Effects of gonadal steroids on reward circuitry function and anhedonia in women with a history of postpartum depression.

BACKGROUND: Reward system dysfunction is evident across neuropsychiatric conditions. Here we present data from a double-blinded pharmaco-fMRI study investigating the triggering of anhedonia and reward circuit activity in women. METHODS: The hormonal states of pregnancy and parturition were simulated in euthymic women with a history of postpartum depression (PPD+; n = 15) and those without such a history (PPD-; n = 15) by inducing hypogonadism, adding back estradiol and progesterone for 8 weeks ("addback"), and then withdrawing both steroids ("withdrawal"). Anhedonia was assessed using the Inventory of Depression and Anxiety Symptoms (IDAS) during each hormone phase. Those who reported a 30 % or greater increase in IDAS anhedonia, dysphoria, or ill temper during addback or withdrawal, compared with pre-treatment, were identified as hormone sensitive (HS+) and all others were identified as non-hormone sensitive (HS-). The monetary incentive delay (MID) task was administered during fMRI sessions at pre-treatment and during hormone withdrawal to assess brain activation during reward anticipation and feedback. RESULTS: On average, anhedonia increased during addback and withdrawal in PPD+ but not PPD-. During reward feedback, both HS+ (n = 10) and HS- (n = 18) showed decreased activation in clusters in the right putamen (p < .031, FWE-corrected) and left postcentral and supramarginal gyri (p < .014, FWE-corrected) at the withdrawal scans, relative to pre-treatment scans. LIMITATIONS: A modest sample size, stringent exclusion criteria, and relative lack of diversity in study participants limit the generalizability of results. CONCLUSION: Although results do not explain differential hormone sensitivity in depression, they demonstrate significant effects of reproductive hormones on reward-related brain function in women.

The effects of intranasal oxytocin on reward circuitry responses in children with autism spectrum disorder.

BACKGROUND: Intranasal oxytocin (OT) has been shown to improve social communication functioning of individuals with autism spectrum disorder (ASD) and, thus, has received considerable interest as a potential ASD therapeutic agent. Although preclinical research indicates that OT modulates the functional output of the mesocorticolimbic dopamine system that processes rewards, no clinical brain imaging study to date has examined the effects of OT on this system using a reward processing paradigm. To address this, we used an incentive delay task to examine the effects of a single dose of intranasal OT, versus placebo (PLC), on neural responses to social and nonsocial rewards in children with ASD. METHODS: In this placebo-controlled double-blind study, 28 children and adolescents with ASD (age: M = 13.43 years, SD = 2.36) completed two fMRI scans, one after intranasal OT administration and one after PLC administration. During both scanning sessions, participants completed social and nonsocial incentive delay tasks. Task-based neural activation and connectivity were examined to assess the impact of OT relative to PLC on mesocorticolimbic brain responses to social and nonsocial reward anticipation and outcomes. RESULTS: Central analyses compared the OT and PLC conditions. During nonsocial reward anticipation, there was greater activation in the right nucleus accumbens (NAcc), left anterior cingulate cortex (ACC), bilateral orbital frontal cortex (OFC), left superior frontal cortex, and right frontal pole (FP) during the OT condition relative to PLC. Alternatively, during social reward anticipation and outcomes, there were no significant increases in brain activation during the OT condition relative to PLC. A Treatment Group × Reward Condition interaction revealed relatively greater activation in the right NAcc, right caudate nucleus, left ACC, and right OFC during nonsocial relative to social reward anticipation during the OT condition relative to PLC. Additionally, these analyses revealed greater activation during nonsocial reward outcomes during the OT condition relative to PLC in the right OFC and left FP. Finally, functional connectivity analyses generally revealed changes in frontostriatal connections during the OT condition relative to PLC in response to nonsocial, but not social, rewards. CONCLUSIONS: The effects of intranasal OT administration on mesocorticolimbic brain systems that process rewards in ASD were observable primarily during the processing of nonsocial incentive salience stimuli. These findings have implications for understanding the effects of OT on neural systems that process rewards, as well as for experimental trials of novel ASD treatments developed to ameliorate social communication impairments in ASD.

Quantitative EEG during seizures induced by electroconvulsive therapy: relations to treatment modality and clinical features. I. Global analyses.

This study examined the effects of electroconvulsive therapy (ECT) treatment conditions, patient individual difference factors, and clinical outcome on global electroencephalogram (EEG) power during and immediately following ECT-induced seizures. Sixty-two patients were randomized to ECT conditions differing in electrode placement (right unilateral versus bilateral) and stimulus dosage (just above seizure threshold versus 2.5 times seizure threshold). At the second and penultimate treatments, global total power (1.5-28.5 Hz) and global power in specific frequency bands were quantified in 19-lead EEG recordings of the generalized seizure and the immediate postictal period. Seizures induced with high dosage, and to lesser extent, with bilateral electrode placement, resulted in greater global power. Patient age, initial seizure threshold, and baseline depression severity were inversely related to global power during seizures. While superior clinical outcome following ECT was associated with greater global power during seizures, this effect was small. The factors associated with more robust seizure expression also resulted in greater postictal bioelectric suppression. Associations with treatment parameters and patient variables were stronger at the second than penultimate treatment. We conclude that manipulations of ECT technique strongly determine the magnitude of seizure expression, but relations with clinical outcome are weak. The findings raise doubt about the clinical utility of algorithms based on analysis of EEG features to guide ECT parameter selection.

Quantitative EEG during seizures induced by electroconvulsive therapy: relations to treatment modality and clinical features. II. Topographic analyses.

This study tested three alternative theories of the mechanisms of therapeutic action of electroconvulsive therapy (ECT). The theories differed in predictions about the global and topographic effects of effective and ineffective forms of ECT on electroencephalogram (EEG) seizure expression. At the second treatment, 19-lead EEG recordings were obtained in 57 depressed patients randomized to conditions that differed in ECT electrode placement and stimulus dosage. Power in the delta frequency band was quantified during the seizure and analyzed with traditional multivariate methods and the Scaled Subprofile Model. Electrical dosage of the ECT stimulus had a powerful effect on ictal global delta power and, more so, than electrode placement. Greater ictal global delta power was associated with superior therapeutic outcome, but the magnitude of this effect was small. Effective forms of ECT resulted in a topography where delta power was accentuated in prefrontal EEG sites. High dosage right unilateral ECT also resulted in stronger asymmetry in prefrontal regions than the ineffective, low dosage right unilateral ECT. Greater bilateral generalization of seizure expression does not appear to be a prerequisite for therapeutic effects. Instead, more intense seizure expression in prefrontal regions may be critical for efficacy.

Elevated plus-maze behavior in adult offspring of selectively bred rats.

Animals sampled from the third generation (S3) of selective breeding of N:NIH strain rats based on ultrasonic vocalization (USV) rates in infancy (High, Low, and Random lines) were tested as adults on the elevated plus maze, a well-validated test of anxiety. Results showed that the Low line spent a greater percent of time in the open arms of the maze than High and Random (control) line animals, and a lower percent of time exploring from a relatively more protected position. There were no significant sex differences. The present study represents a probe into the processes at work during the early stages of selection for infant USV, and suggests that an adult measure of anxiety may be affected by selection for this infantile behavior.