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

Evidence-based treatment pathways for translational studies in obsessive-compulsive disorders.

Obsessive-compulsive disorder (OCD) and related disorders are costly and burdensome long-term illnesses. Whilst evidence-based pharmacological and psychological treatments are available for OCD, a significant proportion of OCD patients fail to respond and for many of the OCD-related disorders no validated treatments are as yet recognised. In addition, predictors of treatment response/non-response to guide clinicians in the management of individual patients are lacking. The introduction of personalised medicine to psychiatry is expected to offer the novel prospect of identifying the most effective treatment for a patient in a timely and cost-effective way. Translational research that investigates endophenotype predictors of treatment response in OCD and related disorders may pave the way toward personalised medicine. Such research is likely to require multidisciplinary collaboration between neuroscientists and clinicians, so that the right clinical questions are addressed, and large datasets, entailing multinational, multicentre sampling. In order to facilitate the translational investigation of the key aspects of the treatment response, these studies would require access to standardised treatment paradigms that are internationally recognised. In this chapter, we introduce some of the most important outstanding questions for personalised medicine that translational research could be expected to address within the next 10 years. We review the available tools and techniques for standardised clinical assessment and the criteria that are used to define the degree of therapeutic response (response, remission, relapse, resistance) that would naturally dictate the direction of treatment. We also present a series of consecutive stepped treatment algorithms based on evidence-based practice and modelled on naturalistic care that we believe could be adapted to multicentre settings as a template for the translational researcher to aid in the design of pragmatic treatment trials that are capable of identifying biomarkers of treatment response or non-response at each key stage of the evidence-based canon.

Manifesto for a European research network into obsessive-compulsive and related disorders.

Obsessive-compulsive and related disorders (O-CRDs) are highly disabling psychiatric illnesses of early-onset. They are responsible for considerable morbidity and socioeconomic burden. Existing treatments are usually only partially successful and there is an urgent need to understand the aetiological factors and neurobiological bases of the disorders in order to develop new and more effective strategies for prevention, early detection and effective treatment. Emerging data from the neurosciences supports the reconceptualisation of obsessive-compulsive disorder as a spectrum disorder, related to but different from the anxiety disorders and closely aligned with other less well understood psychiatric disorders characterised by compulsive acts such as body dysmorphic disorder, trichotillomania, skin-picking disorder, hoarding disorder; and possibly extending to tic disorders and other neurodevelopmental disorders such as autism. A new, O-CRDs research network, supported by the Networks Initiative of the European College of Neuropsychopharmacology and comprising leading figures in preclinical and clinical research, has been established. It aims to provide a European perspective on the current debate around internationally-accepted diagnostic criteria and treatment strategies for O-CRDs. Its objectives include; (1) identifying the key outstanding research questions that depend upon cross-centre collaborative investigation, (2) setting a research agenda that is likely to produce an impact on health-outcomes, and (3) strengthening existing projects and collaborative enterprises with these objectives in mind. This paper reviews some of these critical research priorities. By establishing shared multinational databases, collaborative research networks, multicentre studies and joint publications, it is hoped that progress will be achieved.

Low-frequency rTMS over right dorsolateral prefrontal cortex in the treatment of resistant depression: cognitive improvement is independent from clinical response, resting motor threshold is related to clinical response.

BACKGROUND: Clinical studies have shown that repetitive transcranial magnetic stimulation (rTMS) is effective in a certain percentage of treatment-resistant depression (TRD). The left dorsolateral prefrontal cortex (DLPFC) 10 Hz rTMS stimulation received FDA approval in 2008, although different rTMS protocols have also shown their effectiveness in reducing depressive symptoms. We investigated the clinical, cognitive and neurophysiologic effects of a 3 weeks' protocol of low-frequency rTMS applied over the right DLPFC in resistant depression. METHODS: Twenty-eight patients with TRD (age range 28-55) received low-frequency rTMS (1 Hz) over the right DLPFC in a 3-week open trial. Hamilton scales for depression and anxiety, Corsi block-tapping test, phonemic verbal fluency, right and left resting motor thresholds were evaluated in each subject over the trial period. RESULTS: At the end of the trial 42.9% of the subjects were considered as responders. A significant reduction of both HAMD (p < 0.001) and HAMA (p < 0.01) total scores was observed. At the 3rd week, the performances in Corsi test (p < 0.02) and phonemic verbal fluency (p = 0.065) were improved independently from depressive symptoms variation. At the end of the rTMS protocol, a significantly decreased left hemisphere resting motor threshold was registered (p < 0.01), while right hemisphere resting motor threshold did not show significant variation. CONCLUSION: Low-frequency rTMS over the right DLPFC appeared effective in 42.9% of depressive resistant subjects in this sample. A significant decrease in left hemisphere resting motor threshold was observed only in responders, while a trend for improvement in cognitive function has been found and appeared independent from clinical response.

Autoimmune markers in vitiligo patients appear correlated with obsession and phobia.

BACKGROUND: Current studies have treated a limited portion of the subjective aspects of vitiligo patients and have yet to elucidate possible psychological differences between those with autoimmune markers (AIM) with respect to those without autoimmune markers (NAIM). OBJECTIVE: To perform an age and gender-matched 1:1 case-control study through a comparison of non-segmental vitiligo patients with autoimmune features vs. those without autoimmune features in regards to psychiatric features, psychosomatic aspects and social parameters. METHODS: A total of 112 non-segmental vitiligo patients have been examined at the Florence University dermatology outpatient service (2nd dermatology unit). Vitiligo with an autoimmune background was defined by the presence of autoimmune antibodies and/or autoimmune diseases. Psychiatric screening was performed by dermatologists using the modified Middlesex Healthcare Questionnaire (MHQ); psychosomatic aspects and social impact were analysed with a standardized, Florentine questionnaire. RESULTS: Upon performing a conditional regression model, age, phobia and obsession were significantly predictive of the presence of AIM and a low total MHQ score was significantly predictive of NAIM in vitiligo patients. With univariate analysis, we found significant differences in: identifiable stress related to the onset of vitiligo, vitiligo triggered by stress, and modified interpersonal relationships related to vitiligo, which were associated with the subgroup containing autoimmunity markers. CONCLUSIONS: We found a higher prevalence of age, obsession and phobia among vitiligo patients AIM as compared to vitiligo patients NAIM. Thus, in the presence of demonstrated autoimmunity, screening for particular psychiatric aspects may be useful in the clinical practice of vitiligo.

The lifetime impact of attention deficit hyperactivity disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC).

BACKGROUND: The aim of the study was to present nationally representative data on the lifetime independent association between attention deficit hyperactivity disorder (ADHD) and psychiatric co-morbidity, correlates, quality of life and treatment seeking in the USA. METHOD: Data were derived from a large national sample of the US population. Face-to-face surveys of more than 34 000 adults aged 18 years and older residing in households were conducted during the 2004-2005 period. Diagnoses of ADHD, Axis I and II disorders were based on the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV version. RESULTS: ADHD was associated independently of the effects of other psychiatric co-morbidity with increased risk of bipolar disorder, generalized anxiety disorder, post-traumatic stress disorder, specific phobia, and narcissistic, histrionic, borderline, antisocial and schizotypal personality disorders. A lifetime history of ADHD was also associated with increased risk of engaging in behaviors reflecting lack of planning and deficient inhibitory control, with high rates of adverse events, lower perceived health, social support and higher perceived stress. Fewer than half of individuals with ADHD had ever sought treatment, and about one-quarter had ever received medication. The average age of first treatment contact was 18.40 years. CONCLUSIONS: ADHD is common and associated with a broad range of psychiatric disorders, impulsive behaviors, greater number of traumas, lower quality of life, perceived social support and social functioning, even after adjusting for additional co-morbidity. When treatment is sought, it is often in late adolescence or early adulthood, suggesting the need to improve diagnosis and treatment of ADHD.

Major depression and bipolar disorders in CADASIL: a study using the DSM-IV semi-structured interview.

OBJECTIVE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral microangiopathy characterized by migraine, cerebrovascular events, and cognitive impairment. Although recognized as a cardinal feature of the disease, psychiatric disturbances have rarely been the object of focused studies. We performed a structured evaluation of mood disorders in CADASIL. MATERIALS AND METHODS: Twenty-three patients with CADASIL (five men and 18 women) were assessed by psychiatrists using the Structured Clinical Interview for the DSM-IV, clinician version. For the quantitative assessment of current mood disorder symptoms, the Hamilton Rating Scale for Depression (HRSD) and the Young Mania Rating Scale (YMRS) were used. RESULTS: A lifetime depressive episode was recorded in 17/23 (73.9%) patients with CADASIL. Six (26.1%) patients with CADASIL reported a current depressive episode. A diagnosis of manic lifetime episode was made in 6 (26.1%) patients with CADASIL. The HRSD mean score in patients with current depression was 9.1 ± SD 8.1. The YMRS mean score was 14.2 ± SD 4.1 for manic CADASIL. CONCLUSION: This study confirms that mood disorders are frequent in CADASIL. The use of a structured psychiatric interview outlines a frequency of depression higher than that previously reported but also reveals a considerable frequency of bipolar disorders. If confirmed in larger series, these data suggest that a greater attention should be paid to the psychiatric aspects in CADASIL.

Unilateral low frequency versus sequential bilateral repetitive transcranial magnetic stimulation: is simpler better for treatment of resistant depression?

Repetitive transcranial magnetic stimulation (rTMS) efficacy in the treatment of major depression has been shown in both low frequency right-sided and high frequency left-sided stimulation over the dorsolateral prefrontal cortex (DLPFC). The aim of the present investigation was to evaluate the hypothesis of an additive effect of bilateral stimulation compare to sequential to unilateral stimulation. Sixty patients with treatment-resistant depression were assigned to receive either low-frequency rTMS over the right DLPFC (140 s x 1 Hz) followed by controlateral sham (unilateral group, n=20), low frequency right DLPFC rTMS followed by left DLPFC high frequency rTMS (5 s x 10 Hz) (bilateral group, n=20), or bilateral sham (sham group, n=20) in a 3 weeks double-blind, randomized trial. The primary outcome variable was the score on Hamilton Depression Scale (HAM-D). Low frequency right-sided and sequential bilateral stimulation showed different antidepressant efficacy at 3 weeks and across the full duration of the study, only the unilateral method appearing significantly more effective than sham at the end of the trial, and correlated to the higher percent of remitters (30% of the group vs. 10% -bilateral- and 5% -sham). Unilateral stimulation, but not bilateral, showed higher antidepressant efficacy compared to sham stimulation. The data suggest that right-sided low frequency stimulation may be a first line treatment alternative in resistant depression. To confirm and extend these findings further studies require a longer follow-up period, supported by biological observation and replication.

Successful duloxetine treatment of a binge eating disorder: a case report.

We report the successful treatment of a case of refractory binge eating disorder (BED) with duloxetine, a combined serotonin and norepinephrine reuptake inhibitor, resulting in complete remission of the patient's bingeing behaviours. This case is discussed in the context of the existing literature on the psychopharmacology of BED. Results demonstrate that inhibition of 5-HT and noradrenaline reuptake by duloxetine markedly reduces food intake, suggesting that this may be a novel approach for the treatment of obesity.

Noradrenergic function in pathological gambling: blunted growth hormone response to clonidine.

The noradrenergic system has been linked to impulsive behaviour in animals and humans, yet little data on noradrenergic system exist in specific impulse control disorders. To explore the role of the noradrenergic system in pathological gamblers (PG), we assessed neuroendocrine growth hormone (GH) response to the alpha2-adrenergic receptor agonist clonidine and placebo in PG and controls. The net effects of clonidine are a decrease in neurotransmission by depressing locus coeruleus activity and stimulation of GH secretion through activation of post-synaptic alpha2-adrenergic receptors in the hypothalamus. Twenty-nine PG subjects, free of other comorbid conditions, and 27 healthy controls received a double-blinded, placebo-controlled, single dose of oral clonidine (0.15 mg/kg). Data observed included GH, clonidine levels and levels of the main noradrenergic metabolite, 3-methoxy-4-hydroxy-phenylglycol (MHPG). The area under the curve for GH response to clonidine was significantly lower (separate variance t with 44.3 df = 2.626, P = 0.012, d = 0.58) in the PG group (199.6) than in the control group (426.3). PG had significantly blunted GH responses compared with controls at 120 and 150 min post-clonidine. These results are consistent with the idea that the subsensitivity of post-synaptic alpha-2 receptors is possibly attributable to higher-than-normal noradrenergic secretion in PG. This peripheral noradrenergic dysfunction could be consistent with attenuated cortico-frontal noradrenergic function as shown in positron emission tomography (PET) studies of PG.

Quality of life and clinical characteristics of patients with generalized and performance-focused social anxiety disorder: An Italian study.

Introduction. The aim of this study is to investigate quality of life (QoL) and clinical characteristics of generalized (GSAD) and performance-focused social anxiety disorder (PFSAD). Method. Our sample includes 41 outpatients with social anxiety disorder and 100 control subjects. QoL was assessed using the Quality of Life and Enjoyment questionnaire. Assessments included the MINI Neuropsychiatric Interview, the Symptom Checklist, the Work and Social Adjustment Scale and the Clinical Global Impression Scale (CGI). Using the Liebowitz social anxiety scale, patients were divided into GSAD and PFSAD. Results. QoL of subjects with GSAD was lower than in controls in most areas, while only the areas of physical health and leisure time were impaired in patients with PFSAD. Patients with GSAD were more likely to be depressed, to meet criteria for substance abuse, to have higher severity scores on the CGI and the SCL-90 compared to PFSAD. Conclusions. GSAD is associated with widespread worsening of QoL, while patients with PFSAD had a poorer QoL than controls only in the areas of physical health and leisure time.

Detecting attention-deficit/hyperactivity disorder (ADHD) in adults with intellectual disability The use of Conners' Adult ADHD Rating Scales (CAARS).

There is an increasing interest in the diagnosis of attention-deficit/hyperactivity disorder (ADHD) in adulthood. It is also thought that ADHD is more prevalent in the field of intellectual disability (ID) than in the general population, but there are not many experimental studies. Since ADHD diagnosis in adults is more difficult, specific rating scales correlated to the main diagnostic systems have been created but have not been applied to people with ID. This work presents an application of an ADHD screening rating scale, the Conners' Adult ADHD Rating Scales (CAARS) screening version to 46 adults with ID. The resulting prevalence of "ADHD-positive" was 19.6%. These data are in accord with results reported in the general adult literature. Our data suggest that ID and attention disorders can co-occur. Therefore, not only can ADHD be a valid psychiatric diagnosis for a child with ID but for an adult with ID as well. The CAARS can be considered a useful clinical instrument to survey ADHD in ID.

Validity and reliability of the Italian version of the Quality of Life, Enjoyment and Satisfaction Questionnaire.

The Quality of Life, Enjoyment and Satisfaction Questionnaire (Q-LES-Q) is increasingly used in psychiatry because it gives emphasis to the subjective perspective of patients on physical, psychological and social domains. This paper reports on the validation of the Italian version of the Q-LES-Q in a large multicenter study (EQUIP) conducted at five Italian sites on outpatients in treatment for anxiety disorders. Study participants underwent a broad assessment of psychopathology including the MINI-International Neuropsychiatric Interview, the Symptom Checklist (SCL-90) and the Clinical Global Impression (CGI). Cronbach's alpha was used to determine the internal consistency of the Q-LES-Q areas and Pearson's r was used to analyze the correlation between the areas of Q-LES-Q and those of the other instruments. The internal consistency of the Q-LES-Q proved to be substantial (>0.80 in each of the areas) as well as the test-retest reliability. The convergent validity of the Q-LES-Q vs. the Work and Social Adjustment Scale was examined. High correlations were found between scales measuring similar constructs in the two instruments and lower correlation between scales measuring different constructs. In conclusion, the Italian version of the Q-LES-Q proved to be as valid and reliable as the original English version.

Attachment processes in eating disorders.

Anxious and insecure attachment, fear of abandonment and difficulties with autonomy differentiate young women with eating disorders from their normal peers. This paper uses the Adult Attachment Interview (AAI) as the correlation between eating disorders and state of mind regarding attachment (7 females and 6 males) with anorexia nervosa and EDNOS. There was a higher frequency of dismissing or entangled states of mind. The sample is far too small to allow statistical inferences to be drawn about differences between men and women in the style of state of mind regarding attachment. An inference is none the less made with regard to the role of psychotherapy in these results.

Sumatriptan, 5-HT(1D) receptors and obsessive-compulsive disorder.

BACKGROUND: After considering the effects of 5-HT receptor agonists with different binding profiles on the symptoms of obsessive-compulsive disorder (OCD), Zohar and Kindler hypothesized that the 5-HT(1D) receptor was implicated in this disorder's pathophysiology. METHODS: We explored the 5-HT(1D) hypothesis in a 5-day, random, double-blind, placebo-controlled trial of oral sumatriptan 100 mg/day in medication-free adults with OCD. We hypothesized that sumatriptan, a 5-HT(1D) agonist, would diminish 5-HT release, thereby worsening OCD symptoms. We further hypothesized that by beginning to desensitize 5-HT(1D) receptors, sumatriptan pretreatment would promote a faster response or an increased likelihood of response to subsequent treatment with a selective serotonin reuptake inhibitor. RESULTS: The five sumatriptan subjects' OCD symptom worsening, as measured by the Yale-Brown scale ( upward arrow 17.6% (S.D. 14.6)), was significant when compared to the slight symptom decrease in the five placebo subjects ( downward arrow 5.2% (S.D. 4.9), P<0.015). The sumatriptan group did not exhibit a faster response or greater likelihood of response to a 90-day, open label trial of paroxetine. CONCLUSIONS: Longer term studies of the effects of 5-HT(1D) agonists on OCD symptoms are indicated. Zolmitriptan, a potent 5-HT(1D) receptor agonist with better penetration of the blood-brain barrier, may be a preferred challenge agent.