Modern trends in pharmacopsychiatry最新文献

The brain-gut axis provides a bidirectional means of communication between the microbiota within the gut and the brain. Stress acting via the brain can result in alteration of the microbial composition of the gut, but increasing evidence indicates that bacteria within the gut can influence brain neurochemistry and behaviour. It is clear that post-natal colonisation of the gut plays a key role in regulating the development of the hypothalamic-pituitary-adrenal axis and the development of pivotal neurotransmitter systems. Probiotics are defined as live bacteria which confer a health benefit. Recent studies in rodents have demonstrated the capacity of a probiotic, Lactobacillus rhamnosus, to alter the expression of GABA receptors centrally whilst producing anxiolytic type effects. Preliminary studies in humans are yielding encouraging findings. It may in the future be possible to use probiotic bacteria to treat depression and other stress-related disorder but we await the results of appropriately designed placebo-controlled trials.

Presently available clinical genetic studies point to a considerable heritability of anxiety disorders (30-67%), with multiple vulnerability genes such as 5-HT1A, 5-HTT, MAO-A, COMT, CCK-B, ADORA2A, CRHR1, FKBP5, ACE, RGS2/7 and NPSR1 suggested by molecular genetic association studies. These genes have been shown to partially interact with each other as well as with environmental factors to shape the overall disease risk in a complex genetic model. Additionally, recent studies have pointed out the crucial role of epigenetic signatures such as methylation patterns in modifying environmental influences as well as in driving the functional impact of anxiety disorder risk genes. On a systems level, vulnerability genes of anxiety disorders seem to confer some of the disease risk via intermediate phenotypes like behavioral inhibition, anxiety sensitivity or several neurobiological traits such as increased startle reactivity or dysfunctional corticolimbic activity during emotional processing. Finally, first pharmaco- and psychotherapy-genetic studies provide evidence for certain risk genes to confer interindividual variability in response to a pharmacological or psychotherapeutic intervention in anxiety disorders. Genetic research in anxiety disorders will be discussed regarding its potential to foster innovative and individually tailored therapeutic approaches for patients with anxiety disorders.

Generalized anxiety disorder (GAD) is chiefly characterized by a cognitive focus on threats and risks towards the individual and/or the immediate family. It is accompanied by a sense of tension, worry, muscle pain, disturbed sleep and irritability. The condition impairs work capacity, relations, and leisure activities, and aggravates concurrent somatic diseases. Due to its chronic course, GAD increases costs for the individual, the family, and health care services, and reduces work and educational performance. In cardiovascular or cerebrovascular disease, pulmonary disease, diabetes and neurological diseases, GAD is a risk factor for somatic complications and for lowered adherence to somatic treatments. There is evidence that GAD can be treated with cognitive behavioural therapy (CBT), and/or with medications. First-line pharmacotherapies are selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs) and pregabalin. If such therapies fail, one may reconsider the diagnosis, question adherence with the prescribed schedule, and determine the adverse influence of comorbidity (such as depression, substance use, and physical ill-health) as well as the influence of social stressors. Second-line pharmacotherapies are largely not supported by controlled trials, and so leave much to clinical judgment and careful monitoring. One may attempt treatments with benzodiazepine anxiolytics, with quetiapine, or with pregabalin as an adjunct therapy in patients with partial response to SSRI or SNRI treatment. CBT is a valid alternative to pharmacotherapy, depending on patient preference.