social phobia, generalized type (diagnosed by the Structured Clinical Interview for DSM-IV), in a 12-week open clinical trial. Treatment began at 100 mg of nefazodone daily and was increased according to clinical response and side effects. Patients completed self-report measures at baseline and at weeks 4, 8, and 12. These measures included the Fear of Negative Evaluation scale, the Social Avoidance and Distress scale, the Social Anxiety Thoughts Questionnaire, the Fear Questionnaire, the State-Trait Anxiety Inventory, the Beck Depression Inventory, the Social Adjustment Scale Self-Report, and the Sheehan Disability Scale. Clinicians completed the Liebowitz Panic and Social Phobic Disorders rating form and the Brief Social Phobia Scale. RESULTS: Twenty-one of the 23 patients completed the 12-week trial. Sixteen (69.6%) were considered responders (moderate or marked improvement), and 7 (30.4%) were considered to be nonresponders (minimal improvement or no change in symptoms). Measures of social anxiety, social phobic avoidance, depression, and social functioning showed a statistically significant change at endpoint. CONCLUSION: These findings support a role for nefazodone in the treatment of social phobia, generalized type. Controlled studies will be required to further investigate this preliminary finding as well as to compare nefazodone with other pharmacologic treatments of social phobia.

The potential role of haloperidol in the treatment of trichotillomania.

BACKGROUND: Trichotillomania is categorized as an impulse control disorder in DSM-IV and is considered by some to be closely related to Obsessive Compulsive Disorder (OCD). We review the clinical phenomenology and pharmacological response of trichotillomania, and suggest that it may be more related to Tourette Syndrome than to OCD. Serotonin reuptake inhibitors (SRIs) are typically employed in the treatment of OCD, while neuroleptic medications such as haloperidol are typically used in the treatment of Tourette Syndrome. Evidence for the efficacy of treatment of trichotillomania with drugs typically used for OCD is equivocal. METHOD: Nine patients with trichotillomania were treated with haloperidol. Six patients unresponsive to SSRI medication had haloperidol added to their treatment. Three patients received only haloperidol. Response to treatment was assessed using descriptions of hair pulling, quantity of hair pulled, and severity of depilation at hair pulling sites. RESULTS: Eight of nine patients responded to haloperidol treatment, with seven experiencing complete or near complete cessation of hair pulling. LIMITATIONS: Inferences from the results of this study are limited by the lack of a control group, the small sample size, and the use of unstandardized ratings as measures of symptom severity. CONCLUSIONS: Results suggest that the addition of haloperidol to SSRIs or haloperidol alone may be effective in the treatment of trichotillomania. Results also encourage speculation about the relation between OCD, Tourette Syndrome, and trichotillomania.

Pharmacotherapy for social phobia: what works, what might work, and what does not work at all.

Social phobia is a common psychiatric disorder that is often associated with significant psychiatric comorbidity and disability. In the past, clinicians have underutilized pharmacotherapy as a treatment option for this disorder. This article provides a review of current pharmacotherapeutic options for social phobia, including a review of the results to date of numerous controlled trials, a description of the recent results of open trials of new and promising agents, and a summary of the information available on the use of pharmacotherapy in the treatment of children and adolescents.

The relationship of behavioral inhibition and shyness to anxiety disorder.

Behavioral inhibition to the unfamiliar is a temperamental construct that refers to a characteristic propensity to react to both social and nonsocial novelty with inhibition. In contrast, shyness refers to feelings of discomfort in social situations but not nonsocial situations. Both shyness and behavioral inhibition are associated with anxiety disorders in children and adults. We compared the role of social and nonsocial inhibition in predicting anxiety disorder symptomatology. Patients (N = 225) at a university affiliated Anxiety Disorders Clinic completed several psychometric measures including the Retrospective Self-Report of Behavioral Inhibition (RSRI) and the Revised Shyness Scale. The RSRI has two replicable factors: social fears and general fearfulness. The social fears factor shows a stronger pattern of relationships to clinically relevant variables such as self-reports of symptomatology, social adjustment, and disability. Social, rather than nonsocial, fearfulness may account for the relationship between behavioral inhibition and anxiety disorder symptomatology.

A high-risk pilot study of the children of adults with social phobia.

OBJECTIVE: Children of patients with social phobia were studied to estimate their rates of psychiatric disorder. METHOD: Twenty-six social-phobic outpatients who had at least one child between the ages of 4 and 18 years participated in the study. Information was collected from parents on all 47 children and from the children between 12 and 18 years of age. Diagnoses in the children were made based on DSM-III-R and were done by a best-estimate method, using parent and child reports from a modified Anxiety Disorders Interview Schedule for Children, the Survey Diagnostic Instrument, the Current Self-Report Childhood Inhibition Scale, and the Alcohol Dependence Survey. RESULTS: Of the 47 children, 49% had at least one lifetime anxiety disorder diagnosis. The most common diagnoses were overanxious disorder (30%), social phobia (23%), and separation anxiety disorder (19%). Sixty-five percent had more than one anxiety disorder diagnosis. Lifetime major depression was found, in 8.5% of the children. Parents whose children met criteria for an anxiety disorder had a greater mean number of comorbid diagnoses than did the parents of unaffected children. CONCLUSION: This pilot study suggests that children of social-phobic parents may have increased rates of psychiatric disorder. Further studies incorporating a control group are needed.

Buspirone augmentation of selective serotonin reuptake inhibitors (SSRIs) in social phobia.

We evaluated the efficacy of buspirone, in the augmentation of social phobic symptom response to the selective serotonin reuptake inhibitors (SSRIs). Ten patients meeting DSM-III-R criteria for generalized social phobia were studied. Patients obtaining only a partial response to an adequate trial of an SSRI, received buspirone in addition to the SSRI for 8 weeks in an open trial. Seven patients (70%) were considered responders (moderate or marked improvement) and 3 (30%) were considered nonresponders (minimal improvement or no change). This study provides clinical evidence suggesting that buspirone augmentation may be a useful clinical strategy in social phobic patients who show a partial response to an SSRI.

Relationship of childhood sexual and physical abuse to anxiety disorders.

This study reports on the relationship of childhood sexual and physical abuse in adult outpatients of an anxiety disorders clinic. A total of 205 consecutive patients admitted to two anxiety disorders clinics in Hamilton, Ontario, Canada, were given the Child Maltreatment History-Self-Report to elicit a history of childhood sexual or physical abuse. Childhood sexual abuse was reported by 23.4% and childhood physical abuse by 44.9%. Patients with a history of childhood sexual or physical abuse had significantly higher Beck depression scores and concurrent major depression, as well as more significant impairment in social functioning. They also demonstrated significantly higher state and trait anxiety scores. The occurrence of sexual or physical abuse was not associated with the presence of any particular primary anxiety disorder diagnosis. However, childhood sexual and/or physical abuse may affect the severity of the anxiety disorder as well as the presence of concurrent major depression.