Hypothalamic-pituitary-adrenal axis function and the metabolic syndrome X of obesity

Obesity has negative health consequences related to fat distribution, particularly the central or visceral accumulation of fat. The major complications associated with visceral obesity, termed the "Metabolic Syndrome of Obesity," or "Syndrome X," are type II diabetes, hypertension, and dyslipidemia. As with certain mood disorders, the syndrome may be a consequence of neuroendocrine perturbations typically associated with chronic stress. Our work with bonnet macaque monkeys provides an animal model for the relationship between early stress, behavioral and hypothalamic-pituitary-adrenal (HPA) axis dysregulation, and Syndrome X. During their infant's first half-year, mothers face a variable foraging demand (VFD), in which ample food varies unpredictably in the difficulty of its acquisition, and the offspring show persistent abnormalities in systems known to modulate stress and affective regulation. Early work on the bonnet macaque noted the emergence of a sample of spontaneously obese subjects as they matured. Using the VFD model, the current study showed that there was a clear relationship between early cerebrospinal fluid corticotropin-releasing factor levels and subsequently measured body mass index, supporting the hypotheses regarding the interactive roles of early experience and HPA axis dysregulation in the ontogeny of both metabolic and mood disorders.     

Facets of mindfulness mediate behavioral inhibition systems and emotion dysregulation

Behavioral motivation is regulated through the behavioral inhibition system (BIS) and the behavioral approach system (BAS), which underlie responses to emotional stimuli and are thought to influence emotion dysregulation. Research shows that mindfulness may increase the efficacy of emotion regulation among those with psychological symptoms, but the relationships between behavioral motivation and mindfulness have been only minimally explored. This study examines relationships between behavioral motivation systems and emotion dysregulation as mediated by mindfulness facets. Mediation was tested in a sample of 246 college students (M_age = 19.28, 61.8% female, 81.3% Caucasian) using a multiple mediator bootstrapping method. Results revealed an indirect relationship between BIS sensitivity and increased emotion dysregulation through underutilization of three distinct mindfulness skills: act with awareness, non-judging, and non-reactivity. Mindfulness facets did not mediate relationships between BAS sensitivity and emotion dysregulation, though BAS Reward Responsiveness directly predicted increased emotion dysregulation while BAS Drive was marginally associated with decreased emotion dysregulation. Findings delineate specific relationships between BIS/BAS, mindfulness skills, and emotion dysregulation while suggesting mindfulness training may be useful for BIS sensitive individuals.     

Conditioned suppression or facilitation as a function of the behavioral baseline

Rats were exposed to a multiple schedule of reinforcement. During one component, a bar-press was followed by reinforcement only if it occurred between 15 and 20 sec after the previous response. This differential-reinforcement-of-low-rate (DRL) schedule produced a typical slow rate of responding. During the other component, reinforcement followed the first response to be emitted during limited periods of time which occurred at fixed intervals. These fixed-interval schedules with a limited hold produced higher response rates, described as `interval' or `ratio-like' behavior. Responding during the DRL component increased in frequency during a tone which ended with an unavoidable shock of low intensity, but decreased during the tone when the shock intensity was raised. The `interval' and `ratio-like' responding decreased in frequency during the tone at all shock intensities. Initial acceleration of the DRL responding appeared to be due to adventitious punishment of collateral behavior which was observed between the bar-presses. The more severe conditioned suppression during the fixed-interval components might be the result of the lower probability of reinforcement after any single response.     

Effects of mineralocorticoid receptor blockade on empathy in patients with major depressive disorder

Background

The mineralocorticoid receptor (MR) is highly expressed in the hippocampus and prefrontal cortex and is involved in social cognition. We recently found that pharmacological stimulation of the MR enhances emotional empathy but does not affect cognitive empathy. In the current study, we examined whether blockade of the MR impairs empathy in patients with major depressive disorder (MDD) and healthy individuals.

Methods

In a placebo-controlled study, we randomized 28 patients with MDD without psychotropic medication and 43 healthy individuals to either placebo or 300 mg spironolactone, a MR antagonist. Subsequently, all participants underwent two tests of social cognition, the Multifaceted Empathy Test (MET) and the Movie for the Assessment of Social Cognition (MASC), measuring cognitive and emotional facets of empathy.

Results

In the MET, we found no significant main effect of treatment or main effect of group for cognitive empathy but a highly significant treatment by group interaction (p < 0.01). Patients had higher cognitive empathy scores compared to controls in the placebo condition but not after spironolactone. Furthermore, in the spironolactone condition reduced cognitive empathy was seen in MDD patients but not in controls. Emotional empathy was not affected by MR blockade. In the MASC, no effect of spironolactone could be revealed.

Conclusion

Depressed patients appear to exhibit greater cognitive empathy compared to healthy individuals. Blockade of MR reduced cognitive empathy in MDD patients to the level of healthy individuals. Future studies should further clarify the impact of MR functioning on different domains of social cognition in psychiatric patients.

     

Facets of psychopathy, Axis II traits, and behavioral dysregulation among jail detainees

Forensic evaluations of offender populations often consider psychopathy as an integral component of these consultations. Vexing issues remain of whether psychopathic traits should be evaluated consistently irrespective of demographic characteristics (e.g. gender), comorbidity (e.g. other Axis II pathology), or setting (e.g. jail or community). The current study examined gender differences for psychopathy and Axis II traits in a nonreferred jail sample of predominantly nonviolent offenders. Participants with moderate to high levels of psychopathy evidenced substantial comorbidity, especially with Cluster B personality disorders. Facets of psychopathy and Axis II traits varied substantially across both genders. In addition, the research evaluated Lynam's Hyperactivity, Impulsivity, and Attention difficulties (HIA) model of psychopathy. These initial data found little support for the HIA model in this jail sample. In testing competing hypotheses, the HIA model was substantially better at predicting Cluster B traits than psychopathy per se.     

The use of biofeedback techniques with school-aged children exhibiting behavioral and/or learning problems

This article reviews 44 studies that investigated the efficacy of biofeedback techniques in treating childhood behavioral and learning disorders. Although the data suggest that children can learn voluntary control over a variety of physiological processes, methodological flaws make it impossible to specify the mechanisms responsible for such learning. Further, the data do not suggest that biofeedback techniques are superior to more conventional treatments in remediating learning or behavioral disorders. Suggestions for future research focus upon the elimination of methodological weaknesses, the use of more stringent diagnostic criteria, and the use of more sophisticated biofeedback equipment and procedures.     

Relationships between cognitive and behavioral measures of executive function in children with brain disease.

This study addressed the clinical and construct validity of the Behavior Rating Inventory of Executive Function. (BRIEF: Gioia, Isquith, Guy, & Kenworthy, 2000), a questionnaire designed to tap behavioral aspects of executive functions in children. BRIEF profiles in early treated phenylketonuria (PKU; n=44), early treated hydrocephalus (n=45), frontal focal lesions (n=20) and controls (n=80) were examined. Clinical validity was supported through significant between-group comparisons, especially between the frontal focal lesion group and other groups. To examine construct validity, raw scores on cognitive executive function measures including the Contingency Naming Test (CNT), Rey Complex Figure (RCF), Tower of London (TOL), and Controlled Oral Word Association Test (COWAT), were correlated with BRIEF scale scores. Few significant correlations were found, indicating cognitive and behavioral measures appear to tap different constructs within the executive function domain. A dissociation was found between behavioral and cognitive impairments in the frontal as opposed to PKU and hydrocephalus groups. This is discussed in relation to underlying pathology, the cognitive measures used, and possible limitations in the BRIEF's usefulness for measuring behavioral executive dysfunction in groups only mildly affected by neurological compromise.     

Association of hypothalamic-pituitary-adrenal axis function with neuropsychological performance in children with mild/moderate asthma.

The present study examines the relationship between hypothalamic-pituitary-adrenal (HPA) axis function and child psychological/neuropsychological function in a group of children with mild to moderate asthma. The goal of the study was to determine whether child neuropsychological functioning and psychological functioning were associated with cortisol production in response to adrenocorticotropic hormone(ACTH) stimulation when assessed as area under the curve. Data for this study were gathered from 63 children who participated in an ancillary study within the Childhood Asthma Management Program (CAMP) during the pre-randomization phase of the CAMP trial. At 2 of the 8 CAMP clinical centers participants completed an ACTH stimulation test after an overnight stay in the General Clinical Research Center. Gender differences on baseline cortisol and change in cortisol 30 minutes after infusion of ACTH were present. Results further indicated significant associations between cortisol production and measures of child neuropsychological function. Stepwise multiple regression analysis revealed that cortisol change could be predicted by measures of gender, working memory, and arousal maintenance, providing support for the hypothesis that cortisol plays a modest role in the neuropsychological function of children with mild and moderate asthma. In contrast, cortisol production was not associated with child reports of psychological functioning. Limitations to the methods employed in this study are discussed.     

A local-rate-of-response and interresponse-time analysis of behavioral contrast

Three pigeons were exposed to a two-component multiple schedule in which a variable-interval 3-min schedule was always in effect in one component. The schedule in the other component was either variable-interval 3-min or extinction in alternate blocks of sessions. When the schedule was changed from multiple variable-interval 3-min variable-interval 3-min to multiple variable-interval 3-min extinction in the second and fourth phases of the experiment, overall response rates in the unchanged variable-interval 3-min component increased in two pigeons. Response rate declined when the schedule was changed to multiple variable-interval 3-min variable-interval 3-min again. Correlated with increases in overall response rate in the unchanged component were increases in local response rates at the beginning of the unchanged component and immediately after food presentation. Local rates 40 sec after food presentation did not increase greatly in the presence of the multiple variable-interval 3-min extinction schedule. An interresponse time analysis of three local rate samples showed small increases in the relative frequency of short-duration interresponse times at the beginning of the unchanged component and immediately after food presentation. Neither the postreinforcement pause nor the latency to the first response in the unchanged component changed systematically.     

Behavior analysis and the growth of behavioral pharmacology

Psychologists, particularly those influenced by the work of B. F. Skinner, played a major part in the development of behavioral pharmacology in the 1950s and 1960s. Revolutionary changes in pharmacology and psychiatry, including the discovery of powerful therapeutic agents such as chlorpromazine and reserpine, had produced a surge of interest in drug research. Pharmaceutical companies began hiring psychologists with operant conditioning backgrounds so as to compete successfully in the search for new drugs. Psychologists, most of whom were skilled in the behavior-analytic approach, started to assume prominent positions as authors and editors for the Journal of Pharmacology and Experimental Therapeutics as its emphasis on behavior increased. This also proved true with the other publications founded to deal with the popularity of behavioral pharmacology. Especially important were contributions by B. F. Skinner, Peter B. Dews, and Joseph V. Brady.     

Activational and organizational effects of estradiol on male behavioral neuroendocrine function

Evidence is reviewed that establishes an essential role for estradiol, synthesized locally via aromatization of testosterone in the adult as well as the developing male nervous system of rats, ferrets, and mice, in both the organization and adult activation of neural circuits that control appetitive as well as consummatory components of masculine sexual behavior. Evidence is also reviewed suggesting that perinatal estradiol biosynthesis and action in the female's nervous system may contribute to the development of female-typical sexual behavior.     

Influence of chronic corticosterone and glucocorticoid receptor antagonism in the amygdala on fear conditioning

Glucocorticoid receptor activation within the basolateral amygdala (BLA) during fear conditioning may mediate enhancement in rats chronically exposed to stress levels of corticosterone. Male Sprague-Dawley rats received corticosterone (400 microg/ml) in their drinking water (days 1-21), a manipulation that was previously shown to cause hippocampal CA3 dendritic retraction. Subsequently, rats were adapted to the fear conditioning chamber (day 22), then trained (day 23), and tested for conditioned fear to context and tone (day 25). Training consisted of two tone (20s) and footshock (500 ms, 0.25 mA) pairings. In Experiment 1, muscimol (4.4 nmol/0.5 microl/side), a GABAergic agonist, was microinfused to temporarily inactivate the BLA during training. Rats given chronic corticosterone showed enhanced freezing to context, but not tone, compared to vehicle-supplemented rats. Moreover, BLA inactivation impaired contextual and tone conditioning, regardless of corticosterone treatment. In Experiment 2, RU486 (0, 0.3, and 3.0 ng/0.2 microl/side) was infused on training day to antagonize glucocorticoid receptors in the BLA. Corticosterone treatment enhanced fear conditioning to context and tone when analyzed together, but not separately. Moreover, RU486 (3.0 ng/side) selectively exacerbated freezing to context in chronic corticosterone-exposed rats only, but failed to alter tone conditioning. Serum corticosterone levels were negatively correlated with contextual, not tone, conditioning. Altogether, these suggest that chronic corticosterone influences fear conditioning differently than chronic stress as shown previously. Moreover, chronic exposure to corticosteroids alters BLA functioning in a non-linear fashion and that contextual conditioning is influenced more than tone conditioning by chronic corticosterone and BLA glucocorticoid receptor stimulation.     

Units of analysis and kinetic structure of behavioral repertoires

It is suggested that molar streams of behavior are constructed of various arrangements of three elementary constituents (elicited, evoked, and emitted response classes). An eight-cell taxonomy is elaborated as a framework for analyzing and synthesizing complex behavioral repertoires based on these functional units. It is proposed that the local force binding functional units into a smoothly articulated kinetic sequence arises from temporally arranged relative response probability relationships. Behavioral integration is thought to reflect the joint influence of the organism's hierarchy of relative response probabilities, fluctuating biological states, and the arrangement of environmental and behavioral events in time.     

Determination of a behavioral transfer function: White-noise analysis of session-to-session response-ratio dynamics on concurrent VI VI schedules

Six pigeons were exposed to concurrent variable-interval schedules in which the programmed reinforcer ratios changed from session to session according to a pseudorandom binary sequence. This procedure corresponded to the stochastic identification paradigm (“white-noise experiment”) of systems theory and enabled the relation between log response ratios in the current session and log reinforcer ratios in all previous sessions to be determined. Such dynamic relations are called linear transfer functions. Both nonparametric and parametric representations of these, in the form of “impulse-response functions,” were determined for each bird. The session-to-session response ratios resulting from the session-to-session pseudorandom binary variations in reinforcer ratios were well predicted by the impulse-response functions identified for each pigeon. The impulse-response functions were well fitted by a second-order dynamic model involving only two parameters: a time constant and a gain. The mean time constant was 0.67 sessions, implying that the effects of abrupt changes in log reinforcer ratios should be 96% complete within about five sessions. The mean gain was 0.53, which was surprisingly low inasmuch as it should equal the sensitivity to reinforcement ratio observed under steady-state conditions. The same six pigeons were subjected to a similar experiment 10 months following the first. Despite individual differences in impulse-response functions between birds within each experiment, the impulse-response functions determined from the two experiments were essentially the same.     

Three applications of functional analysis with group dynamic cognitive behavioral group therapy

Case illustrations from group dynamic cognitive behavioral group therapy are presented to demonstrate three applications of functional analysis and the resulting cognitive behavioral interventions. The principles of group dynamic cognitive behavioral group therapy are explained. A functional analysis is applied first to the problem behavior of an individual group member. A clinical case illustrates how the group members help to change this individual group member's behavior from a learning theory perspective. Next, the circular interactional problem behavior between two group members is reduced to the individual functional analysis of each of the two member's problem behaviors. It is then illustrated how the two group member's problem behaviors, as well as feedback from others, contribute toward helping to change each others behavior. The paper concludes that functional analysis and ensuing behavioral interventions can be also applied to group as a whole behavior.     

A growth curve analysis of emotion dysregulation as a mediator for violence in individuals with and without borderline personality disorder

Borderline personality disorder (BPD) is characterized by significant interpersonal conflict, however the factors that contribute to violence among this population are not well known. Individuals with BPD and other severe mental illnesses were followed in the community for 30 weeks post-inpatient discharge. Emotion dysregulation data and detailed measures of violence were collected every 10 weeks, along with measures of antisocial characteristics. Latent growth curve analyses were used to depict individual trajectories of emotion dysregulation throughout the course of the study, and the degree to which changes in emotion dysregulation mediated the risk-enhancing effect of BPD on subsequent interpersonal violence was assessed. Results showed that emotion dysregulation is a significant longitudinal mediator of violent behavior among individuals with BPD, and may serve as the primary mechanism that enhances risk for violence among this population. Implications for modifying existing treatment protocols to reduce interpersonal violence in this population are discussed.