Reduced central serotonin transporters in alcoholism

OBJECTIVE: Dysfunction of monoamine uptake mechanisms has been implicated in the pathogenesis of alcohol dependence. The authors explored whether serotonergic dysfunction is associated with anxiety and depression, which increase the risk of relapse in alcoholics. METHOD: The availability of serotonin and dopamine transporters in 22 male alcoholics and 13 healthy male volunteers was measured with the use of [123I] beta-CIT and single photon emission computed tomography, and psychopathological correlates were assessed. RESULTS: A significant reduction (a mean of about 30%) in the availability of brainstem serotonin transporters was found in the alcoholics, which was significantly correlated with lifetime alcohol consumption and with ratings of depression and anxiety during withdrawal. CONCLUSIONS: The findings support the hypothesis of serotonergic dysfunction in alcoholism and in withdrawal-emergent depressive symptoms.     

Serotonin and serotonin receptors in the central auditory system

Single channel currents were activated by GABA (0.5 to 5 microM) in cell-attached and inside-out patches from cells in the dentate gyrus of rat hippocampal slices. The currents reversed at the chloride equilibrium potential and were blocked by bicuculline (100 microM). Several different kinds of channel were seen: high conductance and low conductance, rectifying and "nonrectifying." Channels had multiple conductance states. The open probability (Po) of channels was greater at depolarized than at hyperpolarized potentials and the relationship between Po and potential could be fitted with a Boltzmann equation with equivalent valency (z) of 1. The combination of outward rectification and potential-dependent open probability gave very little chloride current at hyperpolarized potentials but steeply increasing current with depolarization, useful properties for a tonic inhibitory mechanism.     

Functional consequences of central serotonin depletion produced by repeated fenfluramine administration in rats

Repeated administration of D,L-fenfluramine (FEN) is known to cause prolonged depletion of forebrain serotonin (5-HT) in animals. Ironically, few studies have evaluated functional consequences of such FEN-induced 5-HT loss. In the present work, we examined neuroendocrine and behavioral responses evoked by acute FEN injection in rats that had previously received a 4 d FEN-dosing regimen known to deplete forebrain 5-HT (D,L-FEN, 20 mg/kg, s.c., b. i.d.). Rats were fitted with indwelling jugular catheters before the study to allow for repeated intravenous challenge injections and stress-free blood sampling. At 1 and 2 weeks after the 4 d dosing regimen, acute FEN (1.5 or 3.0 mg/kg, i.v.) produced dose-related elevations in plasma corticosterone and prolactin; these hormonal responses were markedly attenuated in FEN-pretreated rats. Behavioral effects of acute FEN, namely flat body posture and forepaw treading, were also blunted in FEN-pretreated rats. Interestingly, rats exposed to repeated FEN did not display overt abnormalities in hormonal or behavioral parameters under basal (i.e., unprovoked) conditions, despite dramatic decreases in postmortem tissue levels of 5-HT in numerous brain areas. Our results suggest that FEN-induced 5-HT depletion is accompanied by multiple impairments in 5-HT function. Although the clinical relevance of our data are debatable, the findings clearly show the utility of the FEN challenge test for uncovering in vivo functional deficits that might otherwise go undetected. FEN should remain an important pharmacological tool for determining the role of 5-HT neurons in mediating diverse physiological and behavioral processes.     

Novel therapeutic approaches beyond the serotonin receptor

The influence of serotonin (5-HT) on neuronal function is mediated by regulation of receptor-coupled intracellular signal transduction pathways, and the therapeutic action of 5-HT selective reuptake inhibitors (SSRIs), as well as other types of antidepressants, most likely involves regulation of these intracellular pathways. The cyclic adenosine monophosphate (cAMP) second messenger system is one pathway that could be involved in antidepressant action. Chronic administration of antidepressants, including SSRIs, up-regulates the cAMP pathway at several levels, including increased expression of the cAMP response element binding protein (CREB). Among the multiple target genes that could be regulated by CREB and that could be involved in antidepressant actions and the pathophysiology of depression in brain-derived neurotrophic factor (BDNF). Stress decreases the expression of BDNF, and reduce levels of this neurotrophic factor could contribute to the atrophy and decreased function of stress-vulnerable hippocampal neurons. In contrast, antidepressant treatment increases the expression of BDNF in hippocampus, and could thereby reverse the stress-induced atrophy of neurons or protect these neurons from further damage. Up-regulation of the cAMP and BDNF systems has resulted in a novel model for the mechanism of action of antidepressants and new targets for the development of therapeutic agents.     

The impact of familial alcoholism on alcohol reactivity in female social drinkers.

Some individuals may have an inherent reactivity to alcohol that facilitates early development of characteristics associated with alcoholism. Although response to alcohol cues has been used to assess this reactivity, few studies have included women or investigated familial alcoholism as a variable. In this study, 23 female college students were divided into groups according to family history of alcoholism (positive or negative). Alcohol reactivity was measured by salivation, skin temperature, heart rate, mood state, and craving for alcohol following presentation of alcohol-related and neutral cues. Results indicate no correlation between salivary reactivity and alcohol craving, which suggests that these variables tap into different domains of cue reactivity. Findings demonstrate that alcohol cue reactivity can be assessed in female social drinkers and that familial alcoholism may influence salivary reactivity to alcohol-related cues. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Co-localization of serotonin and FMRFamide-like immunoreactivities in the central nervous system of the earthworm, Eisenia fetida

In addition to receptor-type pinealocytes, the mammalian pineal organ contains small and large neurons and ependymal/glial cells as well. Axons of pinealocytes form synaptic ribbon-containing axo-dendritic synapses on large secondary pineal neurons and/or terminate as neurohormonal endings on the basal lamina of the vascular surface of the organ. The small pineal neurons were found to be gamma-aminobutyric acid (GABA)-immunoreactive, while large secondary neurons and pinealocytes contained immunoreactive amino acids (glutamate and aspartate). Glutamate accumulated presynaptically in pinealocytic axon terminals on large secondary neurons and in the axons of these neurons. Glutamate immunoreactive axons of pineal neurons were traced via the pineal tract to the habenular nucleus. Axons containing granular vesicles and coming from extrapineal perikarya are glutamate immunoreactive as well. Aspartate and GABA are also present in some of the myelinated axons, supposedly pinealopetal in the pineal tract.     

The therapeutic alliance and its relationship to alcoholism treatment participation and outcome.

The relationship between the therapeutic alliance and treatment participation and drinking outcomes during and after treatment was evaluated among alcoholic outpatient and aftercare clients. In the outpatient sample, ratings of the working alliance, whether provided by the client or therapist, were significant predictors of treatment participation and drinking behavior during the treatment and 12-month posttreatment periods, after a variety of other sources of variance were controlled. Ratings of the alliance by the aftercare clients did not predict treatment participation or drinking outcomes. Therapists ratings of the alliance in the aftercare sample predicted only percentage of days abstinent during treatment and follow-up. The results document the independent contribution of the therapeutic alliance to treatment participation and outcomes among alcoholic outpatients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Clinical features of hemangioblastomas of the central nervous system]

BACKGROUND: A study of five cases of linear IgA dermatosis (LABD) in a referral hospital in South India is presented. METHODS: A dermatologic examination, skin biopsy, and direct immunofluorescence were carried out on all patients. Patients were then followed up. RESULTS: All five cases showed linear IgA deposits at the dermo-epidermal junction. One case in addition showed IgG and C3 deposits. All cases responded to treatment with dapsone. The treatment duration varied from 14 to 16 months and the fifth patient is still on treatment after 37 months. CONCLUSIONS: Linear IgA bullous dermatosis is a self-limiting bullous disorder. To the best of our knowledge this is the first report of LABD from India.     

The somatosensory system of the neck and its effects on the central nervous system

BACKGROUND: There is some evidence to suggest that dysfunction in the sensory system of the neck may result in a gamut of signs and symptoms. However, a sound understanding of the somatosensory system in the neck and its normal influence on the central nervous system is essential before signs and symptoms can be identified as representations of ill health or disease arising from the neck. OBJECTIVE: To briefly review current knowledge of the somatosensory system of the neck and to consider its connections and influence on the central nervous system. DATA SOURCES: Information was obtained from peer-reviewed scientific journals and proceedings of scientific meetings that have investigated or considered anatomical and physiological aspects of the sensory system in the necks of human and nonhuman vertebrates. CONCLUSION: Studies involving human and nonhuman vertebrates have provided considerable information about the anatomy of the sensory receptors located in the neck and about where information from these receptors is relayed in the spinal cord and brain. Physiological experiments involving electrical and natural stimulation of the head and neck regions have identified a role for some of these receptors in neck-evoked reflexes. It is clear that in addition to signaling nociception, the somatosensory system of the neck may influence the motor control of the neck, eyes, limbs, respiratory muscles and possibly the activity of some preganglionic sympathetic nerves.     

The impact of power in therapeutic relationships

Power is an important factor in how health care is delivered. Neither health care professionals nor clients fully appreciate the power that they exercise, nor how they influence others. Understanding how power works, however, is vital to establishing a helping relationship. In a traditionally rigid health care system, professionals who try to empower clients can create conflicts among colleagues. A possible solution is an explicit contract with a client, setting out the responsibilities of those involved.     

The effects of interferon-gamma on the central nervous system

A 165bp DNA fragment derived from the 12 kDa subunit of Echinococcus granulosus antigen B (AgB), a major hydatid cyst fluid antigen was cloned in the pMa1-c2 expression vector. A 52 kDa maltose binding-AgB fusion protein (rAgB.MBP) was produced and inclusion bodies containing the fusion protein were solubilised in urea and affinity purified on an amylose-Sepharose 6B column. The immunogenicity of the purified recombinant antigen for IgG4 antibody detection was tested with human serum using immunoblotting, ELISA and dot-ELISA assays and compared to native AgB. Both recombinant and native AgB preparations were highly reactive for human IgG4 antibodies in serum of cystic echinococcus (CE) patients. Recombinant AgB.MBP (rAgB.MBP) showed approximately 65% sensitivity in detection of IgG4 serum antibodies by ELISA from confirmed CE patients. Cross-reactivity (33%) occurred with alveolar echinococcosis (E. multilocularis) sera but recombinant AgB showed no seroreactivity with sera from other helminth infections tested (schistosomsis, onchocercsis, cysticercosis) or from uninfected individuals residing in CE endemic or non-endemic regions. The serologic sensitivity (63%) for IgG4 antibodies of a native AgB fraction enriched from human hydatid cyst fluid was similar to that for recombinant AgB (65%) though specificity was slightly lower (81%). A dot-ELISA for detection of total IgG, incorporating the rAgB.MBP resulted in 74% sensitivity and 88% specificity for human CE and 93% sensitivity and 65% specificity for native AgB. Recombinant AgB is a potential replacement for native antigens currently being used and could provide a better standardised E. granulosus specific test for clinical confirmation for CE especially for IgG4 antibody detection which appears to be predominantly associated with advanced disease.     

The electrophysiology of prefrontal serotonin systems: therapeutic implications for mood and psychosis

A newly described synaptic action of serotonin (5-HT) in the cerebral cortex is reviewed, and implications for mood and psychosis are discussed. Recordings in brain slices show that 5-HT induces a rapid increase in excitatory postsynaptic potentials/currents (EPSPs/EPSCs) in virtually all layer V pyramidal cells of neocortex. This effect is mediated by the 5-HT2A receptor, which has been linked to the action of hallucinogenic and atypical antipsychotic drugs. The increase in EPSCs is seen most prominently in medial prefrontal cortex and other frontal regions where 5-HT2A receptors are enriched. The induction of EPSCs by 5-HT appears to occur through a novel mechanism that does not depend on the activation of afferent impulse flow. Instead, 5-HT appears to act presynaptically, directly or indirectly, to induce a focal release of glutamate from a subpopulation of glutamatergic terminals impinging upon the apical (but not basilar) dendrites of layer V pyramidal cells; a working hypothesis of the transduction pathway (involving asynchronous transmitter release) for this process is presented. Consistent with a focal action upon glutamatergic nerve terminals, the 5-HT-induced EPSPs can be suppressed by presynaptic inhibitory modulators such as mu-opiate or group II/III metabotropic agonists. We suggest that the suppression of 5-HT-induced EPSCs by 5-HT2A antagonists and mu-opiate agonists may underlie certain shared clinical effects of 5-HT2A antagonists and mu-opiate agonists. We suggest further that since presynaptic group II/III metabotropic glutamate agonists suppress 5-HT-induced EPSCs, metabotropic glutamate agonists may also possess antidepressant and/or antipsychotic properties.     

The impact of AIDS on practitioner and client: Notes for the therapeutic relationship.

This article discusses the dynamics of the psychotherapeutic relationship using antibody status for the human immunodeficiency virus (HIV) as a frame of reference. The psychological and social ramifications of individuals' knowledge or lack of knowledge about their antibody status are discussed, as well as their reactions to testing either positive or negative for HIV antibodies. The impacts of the combined antibody statuses of therapist and client within the therapeutic interaction are described. Case reports are presented in order to convey a deeper understanding of transference and countertransference issues in those affected by the AIDS epidemic. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Surviving cancer: a review of the impact and consequences

In this critical review of the literature, the author examines articles assessing the effects on patients of cancer survival. Implications for nursing practice, education and research are also discussed.