Brandon L. Goldstein

A Review of Selected Candidate Endophenotypes for Depression

Endophenotypes are proposed to occupy an intermediate position in the pathway between genotype and phenotype in genetically complex disorders such as depression. To be considered an endophenotype, a construct must meet a set of criteria proposed by Gottesman and Gould (2003). In this qualitative review, we summarize evidence for each criterion for several putative endophenotypes for depression: neuroticism, morning cortisol, frontal asymmetry of cortical electrical activity, reward learning, and biases of attention and memory. Our review indicates that while there is strong support for some depression endophenotypes, other putative endophenotypes lack data or have inconsistent findings for core criteria.

Stability of self-referent encoding task performance and associations with change in depressive symptoms from early to middle childhood.

Depressed individuals exhibit memory biases on the self-referent encoding task (SRET), such that those with depression exhibit poorer recall of positive, and enhanced recall of negative, trait adjectives (referred to as positive and negative processing biases). However, it is unclear when SRET biases emerge, whether they are stable, and if biases predict, or are predicted by, depressive symptoms. To address this, a community sample of 434 children completed the SRET and a depressive symptoms measure at ages 6 and 9. Negative and positive processing exhibited low, but significant, stability. At ages 6 and 9, depressive symptoms correlated with higher negative, and lower positive, SRET processing. Importantly, lower positive processing at age 6 predicted increased symptoms at age 9. However, negative processing at age 6 did not predict depressive symptoms at age 9, and depressive symptoms at age 6 did not predict SRET processing scores at age 9. This suggests that less positive processing may reflect vulnerability for future depressive symptoms.

Developmental changes in electroencephalographic frontal asymmetry in young children at risk for depression

BACKGROUND A number of studies have reported that depression is associated with lower relative left frontal activity in the alpha band (i.e. frontal asymmetry, or FA), as measured by electroencephalogram. FA has also been hypothesized to be a vulnerability marker for depression. If this is the case, FA should be evident in offspring of depressed mothers, a group at elevated risk for depression. However, the results of previous offspring studies have been inconsistent and none of these studies has considered whether the relationship between FA and risk changes over development in children. METHOD We assessed FA twice, at ages 3 and 6, in 253 never depressed children from a community sample. Maternal history of depressive disorders was determined by a diagnostic interview completed by the mothers at the first assessment. RESULTS There was a significant interaction between maternal depression and offspring age at assessment, indicating that FA exhibits different developmental trajectories depending on level of familial risk for depression. Offspring of depressed mothers exhibited a decreasing relative left FA over the course of early childhood, while offspring of nondepressed mothers exhibited relatively similar, symmetrical, levels of frontal alpha activity at both assessment points. CONCLUSIONS These results suggest that changes in FA from early to middle childhood distinguish those at risk for depression and that cross-sectional assessment of FA may have limited value in understanding risk. These results highlight the importance of considering development in understanding the role of FA in depression.

Elevated cortisol in healthy female adolescent offspring of mothers with posttraumatic stress disorder

Offspring with maternal PTSD are at increased risk of developing PTSD themselves. Alterations in the hypothalamic-pituitary-adrenal (HPA) axis may play a role and have been noted in offspring, although evidence is mostly from adult offspring with PTSD symptoms themselves. The present study of adolescent girls (N=472) and their mothers (n=18 with lifetime PTSD versus n=454 with no PTSD) sought to determine whether healthy, non-affected offspring of mothers with PTSD would exhibit altered HPA axis function. Saliva samples were collected from the adolescent girls at waking, 30min after waking, and 8 pm on 3 consecutive days. Offspring whose mothers were diagnosed with PTSD demonstrated higher cortisol awakening response (CAR; Cohens d=0.58) and greater total cortisol output (Cohens d=0.62). In this preliminary study, higher cortisol levels during adolescence among offspring of mothers with PTSD may index a vulnerability in these at-risk youth.

Etiologic specificity of waking Cortisol: Links with maternal history of depression and anxiety in adolescent girls

BACKGROUND Many previous studies have indicated that individuals who are depressed or at risk for depression are characterized by increased levels of morning cortisol and a greater cortisol awakening response (CAR). However, despite the high comorbidity between depressive and anxiety disorders, fewer studies have examined whether these diurnal cortisol abnormalities are also characteristic of anxiety or risk for anxiety. METHODS In the present study we examined cortisol in a community sample of 476 female adolescents and related it to maternal history of depression and/or anxiety disorders. Salivary cortisol was collected at waking, 30min post waking, and in the evening on three weekdays. RESULTS Contrary to prior results, offspring at risk for depression did not have increased morning cortisol or CAR. However, offspring at risk for anxiety disorders had elevated 30min cortisol and total cortisol produced throughout the day; this effect was primarily driven by offspring of mothers with panic disorder or agoraphobia. Additionally, levels of cortisol were highest among offspring of mothers with multiple anxiety diagnoses. LIMITATIONS The study is limited to female adolescents and maternal diagnostic history. Additionally, some diagnoses could not be examined as a result of too few cases (e.g. GAD). CONCLUSIONS Overall, these results underscore the importance of considering anxiety when examining the association of diurnal cortisol abnormalities with risk for psychopathology, as it may have influenced prior observations of elevated morning cortisol in depression.

Positive and Negative Emotionality at Age 3 Predicts Change in Frontal EEG Asymmetry across Early Childhood

Depression is characterized by low positive emotionality (PE) and high negative emotionality (NE), as well as asymmetries in resting electroencephalography (EEG) alpha power. Moreover, frontal asymmetry has itself been linked to PE, NE, and related constructs. However, little is known about associations of temperamental PE and NE with resting EEG asymmetries in young children and whether this association changes as a function of development. In a longitudinal study of 254 three-year old children, we assessed PE and NE at age 3 using a standard laboratory observation procedure. Frontal EEG asymmetries were assessed at age 3 and three years later at age 6. We observed a significant three-way interaction of preschool PE and NE and age at assessment for asymmetry at F3-F4 electrode sites, such that children with both low PE and high NE developed a pattern of increasingly lower relative left-frontal cortical activity over time. In addition, F7-F8 asymmetry was predicted by a PE by time interaction, such that the frontal asymmetry in children with high PE virtually disappeared by age 6. Overall, these findings suggest that early temperament is associated with developmental changes in frontal asymmetry, and that the combination of low PE and high NE predicts the development of the pattern of frontal symmetry that is associated with depression.

Assertiveness Training: A Forgotten Evidence‐Based Treatment

The current article discusses assertiveness training, a once highly popular area of investigation that has been neglected in recent years by the field of psychotherapy. A substantial body of research indicates that assertiveness is a relevant factor associated with a variety of clinical problems, populations, and contexts, and that assertiveness training is a valuable transdiagnostic intervention. Despite its demonstrated importance, research on assertiveness and assertiveness training as a stand-alone treatment within clinical psychology has diminished drastically. We review the history of assertiveness training, revisit early research evidence for assertiveness training in treating various clinical problems, discuss the current status of assertiveness training, consider issues of clinical implementation, and comment on how the variables accounting for unassertiveness map onto the NIMH RDoC funding priorities.