Compulsivity Flashcards
Compulsivity definition
Repetitive, irresistable urge to perform a behaviour, with loss of voluntary control over this intense urge and diminished ability to inhibit thoughts or actions leading to habitual acts
Cross-disorder trait
Underlying phenotypically distinct psychiatric disorders that emerge throughout all stages of life
Early life (autism)
Late childhood (OCD)
Addiction (SUD)
ADHD associated with SUD
Mechanisms underlying compulsivity
Cognitive
Neural
Genetic nature
Certain biomarkers underpinning association between compulsivity, impulsivity and addiction
Primary brain mechanism investigated in relation to compulsivity
Corticostriatal glutamate circuit, where altered corticostriatal functional connectivity has been observed in OCD (Harrison et al. 2009)
More recently observed
Abnormal corticostriatal limbic functional connectivity had been demonstrated in OCD patients during reward processing and during resting state, signifying the role of the nucleus accumbens in compulsive behaviour (Jung et al. 2013)
Autism spectrum disorder (ASD)
Characterised by deficits in social interaction and communication, with stereotyped patterns of behaviour, interests and activities including repetitive motor behaviours and body movements.
Comorbidity of ASD with ADHD
High comorbidity
25-50% of ASD individuals presenting with impulsivity, hyperactivity and attentional deficits qualifying for ADHD diagnosis
ASD individuals demonstrate with….
3 fold increase in addictive behaviours and risk of SUD in adolescence
Neurotransmitter hypothesis underlying compulsivity
Decreased serotonin levels, serving as basis for SSRI medication however 30-40% non response rate
Dopaminergic overactivity in BG
Likely the cause of dysregulation in preventing certain actions or thoughts
Dysregulation in frontal regions
Alterations in excitatory and inhibitory balance of glutamate and GABA
Present hypothesis
In the trajectory of addictive behaviours, compulsivity originates prior to obsessions
The TACTICS project (2012-2018)
Preclinical and clinical research to identify neural, genetic and molecular factors involved in pathogenesis of compulsivity
Using a series of ‘proof-of-concept’ studies
cohesion of structural neuroimaging studies (MRI/DTI) neurochemistry (MRS/microdialysis) behaviour, genetics (GWAS) proteomics and Bayesian machine learning tools
Male and female pediatric clinical populations and
behavioural animal mdels to better understand the mechanisms related to glutamate dysfunction in frontostriatal circuits and its remediation by early intervention studies with glutamate-based clinically used drugs
Animal models of compulsive behaviour
provided valuable insights into mechanisms underpinning compulsivity as a cross-disorder trait
Compulsive lever pressing in signal attenuation mouse model of OCD
differentiates between compulsive-like behaviours and behaviours that are repetitive but not compulsive
Adminstration of quinpirole
selective D2 and D3 dopaminergic receptor agonist in rats led to compulsive checking behaviours implicating the role of basal ganglia hyperactivity in compulsivity
SLITKR KO mice
impaired corticostriatal circuitry
compulsive behaviours in form of excessive barbering
SSRI treatment (fluoxetine)
reduced overgrooming in SLITKR KO mice demonstrating the role of serotonin in compulsivity
Reversal learning useful assessment
measure compulsivity in animal models with reduced behavioural flexibility indicative of compulsive-like behaviours
Virtual reality environments
used to explore reversal learning in younf mice (Havenith et al. 2019)
Error detection in reversal learning trial attributed to
ACC function with mice required to overcome learned avoidance of previously learned stimulus in order to acquire new association
Impairments in reversal learning
observed in OCD patients (Remijinse, 2006)
