The study provides good support for the proposed cognitive behavioural model. Patients' perceptions of their head injury and their behavioural responses play important roles in the development of PCS, indicating that cognitive and behavioural factors may be potential targets for early preventive interventions.

Clonidine exerted sympatholytic and sedative effects, whereas modafinil had sympathomimetic and some alerting effects. Modafinil may activate noradrenergic neurones in the LC involved in arousal and pupillary control, without affecting extracoerulear noradrenergic neurones involved in cardiovascular and salivary regulation.

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Introduction-Previous investigations have demonstrated that major depression is associated with particular patterns of cytokine signalling. The primary aim of this study was to examine peripheral pro-inflammatory and anti-inflammatory cytokines and immune balance in generalised anxiety disorder (GAD).Methods-A case-controlled cross-sectional study design was employed: 54 patients with GAD and 64 healthy controls were recruited. Participants completed self-report measures of anxiety and depression. Two pro-inflammatory and two anti-inflammatory cytokines were measured using multiplex technology.Results-Case-control logistic regression analyses revealed significant differences in serum levels of IL-10, TNF-α, and IFN-γ between GAD and control groups after adjusting for age, gender, body mass index, smoking and alcohol consumption: these group differences were independent of the presence or degree of depression. Comparison of pro-inflammatory to antiinflammatory cytokine ratios indicated that there were significantly higher ratios of TNF-α /IL10, TNF-α /IL4, IFN-γ /IL10, and IFN-γ /IL4 in the GAD group compared to the control group.Conclusions-This study is the first to investigate both pro-and anti-inflammatory cytokines and their balance in patients with GAD in comparison to healthy controls. The findings indicate a relatively increased pro-inflammatory response and decreased anti-inflammatory response and Europe PMC Funders Group Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts provide the first demonstration of an altered cytokine balance in GAD. Serum cytokine levels in GAD were independent of the presence of depression.

The noradrenergic locus coeruleus is a major wakefulness-promoting nucleus of the brain, which is also involved in the regulation of autonomic and endocrine functions. The activity of the locus coeruleus is believed to be tonically enhanced by a mesocoerulear dopaminergic pathway arising from the ventral tegmental area of the midbrain. Both modafinil, a wakefulness-promoting drug, and pramipexole, a D(2)/D(3)receptor agonist with sedative properties, may act on this pathway, with modafinil increasing and pramipexole decreasing locus coeruleus activity. The aim of this study was to compare the two drugs on alertness, autonomic and endocrine functions in healthy volunteers. Pramipexole (0.5mg), modafinil (200mg), and their combination were administered to 16 healthy males in a double-blind, placebo-controlled design. Methods included tests of alertness (pupillographic sleepiness test, critical flicker fusion frequency, visual analogue scales), autonomic functions (resting pupil diameter, light and darkness reflex responses, heart rate, blood pressure, salivation, core temperature), and endocrine functions (blood concentrations of prolactin, growth hormone, and thyroid stimulating hormone). Data were analysed by ANOVA. Pramipexole reduced alertness, caused pupil dilatation, increased heart rate, reduced prolactin and thyroid stimulating hormone, and increased growth hormone level. Modafinil caused small increases in blood pressure and core temperature, and reduced prolactin levels. The sedative effect of pramipexole and the autonomic effects of modafinil are consistent with altered activity in the mesocoerulear pathway; the pupil dilatation following pramipexole suggests reduced dopaminergic excitation of the Edinger-Westphal nucleus.

The findings from this study provide support for the cognitive behavioural model and a good basis for developing prevention and early intervention strategies for CFS.

Objective Research into psychoneuroimmunology has led to substantial advances in our understanding of the reciprocal interactions between the central nervous system and the immune system in neuropsychiatric disorders. To date, the presence of inflammatory responses and the crucial role of cytokines in major depression have been addressed in numerous studies. However, neuroinflammatory hypotheses in anxiety disorders have been studied less extensively than in major depression. There is a high research need for better understanding of both the heterogeneous role of specific cytokines in the control of anxious states and in different anxiety disorders and of the immunomodulating effects of antidepressants on anxiety. Methods Relevant literature was identified through a search of MEDLINE via PubMed. We discuss recent research on neuroimmunology in anxiety and make methodological recommendations for future investigation of neuroinflammatory hypotheses in anxiety disorders. Results Some accumulating evidence has indicated modulatory effects of cytokines on neuronal communication and anxiety; however, research has not revealed consistent reproducible findings. Conclusions The availability of inflammatory biomarkers may provide an opportunity to identify patients via specific pathophysiological processes and to monitor therapeutic responses within relevant pathways. Further understanding of the neuroimmunological mechanisms to untangle the reciprocal associations between inflammation and anxiety is warranted.

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