Altered cognitive response to serotonin challenge as a candidate endophenotype for obsessive-compulsive disorder.

RATIONALE: Obsessive-compulsive disorder (OCD) implicates dysfunction of orbitofrontal and insula-related circuitry and of the serotonin system. There is an on-going search in psychiatry for intermediate biological markers, termed 'endophenotypes', that exist not only in patients with a given disorder but also in their clinically unaffected first-degree relatives. OBJECTIVE: Pharmacological challenge is recognized as a means of eliciting an endophenotype, but this strategy has yet to be used in OCD. METHODS: Twenty-three OCD patients without comorbidities (12 [52.2 %] female), 13 clinically asymptomatic first-degree relatives of OCD patients (11 [84.6 %] female) and 27 healthy controls (16 [59.3 %] female) received single-dose escitalopram (20 mg) and placebo in a randomized double-blind crossover design. Effects of treatment on decision-making were quantified using the Cambridge Gamble Task (CGT) in conjunction with a mixed model analysis of covariance (ANCOVA). RESULTS: There was a significant interaction between serotonergic challenge and group for risk adjustment on the CGT (F = 4.1406; p = 0.02). Only controls showed a significant placebo-drug change in risk adjustment (p = 0.02; versus p > 0.10). Numerically, escitalopram was associated with increase in risk adjustment in controls and reductions in the other groups. Change in risk adjustment was similar in OCD patients and relatives (p = 0.806) and differed significantly from controls (p = 0.007; p = 0.041, respectively). CONCLUSIONS: Individuals with OCD, and first-degree relatives, showed an altered cognitive response to serotonin challenge. This is the first demonstration of a candidate pharmacological challenge endophenotype for the disorder. Future work should confirm these findings in a larger sample size and ideally extend them to other cognitive paradigms, utilizing functional neuroimaging.This work was supported by the Medical Research Council of South Africa, the Obsessive-Compulsive Foundation (Prof Stein), the National Research Foundation of South Africa (Prof Lochner), an unrestricted grant from Lundbeck H/S and by a Starter Grant for Clinical Lecturers from the Academy of Medical Sciences UK (Dr Chamberlain).This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s00213-015-4172-

Striatal abnormalities in trichotillomania: a multi-site MRI analysis.

Trichotillomania (hair-pulling disorder) is characterized by the repetitive pulling out of one's own hair, and is classified as an Obsessive-Compulsive Related Disorder. Abnormalities of the ventral and dorsal striatum have been implicated in disease models of trichotillomania, based on translational research, but direct evidence is lacking. The aim of this study was to elucidate subcortical morphometric abnormalities, including localized curvature changes, in trichotillomania. De-identified MRI scans were pooled by contacting authors of previous peer-reviewed studies that examined brain structure in adult patients with trichotillomania, following an extensive literature search. Group differences on subcortical volumes of interest were explored (t-tests) and localized differences in subcortical structure morphology were quantified using permutation testing. The pooled sample comprised N=68 individuals with trichotillomania and N=41 healthy controls. Groups were well-matched in terms of age, gender, and educational levels. Significant volumetric reductions were found in trichotillomania patients versus controls in right amygdala and left putamen. Localized shape deformities were found in bilateral nucleus accumbens, bilateral amygdala, right caudate and right putamen. Structural abnormalities of subcortical regions involved in affect regulation, inhibitory control, and habit generation, play a key role in the pathophysiology of trichotillomania. Trichotillomania may constitute a useful model through which to better understand other compulsive symptoms. These findings may account for why certain medications appear effective for trichotillomania, namely those modulating subcortical dopamine and glutamatergic function. Future work should study the state versus trait nature of these changes, and the impact of treatment

Problematic use of the Internet is a unidimensional quasi-trait with impulsive and compulsive subtypes

Abstract: Background: Problematic use of the Internet has been highlighted as needing further study by international bodies, including the European Union and American Psychiatric Association. Knowledge regarding the optimal classification of problematic use of the Internet, subtypes, and associations with clinical disorders has been hindered by reliance on measurement instruments characterized by limited psychometric properties and external validation. Methods: Non-treatment seeking individuals were recruited from the community of Stellenbosch, South Africa (N = 1661), and Chicago, United States of America (N = 827). Participants completed an online version of the Internet Addiction Test, a widely used measure of problematic use of the Internet consisting of 20-items, measured on a 5-point Likert-scale. The online questions also included demographic measures, time spent engaging in different online activities, and clinical scales. The psychometric properties of the Internet Addiction Test, and potential problematic use of the Internet subtypes, were characterized using factor analysis and latent class analysis. Results: Internet Addiction Test data were optimally conceptualized as unidimensional. Latent class analysis identified two groups: those essentially free from Internet use problems, and those with problematic use of the Internet situated along a unidimensional spectrum. Internet Addiction Test scores clearly differentiated these groups, but with different optimal cut-offs at each site. In the larger Stellenbosch dataset, there was evidence for two subtypes of problematic use of the Internet that differed in severity: a lower severity “impulsive” subtype (linked with attention-deficit hyperactivity disorder), and a higher severity “compulsive” subtype (linked with obsessive-compulsive personality traits). Conclusions: Problematic use of the Internet as measured by the Internet Addiction Test reflects a quasi-trait - a unipolar dimension in which most variance is restricted to a subset of people with problems regulating Internet use. There was no evidence for subtypes based on the type of online activities engaged in, which increased similarly with overall severity of Internet use problems. Measures of comorbid psychiatric symptoms, along with impulsivity, and compulsivity, appear valuable for differentiating clinical subtypes and could be included in the development of new instruments for assessing the presence and severity of Internet use problems

Behavioural addiction-A rising tide?

The term 'addiction' was traditionally used in relation to centrally active substances, such as cocaine, alcohol, or nicotine. Addiction is not a unitary construct but rather incorporates a number of features, such as repetitive engagement in behaviours that are rewarding (at least initially), loss of control (spiralling engagement over time), persistence despite untoward functional consequences, and physical dependence (evidenced by withdrawal symptoms when intake of the substance diminishes). It has been suggested that certain psychiatric disorders characterized by maladaptive, repetitive behaviours share parallels with substance addiction and therefore represent 'behavioural addictions'. This perspective has influenced the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), which now has a category 'Substance Related and Addictive Disorders', including gambling disorder. Could other disorders characterised by repetitive behaviours, besides gambling disorder, also be considered 'addictions'? Potential examples include kleptomania, compulsive sexual behaviour, 'Internet addiction', trichotillomania (hair pulling disorder), and skin-picking disorder. This paper seeks to define what is meant by 'behavioural addiction', and critically considers the evidence for and against this conceptualisation in respect of the above conditions, from perspectives of aetiology, phenomenology, co-morbidity, neurobiology, and treatment. Research in this area has important implications for future diagnostic classification systems, neurobiological models, and novel treatment directions.This research was supported by a Grant from the Academy of Medical Sciences (UK) to Dr Chamberlain. Dr Chamberlain consults for Cambridge Cognition. Dr Grant has received research Grants from the National Center for Responsible Gaming, and Forest and Roche Pharmaceuticals. Dr Grant receives yearly compensation from Springer Publishing for acting as Editor-in-Chief of the Journal of Gambling Studies and has received royalties from Oxford University Press, American Psychiatric Publishing, Inc., Norton Press, and McGraw Hill. Dr. Goudriaan was supported by an innovative scheme Grant of the Dutch Scientific Association (ZonMw VIDI Grant no. 016.136.354) and received support from the European Association for Alcohol Research, the National Center for Responsible Gaming and has consulted for TüV Germany. The other authors report no potential conflicts of interest or funding declarationsThis is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.euroneuro.2015.08.01

The linked survival prospects of siblings : evidence for the Indian states

This paper reports an analysis of micro-data for India that shows a high correlation in infant mortality among siblings. In 13 of 15 states, we identify a causal effect of infant death on the risk of infant death of the subsequent sibling (a scarring effect), after controlling for mother-level heterogeneity. The scarring effects are large, the only other covariate with a similarly large effect being mother’s (secondary or higher) education. The two states in which evidence of scarring is weak are Punjab, the richest, and Kerala, the socially most progressive. The size of the scarring effect depends upon the sex of the previous child in three states, in a direction consistent with son-preference. Evidence of scarring implies that policies targeted at reducing infant mortality will have social multiplier effects by helping avoid the death of subsequent siblings. Comparison of other covariate effects across the states offers some interesting new insights

Associations between dimensions of behaviour, personality traits, and mental-health during the COVID-19 pandemic in the United Kingdom.

The COVID-19 pandemic (including lockdown) is likely to have had profound but diverse implications for mental health and well-being, yet little is known about individual experiences of the pandemic (positive and negative) and how this relates to mental health and well-being, as well as other important contextual variables. Here, we analyse data sampled in a large-scale manner from 379,875 people in the United Kingdom (UK) during 2020 to identify population variables associated with mood and mental health during the COVID-19 pandemic, and to investigate self-perceived pandemic impact in relation to those variables. We report that while there are relatively small population-level differences in mood assessment scores pre- to peak-UK lockdown, the size of the differences is larger for people from specific groups, e.g. older adults and people with lower incomes. Multiple dimensions underlie peoples' perceptions, both positive and negative, of the pandemic's impact on daily life. These dimensions explain variance in mental health and can be statistically predicted from age, demographics, home and work circumstances, pre-existing conditions, maladaptive technology use and personality traits (e.g., compulsivity). We conclude that a holistic view, incorporating the broad range of relevant population factors, can better characterise people whose mental health is most at risk during the COVID-19 pandemic

Behavioral measures of impulsivity and compulsivity in adolescents with nonsuicidal self-injury.

BACKGROUND: Nonsuicidal self-injury (NSSI) is prevalent among adolescents and research is needed to clarify the mechanisms which contribute to the behavior. Here, the authors relate behavioral neurocognitive measures of impulsivity and compulsivity to repetitive and sporadic NSSI in a community sample of adolescents. METHODS: Computerized laboratory tasks (Affective Go/No-Go, Cambridge Gambling Task, and Probabilistic Reversal Task) were used to evaluate cognitive performance. Participants were adolescents aged 15 to 17 with (n = 50) and without (n = 190) NSSI history, sampled from the ROOTS project which recruited adolescents from secondary schools in Cambridgeshire, UK. NSSI was categorized as sporadic (1-3 instances per year) or repetitive (4 or more instances per year). Analyses were carried out in a series of linear and negative binomial regressions, controlling for age, gender, intelligence, and recent depressive symptoms. RESULTS: Adolescents with lifetime NSSI, and repetitive NSSI specifically, made significantly more perseverative errors on the Probabilistic Reversal Task and exhibited significantly lower quality of decision making on the Cambridge Gambling Task compared to no-NSSI controls. Those with sporadic NSSI did not significantly differ from no-NSSI controls on task performance. NSSI was not associated with behavioral measures of impulsivity. CONCLUSIONS: Repetitive NSSI is associated with increased behavioral compulsivity and disadvantageous decision making, but not with behavioral impulsivity. Future research should continue to investigate how neurocognitive phenotypes contribute to the onset and maintenance of NSSI, and determine whether compulsivity and addictive features of NSSI are potential targets for treatment

Problematic internet use (PIU): Associations with the impulsive-compulsive spectrum. An application of machine learning in psychiatry.

Problematic internet use is common, functionally impairing, and in need of further study. Its relationship with obsessive-compulsive and impulsive disorders is unclear. Our objective was to evaluate whether problematic internet use can be predicted from recognised forms of impulsive and compulsive traits and symptomatology. We recruited volunteers aged 18 and older using media advertisements at two sites (Chicago USA, and Stellenbosch, South Africa) to complete an extensive online survey. State-of-the-art out-of-sample evaluation of machine learning predictive models was used, which included Logistic Regression, Random Forests and Naïve Bayes. Problematic internet use was identified using the Internet Addiction Test (IAT). 2006 complete cases were analysed, of whom 181 (9.0%) had moderate/severe problematic internet use. Using Logistic Regression and Naïve Bayes we produced a classification prediction with a receiver operating characteristic area under the curve (ROC-AUC) of 0.83 (SD 0.03) whereas using a Random Forests algorithm the prediction ROC-AUC was 0.84 (SD 0.03) [all three models superior to baseline models p < 0.0001]. The models showed robust transfer between the study sites in all validation sets [p < 0.0001]. Prediction of problematic internet use was possible using specific measures of impulsivity and compulsivity in a population of volunteers. Moreover, this study offers proof-of-concept in support of using machine learning in psychiatry to demonstrate replicability of results across geographically and culturally distinct settings.This research received internal departmental funds of the Department of Psychiatry at the University of Chicago.This is the final version of the article. It first appeared from Elsevier at http://dx.doi.org/10.1016/j.jpsychires.2016.08.010

Brain circuitry of compulsivity.

Compulsivity is associated with alterations in the structure and the function of parallel and interacting brain circuits involved in emotional processing (involving both the reward and the fear circuits), cognitive control, and motor functioning. These brain circuits develop during the pre-natal period and early childhood under strong genetic and environmental influences. In this review we bring together literature on cognitive, emotional, and behavioral processes in compulsivity, based mainly on studies in patients with obsessive-compulsive disorder and addiction. Disease symptoms normally change over time. Goal-directed behaviors, in response to reward or anxiety, often become more habitual over time. During the course of compulsive disorders the mental processes and repetitive behaviors themselves contribute to the neuroplastic changes in the involved circuits, mainly in case of chronicity. On the other hand, successful treatment is able to normalize altered circuit functioning or to induce compensatory mechanisms. We conclude that insight in the neurobiological characteristics of the individual symptom profile and disease course, including the potential targets for neuroplasticity is an unmet need to advance the field.Dr. Soriano-Mas is funded by a ׳Miguel Servet׳ contract from the Carlos III Health Institute (CP10/00604). Dr. Goudriaan is supported by a VIDI Innovative Research Grant (Grant no. 91713354) funded by the Dutch Scientific Research Association (NWO-ZonMW). Dr. Alonso was funded by the Instituto de Salut Carlos III-FISPI14/00413. Dr. Nakamae received Grant support from MEXT KAKENHI (Nos. 24791223 and 26461753).This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.euroneuro.2015.12.00