Determining the optimal clinical cutoff on the CES-D for depression in a community corrections sample.

BACKGROUND: Screening instruments are urgently needed to rapidly and efficiently identify those in need of mental health treatment, particularly among underserved populations. Although designed initially for use in research, the CES-D has become a widely used clinical screening tool for the presence of major depression. Despite four decades and three major revisions to the DSM since the CES-D was first introduced, the cutoff score of 16 remains the marker by which individuals are assessed. The present study aims to examine an optimal cutoff score in a low-income, high-risk sample of ethnically diverse adults involved in some phase of the criminal justice system. The utility of the CES-D to detect depression in this population is unknown as these individuals are unlikely to be included in community studies of mental health. METHODS: A diverse sample of participants under criminal justice supervision (n = 500, ages 19-72) completed the CES-D at up to six time points and the MINI-D at two time-points over a year. RESULTS: Using receiver operating characteristic (ROC) curves, a cut point of 21 on the CES-D was determined to produce the best overall screening characteristics (sens = 0.82, spec = 0.76) using an efficiency calculation when compared with the gold standard MINI-D, though these results varied by race and gender. The optimal cutoff for women in this sample was determined to be 23 as opposed to 15 for men, and 20 for nonwhites versus 23 for whites. LIMITATIONS: This study is limited in its generalizability to low-income individuals without criminal justice involvement or those without substance use. CONCLUSION: Results suggest that the CES-D is a useful screening measure for depressive symptoms among high-risk individuals under criminal justice supervision. However, the current cutoff score of 16 is inadequate for optimizing true positives and false negatives. Possible gender and racial/ethnic bias may limit the utility of this instrument in this population. The current study contributes to the understanding of mental health needs in underserved populations.

Influence of early life stress on intra- and extra-amygdaloid causal connectivity.

Animal models of early life stress (ELS) are characterized by augmented amygdala response to threat and altered amygdala-dependent behaviors. These models indicate the amygdala is a heterogeneous structure with well-differentiated subnuclei. The most well characterized of these being basolateral (BLA) and central nucleus (CeA). Parallel human imaging findings relative to ELS also reveal enhanced amygdala reactivity and disrupted connectivity but the influence of ELS on amygdala subregion connectivity and modulation of emotion is unclear. Here we employed cytoarchitectonic probability maps of amygdala subregions and Granger causality methods to evaluate task-based intra-amygdaloid and extra-amygdaloid connectivity with the network underlying implicit regulation of emotion in response to unconditioned auditory threat in healthy controls with ELS (N=20) and without a history of ELS (N=14). Groups were determined by response to the Childhood Trauma Questionnaire and threat response determined by unpleasantness ratings. Non-ELS demonstrated narrowly defined BLA-driven intra-amygdaloid paths and concise orbitofrontal cortex (OFC)-CeA-driven extra-amygdaloid connectivity. In contrast, ELS was associated with extensive and robust CeA-facilitated intra- and extra-amygdaloid paths. Non-ELS findings paralleled the known anatomical organization and functional relationships for both intra- and extra-amygdaloid connectivity, while ELS demonstrated atypical intra- and extra-amygdaloid CeA-dominant paths with compensatory modulation of emotion. Specifically, negative causal paths from OFC/BA32 to BLA predicted decreased threat response among non-ELS, while a unique within-amygdala path predicted modulation of threat among ELS. These findings are consistent with compensatory mechanisms of emotion regulation following ELS among resilient persons originating both within the amygdala complex as well as subsequent extra-amygdaloid communication.

Early life trauma and directional brain connectivity within major depression.

OBJECTIVE: Early life trauma (ELT) is a significant risk factor for the onset of depression. Emerging findings indicate ELT is associated with enhanced amygdala reactivity to aversive stimuli in never-depressed healthy controls as well as those with acute depression but may be absent in non-ELT exposed depressed. The precise mechanism mediating these differences in amygdala reactivity remains unclear. METHOD: The authors used Granger causality methods to evaluate task-based directional connectivity between medial or lateral prefrontal cortex (PFC) and amygdala in 20 unmedicated patients with current major depressive disorder (MDD) and 19 healthy matched controls while participants engaged in an affective variant of the flanker task comparing response to sad and neutral faces. These data were correlated with childhood trauma history. RESULTS: Exposure to ELT was associated with failure of inhibition within the MDD group based on medial PFC-amygdala connectivity. In contrast, non-ELT exposed MDD was associated with a negative causal pathway from medial prefrontal cortex to amygdala, despite reduced dorsolateral PFC input in comparison to healthy controls. Neither MDD group demonstrated significant lateral PFC-amygdala connectivity in comparison to healthy controls. CONCLUSIONS: Failure of the circuit implicated in emotion regulation was associated with a significant history of ELT but not with MDD more broadly. Non-ELT related depression was associated with intact regulation of emotion despite the absence of difference in severity of illness. These findings indicate opposing system-level differences within depression relative to ELT are expressed as differential amygdala reactivity.

Childhood trauma history differentiates amygdala response to sad faces within MDD.

OBJECTIVE: Heightened amygdala reactivity to aversive stimuli in major depression is regarded as a core feature of the underlying physiology but individual differences in amygdala response may also arise secondary to persistent changes in limbic function during early neurodevelopment relative to stressors such as childhood trauma. We sought to determine whether heightened amygdala response is a core feature of depression or a general risk factor for psychopathology secondary to early life stress. METHOD: Twenty unipolar depressed patients with and without a history of significant early life trauma and 16 healthy comparison subjects underwent functional MRI in a cross-sectional study comparing neural response to sad and neutral faces. RESULTS: We observed a robust positive correlation between physical abuse and right amygdala response. A much weaker relationship with other forms of abuse and neglect was also found, suggesting differences between abuse subtypes and amygdala response. Group differences in amygdala response suggest heightened reactivity was not characteristic of persons with depression in general but was true primarily in those with a significant history of abuse. CONCLUSION: These findings suggest the relationship between childhood trauma and risk for depression is mediated by heightened amygdala response but varies by abuse type. Preliminary evidence for two distinct depression phenotypes based on trauma history was also supported, consistent with differential etiology.

Early adverse events, HPA activity and rostral anterior cingulate volume in MDD.

BACKGROUND: Prior studies have independently reported associations between major depressive disorder (MDD), elevated cortisol concentrations, early adverse events and region-specific decreases in grey matter volume, but the relationships among these variables are unclear. In the present study, we sought to evaluate the relationships between grey matter volume, early adverse events and cortisol levels in MDD. METHODS/RESULTS: Grey matter volume was compared between 19 controls and 19 individuals with MDD using voxel-based morphometry. A history of early adverse events was assessed using the Childhood Trauma Questionnaire. Subjects also provided salivary cortisol samples. Depressed patients showed decreased grey matter volume in the rostral ACC as compared to controls. Rostral ACC volume was inversely correlated with both cortisol and early adverse events. CONCLUSIONS: These findings suggest a key relationship between ACC morphology, a history of early adverse events and circulating cortisol in the pathophysiology of MDD.

Cognitive aspects of chronic depression.

Previous research on chronic depression has focused on its link with other mood disorders and Axis II personality disorders. However, there are few data examining whether the cognitive perspective applies to this condition. In this cross-sectional study, 42 outpatients with chronic depression were compared with 27 outpatients with nonchronic major depressive disorder and 24 never psychiatrically ill controls on cognitive variables thought to be related to vulnerability to depression (e.g., dysfunctional attitudes, attributional style, a ruminative response style, and maladaptive core beliefs). Both depressed groups were more elevated than a never-ill comparison group. However, chronically depressed individuals were generally more elevated on measures of cognitive variables than those with major depressive disorders even after controlling for mood state and personality disorder symptoms.