Background Major depressive disorder (MDD) is a heterogeneous condition and individual patients are likely to be differentially responsive to specific treatments. In an exploratory factor analysis of three rating scales, the Genome-based Therapeutic Drugs for Depression (GENDEP) trial identified three factors that were differentially associated with outcome to nortriptyline and escitalopram. However, this factor analysis has neither been replicated or applied to a psychotherapy treatment. Methods We replicated the GENDEP analytic method in the Emory Predictors of Remission to Individual and Combined Treatments (PReDICT) study. The 17-item Hamilton Depression Rating Scale, Montgomery Asberg Depression Rating Scale, and Beck Depression Inventory were administered to 306 MDD patients in the PReDICT study, which randomized previously untreated adults to 12 weeks of treatment with cognitive behavior therapy (CBT), escitalopram, or duloxetine. Utilizing Item Response Theory methodologies, factor scores were derived from the three scales and the efficacy of the three treatments was compared for the identified factor scores. Results Four factors were identified: “Despair,” “Mood and Interest,” “Sleep,” and “Appetite.” These factors closely aligned with the factors identified in GENDEP. Compared to CBT, escitalopram and duloxetine produced more rapid but ultimately similar improvement on the Despair and Mood and Interest factors; no significant differences between treatments emerged on the other factors. Limitations The scales contained differing numbers of items pertaining to specific depressive symptoms. Conclusion The heterogeneity of MDD can be parsed into a consistent factor structure, with the factors showing differential rapidity, but ultimately similar, improvement across treatments.
Background: Early life trauma, particularly child abuse, has been associated with aberrations in hypothalamic-pituitary-adrenal (HPA) axis functioning in adulthood. However, the relationship of early abuse and later adult neuroendocrine changes may be moderated by additional factors such as comorbid psychopathology and recent life stress. Parental exposure to child abuse may have transgenerational effects, with offspring of abuse victims showing similar neuroendocrine profiles as their mothers. The majority of previous studies in this area focus on adult offspring, and the degree to which the effects of parental child abuse can be detected earlier in the development of the offspring remains obscure.
Methods: The current study utilized a clinical sample of women with a history of MDD (N= 126), to examine the effects of maternal early life sexual and physical abuse (Childhood Trauma Questionnaire (CTQ)) on both maternal and infant salivary cortisol levels during a laboratory stress paradigm at 6 months postpartum.
Results: Maternal child abuse was associated with steeper declines in cortisol in the mothers and lower baseline cortisol in their infants. Comorbid maternal PTSD, current maternal depressive symptoms, and recent life stressors were significant moderators of maternal cortisol change. Maternal abuse history was associated with increases in cortisol levels in those mothers who experienced these additional stressors. Similarly, a history of early maternal abuse and comorbid PTSD was associated with greater increases in infant cortisol levels.
Conclusions: Maternal childhood abuse was associated with HPA axis function in both the mother and the infant during the postpartum period.
by
Poornima Kumar;
George M. Slavich;
Lisa H. Berghorst;
Michael Treadway;
Nancy H. Brooks;
Sunny J. Dutra;
Douglas N. Greve;
Aoife O'Donovan;
Maria E. Bleil;
Nicole Maninger;
Diego A. Pizzagalli
Introduction: Major depressive disorder (MDD) is often precipitated by life stress and growing evidence suggests that stress-induced alterations in reward processing may contribute to such risk. However, no human imaging studies have examined how recent life stress exposure modulates the neural systems that underlie reward processing in depressed and healthy individuals. Methods: In this proof-of-concept study, 12 MDD and 10 psychiatrically healthy individuals were interviewed using the Life Events and Difficulties Schedule (LEDS) to assess their perceived levels of recent acute and chronic life stress exposure. Additionally, each participant performed a monetary incentive delay task under baseline (no-stress) and stress (social-evaluative) conditions during functional MRI.
Results: Across groups, medial prefrontal cortex (mPFC) activation to reward feedback was greater during acute stress versus no-stress conditions in individuals with greater perceived stressor severity. Under acute stress, depressed individuals showed a positive correlation between perceived stressor severity levels and reward-related mPFC activation (r=0.79, p=0.004), whereas no effect was found in healthy controls. Moreover, for depressed (but not healthy) individuals, the correlations between the stress (r=0.79) and no-stress (r=-0.48) conditions were significantly different. Finally, relative to controls, depressed participants showed significantly reduced mPFC gray matter, but functional findings remained robust while accounting for structural differences. Limitation Small sample size, which warrants replication.
Conclusion: Depressed individuals experiencing greater recent life stress recruited the mPFC more under stress when processing rewards. Our results represent an initial step toward elucidating mechanisms underlying stress sensitization and recurrence in depression.
Background: There has been increasing interest in the role of immunologic processes, notably cytokines, in the development of behavioral alterations, especially in medically ill patients. Interferon (IFN)-α is notorious for causing behavioral symptoms, including depression, fatigue, and cognitive dysfunction, and has been used to investigate the effects of cytokines on the brain. Methods: In the present study we assessed the effects of low-dose IFN-α on brain activity, using functional magnetic resonance imaging during a task of visuospatial attention in patients infected with hepatitis C virus (HCV). Results: Despite endorsing symptoms of impaired concentration and fatigue, IFN-α-treated patients (n = 10) exhibited task performance and activation of parietal and occipital brain regions similar to that seen in HCV-infected control subjects (n = 11). Interestingly, however, in contrast to control subjects, IFN-α-treated patients exhibited significant activation in the dorsal part of the anterior cingulate cortex (ACC), which highly correlated with the number of task-related errors. No such correlation was found in control subjects. Conclusions: Consistent with the role of the ACC in conflict monitoring, ACC activation during IFN-α administration suggests that cytokines might increase processing conflict or reduce the threshold for conflict detection, thereby signaling the need to exert greater mental effort to maintain performance. Such alterations in ACC activity might in turn contribute to cytokine-induced behavioral changes.
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Sandra Weintraub;
Sureyya S. Dikmen;
Robert K. Heaton;
David S. Tulsky;
Philip David Zelazo;
Jerry Slotkin;
Noelle E. Carlozzi;
Patricia Bauer;
Kathleen Wallner-Allen;
Nathan Fox;
Richard Havlik;
Jennifer L. Beaumont;
Dan Mungas;
Jennifer J. Manly;
Claudia Moy;
Kevin Conway;
Emmeline Edwards;
Cindy J. Nowinski;
Richard Gershon
This study introduces a special series on validity studies of the Cognition Battery (CB) from the U.S. National Institutes of Health Toolbox for the Assessment of Neurological and Behavioral Function (NIHTB) (Gershon, Wagster et al., 2013) in an adult sample. This first study in the series describes the sample, each of the seven instruments in the NIHTB-CB briefly, and the general approach to data analysis. Data are provided on test-retest reliability and practice effects, and raw scores (mean, standard deviation, range) are presented for each instrument and the gold standard instruments used to measure construct validity. Accompanying papers provide details on each instrument, including information about instrument development, psychometric properties, age and education effects on performance, and convergent and discriminant construct validity. One study in the series is devoted to a factor analysis of the NIHTB-CB in adults and another describes the psychometric properties of three composite scores derived from the individual measures representing fluid and crystallized abilities and their combination. The NIHTB-CB is designed to provide a brief, comprehensive, common set of measures to allow comparisons among disparate studies and to improve scientific communication.
by
Sureyya S. Dikmen;
Patricia Bauer;
Sandra Weintraub;
Dan Mungas;
Jerry Slotkin;
Jennifer L. Beaumont;
Richard Gershon;
Nancy R. Temkin;
Robert K. Heaton
Episodic memory is one of the most important cognitive domains that involves acquiring, storing and recalling new information. In this article, we describe a new measure developed for the NIH Toolbox, called the Picture Sequence Memory Test (PSMT) that is the first to examine episodic memory across the age range from 3 to 85. We describe the development of the measure and present validation data for ages 20 to 85. The PSMT involves presentation of sequences of pictured objects and activities in a fixed order on a computer screen and simultaneously verbally described, that the participant must remember and then reproduce over three learning trials. The results indicate good test-retest reliability and construct validity. Performance is strongly related to well-established gold standard measures of episodic memory and, as expected, much less well correlated with those of a measure of vocabulary. It shows clear decline with aging in parallel with a gold standard summary measure and relates to several other demographic factors and to self-reported general health status. The PSMT appears to be a reliable and valid test of episodic memory for adults, a finding similar to those found for the same measure with children.
Among the most serious sequelae to an initial episode of Major Depressive Disorder (MDD) during adolescence is the significant increase in the probability of recurrence. This study reports on an integrated CBT/IPT program, provided in a group format, that was developed to decrease the rate of MDD recurrence in emerging adults. METHODS: Participants were 89 young adults who were not depressed at study entry but had experienced MDD during adolescence. Participants were assigned to a CBT/IPT prevention program or to an assessment only control condition and were followed through the first 2 years of college. RESULTS: Risk for MDD recurrence was reduced more than 50% for the prevention program participants compared to assessment only controls. The intervention also conferred beneficial effects on academic performance for those students who completed the majority of the group sessions. LIMITATIONS: The study included a self-selected sample of emerging adults who were aware of their history of depression. Due to the small sample size, it will be important to evaluate similar interventions in adequately-powered trials to determine if this is a replicable finding. CONCLUSIONS: With 51% of the assessment only participants experiencing a MDD recurrence during the first 2 years of college, these findings support the need for programs designed to prevent MDD recurrence in young adults. The current program, based on IPT and CBT principles, appears to reduce the rate of MDD recurrence among previously depressed emerging adults.