Serotonin reuptake inhibitors (SRIs), the first-line pharmacological treatment for obsessive-compulsive disorder (OCD), have two limitations: incomplete symptom relief and 2-3 months lag time before clinically meaningful improvement. New medications with faster onset are needed. As converging evidence suggests a role for the glutamate system in the pathophysiology of OCD, we tested whether a single dose of ketamine, a non-competitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, could achieve rapid antiobsessional effects. In a randomized, double-blind, placebo-controlled, crossover design, drug-free OCD adults (n ¼ 15) with nearconstant obsessions received two 40-min intravenous infusions, one of saline and one of ketamine (0.5 mg/kg), spaced at least 1-week apart. The OCD visual analog scale (OCD-VAS) and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) were used to assess OCD symptoms. Unexpectedly, ketamine's effects within the crossover design showed significant (po0.005) carryover effects (ie, lasting longer than 1 week). As a result, only the first-phase data were used in additional analyses. Specifically, those receiving ketamine (n ¼ 8) reported significant improvement in obsessions (measured by OCD-VAS) during the infusion compared with subjects receiving placebo (n ¼ 7). One-week post-infusion, 50% of those receiving ketamine (n ¼ 8) met criteria for treatment response (X35% Y-BOCS reduction) vs 0% of those receiving placebo (n ¼ 7). Rapid anti-OCD effects from a single intravenous dose of ketamine can persist for at least 1 week in some OCD patients with constant intrusive thoughts. This is the first randomized, controlled trial to demonstrate that a drug affecting glutamate neurotransmission can reduce OCD symptoms without the presence of an SRI and is consistent with a glutamatergic hypothesis of OCD.

The ability to differentiate between rewards and losses is critical for motivated action, and aberrant reward and loss processing has been associated with psychopathology. The reward positivity (RewP) and feedback negativity (FN) are ERPs elicited by monetary gains and losses, respectively, and are promising individual difference measures. However, few studies have reported on the psychometric properties of the RewP and FN-crucial characteristics necessary for valid individual difference measures. The current study examined the internal consistency and 1-week test-retest reliability of the RewP and FN as elicited by the doors task among 59 young adults. The RewP, FN, and their difference score (ΔRewP) all showed significant correlations between Time 1 and Time 2. The RewP and FN also achieved acceptable internal consistency at both time points within 20 trials using both Cronbach's α and a generalizability theory-derived dependability measure. Internal consistency for ΔRewP was notably weaker at both time points, which is expected from two highly intercorrelated constituent scores. In conclusion, the RewP and FN have strong psychometric properties in a healthy adult sample. Future research is needed to assess the psychometric properties of these ERPs in different age cohorts and in clinical populations.

Affective science research on reward processing has primarily focused on monetary rewards. There has been a growing interest in evaluating the neural basis of social decision-making and reward processing. The present study employed a within-subject design and compared the reward positivity (RewP), an event-related potential component that is present following favorable feedback and absent or reduced following unfavorable feedback, during monetary and social reward tasks. Specifically, 114 participants (75 females) completed a monetary reward task and a novel social reward task that were matched on trial structure, timing, and feedback stimuli in a counterbalanced order. Results indicated that the monetary and social RewP were of similar magnitude, positively correlated and demonstrated comparable psychometric properties, including reliability and dependability. Across both the monetary and social tasks, women demonstrated a greater RewP compared with men. This study provides a novel methodological approach toward examining the electrocortical response to social reward that is comparable to monetary reward.

Theories of cognitive control argue that response conflict in speeded performance tasks leads to adaptive changes, such that irrelevant information is better ignored on subsequent trials. This study tested whether trial-by-trial changes are driven primarily by conflict on incongruent trials or instead by congruent trials, in which irrelevant and relevant stimulus dimensions match. In a Stroop task including congruent, incongruent, and neutral trials, interference was greater following congruent compared to incongruent and neutral trials, which did not differ. During the intertrial interval, EEG alpha power, an inverse measure of cerebral activation, was significantly lower following congruent than neutral trials, whereas incongruent and neutral trials did not differ. These results imply that trial-by-trial changes in performance may not be driven solely by conflict, but rather by changes in attention triggered by congruent information.

We previously reported the rapid and robust clinical effects of ketamine versus saline infusions in a proof-of-concept crossover trial in unmedicated adults with obsessive-compulsive disorder (OCD). This study examined the concurrent neurochemical effects of ketamine versus saline infusions using proton magnetic resonance spectroscopy (1H MRS) during the clinical proof-of-concept crossover trial. Levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and the excitatory neurochemicals glutamate+glutamine (Glx) were acquired in the medial prefrontal cortex (MPFC), a region implicated in OCD pathology. Seventeen unmedicated OCD adults received two intravenous infusions at least 1 week apart, one of saline and one of ketamine, while lying supine in a 3.0 T GE MR scanner. The order of each infusion pair was randomized. Levels of GABA and Glx were measured in the MPFC before, during, and after each infusion and normalized to water (W). A mixed effects model found that MPFC GABA/W significantly increased over time in the ketamine compared with the saline infusion. In contrast, there were no significant differences in Glx/W between the ketamine and saline infusions. Together with earlier evidence of low cortical GABA in OCD, our findings suggest that models of OCD pathology should consider the role of GABAergic abnormalities in OCD symptomatology.