Positive valence system function and anhedonia in middle-aged and older adults at high suicide risk.

Positive valence systems are disrupted in late-life depression and in individuals at risk for suicide. The reward positivity (RewP) is an event-related potential measure of positive valence system function that relates to depression and anhedonia in children and young adults. However, it is unclear whether a reliable RewP signal can be elicited in middle-aged and older adults at high risk for suicide and, if so, whether this signal is similarly associated with clinical symptoms. In the current study, a RewP was elicited with a standard gambling task in middle-aged and older adults (N = 31) at discharge from a hospitalization for suicidal thought or behaviors. The resulting electrocortical response differed significantly for monetary wins compared to losses. Internal reliability of the RewP and the feedback negativity (FN) to monetary loss was good to excellent. Internal reliability of difference measures was lower but still largely acceptable, with residualized differences scores demonstrating stronger reliability than subtraction-based scores. A smaller residualized RewP, after accounting for the influence of the FN, was associated with greater severity of lassitude, an index of appetitive anhedonia. These findings set the groundwork for future studies of positive valence system function and depression in middle-aged and older adults at high risk for suicide.

Differential response of positive valence systems to psychotherapy for late-life depression: A pilot study.

BACKGROUND: Depression is characterized by deficits in the positive valence systems (PVS), which also decline with age. However, few studies have examined changes in PVS as a mechanism of treatment for depression, and none have done so using reward-focused interventions in older adults. AIM: The aim of this proof-of-concept study was to investigate changes in two event-related potential measures of PVS function, the late positive potential and the reward positivity, during psychotherapy designed to treat late-life depression by increasing rewarding experiences. METHODS: Eighteen adults age ≥ 60 with major depressive disorder recruited for a larger randomized controlled trial received 9 weeks of Problem-Solving Therapy or Engage therapy. The late positive potential and the reward positivity were recorded at baseline and week 6 of treatment. RESULTS: The late positive potential was larger for rewarding compared to neutral stimuli and increased from baseline to week 6. Exploratory analyses found that this increase was specific to rewarding stimuli. There were no significant effects for the reward positivity. LIMITATIONS: The small sample size limited power to detect associations with clinical measures or evaluate moderating effects of treatment modality, age, or gender. CONCLUSIONS: This study provides preliminary evidence that distinct facets of the PVS respond differently to psychotherapy in older adults with major depression. The late positive potential may be a dynamic marker of depressive state, whereas the reward positivity may constitute a vulnerability index for late-life depression.

Cortical Thickness of the Salience Network and Change in Apathy Following Antidepressant Treatment for Late-Life Depression.

OBJECTIVE: Apathy is common in late-life depression and is associated with poor response to antidepressant drugs. In depressed older adults, apathy may be characterized by neuroanatomical abnormalities of the salience network. The current study examined whether cortical thickness of select salience network structures predicted change in apathy following a 12-week treatment with escitalopram. METHODS: A sample of 46 older adults with major depressive disorder received 12 weeks of escitalopram treatment at a daily target dose of 20 mg. All participants underwent a structural brain MRI scan at baseline, and cortical thickness was estimated in key cortical nodes of the salience network: the caudal anterior cingulate cortex and the insula. We measured baseline and post-treatment symptoms using the Apathy Evaluation Scale and the Hamilton Depression Rating Scale. RESULTS: A thicker insula at baseline predicted reduction in apathy symptoms following 12 weeks of treatment with escitalopram, even when controlling for age, baseline depression severity and change in depressive symptoms. CONCLUSION: Reduced insular thickness predicted residual apathetic symptoms following escitalopram treatment. These results converge with our previous findings of abnormal functional connectivity of the insular cortex in older depressed individuals with apathy. Older depressed adults with apathy may benefit from alternative treatment approaches or augmentative interventions that target abnormalities of the salience network.

Engagement in Socially and Interpersonally Rewarding Activities as a Predictor of Outcome in "Engage" Behavioral Activation Therapy for Late-Life Depression.

OBJECTIVE: Loneliness and social isolation are associated with depressive symptoms, cognitive and physical disabilities, and increased risk of mortality among older adults. Socially rewarding activities reduce loneliness, and neurobiological evidence suggests that these activities may activate neural reward systems in older adults to a greater extent than other rewarding experiences. The current study was designed to investigate whether engagement in social and interpersonal activities (i.e., exposure to social rewards) predicts subsequent increase in behavioral activation and reduction in depressive symptoms in reward exposure treatment for late-life depression. METHODS: Forty-eight older adults without cognitive impairment and with major depression received nine sessions of "Engage" psychotherapy. Behavioral activation and depression severity were assessed by trained raters at baseline and weeks 6 and 9. Patients' weekly behavioral plans were categorized into three groups: 1) solitary activities; 2) social-group activities (attending a social gathering or a social setting such as church or a senior center); and 3) interpersonal-individual activities (engaging in an interpersonal interaction with a specific friend or family member). RESULTS: Mixed-effects models showed reduction in depression severity and increase in behavioral activation over time. In linear regression models, a higher percentage of interpersonal-individual activities (but not solitary or social-group activities) predicted subsequent increase in behavioral activation and improvement of depression. CONCLUSION: These findings highlight the importance of understanding the effects of engagement in specific types of rewarding activities in behavioral activation treatments for late-life depression. Exposure to socially rewarding interpersonal interactions could contribute to the efficacy of psychotherapy for late-life depression.

Reward learning impairment and avoidance and rumination responses at the end of Engage therapy of late-life depression.

OBJECTIVES: This study examined the association between reward processing, as measured by performance on the probabilistic reversal learning (PRL) task and avoidance/rumination in depressed older adults treated with Engage, a psychotherapy that uses "reward exposure" to increase behavioral activation. METHODS: Thirty older adults with major depression received 9 weeks of Engage treatment. At baseline and treatment end, the 24-item Hamilton Depression Rating Scale (HAM-D) was used to assess depression severity and the Behavioral Activation for Depression Scale (BADS) to assess behavioral activation and avoidance/rumination. Participants completed the PRL task at baseline and at treatment end. The PRL requires participants to learn stimulus-reward contingencies through trial and error, and switch strategies when the contingencies unexpectedly change. RESULTS: At the end of Engage treatment, the severity of depression was lower (HAM-D: t(19) = -7.67, P < .001) and behavioral activation was higher (BADS: t(19) = 2.23, P = .02) compared to baseline. Response time following all switches (r(19) = -0.63, P = .003) and error switches (r(19) = -0.57, P = .01) at baseline was negatively associated with the BADS avoidance/rumination subscale score at the end of Engage treatment. CONCLUSIONS: Impaired reward learning, evidenced by slower response following all switches and error switches, contributes to avoidant, ruminative behavior at the end of Engage therapy even when depression improves. Understanding reward processing abnormalities of avoidance and rumination may improve the timing and targeting of interventions for these symptoms, whose persistence compromises quality of life and increases the risk of depression relapse.

Maternal Depression Is Related to Reduced Error-Related Brain Activity in Child and Adolescent Offspring.

Chronic parental depression is associated with an increased likelihood of depression in offspring. One mechanism by which parental depression may increase risk is through physiological or cognitive tendencies in offspring. Error processing has been studied using the error-related negativity (ERN), an event-related potential that occurs around the time someone commits an error, and has previously been shown to be heritable and blunted in depressed individuals. The current study examined the ERN as a potential biomarker of risk in a sample of never-depressed children whose mothers had a history of recurrent major depressive disorder (MDD), a single episode of MDD, or no lifetime history of any mood disorder. Seventy-eight mother-child dyads participated. The average age for children was 13.13 years (SD = 2.07) and 50% were female. Diagnostic interviews and self-report questionnaires were used to assess depression in both mothers and children. A flankers task was used to elicit the ERN and the correct response negativity (CRN) in children. Children of mothers with a history of recurrent MDD exhibited a reduced difference between the ERN and CRN compared to children of mothers with no depression history, even after controlling for children's current depression symptoms. Furthermore, current maternal depression symptoms related to a smaller difference between ERN and CRN in children. This pattern of findings suggests that blunted neural activity differentiating error from correct responses may be one mechanism by which recurrent maternal depression increases risk for depression in offspring and may be useful biomarker of risk.

"Engage" therapy: Prediction of change of late-life major depression.

OBJECTIVE: Engage grew out of the need for streamlined psychotherapies that can be accurately used by community therapists in late-life depression. Engage was based on the view that dysfunction of reward networks is the principal mechanism mediating depressive symptoms. Accordingly, Engage uses "reward exposure" (exposure to meaningful activities) and assumes that repeated activation of reward networks will normalize these systems. This study examined whether change in a behavioral activation scale, an index of reward system function, predicts change in depressive symptomatology. METHODS: The participants (N = 48) were older adults with major depression treated with 9 weekly sessions of Engage and assessed 27 weeks after treatment. Depression was assessed with the 24-item Hamilton Depression Rating Scale (HAM-D) and behavioral activation with the four subscales of Behavioral Activation for Depression Scale (activation, avoidance/rumination, work impairment, social impairment) at baseline, 6 weeks (mid-treatment), 9 weeks (end of treatment), and 36 weeks. RESULTS: Change only in the Activation subscale during successive periods of assessment predicted depression severity (HAM-D) at the end of each period (F1, 47 = 21.05, p<0.0001). An increase of one standard deviation in the Activation score resulted in a 2.04 (95% CI: 1.17-2.92) point decrease in HAM-D. For every one point increase in the Activation score, HAM-D was decreased by 0.22 points (95% CI: 0.12-0.31). LIMITATIONS: No comparison group. Partial overlap of Activation Subscale with HAM-D, lack of detailed neurocognitive assessment and social support. CONCLUSION: Change in behavioral activation predicts improvement of depressive symptoms and signs in depressed older adults treated with Engage.

Authoritarian parenting predicts reduced electrocortical response to observed adolescent offspring rewards.

Parenting styles are robust predictors of offspring outcomes, yet little is known about their neural underpinnings. In this study, 44 parent-adolescent dyads (Mage of adolescent = 12.9) completed a laboratory guessing task while EEG was continuously recorded. In the task, each pair member received feedback about their own monetary wins and losses and also observed the monetary wins and losses of the other member of the pair. We examined the association between self-reported parenting style and parents' electrophysiological responses to watching their adolescent winning and losing money, dubbed the observational Reward Positivity (RewP) and observational feedback negativity (FN), respectively. Self-reported authoritarian parenting predicted reductions in parents' observational RewP but not FN. This predictive relationship remained after adjusting for sex of both participants, parents' responsiveness to their own wins, and parental psychopathology. 'Exploratory analyses found that permissive parenting was associated with a blunting of the adolescents' response to their parents' losses'. These findings suggest that parents' rapid neural responses to their child's successes may relate to the harsh parenting behaviors associated with authoritarian parenting.

The stability of the feedback negativity and its relationship with depression during childhood and adolescence.

Feedback negativity (FN) is an event-related potential elicited by monetary reward and loss; it is thought to relate to reward-related neural activity and has been linked to depression in children and adults. In the current study, we examined the stability of FN, and its relationship with depression in adolescents, over 2 years in 45 8- to 13-year-old children. From Time 1 to Time 2, FN in response to monetary loss and in response to monetary gain showed moderate to strong reliability (rs = .64 and .67, respectively); these relationships remained significant even when accounting for related variables. FN also demonstrated high within-session reliability. Moreover, the relationship between a blunted FN and greater depression observed at Time 1 was reproduced at Time 2, and the magnitude of FN at Time 1 predicted depressive symptomatology at Time 2. These findings are consistent with the hypothesis that FN and its relationship with depression remain consistent over the course of development, and that FN may prospectively predict later depressive symptomatology. The current results suggest that FN may be suitable as a biomarker of depressive symptoms during adolescence.

Differentiating anxiety and depression in children and adolescents: evidence from event-related brain potentials.

The current study, which was a reanalysis of previous data, focused on the error-related negativity (ERN)-an event-related potential (ERP) associated with error monitoring-and the feedback negativity (FN)-an ERP associated with reward processing. Two objectives motivated this study: first, to illustrate the relationship between the ERN and anxious symptoms, and the relationship between the FN and depressive symptoms; second, to explore whether the ERN and the FN relate uniquely to anxiety and depression, respectively, in children. EEG was collected from twenty-five 11- to 13-year-old participants (12 female; 23 Caucasian, 1 Asian, 1 of Caucasian and Hispanic ethnicity) during tasks designed to elicit an ERN and an FN. Participants and a parent completed questionnaires assessing the participant's anxious and depressive symptomatology. Increasing anxiety was related to a larger ERN, and increasing depression was related to a smaller FN. Further analysis demonstrated that these relationships remained significant when controlling for the contribution of other variables; that is, the ERN continued to predict anxiety when controlling for the FN and depression, and the FN continued to predict depression when controlling for the ERN and anxiety. Thus, in late childhood and early adolescence, the ERN and the FN appear to relate uniquely to anxious and depressive symptoms, respectively. Although this research is still in early stages, the ERN and the FN have the potential to inform trajectories of risk for anxiety and depression, and could be utilized in clinical settings as cost- and labor-efficient neural biomarkers.

The impact of puberty and social anxiety on amygdala activation to faces in adolescence.

Adolescence is associated with the onset of puberty, shifts in social and emotional behavior and an increased vulnerability to social anxiety disorder. These transitions coincide with changes in amygdala response to social and affective stimuli. Utilizing an emotional face-matching task, we examined amygdala response to peer-aged neutral and fearful faces in relation to puberty and social anxiety in a sample of 60 adolescent females between the ages of 8 and 15 years. We observed amygdala activation in response to both neutral and fearful faces compared to the control condition but did not observe differential amygdala activation between fearful and neutral faces. Right amygdala activity in response to neutral faces was negatively correlated with puberty and positively correlated with social anxiety, and these effects were statistically independent. Puberty and social anxiety did not relate to amygdala activation in response to fearful faces. These findings suggest that emotional differentiation between fearful and neutral faces may arise during later pubertal development and may result from decreasing sensitivity to neutral faces rather than increasing sensitivity to threatening faces. Furthermore, these findings highlight the importance of considering individual differences in social anxiety when examining the neural response to social stimuli in adolescents.

Psychometric properties of the error-related negativity in children and adolescents.

Error processing is frequently examined using the error-related negativity (ERN), a negative-going event-related potential occurring after the commission of an error at frontal-central sites, and has been suggested as a neural biomarker that may be useful in characterizing trajectories of risk for anxiety. While the ERN has been shown to have excellent psychometric properties in adults, few studies have examined psychometric properties of the ERN in children and adolescents. The current study examined the 2-year test-retest reliability of the ERN in a sample of children and adolescents, and the convergent validity of the ERN using a flanker and go/no-go task. Results suggest that the ERN is both reliable and stable across 2 years and across tasks. However, results also indicate that the internal consistency obtained using the flanker task is greater than the internal consistency obtained using the go/no-go task.

Self-report and behavioral measures of reward sensitivity predict the feedback negativity.

Rewards are integral to learning associations that aid in survival. The feedback negativity (FN), an event-related potential that differentiates outcomes indicating monetary losses versus gains, has recently emerged as a possible neural measure of reward processing. If this view is correct, then the FN should correlate with measures of reward sensitivity in other domains, although few studies have investigated this question. In the current study, 46 participants completed a self-report measure of reward responsiveness, a signal detection task that generated a behavioral measure of reward sensitivity, and a gambling task that elicited an FN. Consistent with the view that the FN reflects reward-related neural activity, a larger FN correlated with increased behavioral and self-report measures of sensitivity to reward.

Blunted neural response to rewards prospectively predicts depression in adolescent girls.

The prevalence of depression increases substantially during adolescence. Several predictors of major depressive disorder have been established, but their predictive power is limited. In the current study, the feedback negativity (FN), an event-related potential component elicited by feedback indicating monetary gain versus loss, was recorded in 68 never-depressed adolescent girls. Over the following 2 years, 24% of participants developed a major depressive episode (MDE); illness onset was predicted by blunted FN at initial evaluation. Lower FN amplitude predicted more depressive symptoms during the follow-up period, even after controlling for neuroticism and depressive symptoms at baseline. This is the first prospective study to demonstrate a link between a neural measure of reward sensitivity and the first onset of an MDE. The current results suggest that low reward sensitivity may be an important factor in the development of depression.

Better late than never? The effect of feedback delay on ERP indices of reward processing.

The feedback negativity (FN), an early neural response that differentiates rewards from losses, appears to be generated in part by reward circuits in the brain. A prominent model of the FN suggests that it reflects learning processes by which environmental feedback shapes behavior. Although there is evidence that human behavior is more strongly influenced by rewards that quickly follow actions, in nonlaboratory settings, optimal behaviors are not always followed by immediate rewards. However, it is not clear how the introduction of a delay between response selection and feedback impacts the FN. Thus, the present study used a simple forced choice gambling task to elicit the FN, in which feedback about rewards and losses was presented after either 1 or 6 s. Results suggest that, at short delays (1 s), participants clearly differentiated losses from rewards, as evidenced in the magnitude of the FN. At long delays (6 s), on the other hand, the difference between losses and rewards was negligible. Results are discussed in terms of eligibility traces and the reinforcement learning model of the FN.

Neural response to reward and depressive symptoms in late childhood to early adolescence.

Depression is a major public health concern, and the period from late childhood through early adolescence is a critical time in the development of depressive symptoms. In adults, depression and depressive symptoms are associated with a reduction in the feedback negativity (FN), an ERP component elicited by feedback indicating rewards versus losses. The current study sought to extend these findings to a sample of 64 children aged 8-13, and to examine developmental differences in the FN. Consistent with previous work in adults, higher depressive symptom scores were associated with a blunted FN across the sample. When responses to losses and gains were examined separately, only reduction in the response to monetary gain was associated with increased depressive symptoms. In the current study, the vast majority of children were pre-pubertal, and the FN was unrelated to both age and pubertal development. The FN may be an ideal biomarker for studying changes in reward sensitivity and depression that emerge as children transition through puberty.

Effective utilization and future directions for repetitive transcranial magnetic stimulation: a guide for psychiatric nurses.

Repetitive transcranial magnetic stimulation (rTMS) and magnetic seizure therapy (MST) represent new and promising avenues for treating mild and severe treatment-resistant depression, respectively. A further understanding of these modalities and the contribution of psychiatric nurses in the emerging field of brain stimulation would be of great use to the nursing community. This article serves as a primer for those who are interested in participating in or referring patients for research or treatment with rTMS or MST. Of particular emphasis is the role of certified psychiatric nurses as clinical rater, patient liaison, and evidence-based practitioner: