Obsessive‐compulsive disorder (OCD) is characterized by obsessions (intrusive thoughts) and compulsions (repetitive ritualistic behaviours) leading to functional impairment. Accumulating evidence ...links these conditions with underlying dysregulation of fronto‐striatal circuitry and monoamine systems. These abnormalities represent key targets for existing and novel treatment interventions. However, the brain bases of these conditions and treatment mechanisms are still not fully elucidated. Animal models simulating the behavioural and clinical manifestations of the disorder show great potential for augmenting our understanding of the pathophysiology and treatment of OCD. This paper provides an overview of what is known about OCD from several perspectives. We begin by describing the clinical features of OCD and the criteria used to assess the validity of animal models of symptomatology; namely, face validity (phenomenological similarity between inducing conditions and specific symptoms of the human phenomenon), predictive validity (similarity in response to treatment) and construct validity (similarity in underlying physiological or psychological mechanisms). We then survey animal models of OC spectrum conditions within this framework, focusing on (i) ethological models; (ii) genetic and pharmacological models; and (iii) neurobehavioural models. We also discuss their advantages and shortcomings in relation to their capacity to identify potentially efficacious new compounds. It is of interest that there has been rather little evidence of ‘false alarms’ for therapeutic drug effects in OCD models which actually fail in the clinic. While it is more difficult to model obsessive cognition than compulsive behaviour in experimental animals, it is feasible to infer cognitive inflexibility in certain animal paradigms. Finally, key future neurobiological and treatment research areas are highlighted.
LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue‐4
Mood disorders collectively account for a substantial proportion of disease burden across the globe and have a devastating impact on quality of life and occupational function. Here we evaluate recent ...progress in understanding the neurocognitive mechanisms involved in the manifestation of mood disorders. We focus on four domains of cognitive function that are altered in patients with depression: executive control, memory, affective processing, and feedback sensitivity. These alterations implicate a distributed neural circuit composed of multiple sectors of the prefrontal cortex in interaction with subcortical regions (striatum, thalamus) and temporal lobe structures (amygdala, hippocampus). Affective processing and feedback sensitivity are highly sensitive to serotonergic manipulation and are targeted by antidepressant treatments. By drawing together cognitive, neuroanatomical, and pharmacological tiers of research, we identify treatment targets and directions for future investigation to identify people at risk, minimize relapse, and maximize long-term beneficial outcomes for those suffering from depression.
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 (OCD) is a highly debilitating neuropsychiatric condition with estimated lifetime prevalence of 2–3%, more than twice that of schizophrenia. However, in contrast to ...other neuropsychiatric conditions of a comparable or lesser prevalence, relatively little is understood about the aetiology, neural substrates and cognitive profile of OCD. Despite strong evidence for OCD being familial, with risk to first-degree relatives much greater than for the background population, its genetic underpinnings have not yet been adequately delineated. Although cognitive dysfunction is evident in the everyday behaviour of OCD sufferers and is central to contemporary psychological models, theory-based studies of neurocognitive function have yet to reveal a reliable cognitive signature, and interpretation has often been confounded by failures to control for co-morbidities. The neuroimaging findings in OCD are amongst the most robust reported in the psychiatric literature, with structural and functional abnormalities frequently reported in orbitofrontal cortex, anterior cingulate cortex, and caudate nucleus. In spite of this, our relative lack of understanding of OCD neurochemical processes continues to impede progress in the development of novel pharmacological treatment approaches. Integrating the neurobiological, cognitive, and clinical findings, we propose that OCD might usefully be conceptualised in terms of lateral orbitofrontal loop dysfunction, and that failures in cognitive and behavioural inhibitory processes appear to underlie many of the symptoms and neurocognitive findings. We highlight existing limitations in the literature, and the potential utility of endophenotypes in overcoming these limitations. We propose that neurocognitive indices of inhibitory functions may represent a useful heuristic in the search for endophenotypes in OCD. This has direct implications not only for OCD but also for putative obsessive-compulsive spectrum conditions including attention deficit hyperactivity disorder, Tourette's syndrome, and trichotillomania (compulsive hair pulling).
As a behavioral addiction with clinical and phenomenological similarities to substance addiction, recreational and pathological gambling represent models for studying the neurobiology of addiction, ...without the confounding deleterious brain effects which may occur from chronic substance abuse.
A community sample of individuals aged 18-65 years who gamble was solicited through newspaper advertising. Subjects were grouped a priori into three groups (no-risk, at-risk, and pathological gamblers) based on a diagnostic interview. All subjects underwent a psychiatric clinical interview and neurocognitive tests assessing motor impulsivity and cognitive flexibility. Subjects with a current axis I disorder, history of brain injury/trauma, or implementation or dose changes of psychoactive medication within 6 weeks of study enrollment were excluded.
A total of 135 no-risk, 69 at-risk and 46 pathological gambling subjects were assessed. Pathological gamblers were significantly older, and exhibited significant deficiencies in motor impulse control (stop-signal reaction times), response speed (median 'go' trial response latency) and cognitive flexibility total intra-dimensional/extra-dimensional (IDED) errors versus controls. The finding of impaired impulse control and cognitive flexibility was robust in an age-matched subgroup analysis of pathological gamblers. The no-risk and at-risk gambling groups did not significantly differ from each other on task performance.
Impaired response inhibition and cognitive flexibility exist in people with pathological gambling compared with no-risk and at-risk gamblers. The early identification of such illness in adolescence or young adulthood may aid in the prevention of addiction onset of such disabling disorders.
Background
Binge‐eating disorder (BED) is associated with impaired quality of life and has a number of untoward public health associations. There are few established pharmacological treatments for ...BED, and available options are not suitable for all individuals. Vortioxetine is a recently developed pharmacological agent with effects on the serotonergic but also other neurochemical systems, which has yet to be evaluated in this context.
Method
Eighty adults with BED were recruited for a double‐blind, placebo‐controlled study. Participants received 12‐week treatment with vortioxetine (10 mg/day for 1 week, then increasing to 20 mg/day) or placebo in a parallel design. The primary efficacy outcome measures were binge‐eating frequency and weight. Safety data were collected. Effects of active versus placebo treatment were characterized using linear repeated measures models.
Results
Both vortioxetine and placebo treatment were associated with significant reductions in binge‐eating frequency. Vortioxetine did not differentiate significantly from placebo on any efficacy measure. Frequency of adverse events did not differ between groups.
Discussion
Vortioxetine was not more effective than placebo in the treatment of BED. The ability to detect pharmacological treatment benefit may have been hindered by the relatively high placebo response and drop out. Future work should seek to better understand and predict placebo response in BED, with a view to more targeted treatment interventions and, potentially, sample enrichment.
Objective
Research on health correlates in gamblers has found an association between gambling and obesity. The neurocognitive underpinnings of impulsivity may be useful targets for understanding and ...ultimately treating individuals with both gambling and obesity problems.
Method
207 non‐treatment seeking young adults (18–29 years) with subsyndromal gambling disorder were recruited from the community. Subjects were grouped according to weight (‘normal weight’ BMI < 25, ‘overweight’ BMI ≥ 25; or ‘obese’ BMI ≥ 30). Measures relating to gambling behaviour and objective computerized neurocognitive measures were collected.
Results
Of the 207 subjects, 22 (10.6%) were obese and 49 (23.7%) were overweight. The obese gamblers consumed more nicotine (packs per day equivalent) and reported losing more money per week to gambling. Obese gamblers exhibited significant impairments in terms of reaction times for go trials on the stop‐signal test (SST), quality of decision making and risk adjustment on the Cambridge Gamble Test (CGT), and sustained attention on the rapid visual information processing task (RVP).
Conclusion
Obesity was associated with decision making and sustained attention impairments in gamblers, along with greater monetary loss due to gambling. Future work should use longitudinal designs to examine the temporal relationship between these deficits, weight, other impulsive behaviour, and functional impairment.
This study sought to examine the occurrence of the nonmedical use of prescription stimulants (amphetamines and methylphenidate) in a university sample and their associated physical and mental health ...correlates, including potential relationships with risky sexual practices.
A 156-item anonymous online survey was distributed via e-mail to a sample of 9449 university students. Current use of alcohol and drugs, psychological and physical status, and academic performance were assessed, along with questionnaire-based measures of impulsivity and compulsivity.
A total of 3421 participants (59.7% female) were included in the analysis. 6.7% of the sample reported current/recent nonmedical use of prescription stimulants, while an additional 5.8% reported misuse in the past. Nonmedical use of prescription stimulants was associated with lower grade point averages, and with taking a broad range of other drugs (including alcohol, nicotine, illicit substances, and consumption of caffeinated soft drinks). Nonmedical use of stimulants was also significantly associated with impulsivity (Barratt scale), prior treatment for substance use problems, and elevated occurrence of disordered gambling, post-traumatic stress disorder, and anxiety; but not depression symptoms or binge-eating disorder (though it was associated with using drugs to lose weight). The relationship with probable attention-deficit/hyperactivity disorder (ADHD) on screening was not significant but was numerically elevated. Finally, those using nonmedical prescribed stimulants were significantly more sexually active (including at a younger age), and were less likely to use barrier contraception.
Nonmedical use of prescription stimulants is common in young adults and has profound public health associations including with a profundity of other drug use (licit and illicit), certain mental health diagnoses (especially gambling, anxiety, and post-traumatic stress disorder ), worse scholastic performance, and riskier sexual practices. The majority of people with nonmedical use of prescription stimulants do not have ADHD, and its link with current ADHD symptoms was less marked than for certain other disorders. Clinicians should screen for the misuse of prescription stimulants as they may be associated with a range of problematic behaviors. Risk of diversion (which may be higher for those living in shared accommodation and those with substance use disorder history) merits careful assessment before prescribing stimulant medication.
Introduction Body dysmorphic disorder (BDD) is a debilitating disorder, characterized by obsessions and compulsions relating specifically to perceived appearance, and which has been newly classified ...within the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Obsessive-Compulsive and Related Disorders grouping. Until now, little research has been conducted into the cognitive profile of this disorder.
Participants with BDD (n=12) and participants without BDD (n=16) were tested using a computerized neurocognitive battery investigating attentional set-shifting (Intra/Extra Dimensional Set Shift Task), decision-making (Cambridge Gamble Task), motor response-inhibition (Stop-Signal Reaction Time Task), and affective processing (Affective Go-No Go Task). The groups were matched for age, IQ, and education.
In comparison to controls, patients with BDD showed significantly impaired attentional set-shifting, abnormal decision-making, impaired response inhibition, and greater omission and commission errors on the emotional processing task.
Despite the modest sample size, our results showed that individuals with BDD performed poorly compared to healthy controls on tests of cognitive flexibility, reward and motor impulsivity, and affective processing. Results from separate studies in OCD patients suggest similar cognitive dysfunction. Therefore, these findings are consistent with the reclassification of BDD alongside OCD. These data also hint at additional areas of decision-making abnormalities that might contribute specifically to the psychopathology of BDD.
Although a relatively common behavior, treatment data for pathological skin picking (PSP) are limited. The current study sought to examine the efficacy and tolerability of lamotrigine in adults with ...PSP and to examine neurocognitive predictors of treatment response. Thirty-two subjects (29 female subjects 90.6%; mean age, 32.8 +/- 13.3 years) with PSP were treated in a 12-week randomized, double-blind, placebo-controlled trial of lamotrigine as monotherapy. Baseline cognitive assessment comprised the stop signal and intradimensional/extradimensional set shift tasks. Lamotrigine dosing ranged from 12.5 to 300 mg/d. The primary outcome measure was picking symptoms measured by the Yale-Brown Obsessive Compulsive scale Modified for Neurotic Excoriation. Subjects also were assessed with measures of psychosocial functioning. No significant overall differences were noted between lamotrigine and placebo on the primary or secondary end points. Seven subjects assigned to lamotrigine (43.8%) were considered responders (defined as >or=35% n the Yale-Brown Obsessive Compulsive scale Modified for Neurotic Excoriation) compared with 5 (31.3%) assigned to placebo. Those who ultimately responded to lamotrigine exhibited impaired cognitive flexibility (extradimensional shifting) at baseline compared with lamotrigine nonresponders. These findings suggest that, although safe and well tolerated, lamotrigine treatment may not be efficacious in patients with PSP as a whole, compared with placebo. However, these neurocognitive data suggest that lamotrigine may be valuable in a subset of patients who exhibit relatively impaired cognitive flexibility.
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