Neural and behavioral correlates of negative self-focused thought associated with depression.

A central feature of major depression (MDD) is heightened negative self-focused thought (negative-SFT). Neuroscientific research has identified abnormalities in a network of brain regions in MDD, including brain areas associated with SFT such as medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). To our knowledge no studies have investigated the behavioral and neural correlates of negative-SFT using a sentence completion task in a sample of individuals with varying depression histories and severities. We test the following hypotheses: (1) negative-SFT will be associated with depression; and (2) depression and negative-SFT will be related to resting-state functional connectivity (rsFC) for brain regions implicated in SFT. Seventy-nine women with varying depression histories and severities completed a sentence completion task and underwent resting-state functional magnetic resonance imaging (rs-fMRI). Standard seed-based voxelwise rsFC was conducted for self-network regions of interest: dorsomedial PFC (dmPFC) and pregenual ACC (pgACC). We performed linear regression analyses to examine the relationships among depression, negative-SFT, and rsFC for the dmPFC and pgACC. Greater negative-SFT was associated with depression history and severity. Greater negative-SFT predicted increased rsFC between dmPFC and pgACC seeds and dorsolateral prefrontal (dlPFC) and parietal regions; depression group was also associated with increased pgACC-dlPFC connectivity. These findings are consistent with previous literature reporting elevated negative-SFT thought in MDD. Our rs-fMRI results provide novel support linking negative-SFT with increased rsFC between self-network and frontoparietal network regions across different levels of depression. Broadly, these findings highlight a dimension of social-affective functioning that may underlie MDD and other psychiatric conditions.

Relations between trait impulsivity, behavioral impulsivity, physiological arousal, and risky sexual behavior among young men.

The current study examined how impulsivity-related traits (negative urgency, sensation seeking, and positive urgency), behavioral measures of risk taking and reward seeking, and physiological reactivity related to three different risky sexual behaviors in sexually active undergraduate men (N = 135). Regression analyses indicated that sensation seeking and behavioral risk-taking predicted unique variance in number of sexual partners. These findings suggest that, for young men, acquisition of new partners is associated with need for excitement and reward and willingness to take risks to meet those needs. Sensation seeking, behavioral risk-taking, and skin conductance reactivity to arousing stimuli was related to ever having engaged in sex with a stranger, indicating that, for men, willingness to have sex with a stranger is related not only to the need for excitement and risk-taking but also with innate responsiveness to arousing environmental triggers. In contrast, regression analyses indicated that young men who were impulsive in the context of negative emotions were less likely to use condoms, suggesting that emotion-based impulsivity may be an important factor in negligent prophylactic use. This study adds to the current understanding of the divergence between the correlates of risky sexual behaviors and may lend utility to the development of individualized HIV prevention programming.

Effects of Cortisol Administration on Resting-State Functional Connectivity in Women with Depression.

Previous resting-state functional connectivity (rsFC) research has identified several brain networks impacted by depression and cortisol, including default mode (DMN), frontoparietal (FPN), and salience networks (SN). In the present study, we examined the effects of cortisol administration on rsFC of these networks in individuals varying in depression history and severity. We collected resting-state fMRI scans and self-reported depression symptom severity for 74 women with and without a history of depression after cortisol and placebo administration using a double-blind, crossover design. We conducted seed-based rsFC analyses for DMN, FPN, and SN seeds to examine rsFC changes after cortisol vs. placebo administration in relation to depression history group and severity. Results revealed a main effect of depression group, with lower left amygdala (SN)-middle temporal gyrus connectivity in women with a history of depression. Cortisol administration increased insula (SN)-inferior frontal gyrus and superior temporal gyrus connectivity. We also found that greater depression severity was associated with increased PCC (DMN)-cerebellum connectivity after cortisol. These results did not survive Bonferroni correction for seed ROIs and should be interpreted with caution. Our findings indicate that acute cortisol elevation may normalize aberrant connectivity of DMN and SN regions, which could help inform clinical treatments for depression.

Effects of cortisol administration on heart rate variability and functional connectivity across women with different depression histories.

Abnormalities within the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system have been implicated in depression. Studies have reported glucocorticoid insensitivity and reduced heart rate variability (HRV) in depressive disorders. However, little is known about the effects of cortisol on HRV and resting-state functional connectivity (rsFC) of the central autonomic network (CAN) in depression. We collected resting-state fMRI and cardiac data for women with different depression histories (n = 61) after administration of cortisol and placebo using a double-blind crossover design. We computed rsFC for R-amygdala and L-amygdala seeds and assessed the change in HRV after cortisol (cortisol-placebo). Analyses examined the effects of acute cortisol administration on HRV and rsFC of the R-amygdala and L-amygdala. There was a significant interaction between HRV and treatment for rsFC between the amygdala and CAN regions. We found lower rsFC between the L-amygdala and putamen for those with a greater decrease in HRV after cortisol. There was also reduced rsFC between the R-amygdala and dorsomedial prefrontal cortex, putamen, middle cingulate cortex, insula, and cerebellum in those with lower HRV after cortisol. These results remained significant after adjusting for depression symptoms, age, and race. Our findings suggest that the effect of cortisol on CAN connectivity is related to its effects on HRV. Overall, these results could inform transdiagnostic interventions targeting HRV and the stress response systems across clinical and non-clinical populations.

The effects of psychotherapy for anhedonia on subcortical brain volumes measured with ultra-high field MRI.

BACKGROUND: Anhedonia is a transdiagnostic symptom often resistant to treatment. The identification of biomarkers sensitive to anhedonia treatment will aid in the evaluation of novel anhedonia interventions. METHODS: This is an exploratory analysis of changes in subcortical brain volumes accompanying psychotherapy in a transdiagnostic anhedonic sample using ultra-high field (7-Tesla) MRI. Outpatients with clinically impairing anhedonia (n = 116) received Behavioral Activation Treatment for Anhedonia, a novel psychotherapy, or Mindfulness-Based Cognitive Therapy (ClinicalTrials.gov Identifiers NCT02874534 and NCT04036136). Subcortical brain volumes were estimated via the MultisegPipeline, and regions of interest were the amygdala, caudate nucleus, hippocampus, pallidum, putamen, and thalamus. Bivariate mixed effects models estimated pre-treatment relations between anhedonia severity and subcortical brain volumes, change over time in subcortical brain volumes, and associations between changes in subcortical brain volumes and changes in anhedonia symptoms. RESULTS: As reported previously (Cernasov et al., 2023), both forms of psychotherapy resulted in equivalent and significant reductions in anhedonia symptoms. Pre-treatment anhedonia severity and subcortical brain volumes were not related. No changes in subcortical brain volumes were observed over the course of treatment. Additionally, no relations were observed between changes in subcortical brain volumes and changes in anhedonia severity over the course of treatment. LIMITATIONS: This trial included a modest sample size and did not have a waitlist-control condition or a non-anhedonic comparison group. CONCLUSIONS: In this exploratory analysis, psychotherapy for anhedonia was not accompanied by changes in subcortical brain volumes, suggesting that subcortical brain volumes may not be a candidate biomarker sensitive to response to psychotherapy.

Perimenopausal Effects of Estradiol on Anhedonia and Psychosis Study (PEEPs): study protocol for a neural and molecular mechanistic clinical trial.

BACKGROUND: The perimenopausal transition is accompanied by psychiatric symptoms in over 10% of women. Symptoms commonly include depressed mood and anhedonia and less commonly include psychosis. Psychiatric symptoms have been linked to the depletion and/or variability of circulating estradiol, and estradiol treatment reduces perimenopausal anhedonia and psychosis in some women. Estrogen fluctuations may disrupt function in the mesolimbic reward system in some women, leading to psychiatric symptoms like anhedonia or psychosis. The Perimenopausal Effects of Estradiol on Anhedonia and Psychosis Study (PEEPs) is a mechanistic clinical trial that aims to (1) identify relationships between perimenopausal-onset anhedonia and psychosis and neuromolecular markers of mesolimbic reward responses and (2) determine the extent to which estradiol treatment-induced changes in mesolimbic reward responses are associated with alleviation of perimenopausal onset anhedonia or psychosis. METHODS: This study will recruit 100 unmedicated women ages 44-55 in the late-stage perimenopausal transition, sampling across the range of mild-to-high anhedonia and absent-to-moderate psychosis symptoms. Patients will be randomized to receive either estradiol or placebo treatment for 3 weeks. Clinical outcome measures will include symptoms of anhedonia (measured with Snaith-Hamilton Pleasure Scale; SHAPS) and psychosis (measured with Brief Psychiatric Rating Scale; BPRS psychosis subscale) as well as neural markers of mesolimbic reward system functioning, including reward-related fMRI activation and PET-derived measure of striatal dopamine binding. Pre-treatment associations between (1) SHAPS/BPRS scores and (2) reward-related striatal dopamine binding/BOLD activation will be examined. Furthermore, longitudinal mixed models will be used to estimate (1) symptom and neuromolecular trajectories as a function of estradiol vs. placebo treatment and (2) how changes in reward-related striatal dopamine binding and BOLD activation predict variability in symptom trajectories in response to estradiol treatment. DISCUSSION: This clinical trial will be the first to characterize neural and molecular mechanisms by which estradiol treatment ameliorates anhedonia and psychosis symptoms during the perimenopausal transition, thus laying the groundwork for future biomarker research to predict susceptibility and prognosis and develop targeted treatments for perimenopausal psychiatric symptoms. Furthermore, in alignment with the National Institute for Mental Health Research Domain Criteria initiative, this trial will improve our understanding of a range of disorders characterized by anhedonia, psychosis, and reward system dysfunction. TRIAL REGISTRATION: ClinicalTrials.gov NCT05282277.

Striatal dopamine in anhedonia: A simultaneous [11C]raclopride positron emission tomography and functional magnetic resonance imaging investigation.

BACKGROUND: Anhedonia is hypothesized to be associated with blunted mesocorticolimbic dopamine (DA) functioning in samples with major depressive disorder. The purpose of this study was to examine linkages between striatal DA, reward circuitry functioning, anhedonia, and, in an exploratory fashion, self-reported stress, in a transdiagnostic anhedonic sample. METHODS: Participants with (n = 25) and without (n = 12) clinically impairing anhedonia completed a reward-processing task during simultaneous positron emission tomography and magnetic resonance (PET-MR) imaging with [11C]raclopride, a DA D2/D3 receptor antagonist that selectively binds to striatal DA receptors. RESULTS: Relative to controls, the anhedonia group exhibited decreased task-related DA release in the left putamen, caudate, and nucleus accumbens and right putamen and pallidum. There were no group differences in task-related brain activation (fMRI) during reward processing after correcting for multiple comparisons. General functional connectivity (GFC) findings revealed blunted fMRI connectivity between PET-derived striatal seeds and target regions in the anhedonia group. Associations were identified between anhedonia severity and the magnitude of task-related DA release to rewards in the left putamen, but not mesocorticolimbic GFC. CONCLUSIONS: Results provide evidence for reduced striatal DA functioning during reward processing and blunted mesocorticolimbic network functional connectivity in a transdiagnostic sample with clinically significant anhedonia.

Neural signal variability relates to maladaptive rumination in depression.

Rumination is a common feature of depression and predicts the onset and maintenance of depressive episodes. Maladaptive and adaptive subtypes of rumination contribute to distinct outcomes, with brooding worsening negative mood and reflection related to fewer depression symptoms in healthy populations. Neuroimaging studies have implicated several cortical midline and lateral prefrontal brain regions in rumination. Recent research indicates that blood oxygen level-dependent (BOLD) signal variability may be a novel predictor of cognitive flexibility. However, no prior studies have investigated whether brooding and reflection are associated with distinct patterns of BOLD signal variability in depression. We collected resting-state fMRI data for 79 women with different depression histories: no history, past history, and current depression. We examined differences in BOLD signal variability (BOLDSD) related to rumination subtypes for the following regions of interest previously implicated in rumination: amygdala, medial prefrontal, anterior cingulate, posterior cingulate, and dorsolateral prefrontal cortices (dlPFC). Rumination subtype was associated with BOLDSD in the dlPFC, with greater levels of brooding associated with lower BOLDSD in the dlPFC, even after controlling for depression severity. Depression history was related to BOLDSD in the dlPFC, with reduced BOLDSD in those with current depression versus no history of depression. These findings provide a novel demonstration of the neural circuitry associated with maladaptive rumination in depression and implicate decreased prefrontal neural signal variability in the pathophysiology of depression.

Resting-state neural signal variability in women with depressive disorders.

Aberrant activity and connectivity in default mode (DMN), frontoparietal (FPN), and salience (SN) network regions is well-documented in depression. Recent neuroimaging research suggests that altered variability in the blood oxygen level-dependent (BOLD) signal may disrupt normal network integration and be an important novel predictor of psychopathology. However, no studies have yet determined the relationship between resting-state BOLD signal variability and depressive disorders nor applied BOLD signal variability features to the classification of depression history using machine learning (ML). We collected resting-state fMRI data for 79 women with different depression histories: no history, past history, and current depressive disorder. We tested voxelwise differences in BOLD signal variability related to depression group and severity. We also investigated whether BOLD signal variability of DMN, FPN, and SN regions could predict depression history group using a supervised random forest ML model. Results indicated that individuals with any history of depression had significantly decreased BOLD signal variability in the left and right cerebellum and right parietal cortex (pFWE <0.05). Furthermore, greater depression severity was also associated with reduced BOLD signal variability in the cerebellum. A random forest model classified participant depression history with 74% accuracy, with the ventral anterior cingulate cortex of the DMN as the most important variable in the model. These findings provide novel support for resting-state BOLD signal variability as a marker of neural dysfunction in depression and implicate decreased neural signal variability in the pathophysiology of depression.

Effects of acute estradiol and progesterone on perimenstrual exacerbation of suicidal ideation and related symptoms: a crossover randomized controlled trial.

Female suicide attempts peak peri-menstrually-around the onset of menses-when the ovarian steroids estradiol (E2) and progesterone (P4) fall rapidly. Given preclinical evidence that withdrawal from either E2 or P4 can provoke behaviors consistent with elevated suicide risk, we hypothesized that withdrawal from one or both of these steroids contributes to perimenstrual exacerbation of suicidal ideation (SI) and related symptoms. In a randomized, controlled, double-blind crossover experiment (NCT03720847), a transdiagnostic sample of naturally cycling, medically healthy psychiatric outpatients reporting past-month SI completed two conditions during two different 14-day experimental intervals (days 7-20 where the luteinizing hormone surge = day 0), separated by a monthlong washout cycle. In the E2 and P4 (EP) condition, participants received transdermal E2 (0.1 mg/day) plus oral micronized P4 (200 mg/day as 100 mg twice daily) to buffer perimenstrual steroid withdrawal. A matched placebo (PBO) condition allowed natural perimenstrual steroid withdrawal. Participants reported daily SI and planning (primary outcomes) and indices of depression (low mood, hopelessness), threat sensitivity (anxiety, perceived stress), executive functioning (difficulty concentrating, impulsivity), and social cognitive bias (rejection sensitivity, perceived burdensomeness). In baseline cycles, no participant met prospective criteria for DSM-5 premenstrual dysphoric disorder, but 59% met all criteria except full follicular symptom remission, and 93% showed the highest SI in the perimenstrual phase. Of 29 randomized, 28 were analyzed (14 EP-PBO, 14 PBO-EP). Experimental administration of E2 and P4 (relative to PBO) reduced perimenstrual exacerbation of SI, suicide planning, depression, hopelessness, perceived stress, rejection sensitivity, and perceived burdensomeness, particularly in the perimenstrual (natural E2 and P4 withdrawal) days. Further, delayed withdrawal from experimental E2 and P4 (but not PBO) recapitulated SI, hopelessness, and rejection sensitivity. Acute perimenstrual withdrawal from ovarian steroids may play a causal role in perimenstrual worsening of depression and SI.

Do different facets of impulsivity predict different types of aggression?

This study examined the relations between impulsivity-related traits (as assessed by the UPPS-P Impulsive Behavior Scale) and aggressive behaviors. Results indicated that UPPS-P Lack of Premeditation and Sensation Seeking were important in predicting general violence. In contrast, UPPS-P Urgency was most useful in predicting intimate partner violence. To further explore relations between intimate partner violence and Urgency, a measure of autonomic response to pleasant and aversive stimuli and facets of Neuroticism from the NEO PI-R were used as control variables. Autonomic responsivity was correlated with intimate partner violence at the zero-order level, and predicted significant variance in intimate partner violence in regression equations. However, UPPS-P Urgency was able to account for unique variance in intimate partner violence, above and beyond measures of Neuroticism and arousal. Implications regarding the use of a multifaceted conceptualization of impulsivity in the prediction of different types of violent behavior are discussed.

Epigenetic regulation of milk production in dairy cows.

It is well established that milk production of the dairy cow is a function of mammary epithelial cell (MEC) number and activity and that these factors can be influenced by diverse environmental influences and management practises (nutrition, milk frequency, photoperiod, udder health, hormonal and local effectors). Thus, understanding how the mammary gland is able to respond to these environmental cues provides a huge potential to enhance milk production of the dairy cow. In recent years our understanding of molecular events within the MEC underlying bovine lactation has been advanced through mammary microarray studies and will be further advanced through the recent availability of the bovine genome sequence. In addition, the potential of epigenetic regulation (non-sequence inheritable chemical changes in chromatin, such as DNA methylation and histone modifications, which affect gene expression) to manipulate mammary function is emerging. We propose that a substantial proportion of unexplained phenotypic variation in the dairy cow is due to epigenetic regulation. Heritability of epigenetic marks also highlights the potential to modify lactation performance of offspring. Understanding the response of the MEC (cell signaling pathways and epigenetic mechanisms) to external stimuli will be an important prerequisite to devising new technologies for maximising their activity and, hence, milk production in the dairy cow.

Multilevel growth curve analyses of behavioral activation for anhedonia (BATA) and mindfulness-based cognitive therapy effects on anhedonia and resting-state functional connectivity: Interim results of a randomized trial✰.

BACKGROUND: The neural mechanisms associated with anhedonia treatment response are poorly understood. Additionally, no study has investigated changes in resting-state functional connectivity (rsFC) accompanying psychosocial treatment for anhedonia. METHODS: We evaluated a novel psychotherapy, Behavioral Activation Therapy for Anhedonia (BATA, n = 38) relative to Mindfulness-Based Cognitive Therapy (MBCT, n = 35) in a medication-free, transdiagnostic, anhedonic sample in a parallel randomized controlled trial. Participants completed up to 15 sessions of therapy and up to four 7T MRI scans before, during, and after treatment (n = 185 scans). Growth curve models estimated change over time in anhedonia and in rsFC using average region-of-interest (ROI)-to-ROI connectivity within the default mode network (DMN), frontoparietal network (FPN), salience network, and reward network. Changes in rsFC from pre- to post-treatment were further evaluated using whole-network seed-to-voxel and ROI-to-ROI edgewise analyses. RESULTS: Growth curve models showed significant reductions in anhedonia symptoms and in average rsFC within the DMN and FPN over time, across BATA and MBCT. There were no differences in anhedonia reductions between treatments. Within-person, changes in average rsFC were unrelated to changes in anhedonia. Between-person, higher than average FPN rsFC was related to less anhedonia across timepoints. Seed-to-voxel and edgewise rsFC analyses corroborated reductions within the DMN and between the DMN and FPN over time, across the sample. CONCLUSIONS: Reductions in rsFC within the DMN, FPN, and between these networks co-occurred with anhedonia improvement across two psychosocial treatments for anhedonia. Future anhedonia clinical trials with a waitlist control group should disambiguate treatment versus time-related effects on rsFC.

A simultaneous [11C]raclopride positron emission tomography and functional magnetic resonance imaging investigation of striatal dopamine binding in autism.

The social motivation hypothesis of autism posits that autism spectrum disorder (ASD) is characterized by impaired motivation to seek out social experience early in life that interferes with the development of social functioning. This framework suggests that impaired mesolimbic dopamine function underlies compromised responses to social rewards in ASD. Although this hypothesis is supported by functional magnetic resonance imaging (fMRI) studies, no molecular imaging study has evaluated striatal dopamine functioning in response to rewards in ASD. Here, we examined striatal functioning during monetary incentive processing in ASD and controls using simultaneous positron emission tomography (PET) and fMRI. Using a bolus + infusion protocol with the D2/D3 dopamine receptor antagonist [11C]raclopride, voxel-wise binding potential (BPND) was compared between groups (controls = 12, ASD = 10) in the striatum. Striatal clusters showing significant between-group BPND differences were used as seeds in whole-brain fMRI general functional connectivity analyses. Relative to controls, the ASD group demonstrated decreased phasic dopamine release to incentives in the bilateral putamen and left caudate, as well as increased functional connectivity between a PET-derived right putamen seed and the precuneus and insula. Within the ASD group, decreased phasic dopamine release in the putamen was related to poorer theory-of-mind skills. Our findings that ASD is characterized by impaired striatal phasic dopamine release to incentives provide support for the social motivation hypothesis of autism. PET-fMRI may be a suitable tool to evaluate novel ASD therapeutics targeting the striatal dopamine system.

Alterations in Systemic and Cognitive Glucocorticoid Sensitivity in Depression.

BACKGROUND: Decades of research point to cortisol insensitivity as a biomarker of depression. Despite a vast literature on cortisol's effects on memory, the role of cortisol insensitivity in core psychological features of depression, such as emotional memory biases, is unknown. METHODS: Sixty-five premenopausal women with varying levels of depression completed this study involving an at-home low-dose dexamethasone suppression test and four experimental sessions (i.e., two visits for memory encoding of emotionally arousing pictures, each of which was followed 48 hours later by a recall test). Participants received 20 mg of oral cortisol (CORT) or placebo prior to encoding. We tested whether systemic cortisol insensitivity measured with the dexamethasone suppression test predicted cognitive sensitivity to CORT, which was operationalized as the change in negatively biased memory formation for pictures encoded following CORT versus placebo administration. RESULTS: Cortisol insensitivity was associated with more severe depression and flatter diurnal cortisol levels. Cortisol insensitivity predicted negative memory bias for pictures encoded during the placebo session and reduction in negative memory bias for pictures encoded during the CORT (compared with placebo) session, even after accounting for psychiatric symptomatology. CONCLUSIONS: Our findings replicate research showing that cortisol insensitivity predicts depression severity and flatter diurnal cortisol levels. The results further suggest that systemic cortisol insensitivity is related to negative memory bias and its alleviation by cortisol administration. These novel cognitive findings tie together knowledge regarding endocrine and psychological dysfunction in depression and suggest that boosting cortisol signal may cognitively benefit individuals with cortisol insensitivity.

Pretreatment brain connectivity during positive emotion upregulation predicts decreased anhedonia following behavioral activation therapy for depression.

BACKGROUND: Neurobiological predictors of antidepressant response may help guide treatment selection and improve response rates to available treatments for major depressive disorder (MDD). Behavioral activation therapy for depression (BATD) is an evidence-based intervention designed to ameliorate core symptoms of MDD by promoting sustained engagement with value-guided, positively-reinforcing activities. The present study examined pre-treatment task-based functional brain connectivity as a predictor of antidepressant response to BATD. METHODS: Thirty-three outpatients with MDD and 20 nondepressed controls completed a positive emotion regulation task during fMRI after which participants with MDD received up to 15 sessions of BATD. We used generalized psychophysiological interaction analyses to examine group differences in pre-treatment functional brain connectivity during intentional upregulation of positive emotion to positive images. Hierarchical linear models were used to examine whether group differences in functional connectivity predicted changes in depression and anhedonia over the course of BATD. RESULTS: Compared to controls, participants with MDD exhibited decreased connectivity between the left middle frontal gyrus and right temporoparietal regions during upregulation of positive emotion. Within the MDD group, decreased connectivity of these regions predicted greater declines in anhedonia symptoms over treatment. LIMITATIONS: Future studies should include comparison treatments and longitudinal follow-up to clarify the unique effects of BATD on neural function and antidepressant response. CONCLUSIONS: Results are consistent with previous work showing BATD may be particularly effective for individuals with greater disturbances in brain reward network function, but extend these findings to highlight the importance of frontotemporoparietal connectivity in targeting symptoms of low motivation and engagement.

Exploring the pathophysiology of emotion-based impulsivity: The roles of the sympathetic nervous system and hostile reactivity.

The tendency to engage in impulsive behavior in the context of negative affect, known as negative urgency, has emerged as a powerful transdiagnostic predictor of behavioral dysregulation. Although general vulnerability to negative affect (neuroticism) correlates with negative urgency, not all neurotic individuals engage in urgent behavior. Given prior experimental evidence that sympathetic nervous system (SNS) activation may promote emotion-related impulsivity, the present study examines tonic SNS activity as a moderator of the link between neuroticism and negative urgency. Participants (N = 194) completed measures of neuroticism and negative urgency, as well as a stress task. They also underwent assessment of tonic SNS activity (cardiac pre-ejection period). The link between neuroticism and negative urgency was strengthened for individuals with higher tonic SNS activity; however, this was not the case for behavioral performance on the task. A similar pattern was demonstrated for hostile reactivity to the stress task; increased hostile response partially explained the interaction between SNS activation and neuroticism on negative urgency. These findings suggest a potential facilitative role of the SNS in hostile reactivity and emotion-driven impulsivity among more neurotic individuals.

Early Life Abuse Moderates the Effects of Intranasal Oxytocin on Symptoms of Premenstrual Dysphoric Disorder: Preliminary Evidence From a Placebo-Controlled Trial.

Background: Although intranasal oxytocin (OXT) has been proposed to be a promising treatment for some psychiatric disorders, little research has addressed individual difference factors that may predict response to OXT. One such factor is early life abuse (ELA), which has widespread influences on social-emotional processing and behavior. This single-blind, placebo-controlled crossover trial examined the role of ELA in shaping the effects of intranasal OXT (vs. placebo) on daily behavioral symptoms in women with three or more prospectively-diagnosed cycling symptoms of premenstrual dysphoric disorder (PMDD). Methods: Participants were ten women with PMDD (n = 8) or subthreshold PMDD (n = 2), who had experienced ELA prior to age 13 (n = 5) or no ELA (n = 5). They completed two study visits during the late luteal (premenstrual) phase: once following administration of intranasal OXT and once following intranasal placebo (counterbalanced). Participants then self-administered OXT or placebo at home three times per day for 5 days or until menstrual onset, and prospectively rated daily emotional symptoms of PMDD. Power was adequate to detect medium main and interactive effects. Results: Among women with ELA, intranasal OXT (vs. placebo) increased the premenstrual emotional symptoms of PMDD, whereas among women without ELA, OXT decreased symptoms. Conclusion: This study adds to a growing literature highlighting the importance of considering historical social contexts and traits (such as ELA) as moderators of therapeutic response to OXT.

Reduced resting-state thalamostriatal functional connectivity is associated with excessive daytime sleepiness in persons with and without depressive disorders.

BACKGROUND: Excessive daytime sleepiness (EDS) is a common and significant problem encountered in affective illness, however, the biological underpinnings of EDS in persons with psychiatric disorders are not clear. This study evaluated the associations between thalamic connectivity with cortical and subcortical brain regions with EDS in persons with and without depressive disorders (DD). METHODS: Resting-state functional connectivity magnetic resonance imaging scans from 67 unmedicated young to middle-aged women with current DD (n = 30), remitted DD (n = 13), and healthy controls (n = 24) were utilized to examine the associations between thalamic connectivity with cortical/subcortical structures and EDS. RESULTS: After correction for multiple comparisons and adjustment for age, habitual sleep duration, and depressive symptomatology, reduced resting-state connectivity between the bilateral thalamus and left rostral striatum (caudate/putamen) was significantly associated with EDS. LIMITATIONS: Causal inferences between thalamostriatal connectivity and EDS could not be determined. CONCLUSIONS: These results further implicate the role of the striatum and thalamus as central components of the experience of EDS. Further research is indicated to clarify the specific role these structures play in EDS in psychiatric disorders.

The rewarding nature of provocation-focused rumination in women with borderline personality disorder: a preliminary fMRI investigation.

BACKGROUND: Understanding why individuals with borderline personality disorder (BPD) ruminate on prior provocations, despite its negative outcomes, is crucial to improving interventions. Provocation-focused rumination may be rewarding in the short term by amplifying anger and producing feelings of justification, validation, and increased energy, while reducing self-directed negative affect. If provocation-focused rumination is utilized regularly as a rewarding emotion regulation strategy, it could result in increased activation in reward-related neural regions. The present pilot study examined neural correlates of provocation-focused rumination, relative to other forms of thought, in BPD. METHOD: Functional magnetic resonance imaging (fMRI) was utilized to examine this theory in a pilot study of women diagnosed with BPD (n = 13) and healthy controls (n = 16). All participants received highly critical feedback on a previously written essay in the scanner, followed by prompts to engage in provocation-focused, self-focused, and neutral thought. RESULTS: Whole-brain analyses showed that in response to the provocation, participants with BPD (compared to controls) demonstrated increased activation in the ventrolateral prefrontal cortex (PFC). BPD participants also showed greater activation in the dorsomedial PFC during provocation-focused rumination (relative to neutral-focus). Subsequent ROI analyses revealed that provocation-focused rumination (compared to neutral-focus) increased activation in the nucleus accumbens for the BPD group only. CONCLUSIONS: These findings, while preliminary due to the small sample size and limitations of the protocol, provide initial data consistent with the proposed neurobiological mechanism promoting provocation-focused rumination in BPD. Directions for further research are discussed.