|Generalized Anxiety Disorder|
|image taken from http://www.healthcentral.com/anxiety/17191-146.html|
Generalize anxiety disorder (GAD) is one of the common stress related disease. The distribution of GAD among age groups is rather wide but higher incidence rate occurs in elderly group.  Sadly to say, actual mechanism of how GAD arises still not really known but there are many models that are explainable for the cause of the diseases. In more molecular biology aspect, GAD might cause by the malfunction of GABA receptor complex which is responsible for interacting with inhibitory neurotransmitter.  When it comes to higher brain function and hormonal system, the abnormal secretion of adrenaline and serotonin can lead to over-activation or hypo-function of higher brain complex.  Moreover, Genetic defects like the duplication of DUP25 area in chromosome 15 might also contribute to the anxiety related disorder.  Common syndromes include fatigue and restlessness and these symptoms exist more than 6 months based on current diagnostic criteria. Treatments include both psychological and conventional drug therapy. However, due to the chronic nature of GAD, psychological and drug treatments are limited and relapse cases can occur. Moreover, the co-morbidity characteristic of GAD also put a burden on distinguishing GAD from other mental health disorder.  Therefore, the research on the potential new treatment and diagnostic tools are important to relieve current situation. One important discovery done by Alexander B and others showed that Rhodiola rosea might be able to help patient with GAD.  This has shed a new light on clinical practice and might provide less harmful and sustainable way for dealing with GAD in the future.
Generalized Anxiety Disorder is a disease with uncontrolled fear and anxious toward daily events. The following sections will introduce the prevalence of GAD, potential cause, comorbidity, syndrome and diagnostic criteria and ends up with treatment related issues. In serious cases, GAD can significantly interrupt one’s life. Therefore, the importance of GAD can't be neglected.
An overview of GAD. created by TopicSimple
The occurrence of generalized anxiety disorder distributes widely among ages and larger difference can be seen when it comes to gender group. However, database of General anxiety disorder prevalence are mostly from American and western country and might be region and culture specific. In table 1, the incidence rate among age group is rather wide. GAD can be seen from early in teen age population to late in mid-forties. Based on the data from National Comorbidity Survey and Barlow’s research, higher incidence rate appears in elderly group.  When it comes to gender factor, female has a slightly higher chance to get GAD comparing to male. 
Table 1. GAD distribution among age group and sex. Taken from http://www.calmclinic.com/anxiety
There are various factors that may cause Generalized Anxiety disorder. These factors include neurological aspect, sociological factor, and genetic defects.
Potential model for Generalized Anxiety disorder starts with GABA. GABA serves as an inhibitory neurotransmitter for central nerves system which is important for balancing the activity of neuronal system. In GAD, the activity of GABA system is decreased and this can be due to the abnormality of GABAa receptor complex.  Subunits of GABAa receptor complex have its own function and some of them involves in sedative (alpha-1 subunit) or anxiolytic effect (alpha-2 subunit).  Furthermore, according to the research done by Lesch K-P and others, the gamma 2 subunits knockout mice showed decrease sensitive toward antianxiety agents like benzodiazepines and therefore aroused anxiety symptoms.  In addition, GABA receptor subunits can be found in higher brain complex like hippocampus and damage of these regions might also contribute to GAD. 
When it comes to higher brain function, the lack of inhibiting neurons and abnormal high metabolic rate in certain brain area can cause the diseases. Serotonergic neurons which synthesize serotonin together with GABAnergic neurons are two inhibitory neurons of human body. Serotonergic neurons can be found in limbic system, basal ganglia and prefrontal cortex while GABAnergic neurons are widely distributed.  Hypo-function of these neurons leads to lack of inhibitory effect which cause hyperactive of brain neuronal circuits and this can lead to the feeling of anxiety.  Lacking of inhibition can be one of the explanations but hyper-activation of other areas can also take a part. Over-activation of certain neurons like noradrenaline system can induce excess fight or flight responses. Fight or flight response include raising blood pressure and heart rate, sweating and other autonomic system and main goal of the process is to prepare for stress condition.  However, dysregulation of noradrenaline system over long time might induce excess stress and cause anxiety disorder.
An general Structure Of GABAa receptor, created by http://www.science-approach.com
Generalised anxiety disorder is more common in the elderly group and long term stress from social environment might be one of the explanations.When human body encounters stress condition, certain steroid hormone like cortisol will elevated. The production of cortisol is from adrenal gland and the overall control center is in hypothalamus. When stress comes, hypothalamus will increase the secretion of corticotropin- releasing hormone into pituitary gland and pituitary gland will secrete ACTH to adrenal cortex via vascular system. In this way, cortisol is produced and can serves as an indicator for generalized anxiety disorder which is characterized by a pattern of excess worry and fear toward surrounding events.  According to the research done by Isabelle and others, cortisol level in elderly patient with GAD is higher than the counterpart when present in the same stress conditions. Long-term exposure to stressful condition, ether in work environment or human-human relationship, can lead to hypercortisolism and induce diseases.
Based on the research done by Gratacos M and others, the abnormal duplication of DUP25 region on chromosome 15 might also contribute to the disease.  DUP25 region is responsible for the production of protein involving in fear response.  The abnormal function of this protein might result in uncontrollable fear response.
By definition, comorbidity is the present of multiple diseases along with primary disease or disorder. Sometimes, it is hard to identify the actual causation of mental related diseases because several mental disorders can be seen in one case. Patient with GAD often accompany with other mental disorder like depression and social phobia.  Based on the Wittchen’s research and NCS survey database, more than 50% of GAD patient also develop stress-induced depression syndrome.  In other words, GAD doesn’t come alone and other major mental health disorder might also need to take into consideration. Therefore, the combination of GAD and other mental disorder make it hard to accurately diagnose the disease in clinical practice aspect. 
Symptoms and Diagnostic criteria
People with GAD have symptoms like restlessness, muscle tension, irritability and difficult to concentrate on certain task.  These symptoms may see common in other neuropsychological disease like panic and social phobia but GAD has rather long time course. In order to be diagnosed as GAD, these symptoms should last for more than 6 months. 
Conventional technique to determine GAD is the use of DSM and ICD criteria. DSM, which stands for Diagnostic and statistical Manual of Mental Disorder, is established by American Psychiatric Association and it is one of the criteria for determining mental health disorder.  The latest version of DSM is 4th edition. Different from DSM, ICD which stands for International classification of Disease is published by World Health Organization and it covers not only mental related diseases.  DSM and ICD both emphasize on the actual physiological changes of patient. Recently, a possible way of diagnosing the disease was found. According to the research done by Susann and others, the concentration of cortisol in patient's hair can serve as one important marker for GAD and at the same time provides linkeage between GAD and hypercortisolism. 
Treatment and Dilemma
Treatments for GAD mainly include psychological therapy and drug therapy. Efficacy of the treatment can be varied due to the accessibility of clinical resources and patient’s own personal situation. Because GAD is a chronic disease, the combination of other treatment or introducing new pharmacological supplement can be important for decreasing relapse and tolerance rate. Therefore, the research of alternative therapy like herbal treatment can provide more options for practitioner to cater the need of their patients.
Common Psychological treatment includes cognitive behavioural therapy, acceptance therapy, intolerance of uncertainty and motivational interviewing.  Cognitive behavioural therapy (CBT), which is the most frequent use, emphasize on changing patient’s negative interpretation toward certain events or surrounding objects.  Acceptance therapy, as its name suggest, try to change patient's negative attitude toward uncontrollable things in life and emphasize on self-accomplishment.  Intolerance therapy focus on similar goal like other therapy mentioned above which is to have the ability to tolerate negative emotion and obstacle in life.  At last, motivational interview is different from other therapy in terms of the way it approaches. Motivational interview therapy, just like interviewing someone, undergoes the process in an individual based consultation instead of attention and fear condition training.  Psychological therapy is often viewed as more healthy approach to deal with GAD comparing to conventional drug treatment.
Depending on patient’s status, drug treatments include acute and long term drug treatment. In acute situation, where the onset of the symptoms is more vigorous, drug like benzodiazepine which can be effective within an hour will prefer to be administered.  Benzodiazepines can rapidly decrease uncomfortable condition like restlessness and extreme anxiety but its dependence nature on human body makes it not suitable for long term usage.  Because of the chronic nature of GAD, the importance of long term and sustainable drug usage can’t be neglected. For long term therapy, drug like SSRI (selective serotonin reuptake inhibitor), SNRI (serotonin and noradrenaline reuptake inhibitor) and other antidepressant drug are used.  These drugs often take longer time to show effectiveness but less tolerance are seen throughout the time course. High efficacy and accessibility of pharmacological therapy make it preferable for most clinical practitioner.
Dilemma and Alternative therapy
Drug treatment has been used for most practitioners when dealing with GAD. However, problems like relapse and drug withdrawn symptoms has already questioned the overall efficacy.  Comparing to drug therapy, psychotherapy may see nice and clean without all these side effects but it requires significant amount of clinical resources. In addition, the chronic nature of GAD could make the psychotherapy lengthy and hard for patient to fully participate in the process. This is why most clinical practitioners still prefer conventional drug administration. Alternative treatment like herbal supplement provides another option for treating the disease. Rhodiola rosea, which is a kind of herbal, has shown efficacy toward GAD.  Rhodiola rosea is used as an energy refresher in many countries like Russia, ice land and China.  Since Rhodiola rosean can be made into daily drink like tea, it provides GAD patient with a more convenient to manage the diseases. After all, a cup of hot tea can surely decrease one’s tension toward daily life and nutritional supplement combing with this herbal might serve as prevention for disease relapse after drug withdrawal.