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.

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.

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

Circulatory changes in newborn lambs with experimental polycythemia: comparison between fetal and adult type blood.

Hemodynamic effects of increased hematocrit were compared in two groups of newborn lambs. In the first group (fetal type blood), exchange transfusions were carried out using packed red blood cells obtained from newborn lambs within one to two hours after birth. In the second group (adult type blood), the same procedure was carried out using adult sheep blood. In both groups, hematocrit values ranging between 70% and 80% were reached. The increase in hematocrit caused a decrease in cardiac output due to an increase in peripheral resistance. Pulmonary resistance increased more than systemic resistance. However, the increase in pulmonary resistance was significantly greater in the polycythemic newborn lambs with adult blood. A right-to-left shunt through a patent ductus or a foramen ovale was noted in six of the eight lambs included in this group. On the other hand, none of the seven polycythemic newborn lambs with fetal blood developed signs of right-to-left shunting. It is concluded that during neonatal polycythemia, the level of hematocrit is not the sole factor responsible for the hemodynamic changes observed. Other unknown influences related either to the red cells or the plasma must impinge upon the pulmonary circulation to alter vascular resistance.

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.

Fluoxetine efficacy in social phobia.

BACKGROUND: To determine the efficacy of fluoxetine in the treatment of social phobia, fluoxetine was administered to 16 patients with a primary DSM-III-R diagnosis of social phobia in a 12-week, open, clinical trial. METHOD: Treatment began at 20 mg of fluoxetine daily and was increased according to clinical response and side effects every 4 weeks. Patients completed self-report measures of anxiety and depression at baseline and at Weeks 4, 8, and 12. These included the Beck Depression Inventory, the Social Avoidance and Distress Scale, the Fear of Negative Evaluation Scale, the State-Trait Anxiety Inventory, the Fear Questionnaire, the Social Anxiety Thoughts Questionnaire, and the Social Adjustment Scale-Self-Report. Clinicians completed a Clinical Global Improvement Scale. RESULTS: Thirteen of the 16 patients completed the trial. Three patients (18.8%) were unable to complete the trial due to adverse side effects. Of the 13 (81.2%) remaining patients, 10 were considered to be responders and 3 were considered to be nonresponders. Measures of social anxiety and phobic avoidance showed a significant improvement from baseline to endpoint, achieving a significance of p < .005. Responders to fluoxetine were more likely to have been older at onset of the social phobic symptoms and had a shorter duration of illness. CONCLUSION: These findings suggest that fluoxetine may be effective in the treatment of social phobia. Double-blind studies will be required to further investigate these findings.

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.

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.

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.

Sertraline in social phobia.

Twenty-two patients meeting a primary DSM-III-R diagnosis of Social Phobia, entered a 12 week open trial of sertraline. Twenty patients completed at least 8 weeks of treatment. Sixteen patients (80%) were considered responders and 4 (20%) were considered non-responders. All measures of social anxiety and avoidance, depression and social functioning showed a statistically significant change from baseline to end point.

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 social phobia with other psychiatric illness.

Fifty-seven social phobic patients were studied to identify the comorbidity with other psychiatric illnesses and their temporal relationships. Mood disorders, particularly major depression, was the most common other lifetime diagnosis (70.2%). A large majority (70.2%) suffered from, at least, one other anxiety disorder in their lifetime and, in particular, panic disorder with or without agoraphobia (49.1%). Alcohol (28.1%) and substance (15.8%) abuse or dependence were also common lifetime diagnoses. Social phobia usually predated any episode of mood disorder (81.7%) or any other anxiety disorder (62.7%). Social phobia may predispose individuals to other psychiatric illnesses, in particular major depression.

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.

Evidence for the participation of sodium-sensitive pontine catecholaminergic neurons in the maintenance of DOCA-sodium hypertension in rats.

1. A reduced noradrenaline turnover rate has been previously demonstrated in the brain stem of deoxycorticosterone acetate (DOCA)-sodium hypertensive rats. In the present study, the turnover rate was measured in smaller brain regions and the effect of sodium depletion was studied on the turnover rate of these regions. 2. Catecholamine turnover rate was significantly reduced only in the pons, was slightly but not significantly reduced in the thoracic spinal cord and was normal in the upper and lower medulla oblongata, in the mesencephalon, in the hypothalamus and in the telencephalon. 3. The administration of a sodium-free diet for 3 weeks lowered significantly the blood pressure and concomitantly accelerated the turnover rate in the pons area of DOCA hypertensive rats. 4. It is concluded that pontine catecholaminergic fibres, sensitive to sodium balance, might be involved in the maintenance of DOCA-sodium hypertension in the rat.