Developing User Personas to Aid in the Design of a User-Centered Natural Product-Drug Interaction Information Resource for Researchers.

Pharmacokinetic interactions between natural products and conventional drugs can adversely impact patient outcomes. These complex interactions present unique challenges that require clear communication to researchers. We are creating a public information portal to facilitate researchers' access to credible evidence about these interactions. As part of a user-centered design process, three types of intended researchers were surveyed: drug-drug interaction scientists, clinical pharmacists, and drug compendium editors. Of the 23 invited researchers, 17 completed the survey. The researchers suggested a number of specific requirements for a natural product-drug interaction information resource, including specific information about a given interaction, the potential to cause adverse effects, and the clinical importance. Results were used to develop user personas that provided the development team with a concise and memorable way to represent information needs of the three main researcher types and a common basis for communicating the design's rationale.

Recalling happy memories in remitted depression: a neuroimaging investigation of the repair of sad mood.

Major depressive disorder (MDD) is a recurrent mood disorder. The high rate of recurrence of MDD suggests the presence of stable vulnerability factors that place individuals with a history of major depression at an increased risk for the onset of another episode. Previous research has linked the remitted state, and therefore increased vulnerability for depressive relapse, with difficulties in the use of pleasant autobiographical memories to repair sad mood. In the present study, we examined the neural correlates of these difficulties. Groups of 16 currently euthymic, remitted depressed individuals and 16 healthy (control) women underwent functional magnetic resonance imaging (fMRI) during sad mood induction and during recovery from a sad mood state through recall of mood-incongruent positive autobiographical memories. Sad mood was induced in participants by using film clips; participants then recalled positive autobiographical memories, a procedure previously shown to repair negative affect. During both the sad mood induction and automatic mood regulation, control participants exhibited activation in the left ventrolateral prefrontal cortex (vlPFC) and cuneus; in contrast, remitted participants exhibited a decrease in activation in these regions. Furthermore, exploratory analyses revealed that reduced activation levels during mood regulation predicted a worsening of depressive symptoms at a 20-month follow-up assessment. These findings highlight a dynamic role of the vlPFC and cuneus in the experience and modulation of emotional states and suggest that functional anomalies of these brain regions are associated with a history of, and vulnerability to, depression.

Neural correlates of automatic mood regulation in girls at high risk for depression.

Daughters of depressed mothers are at significantly elevated risk for developing a depressive disorder themselves. We have little understanding, however, of the specific factors that contribute to this risk. The ability to regulate negative affect effectively is critical to emotional and physical health and may play an important role in influencing risk for depression. We examined whether never-disordered daughters whose mothers have experienced recurrent episodes of depression during their daughters' lifetime differ from never-disordered daughters of never-disordered mothers in their patterns of neural activation during a negative mood induction and during automatic mood regulation. Sad mood was induced in daughters through the use of film clips; daughters then recalled positive autobiographical memories, a procedure shown previously to repair negative affect. During the mood induction, high-risk girls exhibited greater activation than did low-risk daughters in brain areas that have frequently been implicated in the experience of negative affect, including the amygdala and ventrolateral prefrontal cortex. In contrast, during automatic mood regulation, low-risk daughters exhibited greater activation than did their high-risk counterparts in brain areas that have frequently been associated with top-down regulation of emotion, including the dorsolateral prefrontal cortex and dorsal anterior cingulate cortex. These findings indicate that girls at high and low risk for depression differ in their patterns of neural activation both while experiencing, and while repairing negative affect, and suggest that anomalies in neural functioning precede the onset of a depressive episode.

Neural correlates of rumination in depression.

Rumination, or recursive self-focused thinking, has important implications for understanding the development and maintenance of depressive episodes. Rumination is associated with the worsening of negative mood states, greater affective responding to negative material, and increased access to negative memories. The present study was designed to use fMRI to examine neural aspects of rumination in depressed and healthy control individuals. We used a rumination induction task to assess differences in patterns of neural activation during ruminative self-focus as compared with a concrete distraction condition and with a novel abstract distraction condition in 14 participants who were diagnosed with major depressive disorder and 14 healthy control participants. Depressed participants exhibited increased activation in the orbitofrontal cortex, subgenual anterior cingulate, and dorsolateral prefrontal cortex as compared with healthy controls during rumination versus concrete distraction. Neural activity during rumination versus abstract distraction was greater for depressed than for control participants in the amygdala, rostral anterior cingulate/medial prefrontal cortex, dorsolateral prefrontal cortex, posterior cingulate, and parahippocampus. These findings indicate that ruminative self-focus is associated with enhanced recruitment of limbic and medial and dorsolateral prefrontal regions in depression. Supplemental materials for this article may be downloaded from http://cabn.psychonomic-journals.org/content/supplemental.

Neural processing of reward and loss in girls at risk for major depression.

CONTEXT: Deficits in reward processing and their neural correlates have been associated with major depression. However, it is unclear if these deficits precede the onset of depression or are a consequence of this disorder. OBJECTIVE: To determine whether anomalous neural processing of reward characterizes children at familial risk for depression in the absence of a personal history of diagnosable disorder. DESIGN: Comparison of neural activity among children at low and high risk for depression as they process reward and loss. SETTING: University functional magnetic resonance imaging facility. PARTICIPANTS: Thirteen 10- to 14-year-old never-disordered daughters of mothers with recurrent depression ("high risk") and 13 age-matched never-disordered daughters with no family history of depression ("low risk"). Main Outcome Measure Neural activity, as measured using functional magnetic resonance imaging, in key reward and attention neural circuitry during anticipation and receipt of reward and loss. RESULTS: While anticipating gains, high-risk participants showed less activation than did their low-risk counterparts in the putamen and left insula but showed greater activation in the right insula. When receiving punishment, high-risk participants showed greater activation in the dorsal anterior cingulate gyrus than did low-risk participants, who showed greater activation in the caudate and putamen. CONCLUSIONS: Familial risk for depression affects neural mechanisms underlying the processing of reward and loss; young girls at risk for depression exhibit anomalies in the processing of reward and loss before the onset of depressive symptoms. Longitudinal studies are needed to examine whether these characteristics predict the subsequent onset of depression.

Neural correlates of inhibitory deficits in depression.

The present study used functional magnetic resonance imaging to examine neural correlates of inhibitory dysfunction in individuals diagnosed with major depressive disorder (MDD). Twelve MDD participants and 12 never-depressed controls completed the negative affective priming (NAP) task in the scanner. Results indicated that, in depressed participants, increased activation in the rostral anterior cingulate cortex (rACC) is associated with inhibition of negative, but not positive, words; in contrast, in nondepressed participants, inhibition of positive, but not negative, words is associated with increased activation in the rACC. These findings indicate that abnormalities in neural function, especially in the rACC, may underlie difficulties experienced by depressed individuals in inhibiting negative thoughts. These results underscore the importance of continuing to examine the relation between cognitive and neural functioning in depression in order to gain a broader and more integrative understanding of this disorder.

The neural bases of obsessive-compulsive disorder in children and adults.

Functional imaging studies have reported with remarkable consistency hyperactivity in the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and caudate nucleus of patients with obsessive-compulsive disorder (OCD). These findings have often been interpreted as evidence that abnormalities in cortico-basal ganglia-thalamo-cortical loops involving the OFC and ACC are causally related to OCD. This interpretation remains controversial, however, because such hyperactivity may represent either a cause or a consequence of the symptoms. This article analyzes the evidence for a causal role of these loops in producing OCD in children and adults. The article first reviews the strong evidence for anatomical abnormalities in these loops in patients with OCD. These findings are not sufficient to establish causality, however, because anatomical alterations may themselves be a consequence rather than a cause of the symptoms. The article then reviews three lines of evidence that, despite their own limitations, permit stronger causal inferences: the development of OCD following brain injury, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection, and neurosurgical lesions that attenuate OCD. Converging evidence from these various lines of research supports a causal role for the cortico-basal ganglia-thalamo-cortical loops that involve the OFC and ACC in the pathogenesis of OCD in children and adults.

Neural responses to monetary incentives in major depression.

BACKGROUND: Reduced responsiveness to positive incentives is a central feature of Major Depressive Disorder (MDD). In the present study, we compared neural correlates of monetary incentive processing in unmedicated depressed participants and never-depressed control subjects. METHODS: Fourteen currently depressed and 12 never-depressed participants underwent functional magnetic resonance imaging while participating in a monetary incentive delay task. During the task, participants were cued to anticipate and respond to a rapidly presented target to gain or avoid losing varying amounts of money. RESULTS: Depressed and never-depressed participants did not differ in nucleus accumbens (NAcc) activation or in affective or behavioral responses during gain anticipation. Depressed participants did, however, exhibit increasing anterior cingulate activation during anticipation of increasing gains, whereas never-depressed participants showed increasing anterior cingulate activation during anticipation of increasing loss. Depressed participants also showed reduced discrimination of gain versus nongain outcomes. CONCLUSIONS: The present findings indicate that although unmedicated depressed individuals have the capacity to experience positive arousal and recruit NAcc activation during gain anticipation, they also exhibit increased anterior cingulate cortex activation, suggestive of increased conflict during anticipation of gains, in addition to showing reduced discrimination of gain versus nongain outcomes.

Remembering the good times: neural correlates of affect regulation.

The ability to regulate one's mood state effectively is critical to emotional and physical health. Recent investigations have sought to delineate the neural mechanisms by which individuals regulate mood states and emotions, positing a critical role of a dorsal system that includes the dorsolateral prefrontal cortex and anterior cingulate. This study extended these efforts by examining the neural correlates of retrieving positive autobiographical memories while experiencing a negative mood state in a sample of healthy female adults. We demonstrated that mood-incongruent recall is associated with activation in ventrolateral and ventromedial prefrontal cortices (including orbitofrontal cortex and subgenual cingulate). These findings suggest that mood-incongruent recall differs from other affect regulation strategies by influencing mood through a ventral regulatory network.

Amygdala activation in the processing of neutral faces in social anxiety disorder: is neutral really neutral?

Previous research has suggested that Social Anxiety Disorder (SAD) is associated with a tendency to interpret ambiguous social stimuli in a threatening manner. The present study used event-related functional magnetic resonance imaging to examine patterns of neural activation in response to the processing of neutral facial expressions in individuals diagnosed with SAD and healthy controls (CTLs). The SAD participants exhibited a different pattern of amygdala activation in response to neutral faces than did the CTL participants, suggesting a neural basis for the biased processing of ambiguous social information in SAD individuals.

Amygdala reactivity to emotional faces predicts improvement in major depression.

Behavioral studies suggest that emotional reactivity in depressed persons predicts subsequent symptom reduction. Using functional magnetic resonance imaging in a prospective study, we show that greater amygdala activation to emotional facial expressions among depressed patients predicts symptom reduction 8 months later, controlling for initial depression severity and medication status. Functional magnetic resonance imaging may thus be used as a method to identify neural markers in depressed patients at risk for poor outcome.