Rapid dopamine transmission within the nucleus accumbens: Dramatic difference between morphine and oxycodone delivery

While most drugs of abuse increase dopamine neurotransmission, rapid neurochemical measurements show that different drugs evoke distinct dopamine release patterns within the nucleus accumbens. Rapid changes in dopamine concentration following psychostimulant administration have been well studied; however, such changes have never been examined following opioid delivery. Here, we provide novel measures of rapid dopamine release following intravenous infusion of two opioids, morphine and oxycodone, in drug‐naïve rats using fast‐scan cyclic voltammetry and rapid (1 min) microdialysis coupled with high‐performance liquid chromatography ‐ tandem mass spectrometry (HPLC‐MS). In addition to measuring rapid dopamine transmission, microdialysis HPLC‐MS measures changes in GABA, glutamate, monoamines, monoamine metabolites and several other neurotransmitters. Although both opioids increased dopamine release in the nucleus accumbens, their patterns of drug‐evoked dopamine transmission differed dramatically. Oxycodone evoked a robust and stable increase in dopamine concentration and a robust increase in the frequency and amplitude of phasic dopamine release events. Conversely, morphine evoked a brief (~ 1 min) increase in dopamine that was coincident with a surge in GABA concentration and then both transmitters returned to baseline levels. Thus, by providing rapid measures of neurotransmission, this study reveals previously unknown differences in opioid‐induced neurotransmitter signaling. Investigating these differences may be essential for understanding how these two drugs of abuse could differentially usurp motivational circuitry and powerfully influence behavior.     

Stochastic dynamic causal modeling of working memory connections in cocaine dependence

Although reduced working memory brain activation has been reported in several brain regions of cocaine‐dependent subjects compared with controls, very little is known about whether there is altered connectivity of working memory pathways in cocaine dependence. This study addresses this issue by using functional magnetic resonance imaging‐based stochastic dynamic causal modeling (DCM) analysis to study the effective connectivity of 19 cocaine‐dependent subjects and 14 healthy controls while performing a working memory task. Stochastic DCM is an advanced method that has recently been implemented in SPM8 that can obtain improved estimates, relative to deterministic DCM, of hidden neuronal causes before convolution with the hemodynamic response. Thus, stochastic DCM may be less influenced by the confounding effects of variations in blood oxygen level‐dependent response caused by disease or drugs. Based on the significant regional activation common to both groups and consistent with previous working memory activation studies, seven regions of interest were chosen as nodes for DCM analyses. Bayesian family level inference, Bayesian model selection analyses, and Bayesian model averaging (BMA) were conducted. BMA showed that the cocaine‐dependent subjects had large differences compared with the control subjects in the strengths of prefrontal–striatal modulatory (B matrix) DCM parameters. These findings are consistent with altered cortical–striatal networks that may be related to reduced dopamine function in cocaine dependence. As far as we are aware, this is the first between‐group DCM study using stochastic methodology. Hum Brain Mapp 35:760–778, 2014. © 2012 Wiley Periodicals, Inc.     

A commonly carried genetic variant in the delta opioid receptor gene,OPRD1, is associated with smaller regional brain volumes: Replication in elderly and young populations

Delta opioid receptors are implicated in a variety of psychiatric and neurological disorders. These receptors play a key role in the reinforcing properties of drugs of abuse, and polymorphisms in OPRD1 (the gene encoding delta opioid receptors) are associated with drug addiction. Delta opioid receptors are also involved in protecting neurons against hypoxic and ischemic stress. Here, we first examined a large sample of 738 elderly participants with neuroimaging and genetic data from the Alzheimer's Disease Neuroimaging Initiative. We hypothesized that common variants in OPRD1 would be associated with differences in brain structure, particularly in regions relevant to addictive and neurodegenerative disorders. One very common variant (rs678849) predicted differences in regional brain volumes. We replicated the association of this single‐nucleotide polymorphism with regional tissue volumes in a large sample of young participants in the Queensland Twin Imaging study. Although the same allele was associated with reduced volumes in both cohorts, the brain regions affected differed between the two samples. In healthy elderly, exploratory analyses suggested that the genotype associated with reduced brain volumes in both cohorts may also predict cerebrospinal fluid levels of neurodegenerative biomarkers, but this requires confirmation. If opiate receptor genetic variants are related to individual differences in brain structure, genotyping of these variants may be helpful when designing clinical trials targeting delta opioid receptors to treat neurological disorders. Hum Brain Mapp 35:1226–1236, 2014. © 2013 Wiley Periodicals, Inc.     

Internet use and addiction among Finnish Adolescents (15–19 years)

This study investigates Internet use among Finnish adolescents (n = 475) combining qualitative and quantitative research. Internet use was evaluated using the Internet Addiction Test (Young, 1998a, Young, 1998b). The data was divided into three parts according to the test scores: normal users (14.3%), mild over-users (61.5%), and moderate or serious over-users (24.2%). The most common reason for use was having fun. While half the students reported disadvantages associated with their use, further qualitative analysis revealed that students with serious overuse did not report any harm caused by using the Internet. As disadvantages of using the Internet, students reported that it is time-consuming and causes mental, social, and physical harm and poor school attendance. Four factors of Internet addiction were found, and for two of them, a statistical difference between females and males was found.     

Attachment and family functioning in patients with Internet addiction

Objective

Although the Internet is used effectively in many areas of life, some users experience problems because of over-use due to a lack of control. The diagnostic criteria for Internet addiction include disruptions in family relationships, but adequate data on the attachment styles and family functioning associated with this condition are limited. This study aimed to investigate the attachment styles and family functioning of patients with Internet addiction.

Method

The sample included 30 male patients consecutively admitted to the Bak?rköy Mental Health and Research Hospital Internet Addiction Outpatient Clinic, who were diagnosed in clinical interviews as having Internet addiction according to Young’s (1998) criteria. Thirty healthy males who were matched with the experimental group in terms of sociodemographic characteristics were included as control subjects. Both groups provided sociodemographic data and completed the Beck Depression Inventory (BDI), the Experiences in Close Relationships Questionnaire-r (ECR-r) and the Family Assessment Device (FAD).

Results

Patients with Internet addiction had higher BDI scores (P< .001) and higher attachment anxiety subscores on ECR-r (P< .001) compared with those in the control group. Patients with Internet addiction evaluated their family functioning as more negative and reported problems in every aspect addressed by the FAD. Scores on the FAD behaviour control, affective responsiveness, and problem-solving subscales (P< .05) and on the FAD communication, roles, and general functioning subscales (P< .001) were significantly higher in the patient compared with the control group.

Conclusion

Patients with Internet addiction have more anxious attachment styles as well as prominent disruptions in family functioning. Thus, it may be important to evaluate the attachment styles and family functioning of patients with Internet addiction. Indeed, comprehensive treatment approaches including other family members may make important contributions to treatment success.     

Anhedonia in obsessive-compulsive disorder: Beyond comorbid depression

Obsessive-compulsive disorder (OCD) has been linked to reward dysfunctions, highlighting a possible role of anhedonia in OCD. Surprisingly, anhedonia in OCD has never been evaluated. Moreover, although nicotine typically has anti-anhedonic effects, anecdotal reports suggest low prevalence rates of smoking in OCD. To address these two phenomena, 113 individuals with OCD completed a battery of questionnaires assessing symptom severity, anhedonia, and smoking. 28.3% of the sample met criteria for clinically significant anhedonia, which correlated with Y-BOCS scores (r=0.44), even when controlling for depressive symptoms. 13.3% of the sample endorsed current smoking, a lower rate than seen in psychiatric disorders (40–90%) and the general adult population (19%). Results highlight high rates of anhedonia and yet reduced prevalence of smoking in OCD. In contrast to the known positive association between anhedonia and smoking, a negative association emerged. Future research is needed to address the unique interface between anhedonia and reward responsiveness in OCD. Potential clinical implications are discussed.     

Causes of metabolic syndrome and obesity-related co-morbidities Part 1: A composite unifying theory review of human-specific co-adaptations to brain energy consumption

One line summary

Metabolic syndrome and obesity-related co-morbidities are largely explained by co-adaptations to the energy use of the large human brain in the cortico-limbic-striatal and NRF2 systems.

The medical, research and general community is unable to effect significantly decreased rates of central obesity and related type II diabetes mellitus (TIIDM), cardiovascular disease (CVD) and cancer. All conditions seem to be linked by the concept of the metabolic syndrome (MetS), but the underlying causes are not known. MetS markers may have been mistaken for causes, thus many treatments are destined to be suboptimal.The current paper aims to critique current paradigms, give explanations for their persistence, and to return to first principles in an attempt to determine and clarify likely causes of MetS and obesity related comorbidities. A wide literature has been mined, study concepts analysed and the basics of human evolution and new biochemistry reviewed. A plausible, multifaceted composite unifying theory is formulated.The basis of the theory is that the proportionately large, energy-demanding human brain may have driven co-adaptive mechanisms to provide, or conserve, energy for the brain. A ‘dual system’ is proposed. 1) The enlarged, complex cortico-limbic-striatal system increases dietary energy by developing strong neural self-reward/motivation pathways for the acquisition of energy dense food, and (2) the nuclear factor-erythroid 2-related factor 2 (NRF2) cellular protection system amplifies antioxidant, antitoxicant and repair activity by employing plant chemicals, becoming highly energy efficient in humans.The still-evolving, complex human cortico-limbic-striatal system generates strong behavioural drives for energy dense food procurement, including motivating agricultural technologies and social system development. Addiction to such foods, leading to neglect of nutritious but less appetizing ‘common or garden’ food, appears to have occurred. Insufficient consumption of food micronutrients prevents optimal human NRF2 function. Inefficient oxidation of excess energy forces central and non-adipose cells to store excess toxic lipid. Oxidative stress and metabolic inflammation, or metaflammation, allow susceptibility to infectious, degenerative atherosclerotic cardiovascular, autoimmune, neurodegenerative and dysplastic diseases.Other relevant human-specific co-adaptations are examined, and encompass the unusual ability to store fat, certain vitamin pathways, the generalised but flexible intestine and microbiota, and slow development and longevity.This theory has significant past and future corollaries, which are explored in a separate article by McGill, A-T, in Archives of Public Health, 72: 31.     

Pathogenomics insights for understanding Pasteurella multocida adaptation

Pasteurella multocida is an important veterinary pathogen able to infect a wide range of animals in a broad spectrum of diseases. P. multocida is a complex microorganism in relation to its genomic flexibility, host adaptation and pathogenesis. Epidemiological analysis based on multilocus sequence typing, serotyping, genotyping, association with virulence genes and single nucleotide polymorphisms (SNPs), enables assessment of intraspecies diversity, phylogenetic and strain-specific relationships associated with host predilection or disease. A high number of sequenced genomes provides us a more accurate genomic and epidemiological interpretation to determine whether certain lineages can infect a host or produce disease. Comparative genomic analysis and pan-genomic approaches have revealed a flexible genome for hosting mobile genetic elements (MGEs) and therefore significant variation in gene content. Moreover, it was possible to find lineage-specific MGEs from the same niche, showing acquisition probably due to an evolutionary convergence event or to a genetic group with infective capacity. Furthermore, diversification selection analysis exhibits proteins exposed on the surface subject to selection pressures with an interstrain heterogeneity related to their ability to adapt. This article is the first review describing the genomic relationship to elucidate the diversity and evolution of P. multocida.     

Imaging natural cognition in action

The primary function of the human brain is arguably to optimize the results of our motor actions in an ever-changing environment. Our cognitive processes and supporting brain dynamics are inherently coupled both to our environment and to our physical structure and actions. To investigate human cognition in its most natural forms demands imaging of brain activity while participants perform naturally motivated actions and interactions within a full three-dimensional environment. Transient, distributed brain activity patterns supporting spontaneous motor actions, performed in pursuit of naturally motivated goals, may involve any or all parts of cortex and must be precisely timed at a speed faster than the speed of thought and action. Hemodynamic imaging methods give information about brain dynamics on a much slower scale, and established techniques for imaging brain dynamics in all modalities forbid participants from making natural extensive movements so as to avoid intractable movement-related artifacts. To overcome these limitations, we are developing mobile brain/body imaging (MoBI) approaches to study natural human cognition. By synchronizing lightweight, high-density electroencephalographic (EEG) recording with recordings of participant sensory experience, body and eye movements, and other physiological measures, we can apply advanced data analysis techniques to the recorded signal ensemble. This MoBI approach enables the study of human brain dynamics accompanying active human cognition in its most natural forms. Results from our studies have provided new insights into the brain dynamics supporting natural cognition and can extend theories of human cognition and its evolutionary function — to optimize the results of our behavior to meet ever-changing goals, challenges, and opportunities.     

Use of mobile-stroke risk scale and lifestyle guidance promote healthy lifestyles and decrease stroke risk factors

ObjectiveThe purpose of this study was to determine the effectiveness of Mobile-Stroke Risk Scale and Life Style Guidance (M-SRSguide) in promoting a healthy lifestyle and reducing stroke risk factors in at-risk persons.MethodsThis research was an clinical trial with a pre-test and post-test control group design. The accessible population is persons at risk of stroke in the community (West and East Kalimantan Province, Indonesia). Thirty-two participants in the intervention group and 32 participants in the control group participated in this study. The sampling method was systematic random sampling. We allocate the sample into the intervention and control groups using a randomized block design. The intervention group used the M-SRSguide. The control group used manual book for a self-assessment of stroke risk. The measurement of a healthy lifestyle and the stroke risk factors was performed before and six months after the intervention.ResultsThere are no significant differences in healthy lifestyle and stroke risk factors between the two groups after the intervention (P > 0.05). Analysis of healthy lifestyle behavior assessment items in the intervention group showed an increase in healthy diets, activity patterns, and stress control after the use of the M-SRSguide (P < 0.01).ConclusionThe use of M-SRSguide is effective in promoting a healthy lifestyle.