Transdiagnostic phenotypes of compulsive behavior and associations with psychological, cognitive, and neurobiological affective processing

Compulsivity is a poorly understood transdiagnostic construct thought to underlie multiple disorders, including obsessive-compulsive disorder, addictions, and binge eating. Our current understanding of the causes of compulsive behavior remains primarily based on investigations into specific diagnostic categories or findings relying on one or two laboratory measures to explain complex phenotypic variance. This proof-of-concept study drew on a heterogeneous sample of community-based individuals (N = 45; 18–45 years; 25 female) exhibiting compulsive behavioral patterns in alcohol use, eating, cleaning, checking, or symmetry. Data-driven statistical modeling of multidimensional markers was utilized to identify homogeneous subtypes that were independent of traditional clinical phenomenology. Markers were based on well-defined measures of affective processing and included psychological assessment of compulsivity, behavioral avoidance, and stress, neurocognitive assessment of reward vs. punishment learning, and biological assessment of the cortisol awakening response. The neurobiological validity of the subtypes was assessed using functional magnetic resonance imaging. Statistical modeling identified three stable, distinct subtypes of compulsivity and affective processing, which we labeled “Compulsive Non-Avoidant”, “Compulsive Reactive” and “Compulsive Stressed”. They differed meaningfully on validation measures of mood, intolerance of uncertainty, and urgency. Most importantly, subtypes captured neurobiological variance on amygdala-based resting-state functional connectivity, suggesting they were valid representations of underlying neurobiology and highlighting the relevance of emotion-related brain networks in compulsive behavior. Although independent larger samples are needed to confirm the stability of subtypes, these data offer an integrated understanding of how different systems may interact in compulsive behavior and provide new considerations for guiding tailored intervention decisions.

Impulsivity-compulsivity axis in the abuse of Information and Communication Technologies (ICT) from the perspective of the Research Domain Criteria Project (RDoC)

The habit formation model to explain addiction involves the transition from an initial phase in which the prefrontal cortex ceases to control the behavior, to a phase in which control is transferred to the dorsal striatum, progressing towards compulsive consumption. This model, widely supported by empirical evidence, implies that each subject is at a certain point in the impulsivity-compulsivity continuum. Using two questionnaires recommended within the framework of the Research Domain Criteria Project which measure impulsivity and compulsivity, an attempt was made to confirm the existence of such a bipolar axis, applied to the abuse of information and communication technologies (ICT). The results of this study provide empirical support for the existence of this axis. The abuse of ICT seems to have many more compulsive components than impulsive ones, except in the case of video games, which are little related to both concepts. These results have important clinical implications since there are very different therapeutic approaches for impulsivity and compulsive behavior.

Writing Abilities in Compulsive Prisoners

Research has found links between academic failure and criminal offending and suggest that many incarcerated young people have experienced significant behavioral and learning problems in school, which could result in criminal outcomes and poor academic performance. The objective of this study was to analyse writing disorders in impulsive and compulsive prisoners. The sample was composed of 194 male prisoners, of which 81 had been diagnosed with Antisocial Personality Disorder and 113 with Obsessive Compulsive Personality Disorder. Male participants were recruited at the Granada Prison Center. They completed the Demographic, Crime, and Institutional Behavior Interview; the International Personality Disorder Examination (IPDE); The Symptom Checklist (SCL-90-R) and Assessment Battery of Writing Processes (PROESC in its Spanish acronym). We found that prisoners with writing disorders generally have difficulties in the skills necessary to write properly due to impulsive and compulsive behavior.

Eficácia do uso da Fluoxetina no Tratamento do Transtorno dos Comportamentos Obsessivo-Compulsivo em Autistas / Effectiveness of Fluoxetine use in the Treatment of Obsessive-Compulsive Behavior Disorders in Autistic Persons

RESUMO Objetivo: Verificar a eficácia do uso da fluoxetina no tratamento do transtorno do espectro autista (TEA). Métodos: Efetuou-se uma revisão sistemática da literatura a partir da questão de pesquisa “Em pacientes portadores do transtorno do espectro autista, o uso da fluoxetina em comparação ao placebo, é eficaz no tratamento dessa condição?”. Para seleção dos artigos realizou-se uma busca nas seguintes bases de dados: Biblioteca Virtual em Saúde (BVS) e PUBMED, utilizando-se como critérios de elegibilidade apenas ensaios clínicos randomizados e de qualquer ano. A amostra final foi composta por seis artigos. Resultados: em mais de 60% dos estudos, o tratamento com a fluoxetina resultou na redução dos comportamentos obsessivo-compulsivos encontrados no TEA. Os demais resultados foram conflitantes ou inconclusivos. Conclusão: Embora a maior parte dos estudos tenha apresentado que o uso da fluoxetina como redutor dos comportamentos obsessivo-compulsivo, não se pode asseverar eficácia comprovada devido ao número limitado de pesquisas e pelo pequeno grupo de pessoas que foram randomizadas. Mesmo não havendo uma comprovação “universal” os médicos optam por utilizar este medicamento desde que seja ponderado os riscos e benefícios.

Effects and interventions regarding the therapy in relation to the addiction of gambling

In nowadays society, gambling and bets are a type of entertainement socially accepted, but the risk that their usage turn into an unrestrained practice with several negative consequences turned gambling into a subject for psychologists and sociologs. The reason for choosing this subject was generated by the need of pointing out the serious problem of gambling addiction with which more and more people have been confronting lately and which affects addicted gamblers, their families and the entire Romanian society. When a person starts gambling more and more and uses more money for it at the expense of the other daily activities, one could state that this person adopts and develops an unduly and compulsive behavior that might become addictive. The consequences of gambling addiction vary from financial problems to increased or prolonged stress, to disrupted families, wasted fortunes, destroyed lives, dropouts, and it is more and more important that, especially, the young generation, but also the rest of the population that gambles more and more in the arcades and casinos realise the importance of a responsable gambling and how to avoid addictions.

Parallel valence processing alterations associated with compulsive behavior in SAPAP3 knockout mice and human OCD

Abnormalities in valence processing - the processing of aversive or appetitive stimuli - may be an underrecognized component of obsessive-compulsive disorder (OCD). Independent experimental paradigms have suggested disturbance of emotional valence systems in OCD, yet no standardized assay has been employed to assess both negative and positive valence processing in clinical studies of OCD patients, either at baseline or in response to therapeutic interventions. Additionally, preclinical rodent models are critical for treatment discovery in OCD, yet investigations examining whether rodent models of compulsive behavior similarly show alterations in valence systems have been limited. We sought to establish paradigms for assessing valence processing across both human OCD patients and in a preclinical rodent model: in OCD patients, we used validated behavioral tests to assess explicit and implicit processing of fear-related facial expressions (negative valence) and socially-rewarding happy expressions (positive valence); in the SAPAP3 knockout (KO) mouse model of compulsive behavior, we used auditory fear conditioning and extinction (negative valence) and reward-based operant conditioning (positive valence). We find that OCD patients show enhanced negative and impaired positive valence processing, and that performance on valence processing tasks correlates with clinical measures of OCD severity. We further find that SAPAP3 KO mice show heightened negative and impaired positive valence processing alterations similar to those of OCD patients. Our results show parallel valence processing abnormalities in OCD patients and a preclinical rodent model of compulsive behavior, and suggest valence processing alterations as novel therapeutic targets across a translational research spectrum.

Lost in translation: no effect of repeated optogenetic cortico-striatal stimulation on compulsivity in rats

The orbitofrontal cortex–ventromedial striatum (OFC–VMS) circuitry is widely believed to drive compulsive behavior. Hyperactivating this pathway in inbred mice produces excessive and persistent self-grooming, which has been considered a model for human compulsivity. We aimed to replicate these findings in outbred rats, where there are few reliable compulsivity models. Male Long-Evans rats implanted with optical fibers into VMS and with opsins delivered into OFC received optical stimulation at parameters that produce OFC–VMS plasticity and compulsive grooming in mice. We then evaluated rats for compulsive self-grooming at six timepoints: before, during, immediately after, and 1 h after each stimulation, 1 and 2 weeks after the ending of a 6-day stimulation protocol. To further test for effects of OFC–VMS hyperstimulation, we ran animals in three standard compulsivity assays: marble burying, nestlet shredding, and operant attentional set-shifting. OFC–VMS stimulation did not increase self-grooming or induce significant changes in nestlet shredding, marble burying, or set-shifting in rats. Follow-on evoked potential studies verified that the stimulation protocol altered OFC–VMS synaptic weighting. In sum, although we induced physiological changes in the OFC–VMS circuitry, we could not reproduce in a strongly powered study in rats a model of compulsive behavior previously reported in mice. This suggests possible limitations to translation of mouse findings to species higher on the phylogenetic chain.

Disruption of prepulse inhibition is associated with compulsive behavior severity and nucleus accumbens dopamine receptor changes in Sapap3 knockout mice

Obsessive compulsive disorder (OCD) is associated with disruption of sensorimotor gating, which may contribute to difficulties inhibiting intrusive thoughts and compulsive rituals. Neural mechanisms underlying these disturbances are unclear; however, striatal dopamine is implicated in regulation of sensorimotor gating and OCD pathophysiology. The goal of this study was to examine the relationships between sensorimotor gating, compulsive behavior, and striatal dopamine receptor levels in Sapap3 knockout mice (KOs), a widely used preclinical model system for OCD research. We found a trend for disruption of sensorimotor gating in Sapap3-KOs using the translational measure prepulse inhibition (PPI); however, there was significant heterogeneity in both PPI and compulsive grooming in KOs. Disruption of PPI was significantly correlated with a more severe compulsive phenotype. In addition, PPI disruption and compulsive grooming severity were associated with reduced dopamine D1 and D2/3 receptor density in the nucleus accumbens core (NAcC). Compulsive grooming progressively worsened in Sapap3-KOs tested longitudinally, but PPI disruption was first detected in high-grooming KOs at 7 months of age. Through detailed characterization of individual differences in OCD-relevant behavioral and neurochemical measures, our findings suggest that NAcC dopamine receptor changes may be involved in disruption of sensorimotor gating and compulsive behavior relevant to OCD.