Modern trends in pharmacopsychiatry最新文献

Comorbidity between major depressive disorder (MDD), anxiety (generalized anxiety, panic disorder, social anxiety disorder) and pain is a major complicating factor in the diagnosis and treatment of psychiatric and neurological disorders. Although numerous neurotransmitters and/or neuromodulators may be involved, abnormalities in the GABAergic and glutamatergic systems seem to be a common factor in all these disorders. Neuroactive steroids (NASs) have been the object of considerable interest in this area in recent years since they appear to act predominantly on GABA-A and glutamate NMDA receptors. An overview of the possible involvement of NASs in MDD, anxiety and pain is provided in this chapter.

Although it is well known that there is a high degree of comorbidity between chronic pain and mood and anxiety disorders, the mechanisms involved in these co-occurrences are not clear. It appears that numerous neurotransmitters and neuromodulators are involved, and this chapter focuses on the monoamine neurotransmitters noradrenaline, 5-hydroxytryptamine (5-HT, serotonin), and dopamine and the amino acid neurotransmitters GABA (γ-aminobutyric acid) and glutamate in chronic pain and depression. Numerous preclinical and clinical neurochemical, neuroanatomical, pharmacological and molecular biological studies as well as clinical pharmacological treatment investigations implicate noradrenaline, 5-HT and, to a lesser extent, dopamine in the etiology of pain and depression. Similarly, preclinical and clinical studies on GABAergic and glutamatergic mechanisms as well as reports on the actions of neuroactive steroids suggest that GABA and glutamate play an important role in the etiology of pain and depression and may contribute to comorbidity.

Pain processing in patients with borderline personality disorder (BPD) is abnormal primarily with respect to pain thresholds which are typically elevated or perception of phasic nociceptive stimuli which is reduced. In spite of this common finding, nonsuicidal self-injury (NSSI), often expressed as cutting, is a hallmark sign of the disease and serves to release aversive inner tension. The question thus arises, how does a painful stimulus release inner tension when these patients feel less pain than healthy people? However, intensity discrimination is normal in these patients. Imaging data have provided evidence that inhibitory top-down modulation is increased in BPD patients, and that processing of the affective-emotional pain component is altered. Recent studies have focused on the role of pain, tissue injury and seeing blood in the context of NSSI. Preliminary findings suggest a significant role of pain irrespective of concomitant tissue injury, and of seeing blood expressed as a stronger immediate stress release. Taken together, BPD patients exhibit altered pain processing that can be assigned to altered processing of nociceptive stimuli in prefrontal and limbic brain areas, which may help to mechanistically explain the clinical behavior.

In this article, the co-occurrence of anxiety disorders (in particular generalized anxiety disorder) and pain conditions is described, characteristics of chronic pain are explained, and data on the prevalence of co-comorbidity of both conditions are reviewed. Further, hypotheses on the possible psychosocial and neurobiological backgrounds of the high rate of co-occurrence are discussed. This review will also focus on the role of 'unexplained' pain syndromes (e.g. somatic symptom disorder and fibromyalgia) and anxiety. Finally, we address possible treatment strategies for patients with both conditions. There is a need for a rigorous assessment of pain syndromes in generalized anxiety disorder and anxiety in chronic pain conditions in order to prevent subsequent mortality by early treatment of both conditions.

There is growing interest in the application of evolutionary theory to medicine. In this review, we outline an evolutionary approach to the anxiety disorders. We begin by considering the nature of fear and anxiety, and their evolutionary benefits. We emphasize that fear and anxiety exist in multiple organisms, and note the implications of brain complexity in Homo sapiens for the anxiety disorders. This account emphasizes the importance of distance from a threat; in H. sapiens, it is possible to experience fear and anxiety even when threats are temporally and spatially distant.

Like all psychiatric conditions, depression is a complex phenomenon that is unlikely to yield to simple monolithic explanatory paradigms. Nonetheless, increasing evidence suggests that the immune system in general and inflammatory processes in particular, may contribute to depressive pathogenesis in a significant proportion of otherwise medically healthy individuals struggling with the disorder. In this chapter, we review the best current evidence suggesting that inflammatory processes contribute to the development of depression, both via direct actions on the brain as well as by effects on secondary pathways that marry brain to body. We review epidemiological evidence linking inflammation to depression before reviewing findings that exposure to inflammatory stimuli produce depressive symptoms in concert with brain-body changes known to be common in depression. Following this review of the role of inflammation in depressive causation, we consider emerging evidence that immunomodulatory interventions may hold promise as antidepressants, especially in individuals with elevations in peripheral inflammatory biomarkers. Interventions discussed include cytokine and cyclo-oxygenase antagonists, as well as agents that impact inflammatory transcription factors/signaling cascades. We conclude with a brief discussion of the potential role of various behavioral strategies in reducing inflammation and thereby enhancing emotional well-being.

Social anxiety disorder (social phobia) is a common and typically long-standing medical condition, characterized by an excessive fear of being observed or evaluated negatively in social or performance situations. Efficacious interventions in acute treatment include cognitive behavioural therapy and a range of medications including many antidepressants, some benzodiazepines and anticonvulsants, and the antipsychotic olanzapine. Most studies report no significant differences in overall efficacy or tolerability between active compounds. Responders to previous acute treatment benefit from continuing active medication for 6 months. Evidence of a dose-response relationship with antidepressant drugs is inconsistent, though only higher doses of pregabalin are efficacious. Switching between treatments with proven efficacy may be helpful. Augmentation of a selective serotonin reuptake inhibitor with buspirone or clonazepam can be beneficial. It is unlikely that combining pharmacotherapy with psychotherapy results in greater overall efficacy compared to either treatment given alone. Proof-of-concept and other preliminary studies suggest the efficacy of psychotherapy can be enhanced through prior administration of D-cycloserine, cannabidiol, or oxytocin.

Neuroimaging studies using functional magnetic resonance imaging (fMRI), positron emission tomography (PET) and single-photon emission computed tomography (SPECT) to evaluate neurofunctional and neurochemical alterations related to the generation and control of affect in patients with anxiety disorders are reviewed. We performed a meta-analysis of symptom provocation studies, where neural activity was measured using fMRI, PET or SPECT to test the hypothesis that prefrontal regions modulate amygdala activity. Data revealed that reactivity in the amygdala was enhanced in patients with phobia as well as posttraumatic stress disorder (PTSD). The dorsal anterior cingulate cortex was activated in concert with the amygdala, both in PTSD and in phobic states, suggesting a role in fear expression, rather than emotional control. Activity in emotion-regulating areas in the ventromedial prefrontal cortex including the subgenual anterior cingulate cortex and the medial orbitofrontal cortex was compromised in the symptomatic state in PTSD and phobic disorders, respectively. Increased amygdala reactivity was restored with psychological treatment. Treatment effects across different modalities including pharmacological and psychological interventions as well as with placebo regimens support that reduction of neural activity in the amygdala may be a final common pathway for successful therapeutic interventions irrespective of method, thereby linking neurotransmission to plasticity in a pivotal node of the core fear network of the brain.

Morbidity and mortality of cardiovascular disease is exceedingly high worldwide. Depressive illness is a serious psychiatric illness that afflicts a significant portion of the population worldwide. Epidemiological studies have confirmed the high co-morbidity between these two entities and the co-morbidity is bidirectional. Systems that are involved in and accountable for this co-morbidity in a major, complex and interactive way include the central and autonomic nervous systems, the neuroendocrine system, the immune system, and the vascular and hematologic systems. Specific pathophysiologic factors across these systems include homeostatic imbalance between the sympathetic and the parasympathetic systems with loss of heart rate variability in depression, sympathoadrenal activation, hypothalamic-pituitary-adrenal axis activation resulting in hypercortisolemia, immune system dysregulation with release of pro-inflammatory cytokines and chemokines, platelet activation and hypercoagulability. All of these abnormalities have been demonstrated in most individuals diagnosed with major depressive disorder. This chapter will focus on inflammatory processes. Inflammation occurs in cardiac and cardiovascular pathology independent of the presence or absence of depression. A chronic pro-inflammatory status has been documented in numerous studies of depression. Inflammation is closely associated with endothelial dysfunction which is a preamble to atherosclerosis and atherothrombosis. Endothelial dysfunction has been detected in depression and may prove to be a trait marker for this illness. Thus, understanding vascular biology in conjunction with psychiatric co-morbidity will be of critical importance. A likely common instigator underlying the co-morbidity between cardiovascular pathology and depression is mental stress. Chronic stress shifts the homeostatic balance in the autonomic nervous system with sustained sympathetic overdrive and diminished vagal tone. Diminished vagal tone contributes to a pro-inflammatory status which affects neurotransmitter regulation, specifically serotonergic transmission. Antidepressant drug therapy is of definite benefit to patients with medical and psychiatric co-morbidity and may reverse the pro-inflammatory status associated with depression.