Dopamine response to psychosocial stress in humans and its relationship to individual differences in personality traits

BackgroundPrevious studies have reported inter-individual variability in the dopamine (DA) response to stress. This variability might be related to individual differences in the vulnerability to experience the negative effect of stress.ObjectiveTo investigate whether personality traits as measured by the Revised NEO Personality Inventory explain variability in DA response to a psychosocial stress task.MethodsEleven healthy adults, mean age of 26 ± 3.87 underwent two Positron Emission Tomography (PET) scans using the dopamine D_2/3 agonist, [¹¹C]-(+)-PHNO under a control and stress condition. The Simplified Reference Tissue Model (SRTM) was used to obtain [¹¹C]-(+)-PHNO Binding Potential (BP_ND). Stress-induced DA response was indexed as a percent change in [¹¹C]-(+)-PHNO BP_ND between control and stress conditions. The regions of interest were defined into D₂-rich regions, which included the Associative and Sensorimotor Striatum (AST and SMST); D₂/₃ mixed regions, which included the Limbic Striatum (LST) and Globus Pallidus (GP); and D₃-rich region, which included the Substantia Nigra (SN).ResultsSeveral personality traits within the Neuroticism and Openness to Experience domain were significantly correlated with blunted DA response to stress. Specifically, the Angry-Hostility, Vulnerability, and Depression trait were associated with blunted DA stress response in the AST (r = ?0.645, p = 0.032), LST (r = ?0.677, p = 0.022) and GP (r = ?0.736, p = 0.010), respectively. The Openness to Values was correlated with a decreased DA release in the SN (r = ?0.706, p = 0.015).ConclusionVariability in DA stress response might be related to individual differences in personality.     

Does shy-inhibited temperament in childhood lead to anxiety problems in adolescence?

OBJECTIVE: To assess the relationships between shy-inhibited temperament in childhood and anxiety problems in early adolescence using a prospective, longitudinal data set from a large community sample. METHOD: Relationships between shyness ratings on age-appropriate temperament scales and anxiety problems were analyzed, looking both forward and backward in time from infancy to adolescence. RESULTS: Forty-two percent of children rated as shy on 6 or more occasions over 8 surveys in childhood had anxiety problems in adolescence, compared with 11% who were never shy. Persistence of shyness and its presence in middle childhood increased risk for anxiety. A highly reactive temperament added to shyness did not increase the risk for anxiety. Few children with an anxiety diagnosis in early adolescence had a history of shyness. CONCLUSIONS: Prediction from childhood shyness to adolescent anxiety disorder is modest but clinically meaningful in a community sample. However, most shy children did not develop an anxiety disorder and most adolescents with anxiety disorders had not been especially shy.     

Nerve conduction studies in relation to residual fatigue in Guillain-Barré syndrome

Many Guillain-Barré syndrome (GBS) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) patients recover well, but suffer from excessive fatigue, which may persist for years and reduce the quality of life considerably. In order to determine whether residual subclinical peripheral nerve dysfunction is a possible underlying mechanism of fatigue, we performed standardized nerve conduction (NC) studies in 16 fatigued patients, mean 6.5 years after diagnosis. Thirteen were relatively well recovered from GBS and 3 had stable CIDP. In contrast to CIDP, most NC values in GBS patients were remarkably restored and within normal values.No correlations were found between the electrophysiological findings and the fatigue scores,muscle strength, or functional scores. This study demonstrates that fatigue in GBS is not explained by residual nerve dysfunction, using conventional NC measurements.     

Neuroemergencies in South America: How to Fill in the Gaps?

Neurocritical Care - South America is a subcontinent with 393 million inhabitants with widely distinct countries and diverse ethnicities, cultures, political and societal organizations. The...     

How to improve neuroprotection in Parkinson's disease?

Several factors involved in the etiology of Parkinson's disease (PD) have been proposed, including genetic and environmental factors or even a combination of both. Thus, multiple cellular hits are likely to contribute to neurodegeneration in PD. If such a mechanism happens to occur, our therapeutic intervention may perhaps require a cocktail of molecules acting on various pathways simultaneously. Furthermore, recent evidence suggests that PD may progress even when the initial cause of neurodegeneration has disappeared, suggesting that toxic substances released by the glial cells may be involved in the perpetuation of neuronal degeneration. This may thus represent a therapeutic target for PD.     

Neutralising antibodies to interferon β in multiple sclerosis

Abstract Interferon beta (IFNβ) therapy for multiple sclerosis (MS) is associated with a potential for the development of neutralising antibodies (NAbs) that negatively affect therapy. Several factors influence the development of NAbs, such as lack of complete sequence homology with the endogenous IFNβ sequence, frequency of administration, level of dose and formulation of IFNβ. Taken together, the evidence that NAb status reduces clinical efficacy in MS patients is strong. Standardised assays for NAbs are lacking, and titres vary over time. NAb testing is a critical component of care for MS patients because it provides information on one of the most important factors determining clinical responsiveness to IFNβ therapy. This expert panel report attempts to move the field towards resolution of the remaining issues and considers several aspects of NAbs, including their clinical relevance, factors influencing immunogenicity, assays to quantify NAbs and the definition of clinically relevant titres.     

Understanding adherence to neuroleptic treatment in schizophreniaí

Understanding the factors that impede and promote adherence by people with schizophrenia to neuroleptic medication is important for treatment planning and relapse prevention. A total of 184 DSM-IV schizophrenia inpatients were examined with the Rating of Medication Influences (ROMI) scale within a context of inpatient vocational rehabilitation. Confirmatory factor analysis was used to evaluate the underlying dimensions of compliance behavior. The three-dimensional model of Weiden and his associates was confirmed by this study; specific factors included influence of others, medication affinity, and prevention. Additional analyses examined cognitive variables, symptoms, and course variables as predictors of individual factors. Verbal memory and cognitive flexibility were found to be associated with influence of others. Possible consequences for designing compliance enhancing therapeutic interventions are discussed.     

Periodic limb movements in sleep: to treat or not to treat?

Background: Approximately 50% of our patients with sleep disturbances have periodic limb movements in sleep (PLMS). We have found that a high PLMS index is not correlated with the severity of symptoms on the Epworth Sleepiness Scale or response to pharmacologic therapy for restless legs syndrome (RLS)/PLMS. We hypothesized that differences in rhythm of contraction, predominance of periodic leg movements (PLMs) in different sleep stages, or PLM interval might distinguish responders from nonresponders.Methods: We analyzed the hypnograms of 20 consecutive patients with PLMS, noting the number of PLMs and the PLM intervals in different sleep stages, the PLMS index, and the percentage of PLMs that led to arousals.Results: We distinguished two groups of patients. The 13 patients in group A had a PLM arousal percentage of 10.9±5% (mean±SD), compared with 41.9±9% for the seven patients in group B. Group B had a lower PLMS index. Group A showed little variance in PLM intervals and experienced more delta sleep.Conclusions: PLMS index was not correlated with arousals. A strict rhythm of contractions was associated with fewer arousals and better quality of sleep. This subgroup may not benefit substantially from specific RLS/PLMS therapy.     

Is It Safe to Use a Diuretic to Treat Seizures Early in Development ?

There has been considerable interest in using bumetanide, a diuretic chloride importer NKCC1 antagonist, to reduce intracellular chloride ([Cl⁻]_i) in epileptic neurons, thereby shifting the polarity of GABA from excitatory to inhibitory and ameliorating the actions of GABA-acting antiepileptic drugs. However, a recent study raises the important issue of potential deleterious actions of bumetanide on immature neurons, because reduction of (Cl⁻)_i also alleviates a major source of excitation in developing neurons, upon which GABA exerts a trophic action. This review considers the importance of separating intrauterine from postnatal effects of bumetanide in normal versus pathologic neurons.Immature neurons have higher intracellular concentrations of chloride ([Cl⁻]_i) than adult neurons, leading to depolarizing and excitatory actions of GABA, which exert trophic actions on the formation of cortical networks (1). These actions are mediated by many mechanisms, most notably an early expression of the chloride importer NKCC1and a somewhat delayed expression of the chloride exporter KCC2 (2–9). Blocking NKCC1 with the diuretic NKCC1 antagonist bumetanide reduces (Cl⁻) i and the depolarizing actions of GABA (1). Immature neurons need excitatory GABA during development, because GABA exerts a clear trophic action on many major developmental processes, including migration; growth; synapse formation; and early network activities, notably giant depolarizing potentials that provide much of early synapse-driven activity (1, 10–13). However, recurrent seizures and epilepsies that also have a higher incidence in immature neurons also shift GABA polarity to excitation as (Cl⁻)_i is elevated in human and animal epileptic neurons (9, 14, 15). Therefore, immature neurons require “GABA to be excited but also to be hyperexcited” (16). These observations raise considerable interest in using agents that reduce (Cl⁻)_i to reinstate hyperpolarizing and inhibitory GABA in epileptic neurons, thereby also enabling the use of GABA-acting AEDs that often exert paradoxical aggravating actions on these neurons (9, 14, 17). In addition to epilepsies, elevated neuronal (Cl⁻)_i has been documented in autism spectrum disorders (ASDs), brain edema, spinal cord lesions, spasticity, and other disorders. Two clinical trials are presently being conducted—the CRA/INMED trial (18) on the use of bumetanide to treat children with ASD the NEMO project of the European Community (19) and the US trial gov/ct2/show/NCT00830531on the use of bumetanide to treat phenobarbital-refractory encephalopathy in 2-day-old babies.Clearly, the excitatory actions of GABA have both positive and deleterious actions in physiologic and pathologic conditions, challenging its usefulness in the neonatal period. A recent elegant study reports that long-lasting administration of bumetanide at early developmental stages leads to cortical malformations and behavioral sequelae that are reminiscent of autism and schizophrenia (20). The authors suggest that the use of bumetanide may have teratogenic actions on the developing brain, challenging the promising therapeutic efficacy of this drug. Here, I discuss two issues: 1) the precise period during which long-term diuretic use is potentially deleterious, and 2) the major differences in GABA actions on normal versus pathologic neurons and the need to differentiate excitation (of normal neurons) and hyperexcitation (of pathologic neurons).     

Decreased estrogen receptor-α expression in hippocampal neurons in relation to hyperphosphorylated tau in Alzheimer patients

Emerging evidence has demonstrated the neuroprotection of estrogen in Alzheimer's disease (AD). The hippocampus, an important target of estrogen action, is severely affected in the Alzheimer process. The aim of present study was to detect the distribution of estrogen receptor- (ER-) and the relationship between ER--containing neurons and the pretangles stained by Alz-50 in the hippocampus of AD patients. The results showed that more than half of hippocampal neurons expressed ER-. The number of cytoplasmic ER--positive neurons was significantly decreased in the CA1 and CA2 subfields of AD hippocampus, but the ratio of these ER--expressing neurons to the nucleolated neuronal profiles stained by thionin was not different between the two groups. Interestingly, the number of nuclear ER--staining neurons was also markedly decreased in the CA1 and CA2 subfields of AD hippocampus, and the percentage of these nuclear staining neurons was also significantly decreased in the same subfields. Furthermore, some double-labeled neurons containing ER- and Alz-50 were found in AD patients. However, in these double-labeled neurons, ER- was only located in the cytoplasm. Thus, we hypothesize that the nuclear ER- may play more important roles of neuroprotection during the process of AD.     

Diurnal Melatonin Patterns in Children: Ready to Apply in Clinical Practice?

Experimental and clinical studies suggest that endogenous melatonin plays an important role in pediatric sleep regulation. This finding led to the introduction of exogenous melatonin to treat sleep disturbances. Optimizing the treatment algorithm involves a review of melatonin measurements and interpretations in clinical practice. Diurnal patterns of salivary melatonin and urinary metabolite 6-sulfatoxymelatonin were investigated in 29 children and adolescents (age, 5.5-17.3 years) by measuring concentrations every 3 hours. Relationships between melatonin parameters (peak concentrations and area under the time curve) and anthropometric measures (height, weight, and body mass index), age, and sleep scores (Sleep Disturbance Scale for Children) were investigated. High interindividual variability was evident in melatonin diurnal profiles. Melatonin production (adjusted to body weight) decreased with age and sexual maturation (P < 0.00). Both salivary melatonin and its urinary metabolite measurements can be used to evaluate the melatonin system in children. However, the high interindividual variability of diurnal melatonin concentrations challenges clinical applications in regard to diagnostic purposes and the criteria for initiating exogenous melatonin therapy. Further investigations and the development of criteria for clinical evaluations of the pediatric melatonin system are needed.     

β-Catenin Deletion in Regional Neural Progenitors Leads to Congenital Hydrocephalus in Mice

Congenital hydrocephalus is a major neurolog-ical disorder with high rates of morbidity and mortality;however,the underlying cellular and molecular mecha-nisms ...     

Müller cell response to laser-induced increase in intraocular pressure in rats

The goal of this study was to investigate the reaction of the Müller cells to elevated intraocular pressure (IOP). Elevated IOP is one of the risk factors in glaucomatous retinal ganglion cell (RGC) degeneration. Müller cells play an important role in retinal homeostasis. The reaction of Müller cells was examined by evaluating temporal changes in glutamate aspartate transporter (GLAST), glutamine synthase (GS), glial fibrillary acidic protein (GFAP), and the B-cell lymphoma (Bcl-2) using immunoblotting and immunohistochemical techniques. After IOP was elevated for 4-60 days, there was a time-related decrease in RGC ranging from 6% to 44%. There was also a time-related increase in GLAST protein reaching maximum after 3 weeks of elevated IOP. On the other hand, there was very little change in the expression of GS during the first 2 weeks followed by some increase between 21 and 60 days. An increase in Bcl-2 was biphasic with maximum increase after 4 days followed by decline after 15 and 21 days. GFAP, which is usually not expressed in normal Müller cells, was present at all time points. In all cases, the increase was most intense in the vicinity of the ganglion cells where the astrocytes and endfeet of the Müller cells are located. These results indicate that Müller cells react to the insult of elevated IOP by expressing GFAP and Bcl-2, proteins that are expressed in reactive gliosis and other pathological conditions. The increase in GLAST along with minimum change in GS indicates a disturbance in glutamate homeostasis.     

“I Have Been Trying to Get Them to Respond to Me”: Sexuality and Agency in Psychoanalysis

Psychoanalytic theory has seen many changes in the past 100 years. But in the process, sexuality, as the centerpiece of our understanding of human motivation and conflict, seems to have gotten lost. As they did a century ago, clinicians today deal with sexual transferences and countertransferences. And issues of gender and sexual orientation are widely discussed. Yet, across most current theoretical perspectives, nothing compels us to focus on sexuality, as such, in the way that was once absolutely essential.

During the same period, psychoanalytic approaches have consistently been concerned with questions of personal agency, i.e., its disruption in development and restoration in treatment. Indeed, the aim of treatment was traditionally understood as enabling patients to repossess their experience of themselves as “agents” in relation to their own disowned motives, affects, and drives (“where id was, there shall ego be”). In contemporary interpersonal, intersubjective, and relational perspectives, the issue of agency takes on even more central significance.

This article explores how these two seemingly different conceptual and developmental frameworks—sexuality as a function of mind, and agency as a derivative of relational experience—may be compatible. Here, I examine the relationship of sexuality and the experience of agency in parent–child and analyst–patient relationships, and suggest that sexuality as such may yet have a central role in contemporary psychoanalytic thinking and in our understanding of the basic nature of psychic functioning.     

Cellular hypersensitivity to nervous antigens in Guillain-Barré syndrome

Cell-mediated immune responses to various nervous antigens were examined in 12 cases of Guillain-Barré syndrome (GBS), 24 cases of noninflammatory peripheral neuropathy (NIPN), and 18 cases of degenerative disorders of central nervous system (CNSDD), using the lymphocyte-transformation technique. Cellular hypersensitivity to bovine P2 protein (P2) and a synthetic peptide, SP66-78, corresponding to the residues 66–78 of P2, was detected in about two-thirds of GBS cases, especially in the active or improving stages, but not in NIPN and CNSDD. The lymphocytes sensitized to these nervous antigens might play an important role in the pathogenesis of GBS.     

A new road to neuroinflammation in Parkinson's disease?

Common architecture of cytokine receptors and G-protein coupled receptors (GPCRs) may underlie pathological receptor heteromer formation and signaling. Here, we clarify how chemokines and cytokines can participate in pathogenic processes of Parkinson's disease, especially in dopaminergic neurons of substantia nigra. Possible common architecture of GPCRs and cytokine receptors suggests that they may act as molecular switches similar to the prototypical innate immune receptors: Toll-like receptors. Thus, pathological signaling (as well as trafficking and internalization) of receptors may be initiated by their incorrect dimerization depending on direct or indirect (via adaptor proteins) receptor-receptor interactions, leading to neuroinflammatory responses.