Cortisol responses on the dexamethasone suppression test among women with Bulimia-spectrum eating disorders: associations with clinical symptoms

Introduction

Evidence associates Bulimia Nervosa (BN) with altered functioning of the hypothalamic-pituitary-adrenal (HPA) axis, but the clinical implications of such alterations need to be better understood. We contrasted cortisol responses to the dexamethasone suppression test (DST) in bulimic and non-eating disordered women and examined relationships among DST cortisol responses, eating symptoms and co-morbid disturbances.

Method

Sixty women with Bulimia Spectrum (BS) Disorders (either BN or normal weight Eating Disorder NOS with regular binge eating or purging) and 54 non-eating disordered women of similar age and body mass index participated in a 0.5 mg DST, and completed interviews and questionnaires assessing eating symptoms and co-morbid psychopathology.

Results

Compared with the normal-eater group, the BS women demonstrated significantly less DST suppression. Among BS women, DST non-suppression was associated with more severe depression, anxiety and eating preoccupations.

Conclusions

Our findings show BS women to show less DST suppression compared to normal eater women, and results link extent of non-suppression, in BS individuals, to severity of depression, anxiety and eating preoccupations.     

Alternative reinforcer response cost impacts cocaine choice in humans

Cocaine use disorders are an unrelenting public health concern. Behavioral treatments reduce cocaine use by providing non-drug alternative reinforcers. The purpose of this human laboratory experiment was to determine how response cost for non-drug alternative reinforcers influenced cocaine choice. Seven cocaine-using, non-treatment-seeking subjects completed a crossover, double-blind protocol in which they first sampled doses of intranasal cocaine (5, 10, 20 or 30 mg) and completed a battery of subject-rated and physiological measures. Subjects then made eight discrete choices between the sampled dose and an alternative reinforcer (US$0.25). The response cost to earn a cocaine dose was always a fixed ratio (FR) of 100 responses. The response cost for the alternative reinforcer varied across sessions (FR1, FR10, FR100, FR1000). Dose-related increases were observed for cocaine choice. Subjects made fewer drug choices when the FR requirements for the alternative reinforcers were lower than that for drug relative to when the FR requirements were equal to or higher than that for drug. Intranasal cocaine also produced prototypical stimulant-like subject-rated and physiological effects (e.g., increased ratings of Like Drug; elevated blood pressure). These data demonstrate that making alternative reinforcers easier to earn reduces cocaine self-administration, which has implications for treatment efforts.     

Analysis of association between common SNPs in ErbB4 and bipolar affective disorder, major depressive disorder and schizophrenia in the Han Chinese population

Neuregulin-1 (NRG1) is associated with schizophrenia. As one of the receptors of NRG1, v-erb-a erythroblastic leukemia viral oncogene homolog 4 (ErbB4) has also been reported to be associated with schizophrenia. Since there can be shared genetic variants among bipolar affective disorder, major depressive disorder and schizophrenia, we tested the association between ErbB4 and these three major psychiatric disorders in the Han Chinese population. Five single nucleotide polymorphisms (SNPs) were selected based on previous positive reports and linkage disequilibrium information of the HapMap Han Chinese individuals from Beijing (CHB) + individuals from Tokyo, Japan (JPT) population. These SNPs were genotyped in 1140 bipolar affective disorder (BPAD) patients, 1140 schizophrenia (SCZ) patients, 1139 major depressive disorder (MDD) patients and 1140 normal controls. Two SNPs (rs707284 and rs839523) showed nominal significance in the BPAD patients but this was eliminated after permutation. No significant association between ErbB4 and the two other psychiatric disorders was observed, nor did haplotype analysis reveal any positive signal.     

The association between gambling pathology and personality disorders

Research supports increased risk of problem gambling (PG) and pathological gambling disorder (PGD) among individuals with substance abuse/dependence and psychiatric disorders, but studies considering personality disorder comorbidity have not adjusted for confounding relationships with other Axis I disorders. Using targeted advertising, we enrolled 153 gamblers (55% female; 32% minority; Mean age=47; SD=18.2) in a clinical validation study of the newly developed computerized gambling assessment module (C-GAM). For these analyses, we classified gamblers into three groups based on their endorsement of DSM-IV PGD: Non-gamblers (0 criteria; n=64; 44%); PG (1-4 criteria; n=60; 41%); and PGD (5-10 criteria; n=22; 15%). We evaluated PG and PGD risk associated with personality disorder pathology using the computerized structured clinical interview of DSM-IV Axis II (SCID-II). Using multinomial logistic regression, we found increased odds of PGD among individuals with greater symptoms of borderline personality disorder after adjusting for socio-demographics, substance abuse/dependence and other personality disorders significant at the bivariate level. Yet after adjusting for depressive symptoms, borderline personality disorder criteria were nonsignificant, suggesting a complex relationship between personality pathology, depression, and gambling. These findings bolster the position that further investigation is needed regarding the association of gambling pathology with personality disorders and depressive symptoms.     

Comparative remission rates of schizophrenic patients using various remission criteria

Rationale

New standardized criteria for remission in schizophrenia were presented in 2005 which need to be examined in regard to their significance for clinical trials.

Objectives and methods

Data of six antipsychotic drug trials (n = 2463) were analyzed by evaluating the proportion of participants who meet the new remission criteria, their symptomatic components, other criteria for remission and simple response-measures (at least 50% Brief Psychiatric Rating Scale (BPRS) reduction and an at least 50% PANSS reduction or a CGI-severity score of “mild or better”).Results: A total of 23.3%/27.2% (last-observation-carried-forward (LOCF)/completer analysis (CO)) of the patients with positive symptoms at baseline met the severity criteria of remission at 4 weeks, 10.5%/20.3% (worst case/CO) met the severity and time criteria at 28 weeks (three studies) and 10.9%/32.4% (worst case/CO) met the severity and time criteria at 52 weeks (one study). At 4 weeks 4.5%/5.5% (LOCF/CO) met the severity criteria when a more stringent severity threshold of “very mild or better” was applied. Absence of symptoms was attained only sporadically. The psychotic symptoms component was met by fewer patients than the negative component. The criteria were more stringent than “at least 50% BPRS reduction” and “CGI-severity score not more than mild” and – for the long-term results – than “at least 50% PANSS reduction”. In the short-term analysis, the criteria were less stringent than “at least 50% PANSS reduction”.

Conclusions

The applicability of the severity component of the new criteria in clinical trials was confirmed. The time criterion remains difficult to evaluate.     

High-field MRS study of GABA, glutamate and glutamine in social anxiety disorder: response to treatment with levetiracetam

OBJECTIVE: Abnormalities in brain gamma-aminobutyric acid (GABA) and glutamate may be relevant to the underlying pathophysiology of anxiety disorders including social anxiety disorder (SAD). METHODS: We used proton magnetic resonance spectroscopy (pMRS) to examine whole brain and regional GABA, glutamate and glutamine in patients (N=10) with SAD at baseline compared to a matched group of healthy controls (HC), and changes following 8 weeks of pharmacotherapy with levetiracetam. RESULTS: For SAD subjects, there were significantly higher whole brain levels of glutamate and glutamine, though no significant differences in GABA. In the thalamus, glutamine was higher and GABA lower for SAD subjects. There was a significant reduction in thalamic glutamine with levetiracetam treatment. CONCLUSION: Our findings provide preliminary support for impaired GABAergic and overactive glutamatergic function in social anxiety disorder and the potential relevance of changes in these systems for the anxiolytic response to levetiracetam.     

A systematic review of off-label uses of memantine for psychiatric disorders

Recent data points to glutamatergic dysfunction in mood disorders, anxiety disorders, obsessive-compulsive disorder, and schizophrenia. Memantine, a drug approved by the FDA for the treatment of moderate to severe Alzheimer's disease that acts at the N-methyl-d-aspartate receptor, has been used off-label for various psychiatric disorders. Although promising, the available data for the use of memantine in these disorders is limited. Given this data, the routine use of memantine for depression, schizophrenia, obsessive-compulsive disorder, substance abuse, pervasive developmental disorders, bipolar disorder, and binge eating disorder cannot be recommended at this time.     

Female specific anterior cingulate abnormality and its association with empathic disability in schizophrenia

Evidence suggests that impairments of empathy are present in schizophrenia and that such deficits lead to social dysfunction. However, the relationship between brain morphological abnormalities of the disorder and empathic disabilities has not been fully investigated. As the anterior cingulate cortex (ACC) is one of the critical structures for empathy processing, the pathology of this structure might be a major source of social dysfunction, including interpersonal miscommunication in schizophrenia. In addition, as recent studies suggest that different facets of empathic ability depend on different subdivisions of the ACC, pathology of each subdivision would affect the empathic disability of schizophrenia differentially. Structural MRI data were acquired at 3.0 T from 24 schizophrenic patients and 20 healthy participants, and the volumes of ventral and dorsal ACC were measured and compared between the groups. Subjects' empathic abilities were evaluated using a multidimensional questionnaire, the Interpersonal Reactivity Index (IRI). The relationships of structural abnormalities with empathic disabilities were investigated, by correlating ACC subdivisional volumes with each IRI subscale score. Female schizophrenic patients exhibited volume reductions in the ventral ACC bilaterally and in the left dorsal ACC compared with healthy subjects. Schizophrenic patients performed poorly on fantasy and personal distress subscales of the IRI. Furthermore, volumes of the left dorsal ACC were inversely correlated with personal distress subscale scores within female patients with schizophrenia. These results suggest that pathology of specific ACC subdivisions would have an impact on specific empathic disabilities in schizophrenia, with potential gender specificity.     

Antidepressant response to electroconvulsive therapy is sustained after catecholamine depletion

Although the antidepressant mechanism of ECT is unknown, there are data to support noradrenergic involvement. Patients who had been recently successfully treated with ECT for major depression were studied in a randomized double-blind cross-over design comparing catecholamine depletion using α-methyl-para-tyrosine to a placebo procedure. Mean MADRS scores at baseline (4.2 SD 2.7) and following depletion (4.6 SD 1.1) were similar, despite a 57.7% decrease in serum homovanillic acid (HVA) and a 61.5% decrease in 3-methoxy-4-hydroxyenylethyleneglycol (MHPG). These data suggest that catecholamine availability may not be necessary for acutely maintaining an antidepressant response to ECT.     

Abnormal regional spontaneous neural activity in first-episode,treatment-naive patients with late-life depression: A resting-state fMRI study

Background

The previous resting perfusion or task-based studies have provided evidence of functional changes in the brains of patients with late-life depression (LLD). Little is known, so far, about the changes in the spontaneous brain activity in LLD during the resting state. The aim of this study was to investigate the spontaneous neural activity in first-episode, treatment-naive patients with LLD by using resting-state functional magnetic resonance imaging (fMRI).

Methods

A novel analytical method, coherence-based regional homogeneity (Cohe-ReHo), was used to assess regional spontaneous neural activity during the resting state in 15 first-episode, treatment-naive patients with LLD and 15 age- and gender-matched healthy controls.

Results

Compared to the healthy controls, the LLD group showed significantly decreased Cohe-ReHo in left caudate nucleus, right anterior cingulate gyrus, left dorsolateral prefrontal cortex, right angular gyrus, bilateral medial prefrontal cortex, and right precuneus, while significantly increased Cohe-ReHo in left cerebellum posterior lobe, left superior temporal gyrus, bilateral supplementary motor area, and right postcentral gyrus (p < 0.005, corrected for multiple comparisons).

Conclusions

These findings indicated abnormal spontaneous neural activity was distributed extensively in first-episode, treatment-naive patients with LLD during the resting state. Our results might supply a novel way to look into the underlying pathophysiology mechanisms of patients with LLD.