Correlation of Antibodies to Neurotransmitters in the Sera of Women with Alcohol Dependence and Depressive Disorders.

Comparative analysis of blood sera from women with alcohol dependence and depressive disorders or from conditionally healthy women revealed reduced level of antibodies to dopamine, norepinephrine, serotonin, glutamate, and GABA in blood serum in women with dysthymic disorder and a depressive episode and their increased content in women with alcohol dependence in combination with depressive disorders.

Irritability and Inattention Not Sad Low Mood Predict Impulsiveness in Children and Adolescents With Major Depressive Disorder and Persistent Depressive Disorder.

ABSTRACT: The specific relationships between impulsiveness, inattention, sad, low mood, and irritability have not been systematically examined in young people with major depressive disorder with and without persistent depressive disorder. The relationships are important to clarify because these symptom dimensions may increase suicidal risk in children and adolescents with these depressive disorders. A total of 313 medication-naive young people (aged 6-16 years) with active major depressive disorder (MDD) alone, persistent depressive disorder (DD) alone, and comorbid MDD and DD were identified. "Inattention," "sad/unhappy," and "irritable" mood were identified by parent standardized questionnaire. Standard multiple regression was used to investigate how well inattention, sad/unhappy, and irritable mood predict impulsiveness. Inattention (32% of the variance, increased) and irritable mood (5% of the variance, increased) both made independent significant contributions to impulsiveness, whereas sad/unhappy mood did not. Decreasing irritability via more targeted and comprehensive management approaches may ameliorate impulsiveness in young people with these depressive disorders.

A reduced P300 prospectively predicts increased depressive severity in adults with clinical depression.

Neurocognitive impairments commonly observed in depressive disorders are thought to be reflected in reduced P300 amplitudes. To date, depression-related P300 amplitude reduction has mostly been demonstrated cross-sectionally, while its clinical implication for the course of depression remains largely unclear. Moreover, the relationship between P300 and specific clinical characteristics of depression is uncertain. To shed light on the functional significance of the P300 in depression, we examined whether initial P300 amplitude prospectively predicted changes in depressive symptoms among a community sample of 58 adults (mean age = 38.86 years old, 81% female) with a current depressive disorder. This sample was assessed at two-time points, separated by approximately nine months (range = 6.6-15.9). At the initial visit, participants completed clinical interviews, self-report measures, and a flanker task, while EEG was recorded to derive P300 amplitude. At the follow-up visit, participants again completed the same clinical interviews and self-report measures. Results indicated that a reduced P300 amplitude at the initial visit was associated with higher total depressive symptoms at follow-up, even after controlling for initial depressive symptoms. These data indicate the potential clinical utility for the P300 as a neural marker of disease course among adults with a current depressive disorder. Future research may target P300 in interventions to determine whether depression-related outcomes can be improved.

Predicting the naturalistic course of depression from a wide range of clinical, psychological, and biological data: a machine learning approach.

Many variables have been linked to different course trajectories of depression. These findings, however, are based on group comparisons with unknown translational value. This study evaluated the prognostic value of a wide range of clinical, psychological, and biological characteristics for predicting the course of depression and aimed to identify the best set of predictors. Eight hundred four unipolar depressed patients (major depressive disorder or dysthymia) patients were assessed on a set involving 81 demographic, clinical, psychological, and biological measures and were clinically followed-up for 2 years. Subjects were grouped according to (i) the presence of a depression diagnosis at 2-year follow-up (yes n = 397, no n = 407), and (ii) three disease course trajectory groups (rapid remission, n = 356, gradual improvement n = 273, and chronic n = 175) identified by a latent class growth analysis. A penalized logistic regression, followed by tight control over type I error, was used to predict depression course and to evaluate the prognostic value of individual variables. Based on the inventory of depressive symptomatology (IDS), we could predict a rapid remission course of depression with an AUROC of 0.69 and 62% accuracy, and the presence of an MDD diagnosis at follow-up with an AUROC of 0.66 and 66% accuracy. Other clinical, psychological, or biological variables did not significantly improve the prediction. Among the large set of variables considered, only the IDS provided predictive value for course prediction on an individual level, although this analysis represents only one possible methodological approach. However, accuracy of course prediction was moderate at best and further improvement is required for these findings to be clinically useful.

CBT and positive psychology interventions for clinical depression promote healthy attentional biases: An eye-tracking study.

BACKGROUND: Although there is a growing interest in the role of attentional biases in depression, there are no studies assessing changes in these biases after psychotherapeutic interventions. METHODS: We used a validated eye-tracking procedure to assess pre-post therapy changes in attentional biases toward emotional information (i.e., happy, sad, and angry faces) when presented with neutral information (i.e., neutral faces). The sample consisted of 75 participants with major depression or dysthymia. Participants were blindly assigned to one of two 10 weekly sessions of group therapy: a cognitive behavior therapy intervention (N = 41) and a positive psychology intervention (N = 34). RESULTS: Both treatments were equally efficacious in improving depressive symptoms (p = .0001, η² = .68). A significant change in attentional performance after therapy was observed irrespective of the intervention modality. Comparison of pre-post attentional measures revealed a significant reduction in the total time of fixations (TTF) looking at negative information (i.e., sad and angry faces) and a significant increase in the TTF looking at positive information (i.e., happy faces)-all p < .02. CONCLUSIONS: Findings reveal for the first time that psychotherapeutic interventions are associated with a significant change in attentional biases as assessed by a direct measure of attention. Furthermore, these changes seem to operate in the same direction typically found in healthy populations (i.e., a bias away from negative information and a parallel bias toward positive information). These findings illustrate the importance of considering attentional biases as clinical markers of depression and suggest the viability of modifying these biases as a potential tool for clinical change.

Spontaneous Changes in Functional Connectivity of Independent Components of fMRI Signal in Healthy Volunteers at Rest and in Subjects with Mild Depression.

Depression is associated with changes in the pattern of interaction of cerebral networks, which can reflect both existing symptoms and compensatory processes. The study is based on analysis of resting state fMRI data from 15 patients with mild depression and 19 conventionally healthy individuals. From fMRI signal recorded at rest for 4 min, the independent components were reconstructed. The intergroup differences and dynamics of functional connectivity from the first to the second recording were analyzed. Initially, depressive patients demonstrated weaker connectivity between cerebellar declive network (CN) and left central executive network (CEN) and also sensorimotor network (SMN); left CEN and primary visual network (PVN). During the second recording, the patients demonstrated more intensive reciprocal connection of the dorsal domain of default mode network (DMN) and auditory network (AN). In healthy subjects, positive correlations of the dorsal DMN and left CEN, right CEN and CN, and negative correlation of dorsal DMN and visuospatial network weakened from the first to second record. In the depression group, the interaction of AN with PVN, the right CEN with the anterior salience network and with ventral DMN weakened. At the same time, the connectivity between SMN and CN were strengthened. The results can be interpreted as spontaneous normalization of brain activity, but no direct evidence for their relation to the improvement of depression symptoms was found.

Psychophysiological characteristics in the ChNPP accident clean-up workers, exclusion zone evacuees and anti-terrorist operation servicemen. / PSYKhOFIZIOLOGIChNI OSOBLYVOSTI UChASNYKIV AVARIÏ NA ChAES, EVAKUY̆OVANYKh IZ ZONY VIDChUZhENNIa TA UChASNYKIV ANTYTERORYSTYChNOÏ OPERATsIÏ.

OBJECTIVE: Evaluation of interdependencies between psychometric parameters and spontaneous cerebral electric activity in the ChNPP accident clean up workers, evacuees from exclusion zone, and anti terrorist operation service men. OBJECT AND METHODS: Psychometric and neurophysiological parameters were reviewed in the study subjects retro spectively and in comparison. Study population included the ChNPP accident clean up workers (ACUW), evacuees from the 30 kilometer exclusion zone, specifically in a sample from a cohort of the NRCRM Clinical Epidemiological Register (n=316), and anti terrorist operation servicemen (n=81) undergoing rehabilitation in the NRCRM Radiation psychoneurology department. A control group of persons (n=84) was also involved in the study. Diagnostic method ology for the characteristic personality features, namely the personality test of character accentuation by G. Shmishek and K. Leonhard, and Eysenck Personality Inventory (by H. J. Eysenck) were applied. Computer EEGs were registered and analyzed on the 16 channel electroencephalograph DX 4000 (Kharkiv, Ukraine). RESULTS: In the aftermath of the emergency period, a personality deformation occurs in the clean up workers and survivors of the ChNPP accident, which is characterized by aggravation of such personality traits as jam (fixedness), emotiveness, pedantry, anxiety, cyclothymia, excitability and disthymia, with diminished hyperthymia and ostenta tion (demonstrability). Increased incidence of fixedness, pedantry, cyclothymia, affectability and disthymia with decreased hyperthymia were revealed in the group of ATO participants. Cerebral bioelectrical activity in the ChNPP ACUW was characterized by an increased delta activity power with decreased beta and theta activity power and dom inant frequency in comparison with all groups of survivors and control group. The ATO group was different from groups of survivors and control group with a lower power of delta, theta and beta activity, and a higher dominant frequency. Introversion featured a negative correlation with delta and theta activity index along with positive cor relation with alpha activity index. The absolute spectral power of beta, alpha and theta bands positively correlated with introversion. Increase in neuroticism featured a decrease in theta activity index and an increase in beta activ ity index along with decreased theta and delta band absolute spectral power. CONCLUSIONS: There is a deformation of personality in the group of ChNPP ACUW, evacuees from the 30 kilometer zone and ATO servicemen. Deformation of personality correlates with abnormal cerebral bioelectrical activity.

Heartbeat Complexity Modulation in Bipolar Disorder during Daytime and Nighttime.

This study reports on the complexity modulation of heartbeat dynamics in patients affected by bipolar disorder. In particular, a multiscale entropy analysis was applied to the R-R interval series, that were derived from electrocardiographic (ECG) signals for a group of nineteen subjects comprised of eight patients and eleven healthy control subjects. They were monitored using a textile-based sensorized t-shirt during the day and overnight for a total of 47 diurnal and 27 nocturnal recordings. Patients showed three different mood states: depression, hypomania and euthymia. Results show a clear loss of complexity during depressive and hypomanic states as compared to euthymic and healthy control states. In addition, we observed that a more significant complexity modulation among healthy and pathological mood states occurs during the night. These findings suggest that bipolar disorder is associated with an enhanced sleep-related dysregulation of the Autonomic Nervous System (ANS) activity, and that heartbeat complex dynamics may serve as a viable marker of pathological conditions in mental health.

Avoidance in Anxiety and Depression: Adaptation of the Cognitive-Behavioral Avoidance Scale in a Spanish Sample.

This study examines how cognitive, behavioral and experiential avoidance differs between clinical patients (N = 100), the general population (N = 100), and undergraduate students (N = 54). For this purpose, a Spanish adaptation of the Cognitive-Behavioral Avoidance Scale (CBAS; Ottenbreit & Dobson, 2004) was made. Confirmatory factor analysis supports the four factors structure similar to the original one, yet question the value of three of the items (CFI = .929, RMSEA = .057, SRMR = .051, χ2(333) = 603.28, p < .001, χ2/df = 1.81). Effect sizes calculated using Cohen's ƒ2 were between 0.30 and 2.57 in all cases, and only one item showed value < 0.35. The internal consistency for the total scale was .95, and adequate alpha values for the four subscales were found (α between .74 and .93). Statistical differences were found between the clinical and non-clinical groups, and also between the clinical and undergraduate groups (GLM, p < .001). The validity was verified using correlations with AAQ-II, MAAS, BDI-II and BAI. There is a correlation between cognitive-behavioral avoidance and experiential avoidance in both the clinical and control groups (rho = .382, rho = .361, p < .01). Patients with higher levels of cognitive-behavioral avoidance have higher levels of depression (rho = .36, p < .01). A score of 53 is suggested as the optimum cut-off point, because at this point, sensitivity and specificity are both 86%. The results suggest that cognitive-behavioral avoidance represents a significant factor in psychopathology. Recommendations for future studies are discussed.

Emotion recognition in depression: An investigation of performance and response confidence in adult female patients with depression.

Abnormalities in emotion recognition are frequently reported in depression. However, emotion recognition is not compromised in some studies, and confidence judgments, which are essential for social interaction, have not been considered to date. Due to the high prevalence rate of depression in women, and sex differences in emotion recognition, the aim of the present study was to investigate emotion recognition and confidence judgments in women with depression. A sample of female patients with depressive disorders (n=45) was compared with female healthy controls (n=30) in their ability to correctly identify facial emotion expressions along with confidence judgments. Groups performed similarly on emotional face recognition and showed no difference regarding confidence ratings. A negative correlation between self-assessed depression and response confidence was found. While some limitations of the study must be taken in consideration (e.g., small number of items per emotion category, low severity of depression), abnormalities in emotion recognition do not seem to be a major feature of depression. As self-assessed depression is accompanied by low response confidence for emotional faces, it is crucial to further examine the role of confidence judgments in emotion recognition, as underconfidence may foster interpersonal insecurity in depression.

Temperament, character, and suicide attempts in unipolar and bipolar mood disorders.

OBJECTIVE: Personality features may indicate risk for both mood disorders and suicidal acts. How dimensions of temperament and character predispose to suicide attempts remains unclear. METHOD: Patients (n = 597) from 3 prospective cohort studies (Vantaa Depression Study [VDS], Jorvi Bipolar Study [JoBS], and Vantaa Primary Care Depression Study [PC-VDS]) were interviewed at baseline, at 18 months, and, in VDS and PC-VDS, at 5 years (1997-2003). Personality was measured with the Temperament and Character Inventory-Revised (TCI-R), and follow-up time spent in major depressive episodes (MDEs) as well as lifetime (total) and prospectively ascertained suicide attempts during the follow-up were documented. RESULTS: Overall, 219 patients had 718 lifetime suicide attempts; 88 patients had 242 suicide attempts during the prospective follow-up. The numbers of both the total and prospective suicide attempts were associated with low self-directedness (ß = -0.266, P = .004, and ß = -0.294, P < .001, respectively) and high self-transcendence (ß = 0.287, P = .002, and ß = 0.233, P = .002, respectively). Total suicide attempts were linked to high novelty seeking (ß = 0.195, P = .05). Prospective, but not total, suicide attempts were associated with high harm avoidance (ß = 0.322, P < .001, and ß = 0.184, P = .062, respectively) and low reward dependence (ß = -0.274, P < .001, and ß = -0.134, P = .196, respectively), cooperativeness (ß = -0.181, P = .005, and ß = -0.096, P = .326, respectively), and novelty seeking (ß = -0.137, P = .047). No association remained significant when only prospective suicide attempts during MDEs were included. After adjustment was made for total time spent in MDEs, only high persistence predicted suicide attempts (ß = 0.190, P < .05). Formal mediation analyses of harm avoidance and self-directedness on prospectively ascertained suicide attempts indicated significant mediated effect through time at risk in MDEs, but no significant direct effect. CONCLUSIONS: Among mood disorder patients, suicide attempt risk is associated with temperament and character dimensions. However, their influence on predisposition to suicide attempts is likely to be mainly indirect, mediated by more time spent in depressive episodes.

Comparison of steady state development and reduction of menopausal symptoms after oral or transdermal delivery of 17-ß-estradiol in young healthy symptomatic menopausal women.

OBJECTIVE: There is a renewed interest in the delivery of estradiol (E2) for the reduction of menopausal symptoms in young symptomatic menopausal women. This paper compares experimentally and theoretically obtained E2 plasma values by oral and transdermal delivery and compares them with relevant menopausal symptoms. STUDY DESIGN: Two independent previously published studies were compared, which each contained 42 young symptomatic menopausal women. Experimentally obtained plasma values at days 1, 7 and 21 were compared with a theoretical model, taken from the literature, for describing plasma values for an oral immediate release formulation, consecutively for 21 days. Menopausal symptoms were determined in the steady state for oral and transdermal delivery with the Kuppermann index, previously not reported. In the case of oral delivery, estradiol was compared with estradiol valerate. RESULTS: Previously published results for transdermal delivery of E2 showed that the matrix system establishes a steady state condition with the application of the first patch. Excellent agreement between theoretically predicted and experimentally obtained E2 plasma values for oral delivery in menopausal women was obtained. Circadian E2 plasma levels were observed continuously for transdermal delivery, were seen in oral delivery during first application and disappeared when steady state was achieved. Application of the prodrug E2-valerate delayed the maximum plasma peak from 1 pm to 4 pm, similar to the transdermal matrix patch. Investigating menopausal symptoms determined with the Kuppermann index did not reveal differences between oral or transdermal "E2 kinetic (hot flushes) relationship". This relationship was similar to symptomatic women suffering from hot flushes in untreated menopausal women or premenopausal women. Different menopausal symptoms required different E2 plasma levels: the average E2 levels higher than 23 pg/mL in plasma did abolish insomnia in 50% of postmenopausal women, with 28 pg/mL is needed to suppress 50% of dysthymia; however, rather high levels of 41 pg/mL are needed to suppress 50% of hot flushes, suggesting a rather complex mechanism beyond an E2 receptor mediated process. CONCLUSION: There is a difference in the steady state between oral and transdermal E2 delivery. Steady state condition is achieved in the first application of a matrix patch, whereas with the application of a tablet the steady state is achieved in transdermal delivery within 12-14 days. Our reported calculated missed intake of a E2 tablet shows that E2 plasma levels drop for 4 days consecutively. Our conducted study has several limitations: firstly, no cross-over was conducted, but a rather cumbersome mathematical modeling; secondly, healthy women with no accompanying severe diseases were included in this study. The higher the oral dose, the higher the E2 steady state levels, but the time to achieve steady state levels is independent from the E2 dose.

Frontoparietal function in young people with dysthymic disorder (DSM-5: Persistent depressive disorder) during spatial working memory.

BACKGROUND: Dysthymic disorder (DD) is a depressive disorder characterised by persistent low and/or irritable mood and has been identified as a major risk factor for developing major depressive disorder (MDD). MDD and DD have been associated with executive function difficulties of working memory and attention. Little is known about how executive function networks in the brain are affected in children and adolescents with MDD and even less in DD. This study used fMRI and two spatial working memory paradigms to investigate associated brain function in young people with DD and an age-, gender- and IQ- matched typically developing group. METHODS: Nineteen male patients with DD (mean age 11.2±1.5 years) diagnosed according to DSM-IV criteria and 16 typically developing boys (mean age 10.5±1.1 years) performed a mental rotation and a delay-match to sample (DMTS) task while undergoing fMRI. All participants were medication-naïve at the time of testing. RESULTS: Compared to typically developing young people, the DD group showed less activation in left frontal regions including left ventro- and dorsolateral prefrontal cortices (PFC) during mental rotation. Medial frontal regions including dorsomedial PFC, anterior cingulate cortex and frontal pole also showed relatively reduced activation. During the DMTS task patients showed significantly more activation in the right precuneus and posterior cingulate cortex. LIMITATIONS: This was a cross-sectional study with a small sample limiting the generalizability of the results. CONCLUSIONS: The results complement previous findings in adults with MDD that have shown differential activation of left PFC regions during working memory tasks. Additionally, altered function of cortical midline structures in young patients with DD was identified. This supports findings in children, adolescents and adults with MDD suggesting that the pathophysiology of depressive disorders extends to DD as a risk factor for MDD and exhibits continuity over the lifespan.

Antidepressants normalize the default mode network in patients with dysthymia.

IMPORTANCE: The default mode network (DMN) is a collection of brain regions that reliably deactivate during goal-directed behaviors and is more active during a baseline, or so-called resting, condition. Coherence of neural activity, or functional connectivity, within the brain's DMN is increased in major depressive disorder relative to healthy control (HC) subjects; however, whether similar abnormalities are present in persons with dysthymic disorder (DD) is unknown. Moreover, the effect of antidepressant medications on DMN connectivity in patients with DD is also unknown. OBJECTIVE: To use resting-state functional-connectivity magnetic resonance imaging (MRI) to study (1) the functional connectivity of the DMN in subjects with DD vs HC participants and (2) the effects of antidepressant therapy on DMN connectivity. DESIGN: After collecting baseline MRI scans from subjects with DD and HC participants, we enrolled the participants with DD into a 10-week prospective, double-blind, placebo-controlled trial of duloxetine and collected MRI scans again at the conclusion of the study. Enrollment occurred between 2007 and 2011. SETTING: University research institute. PARTICIPANTS: Volunteer sample of 41 subjects with DD and 25 HC participants aged 18 to 53 years. Control subjects were group matched to patients with DD by age and sex. MAIN OUTCOME MEASURES: We used resting-state functional-connectivity MRI to measure the functional connectivity of the brain's DMN in persons with DD compared with HC subjects, and we examined the effects of treatment with duloxetine vs placebo on DMN connectivity. RESULTS: Of the 41 subjects with DD, 32 completed the clinical trial and MRI scans, along with the 25 HC participants. At baseline, we found that the coherence of neural activity within the brain's DMN was greater in persons with DD compared with HC subjects. Following a 10-week clinical trial, we found that treatment with duloxetine, but not placebo, normalized DMN connectivity. CONCLUSIONS AND RELEVANCE: The baseline imaging findings are consistent with those found in patients with major depressive disorder and suggest that increased connectivity within the DMN may be important in the pathophysiology of both acute and chronic manifestations of depressive illness. The normalization of DMN connectivity following antidepressant treatment suggests an important causal pathway through which antidepressants may reduce depression.

L-Acetylcarnitine in dysthymic disorder in elderly patients: a double-blind, multicenter, controlled randomized study vs. fluoxetine.

INTRODUCTION: L-Acetylcarnitine (LAC), the acetyl ester of carnitine naturally present in the central nervous system and involved in several neural pathways, has been demonstrated to be active in various animal experimental models resembling some features of human depression. The aim of the study is to verify whether LAC can have an antidepressant action in a population of elderly patients with dysthymic disorder in comparison with a traditional antidepressant such as fluoxetine. METHODS: Multicentric, double-blind, double-dummy, controlled, randomized study based on a observation period of 7 weeks. 80 patients with DSM-IV diagnosis of dysthymic disorder were enrolled in the study and subdivided into 2 groups. Group A patients received LAC plus placebo; group B patients received fluoxetine 20 mg/die plus placebo. Clinical assessment was performed through several psychometric scales at 6 different moments. RESULTS: Group A patients showed a statistically significant improvement in the following scales: HAM-D, HAM-A, BDI and Touluse Pieron Test. Comparison between the two groups, A and B, generally showed very similar clinical progression. DISCUSSION: The results obtained with LAC and fluoxetine were equivalent. As the subjects in this study were of senile age, it is possible to hypothesize that the LAC positive effect on mood could be associated with improvement in subjective cognitive symptomatology. The difference in the latency time of clinical response (1 week of LAC treatment, compared with the 2 weeks' latency time with fluoxetine) suggests the existence of different mechanisms of action possibly in relation to the activation of rapid support processes of neuronal activity.

Characterization of the theta to beta ratio in ADHD: identifying potential sources of heterogeneity.

OBJECTIVE: The goal of this study is to characterize the theta to beta ratio (THBR) obtained from electroencephalogram (EEG) measures, in a large sample of community and clinical participants with regard to (a) ADHD diagnosis and subtypes, (b) common psychiatric comorbidities, and (c) cognitive correlates. METHOD: The sample includes 871 participants (595 youth and 276 adults) with and without ADHD. All participants underwent extensive assessment, including semistructured diagnostic interviews, cognitive testing, and EEG recording. RESULTS: The THBR did not differ significantly by ADHD status for youth but was significantly lower in adults with ADHD compared with controls. ADHD subtype and psychiatric comorbidities such as disruptive behavior disorders and depression have opposing and significant mediating effects on the THBR. CONCLUSION: The THBR is affected by several mediating factors associated with ADHD such as ADHD subtype and psychiatric comorbidity. More research is needed to understand the functional significance of the THBR in ADHD.

Eye movement evidence for defocused attention in dysphoria--a perceptual span analysis.

The defocused attention hypothesis (von Hecker and Meiser, 2005) assumes that negative mood broadens attention, whereas the analytical rumination hypothesis (Andrews and Thompson, 2009) suggests a narrowing of the attentional focus with depression. We tested these conflicting hypotheses by directly measuring the perceptual span in groups of dysphoric and control subjects, using eye tracking. In the moving window paradigm, information outside of a variable-width gaze-contingent window was masked during reading of sentences. In measures of sentence reading time and mean fixation duration, dysphoric subjects were more pronouncedly affected than controls by a reduced window size. This difference supports the defocused attention hypothesis and seems hard to reconcile with a narrowing of attentional focus.

Neural processing of emotional overinvolvement in borderline personality disorder.

OBJECTIVE: Patients with borderline personality disorder (BPD) fare better clinically if their families are rated as being high in emotional overinvolvement, which is characterized by marked emotionality, anxious concern, and protective behavior. This is not true of patients with disorders such as schizophrenia or major depression. We used functional magnetic resonance imaging methods to explore the link between emotional overinvolvement (EOI) and better clinical outcome in BPD. Specifically, we tested the hypothesis that, unlike healthy controls or people with other psychiatric problems, people with BPD process EOI as an approach-related stimulus. METHOD: Participants with BPD (n = 13) and dysthymia (n = 10) (DSM-IV criteria for both) and healthy controls (n = 11) were imaged using a high field strength (3T) scanner while they listened to a standardized auditory stimulus consisting of either 4 neutral or 4 EOI comments. Participants also rated their mood before and after exposure to the comments. RESULTS: All participants reported increased negative mood after hearing EOI and rated the EOI comments as negative stimuli. However, after subtracting activation to neutral comments, participants with BPD showed higher activation in left prefrontal regions during EOI compared to the other groups. Increased left prefrontal activation during EOI was also correlated with clinical measures indicative of borderline pathology. Participants with dysthymia showed increased amygdala activation during EOI. This was not true for the healthy controls or participants with BPD. CONCLUSIONS: For people with BPD, EOI may be activating neural circuitry implicated in the processing of approach-related stimuli. Increased left prefrontal activation to EOI may be a vulnerability marker for BPD. These findings may also help explain why BPD patients do better clinically in high EOI family environments.

Hypothalamic-pituitary-adrenal axis dysregulation in depressed children and adolescents: a meta-analysis.

Research findings on the hypothalamic-pituitary-adrenal (HPA) axis and pediatric depression reflect a variety of methodological approaches that tap different facets of HPA-axis functions. Partly owing to the methodological heterogeneity of studies, descriptive reviews of this area have produced inconsistent conclusions. Therefore, we conducted formal meta-analyses of pertinent studies in order to advance our understanding of HPA-axis dysregulation in pediatric depression. We examined: (a) 17 published studies of HPA-axis response to the dexamethasone suppression test (DST) in depressed youth (DST; N=926) and (b) 17 studies of basal HPA-axis functioning (N=1332). We also examined descriptively studies that used corticotropin-releasing hormone (CRH) infusion, and those that used psychological probes of the HPA-axis. The global standardized mean effect size difference in HPA-axis response to the DST between depressed and non-depressed youth was 0.57, z=4.18, p<0.01. The global standardized mean difference effect size in basal HPA-axis functioning was 0.20, z=4.53, p<0.01. Age, sex, timing of sampling, dexamethasone dosage, or type of control group was not a significant source of variability for the DST or basal studies. In addition, when compared to non-depressed peers, depressed youth have a normative response to CRH infusion but an overactive response to psychological stressors. In conclusion, the HPA-axis system tends to be dysregulated in depressed youth, as evidenced by atypical responses to the DST, higher baseline cortisol values, and an overactive response to psychological stressors. This pattern of dysregulation suggests anomalies within the axis's negative feedback system and CRH production, but intact pituitary and adrenal sensitivity.