The Psychopharmacology of Obsessive-Compulsive Disorder: A Preclinical Roadmap.

This review evaluates current knowledge about obsessive-compulsive disorder (OCD), with the goal of providing a roadmap for future directions in research on the psychopharmacology of the disorder. It first addresses issues in the description and diagnosis of OCD, including the structure, measurement, and appropriate description of the disorder and issues of differential diagnosis. Current pharmacotherapies for OCD are then reviewed, including monotherapy with serotonin reuptake inhibitors and augmentation with antipsychotic medication and with psychologic treatment. Neuromodulatory therapies for OCD are also described, including psychosurgery, deep brain stimulation, and noninvasive brain stimulation. Psychotherapies for OCD are then reviewed, focusing on behavior therapy, including exposure and response prevention and cognitive therapy, and the efficacy of these interventions is discussed, touching on issues such as the timing of sessions, the adjunctive role of pharmacotherapy, and the underlying mechanisms. Next, current research on the neurobiology of OCD is examined, including work probing the role of various neurotransmitters and other endogenous processes and etiology as clues to the neurobiological fault that may underlie OCD. A new perspective on preclinical research is advanced, using the Research Domain Criteria to propose an adaptationist viewpoint that regards OCD as the dysfunction of a normal motivational system. A systems-design approach introduces the security motivation system (SMS) theory of OCD as a framework for research. Finally, a new perspective on psychopharmacological research for OCD is advanced, exploring three approaches: boosting infrastructure facilities of the brain, facilitating psychotherapeutic relearning, and targeting specific pathways of the SMS network to fix deficient SMS shut-down processes. SIGNIFICANCE STATEMENT: A significant proportion of patients with obsessive-compulsive disorder (OCD) do not achieve remission with current treatments, indicating the need for innovations in psychopharmacology for the disorder. OCD may be conceptualized as the dysfunction of a normal, special motivation system that evolved to manage the prospect of potential danger. This perspective, together with a wide-ranging review of the literature, suggests novel directions for psychopharmacological research, including boosting support systems of the brain, facilitating relearning that occurs in psychotherapy, and targeting specific pathways in the brain that provide deficient stopping processes in OCD.

Developing the Sense of Agency Rating Scale (SOARS): an empirical measure of agency disruption in hypnosis.

Two experiments report on the construction of the Sense of Agency Rating Scale (SOARS), a new measure for quantifying alterations to agency. In Experiment 1, 370 participants completed a preliminary version of the scale following hypnosis. Factor analysis revealed two underlying factors: Involuntariness and Effortlessness. In Experiment 2, this two factor structure was confirmed in a sample of 113 low, medium and high hypnotisable participants. The two factors, Involuntariness and Effortlessness, correlated significantly with hypnotisability and pass rates for ideomotor, challenge and cognitive items. Twelve week test-retest correlations showed that Involuntariness was highly stable, but Effortlessness only moderately stable. Analysis of the combined datasets from Experiments 1 and 2 showed both SOARS scores were significantly related to the derived factors of Woody, Barnier, and McConkey's (2005) 4-factor model of hypnotisability. This scale clarifies conceptual confusion around agentive action and provides empirical support for a multifactorial account of sense of agency.

Multicomponent Theories of Hypnotizability: History and Prospects.

This review addresses multicomponent theories of hypnotizability by focusing on 3 important exemplars from the history of hypnosis research: E. R. Hilgard's (1965) Hypnotic susceptibility; R. E. Shor's (1962) Three dimensions of hypnotic depth; and T.X. Barber's (1999) A comprehensive three-dimensional theory of hypnosis. Taken together, they illustrate the variety of hypnotic phenomena examined in research - overt responses, subjective experiences, and underlying processes - and the ways in which evidence about each has implied the existence of multiple underlying components. Particularly highlighted are the different ways in which the theories conceptualize the joint contribution of multiple individual differences. Also covered is relevant later work by other researchers as well as important issues remaining to be resolved.

Interpersonal interactions on online forums addressing eating concerns.

OBJECTIVE: Although some research suggests that online eating disorder forums promote "pro-eating-disorder" lifestyles and discourage recovery, other research suggests that such forums are an important source of interpersonal support. The current study extends this research by exploring the positive and negative behaviors encouraged on these forums and by comparing forum members' perceptions of support received from online and offline relationships to support received in relationships of age-matched controls. METHOD: In a survey of 60 forum members, we assessed information exchanged and support provided on eating disorder forums. Further, we assessed perceptions of social support for general and specific life concerns in this group of forum members as well as 64 age-matched university controls. RESULTS: Results show that both adaptive and maladaptive behaviors are encouraged on the forums, and that this encouragement has some influence on forum members trying out these behaviors. Overall, forum members reported receiving less support for their eating concerns as compared to their general life stressors, and they perceived less support for both their general concerns and eating concerns in their offline relationships as compared to their online forum relationships. Moreover, forum members reported receiving less support from their offline relationships as compared to support received in relationships by age-matched controls. DISCUSSION: Forum members perceive less support in their important relationships than other peers do, and they seek out and participate in forums as a means of attaining greater social support. However, our research suggests that these forums also encourage dysregulated eating behaviors. Implications of online forum support and its impact on recovery are discussed further.

Obsessive compulsive disorder (OCD): Current treatments and a framework for neurotherapeutic research.

We briefly review current approaches to the diagnosis and treatment of OCD, noting their lack of a strong theoretical foundation. In keeping with the Research Domain Criteria project (RDoC) calls for reconceptualizing psychopathology in ways that better link up with normal brain systems, we advance an adaptationist, brain-network perspective on OCD and propose that OCD represents a dysfunction in the stopping dynamics of a normal brain network that evolved to handle potential danger. We then illustrate how this theoretical perspective can be used to organize possibilities for research on neurotherapeutics for OCD and suggest novel directions for future work.

Expect the unexpected: ability, attitude, and responsiveness to hypnosis.

Participants' expectancies and hypnotic performance throughout the course of a standardized, individually administered hypnotic protocol were analyzed with a structural equation model that integrated underlying ability, expectancy, and hypnotic response. The model examined expectancies and ability as simultaneous predictors of hypnotic responses as well as hypnotic responses as an influence on subsequent expectancies. Results of the proposed model, which fit very well, supported each of the 4 major hypothesized effects: Expectancies showed significant stability across the course of the hypnosis protocol; expectancies influenced subsequent hypnotic responses, controlling for latent ability; hypnotic responses, in turn, affected subsequent expectancies; and a latent trait underlay hypnotic responses, controlling for expectancies. Although expectancies had a significant effect on hypnotic responsiveness, there was an abundance of variance in hypnotic performance unexplained by the direct or indirect influence of expectation and compatible with the presence of an underlying cognitive ability.

Does the more vivid imagery of high hypnotizables depend on greater cognitive effort? A test of dissociation and social-cognitive theories of hypnosis.

In an investigation of the role of cognitive effort in hypnotic responding, high and low hypnotizable participants produced emotionally neutral imagery in response to effortful versus effortless hypnotic suggestions. Heart-rate increase served as an objective index of cognitive effort, and subjective ratings of imagery vividness, absorption, effort, and control were collected. Compared to lows, high hypnotizable participants experienced their imagery as more vivid and absorbing, yet their heart rates indicated no higher level of cognitive effort than lows. Compared to effortless wording, effortful wording of suggestions increased cognitive effort in lows, as indexed by heart-rate increase, but had no effect on the effort expended by highs. Ratings of subjective control were strongly correlated with subjective effort for lows but unrelated for highs. These results support the dissociated-control theory of hypnosis rather than the dissociated-experience or social-cognitive theories.

The longitudinal association of relationship satisfaction and sexual satisfaction in long-term relationships.

Several prominent models of relationship satisfaction and sexual satisfaction imply directional relationships between these constructs (e.g., attachment theory, social exchange models of relationship satisfaction, the interpersonal exchange model of sexual satisfaction). Previous research has demonstrated that sexual satisfaction and relationship satisfaction are distinct but correlated constructs, but relatively few studies have examined how they are related over time. Thus, the purpose of this study was to examine this association. A sample of heterosexual couples (N = 113) completed a longitudinal study spanning 2 years. At Times 1 and 2 they completed measures of relationship satisfaction and sexual satisfaction. Data were analyzed according to the principles of the actor-partner interdependence model using structural equation modeling. Significant actor effects were detected such that, for both men and women, one's own earlier sexual satisfaction predicted one's later relationship satisfaction. In contrast, one's own earlier relationship satisfaction did not significantly predict one's subsequent sexual satisfaction. Sexual satisfaction was a stronger predictor of subsequent relationship satisfaction for men than women. There were no significant partner effects. These results contribute to our theoretical understanding of sexuality and sexual satisfaction in the context of long-term relationships by providing support for theories that conceptualize sexual satisfaction as one factor that contributes to relationship satisfaction. (PsycINFO Database Record

Induction of compulsive-like washing by blocking the feeling of knowing: an experimental test of the security-motivation hypothesis of obsessive-compulsive disorder.

BACKGROUND: H. Szechtman and E. Woody (2004) hypothesized that obsessive-compulsive disorder results from a deficit in the feeling of knowing that normally terminates thoughts or actions elicited by security motivation. To test the plausibility of this proposed mechanism, an experiment was conducted to produce an analog of washing in obsessive-compulsive disorder by eliciting a scenario of potential harm and using hypnosis to block changes in internally generated feelings that would normally occur during washing. RESULTS: Participants reacted with increased disgust, anxiety, and heart rate to their mental images of contamination and potential danger. As predicted, high but not low hypnotizable participants showed a significant prolongation of washing when change in feelings during washing was blocked hypnotically. CONCLUSION: Results show that blocking the affective signal that is normally generated during security-related behaviors, such as washing, leads to prolonged performance of these behaviors. This finding lends support to the plausibility of the proposed model of obsessive-compulsive disorder.

Multiple hypnotizabilities: differentiating the building blocks of hypnotic response.

Although hypnotizability can be conceptualized as involving component subskills, standard measures do not differentiate them from a more general unitary trait, partly because the measures include limited sets of dichotomous items. To overcome this, the authors applied full-information factor analysis, a sophisticated analytic approach for dichotomous items, to a large data set from 2 hypnotizability scales. This analysis yielded 4 subscales (Direct Motor, Motor Challenge, Perceptual-Cognitive, Posthypnotic Amnesia) that point to the building blocks of hypnotic response. The authors then used the subscales as simultaneous predictors of hypnotic responses in 4 experiments to distinguish the contribution of each component from general hypnotizability. This analysis raises interesting questions about how best to conceptualize and advance measurement of the ability to experience hypnosis.

In the wake of a possible mistake: Security motivation, checking behavior, and OCD.

BACKGROUND AND OBJECTIVES: In previous experiments, OCD washers did not differ significantly from controls in their initial level of activation in response to the potential threat of contamination; however, they were less able to reduce their activation by engaging in hand-washing, suggesting that the key problem in OCD is a faulty stopping mechanism. The main objectives of the present experiments were to develop a similar experimental paradigm for investigating checking behavior, and to use it to test the hypothesis that a faulty stopping mechanism also underlies OCD checking. METHODS: Participants sorted pills under the guise of beta testing a new medication system and then were given suggestions of the possibility of having made mistakes with potentially serious consequences. Later, participants engaged in a 90-s checking period and an unlimited period of checking. At baseline and three other times during the experiment, security motivation was measured with respiratory sinus arrhythmia (RSA) and subjective ratings of confidence. Experiment 1 established the parameters of the paradigm in non-patient participants, and Experiment 2 contrasted OCD checkers with OCD washers and non-patients. RESULTS: Results for both subjective and physiological measures of security motivation closely replicated previous findings for washing behavior. Groups did not differ significantly in initial activation, but the OCD checkers were unable to reduce their activation by engaging in period of checking that was ample for returning controls to baseline. LIMITATIONS: The sample size for the patient groups was modest. CONCLUSIONS: These results lend further support to the security-motivation theory of OCD.

Frontal EEG alpha activity and obsessive-compulsive behaviors in non-clinical young adults: a pilot study.

Previous studies have shown that the resting electroencephalogram (EEG) alpha patterns of non-clinical participants who score high on measures of negative affect, such as depression and shyness, are different from those who score low. However, we know relatively little about patterns of resting EEG alpha patterns in a non-clinical sample of individuals with high levels of obsessive-compulsive behaviors indicative of obsessive-compulsive disorder (OCD). Here we measured resting EEG alpha activity in frontal and parietal regions of non-clinical participants who scored high and low on the Padua-R, a measure of the severity of OCD-related behaviors. We found that participants who scored high on the Padua-R exhibited decreased overall activity in frontal regions relative to individuals who scored low on the measure. We speculate that frontal hypoactivity may be a possible marker and/or index of risk for OCD.

Hypnosis, memory, and frontal executive functioning.

According to the dissociated-control hypothesis forwarded by Woody and Bowers (1994), the effects of hypnosis are consistent with attenuated frontal lobe functioning. The present study was designed to compare the performance of participants with high and low hypnotic ability on a variety of memory tasks thought to be sensitive to frontal lobe functioning, as well as some control memory tasks not considered to be sensitive to such functioning. Results generally indicated that participants with high hypnotic ability have more difficulty with tasks sensitive to frontal lobe functioning, including free recall, proactive interference, and source amnesia tasks, both within and outside of the context of hypnosis. These differences, which were not found for nonfrontal tasks, are generally supportive of the dissociated control theory of hypnotic responding.

How can brain activity and hypnosis inform each other?

Applying P. Teitelbaum's conception of the method of physiological psychology as interlocking stages of analysis and synthesis, the authors examine how studies of brain function can advance the understanding of hypnosis as a psychological process. They consider the exploration of animal analogues of human hypnosis, the study of brain injury in humans as a window on mechanisms underlying hypnosis, the distinct questions that brain-imaging studies of hypnosis can address, and the potential for comparative and developmental approaches to hypnosis as close allies to psychophysiological approaches. They conclude both that hypnosis is a powerful technique for studying the brain mechanisms of conscious experience and that underlying brain mechanisms may shed new light on longstanding theoretical debates about hypnosis.

What we don't know about the brain and hypnosis, but need to: a view from the Buckhorn Inn.

Based on reflections on the University of Tennessee Conference on Brain Imaging and Hypnosis, the authors point the field of hypnosis toward a new generation of research that can successfully coordinate multiple methods of inquiry and effectively connect psychological with biological understanding. They examine issues concerning hypnosis as a state, hypnotic susceptibility as a trait, and the psychological processes that underlie hypnotic responses. The article indicates ways in which some old questions can, and need to, be asked in new ways. The authors illustrate how to move toward a neuropsychological understanding of hypnosis by describing the classic suggestion effect and consider candidate psychological mechanisms to explain this effect. They argue that the neuroscience of hypnosis needs to build on a sound psychological foundation and add to, rather than replace, existing levels of analysis.

Four decades of group hypnosis scales: what does item-response theory tell us about what we've been measuring?

To overcome problems with previous psychometric approaches to hypnosis scales, the authors applied full-information factor analysis, based on multidimensional item-response theory (IRT), to a 39-year sample of 11,517 records of the Harvard Group Scale of Hypnotic Susceptibility, Form A (HGSHS:A). They also performed a comparable analysis on the standardization sample of the Waterloo-Stanford Group C Scale (WSGC). The HGSHS:A emerges as two-factored, whereas the WSGC more closely approaches unidimensionality. The HGSHS:A factor structure and means show very little change over 4 decades. However, IRT-based item analysis on the HGSHS:A indicates that problems such as "pseudoguessing" on 2 items limit the quality of the item set. The authors propose alternative substantive interpretations of the traits that may underlie the two-factor structure.

A biological security motivation system for potential threats: are there implications for policy-making?

Research indicates that there is a specially adapted, hard-wired brain circuit, the security motivation system, which evolved to manage potential threats, such as the possibility of contamination or predation. The existence of this system may have important implications for policy-making related to security. The system is sensitive to partial, uncertain cues of potential danger, detection of which activates a persistent, potent motivational state of wariness or anxiety. This state motivates behaviors to probe the potential danger, such as checking, and to correct for it, such as washing. Engagement in these behaviors serves as the terminating feedback for the activation of the system. Because security motivation theory makes predictions about what kinds of stimuli activate security motivation and what conditions terminate it, the theory may have applications both in understanding how policy-makers can best influence others, such as the public, and also in understanding the behavior of policy-makers themselves.

When too much is not enough: obsessive-compulsive disorder as a pathology of stopping, rather than starting.

BACKGROUND: In obsessive-compulsive disorder (OCD), individuals feel compelled to repeatedly perform security-related behaviors, even though these behaviours seem excessive and unwarranted to them. The present research investigated two alternative ways of explaining such behavior: (1) a dysfunction of activation--a starting problem--in which the level of excitation in response to stimuli suggesting potential danger is abnormally strong; versus (2) a dysfunction of termination--a stopping problem--in which the satiety-like process for shutting down security-related thoughts and actions is abnormally weak. METHOD: In two experiments, 70 patients with OCD (57 with washing compulsions, 13 with checking compulsions) and 72 controls were exposed to contamination cues--immersing a hand in wet diapers--and later allowed to wash their hands, first limited to 30 s and then for as long as desired. The intensity of activation of security motivation was measured objectively by change in respiratory sinus arrythmia. Subjective ratings (e.g., contamination) and behavioral measures (e.g., duration of hand washing) were also collected. RESULTS: Compared to controls, OCD patients with washing compulsions did not differ significantly in their levels of initial activation to the threat of contamination; however, they were significantly less able to reduce this activation by engaging in the corrective behavior of hand-washing. Further, the deactivating effect of hand-washing in OCD patients with checking compulsions was similar to that for controls, indicating that the dysfunction of termination in OCD is specific to the patient's symptom profile. CONCLUSIONS: These results are the first to show that OCD is characterized by a reduced ability of security-related behavior to terminate motivation evoked by potential danger, rather than a heightened initial sensitivity to potential threat. They lend support to the security-motivation theory of OCD (Szechtman & Woody, 2004) and have important implications both for research into the biological mechanisms underlying OCD and for the development of new treatment approaches.

Adaptation to potential threat: the evolution, neurobiology, and psychopathology of the security motivation system.

The risk of improbable, uncertain, but grave potential dangers poses unique adaptive challenges. We argue that to manage such risks, a special motivational system evolved, which we term the security motivation system. Review of work across a range of species indicates that this system is designed to detect subtle indicators of potential threat, to probe the environment for further information about these possible dangers, and to motivate engagement in precautionary behaviors, which also serves to terminate security motivation. We advance a neurobiological-circuit model of the security motivation system, which consists of a cascade of cortico-striato-pallido-thalamo-cortical loops with brainstem-mediated negative feedback. We also detail the broader physiological network involved, including regulation of the parasympathetic nervous system, with emphasis on vagal regulation of cardiac output, and activation of the hypothalamic-pituitary-adrenocortical axis. Finally, we propose that some kinds of psychopathology stem from dysfunction of the security motivation system. In particular, obsessive compulsive disorder may result from the failure of a mechanism by which engagement in precautionary behavior normally terminates activation of the system.

Motion in response to the hypnotic suggestion of arm rigidity: a window on underlying mechanisms.

Among hypnotized subjects passing a challenge suggestion of arm rigidity, how might patterns of motor activity (strategies) contribute to the illusion that the elbow cannot be bent? Kinematic analyses of upper limb and trunk were performed. Nonhypnotized subjects carefully enacted a set of prescribed strategies typifying responses possibly adopted by a hypnotized subject. Profile analysis showed striking heterogeneity of response in hypnotic subjects. Half of participants showed no perceivable strategy consistent with the hypothesis that subjects hallucinate the suggestion and so do not engage the motor periphery. Equally common were subtle oscillations or trembling of the arm implying that motion resembling difficulty in bending was initiated. This can be misperceived as unintentional and thus evidence of inability to bend. The lack of a motor strategy is more consistent with dissociated-control theory, whereas the trembling response is more consistent with social-cognitive and dissociated-experience theories.