Anhedonia in obsessive-compulsive disorder: Beyond comorbid depression

Abramovitch, Amitai; Pizzagalli, Diego A.; Reuman, Lillian; Wilhelm, Sabine

doi:10.1016/j.psychres.2014.02.002

Cited by 46 publications

(35 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some studies have indicated exacerbation of OCD symptoms induced by nicotine (Abramovitch et al, 2015). In contrast to the higher rates of smoking in patients with psychiatric disorders, such as schizophrenia, bipolar disorder and ADHD, OCD patients report less smoking behavior (Bejerot and Humble, 1999; Bejerot et al, 2000; McCabe et al, 2004; Abramovitch et al, 2014). It has been suggested that nicotinic activation of an already hyperactivated fronto-striatal circuit worsens OCD symptoms (Abramovitch et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Attenuation of Compulsive-Like Behavior Through Positive Allosteric Modulation of α4β2 Nicotinic Acetylcholine Receptors in Non-Induced Compulsive-Like Mice

Mitra

Mucha

Khatri

et al. 2017

Front. Behav. Neurosci.

View full text Add to dashboard Cite

Nicotinic α4β2 receptors are the most abundant subtypes of nicotinic acetylcholine receptors (nAChRs) expressed in brain regions implicated in obsessive compulsive disorder (OCD). These receptors are known to modify normal and addictive behaviors by modulating neuronal excitability. Desformylflustrabromine (dFBr) is a novel, positive allosteric modulator (PAM) of high acetylcholine sensitivity (HS) and low acetylcholine sensitivity (LS) α4β2 nAChRs. The present study tested the hypothesis that positive allosteric modulation of α4β2 receptors by dFBr will attenuate compulsive-like behavior in a non-induced compulsive-like mouse model. Male mice (Mus musculus) selected for compulsive-like nesting behavior (NB; 48 animals; 12 per group) received acute (once) and chronic (every day for 32 days) subcutaneous injection of dFBr at 2, 4 and 6 mg/kg doses. Saline was used as a control (0 mg/kg). Compulsive-like NB was assessed after 1, 2, 3, 4, 5 and 24 h, while compulsive-like marble burying (MB) and anxiety-like open field (OF) behaviors were performed 2 h after dFBr administration. In the acute administration protocol, dFBr dose dependently attenuated NB and MB. Rapid effects (1–2 h after drug administration) of dFBr on MB and NB were observed for the chronic administration which was in congruence with the acute study. Chronic administration also revealed sustained suppression of NB by dFBr following 5 weeks of treatment. In both the acute and chronic regimen dFBr did not modulate OF behaviors. This research demonstrates the novel role of positive allosteric modulation of α4β2 nicotinic receptors by dFBr as a translational potential for OCD.

show abstract

Section: Discussionmentioning

confidence: 99%

Attenuation of Compulsive-Like Behavior Through Positive Allosteric Modulation of α4β2 Nicotinic Acetylcholine Receptors in Non-Induced Compulsive-Like Mice

Mitra

Mucha

Khatri

et al. 2017

Front. Behav. Neurosci.

View full text Add to dashboard Cite

show abstract

“…For the treatment of OCD, NAcc-DBS leads to reductions in obsessive-compulsive behavior and anxiety symptoms, while at the same time increasing libido (Denys et al, 2010). Although OCD is typically thought of as an anxiety disorder, the presence of anhedonic symptomatology, separate from that explained by comorbid depression, has been observed in patients with OCD (Abramovitch et al, 2014). Thus, it is possible that by targeting the NAcc with DBS in OCD patients, a similar pattern of activation changes as Bewernick et al (2010) reported in depressed patients would be observed.…”

Section: Therapeutic Mechanisms Of Neurostimulation Techniques Targetmentioning

confidence: 99%

Cortico-Striatal-Thalamic Loop Circuits of the Orbitofrontal Cortex: Promising Therapeutic Targets in Psychiatric Illness

Fettes

Schulze

Downar

2017

Front. Syst. Neurosci.

229

164

View full text Add to dashboard Cite

Corticostriatal circuits through the orbitofrontal cortex (OFC) play key roles in complex human behaviors such as evaluation, affect regulation and reward-based decision-making. Importantly, the medial and lateral OFC (mOFC and lOFC) circuits have functionally and anatomically distinct connectivity profiles which differentially contribute to the various aspects of goal-directed behavior. OFC corticostriatal circuits have been consistently implicated across a wide range of psychiatric disorders, including major depressive disorder (MDD), obsessive compulsive disorder (OCD), and substance use disorders (SUDs). Furthermore, psychiatric disorders related to OFC corticostriatal dysfunction can be addressed via conventional and novel neurostimulatory techniques, including deep brain stimulation (DBS), electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS). Such techniques elicit changes in OFC corticostriatal activity, resulting in changes in clinical symptomatology. Here we review the available literature regarding how disturbances in mOFC and lOFC corticostriatal functioning may lead to psychiatric symptomatology in the aforementioned disorders, and how psychiatric treatments may exert their therapeutic effect by rectifying abnormal OFC corticostriatal activity. First, we review the role of OFC corticostriatal circuits in reward-guided learning, decision-making, affect regulation and reappraisal. Second, we discuss the role of OFC corticostriatal circuit dysfunction across a wide range of psychiatric disorders. Third, we review available evidence that the therapeutic mechanisms of various neuromodulation techniques may directly involve rectifying abnormal activity in mOFC and lOFC corticostriatal circuits. Finally, we examine the potential of future applications of therapeutic brain stimulation targeted at OFC circuitry; specifically, the role of OFC brain stimulation in the growing field of individually-tailored therapies and personalized medicine in psychiatry.

show abstract

“…Later, with repeated use, this behavior becomes compulsive, where the major motivation changes from sensation seeking and positive reward, to negative reinforcement in which drug administration alleviates withdrawal symptoms. We have previously maintained that the behavioral addiction paradigm may be a useful framework in the context of OCD (Abramovitch, Pizzagalli, Reuman, & Wilhelm, 2014). However, this does not suggest that OCD is a disorder that is similar to drug addiction.…”

mentioning

confidence: 99%

Behavioral Impulsivity in Obsessive–Compulsive Disorder

Abramovitch¹,

McKay²

2016

J Behav Addict

Self Cite

View full text Add to dashboard Cite

BackgroundGrassi et al. (2015) collected data to examine impulsivity in individuals with obsessive–compulsive disorder (OCD) compared to nonpsychiatric controls. Their aim was to examine whether OCD may be fully captured by the behavioral addiction model, using the prototypical mechanism underlying drug addiction as their framework. Based on their findings, Grassi et al. concluded that OCD shares behavioral components with addictions, particularly behavioral impulsivity and risky decision making. Furthermore, the authors suggested that this model may be superior to the prevailing psychological model of OCD.FindingsWe argue that based on the nature of their data as well as the current dominant conceptualization of OCD in the literature, this conclusion is untenable. The authors inferred behavioral impulsivity, whereas their main finding was concerning cognitive impulsivity or difficulties in planning. Such items on the Barratt impulsiveness scale have been shown in other research to overpredict behavioral impulsive tendencies in OCD, where the nature of the condition involves doubting of action and a conservative estimate of how one’s cognitions may impact behavior.ConclusionsWe conclude that similar to drug addiction, compulsive rituals in OCD may be governed by a negative reinforcement mechanism; the available data indicate that OCD does not share the two main components seen in addiction, namely, behavioral impulsivity and risky decision making.

show abstract

Anhedonia in obsessive-compulsive disorder: Beyond comorbid depression

Cited by 46 publications

References 66 publications

Attenuation of Compulsive-Like Behavior Through Positive Allosteric Modulation of α4β2 Nicotinic Acetylcholine Receptors in Non-Induced Compulsive-Like Mice

Attenuation of Compulsive-Like Behavior Through Positive Allosteric Modulation of α4β2 Nicotinic Acetylcholine Receptors in Non-Induced Compulsive-Like Mice

Cortico-Striatal-Thalamic Loop Circuits of the Orbitofrontal Cortex: Promising Therapeutic Targets in Psychiatric Illness

Behavioral Impulsivity in Obsessive–Compulsive Disorder

Contact Info

Product

Resources

About