The endogenous opioid system, which alleviates physical pain, is also known to regulate social distress and reward in animal models. To test this hypothesis in humans (n = 18), we used a μ-opioid receptor (MOR) radiotracer to measure changes in MOR availability in vivo with positron emission tomography (PET) during social rejection (not being liked by others) and acceptance (being liked by others). Social rejection significantly activated the MOR system (i.e., reduced receptor availability relative to baseline) in the ventral striatum, amygdala, midline thalamus, and periaqueductal gray (PAG). This pattern of activation is consistent with the hypothesis that the endogenous opioids play a role in reducing the experience of social pain. Greater trait resiliency was positively correlated with MOR activation during rejection in the amygdala, PAG, and subgenual anterior cingulate cortex (sgACC), suggesting that MOR activation in these areas is protective or adaptive. In addition, MOR activation in the pregenual ACC was correlated with reduced negative affect during rejection. In contrast, social acceptance resulted in MOR activation in the amygdala and anterior insula, and MOR deactivation in the midline thalamus and sgACC. In the left ventral striatum, MOR activation during acceptance predicted a greater desire for social interaction, suggesting a role for the MOR system in social reward. The ventral striatum, amygdala, midline thalamus, PAG, anterior insula, and ACC are rich in MORs and comprise a pathway by which social cues may influence mood and motivation. MOR regulation of this pathway may preserve and promote emotional well-being in the social environment.

No abstract

Frontal, limbic and temporal regions of the brain important in emotion perception and executive functioning also have been implicated in the etiology and maintenance of depression; yet, the relationships among these topics remain poorly understood. The present study evaluated emotion perception and executive functioning among 21 depressed women and 20 nondepressed women controls. Depressed women performed significantly worse than controls in emotion perception accuracy and in inhibitory control, an aspect of executive functioning, whereas the groups did not differ in other cognitive tests assessing memory, visual-spatial, motor, and attention skills. The findings suggest that emotion perception and executive functioning are disproportionately negatively affected relative to other cognitive functions, even in a high-functioning group of mildly depressed women. Measures of emotion perception and executive functioning may be of assistance in objectively measuring functional capability of the ventral and dorsal neural systems, respectively, as well as in the diagnosis of depression.

Traditional neuropsychological measures of executive functioning are difficult to employ in functional imaging and clinical trial contexts and have tremendous practice effects. They also have poor sensitivity and specificity, while test-retest reliability is often not assessed in computer-based tests. The present study evaluates some psychometric properties of a new Parametric Go/No-Go (PGNG) Task. The PGNG consists of three levels of difficulty assessing attention, set-shifting, and processing speed, with the two more difficult levels assessing inhibitory control. A total of 63 healthy control participants were recruited at two sites to evaluate the psychometric properties of the PGNG. The PGNG was found to have solid parametric characteristics and strong test-retest reliability. Modest convergent validity was also demonstrated with other executive-functioning tests. Learning effects were significantly less than those for the Trail Making Test. The present results provide solid initial support for the validity and reliability of the PGNG.

Background-Inhibitory control or regulatory difficulties have been explored in major depressive disorder (MDD) but typically in the context of affectively salient information. Inhibitory control is addressed specifically by using a task devoid of affectively-laden stimuli, to disentangle the effects of altered affect and altered inhibitory processes in MDD.

BackgroundMood disorders are common and associated with significant morbidity and mortality. Better tools are needed for their diagnosis and treatment. Deeper phenotypic understanding of these disorders is integral to the development of such tools. This study is the first effort to use passively collected mobile phone keyboard activity to build deep digital phenotypes of depression and mania.ObjectiveThe objective of our study was to investigate the relationship between mobile phone keyboard activity and mood disturbance in subjects with bipolar disorders and to demonstrate the feasibility of using passively collected mobile phone keyboard metadata features to predict manic and depressive signs and symptoms as measured via clinician-administered rating scales.MethodsUsing a within-subject design of 8 weeks, subjects were provided a mobile phone loaded with a customized keyboard that passively collected keystroke metadata. Subjects were administered the Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) weekly. Linear mixed-effects models were created to predict HDRS and YMRS scores. The total number of keystrokes was 626,641, with a weekly average of 9791 (7861), and that of accelerometer readings was 6,660,890, with a weekly average 104,076 (68,912).ResultsA statistically significant mixed-effects regression model for the prediction of HDRS-17 item scores was created: conditional R2=.63, P=.01. A mixed-effects regression model for YMRS scores showed the variance accounted for by random effect was zero, and so an ordinary least squares linear regression model was created: R2=.34, P=.001. Multiple significant variables were demonstrated for each measure.ConclusionsMood states in bipolar disorder appear to correlate with specific changes in mobile phone usage. The creation of these models provides evidence for the feasibility of using passively collected keyboard metadata to detect and monitor mood disturbances.

The μ-opioid receptor (MOR) system, well known for dampening physical pain, is also hypothesized to dampen “social pain.” We used positron emission tomography scanning with the selective MOR radioligand [11C]carfentanil to test the hypothesis that MOR system activation in response to social rejection and acceptance is altered in medication-free patients diagnosed with current major depressive disorder (MDD, n = 17) compared to healthy controls (HCs, n = 18). During rejection, MDD patients showed reduced MOR activation (e.g., reduced endogenous opioid release) in brain regions regulating stress, mood, and motivation, and slower emotional recovery compared to HCs. During acceptance, only HCs showed increased social motivation, which was positively correlated with MOR activation in the nucleus accumbens, a reward structure. Abnormal MOR function in MDD may hinder emotional recovery from negative social interactions and decrease pleasure derived from positive interactions. Both effects may reinforce depression, trigger relapse, and contribute to poor treatment outcomes.

ObjectiveFunctional connectivity MRI (fcMRI) studies of individuals currently diagnosed with major depressive disorder (MDD) document hyperconnectivities within the default mode network (DMN) and between the DMN and salience networks (SN) with regions of the cognitive control network (CCN). Studies of individuals in the remitted state are needed to address whether effects derive from trait, and not state or chronic burden features of MDD.MethodfcMRI data from two 3.0 Tesla GE scanners were collected from 30 unmedicated (47% medication naïve) youth (aged 18–23, modal depressive episodes = 1, mean age of onset = 16.2, SD = 2.6) with remitted MDD (rMDD; modal years well = 4) and compared with data from 23 healthy controls (HCs) using four bilateral seeds in the DMN and SN (posterior cingulate cortex (PCC), subgenual anterior cingulate (sgACC), and amygdala), followed by voxel-based comparisons of the whole brain.ResultsCompared to HCs, rMDD youth exhibited hyperconnectivities from both PCC and sgACC seeds with lateral, parietal, and frontal regions of the CCN, extending to the dorsal medial wall. A factor analysis reduced extracted data and a PCC factor was inversely correlated with rumination among rMDD youth. Two factors from the sgACC hyperconnectivity clusters were related to performance in cognitive control on a Go/NoGo task, one positively and one inversely.ConclusionsFindings document hyperconnectivities of the DMN and SN with the CCN (BA 8/10), which were related to rumination and sustained attention. Given these cognitive markers are known predictors of response and relapse, hyperconnectivities may increase relapse risk or represent compensatory mechanisms.