On Anxiety

Last class, when I talked about anxiety, I focused on the methods of treating anxiety, specifically, psychotherapy and pharmacotherapy.  I did a bit more research and looked at the biological basis of the anxiety disorder, so here, I will touch upon that as well.

According to the National Institute of Mental Health, anxiety is a “normal reaction to stress”, but if it becomes excessive, “it has become a disabling disorder”.  There are five major types of anxiety disorders: generalized anxiety disorder (GAD), obsessive- compulsive disorder (OCD), panic disorder (PD), post-traumatic stress disorder (PTSD), and social anxiety disorder (SAD). For treatment options, the NIMH states that anxiety disorders are commonly treated with medications, including, antidepressants, anti-anxiety drugs, or beta-blockers as well as with psychotherapy, including cognitive-behavioral therapy (CBT). A review article by Zwanzger, Diemer, and Jabs (2009) looked at meta-analyses to compare the psycho- and pharmacotherapy with monotherapy for anxiety disorder treatment. They found that there is experimental evidence to support that both psycho- and pharmacotherapy are effective treatments.  However, there is some disagreement on whether the combination approach (using both psych- and pharmacotherapy) is more effective than not having treatment at all (monotherapy). Many researchers support the former claim and have conducted studies to provide evidence that the combination approach is superior to monotherapy.  Bandelow et al. (2007) conducted 24 studies on patients with PD and found that the combination treatment had robust effects in the pre-post comparison compared to monotherapy. Additionally, Barlow et al. (2000), who conducted the largest study to date (n=312), compared 5 treatment strategies including CBT, imipramine, placebo, CBT plus imipramine, and CBT plus placebo in patients with PD and with or without agoraphobia.  They found that the combined treatment of CBT and imipramine showed the highest response for relieving anxiety symptoms.

To explore the neurobiology aspect of anxiety, I located a paper by Clement and Chapoutheier entitled, “Biological Basis of Anxiety” (1998). Scientists have developed animal models to induce anxiety, including a mild negative reinforcement (painful shock) associated with a positive reinforcement (food and water) and a non-conditioned behavioral response, including novelty-induced variations in exploratory activity.  In the open field test, “anxious animals” will spend more time in the outer grid spaces and less time in the middle.  In the elevated plus maze, rodents who spend more time in the open arms rather than the enclosed arms may reflect the animals aversion to open spaces. Anxiolytics, or drugs used to treat the symptoms of anxiety, have been shown to increase the time spend in the open arms; anxiogenic compounds reduce the time spent in open arms. On the pharmacology side, many anxioloytic drugs are used.  It is widely agreed that the “GABA (A) – benzodiazepines (BZ) system is involved in the pathophysiology of anxiety disorders”. The central BZ receptor (cBZR) has effects on the sedative, anticonvulsant and anxiologic properties of BZs.  Changes to the “density, affinity and/or regional brain distribution of cBZR may be associated with anxiety disorders” (Clement & Champouthier, 1998). The serotoninergic neurotransmission system is also highly involved.  There is evidence to suggest that this system (5-HT) may be involved in the expression and treatment of anxiety as anxiety is usually associated with endogenous 5-HT. The third main NT system associated with symptoms of anxiety is the cholecystokinin system or CCK. CCK is the most well known neuropeptide in the cerebral cortex and limbic system. A CCK agonist has been shown to induce an “anxiogenic-like behavioral response” such as panic attacks.

Clement and Chapouthier cite three main hypotheses for the neurobiological mechanisms involved in physiological reactions to stimuli.  First, anxiety is caused when there is a decrease in the inhibitory pathway function from the secretion of the “endogenous inverse agonists in the region of the BZ receptor”.  Second, when the BZ receptor is shifted “towards the inverse agonist position”, changes occur that make patients more vulnerable to stressors.  Third, in normal individuals, an endogenous agonist is observed; in the presence of anxiety disorders, this agonist tone is diminished or less effective. Much more work is needed to determine which hypothesis holds more validity.

If we find more evidence to support any of these hypotheses, we can better understand the neurobiological responses to anxiety on our brain and behavior.  Thus, we can understand why the combination approach is shown to be more effective in the treatment of anxiety disorders. Many people suffer from one type or another of anxiety disorders.  It would to be beneficial to mankind to find a “cure” for this disorder without having to inject pharmaceutical substances into our bodies as a treatment method.

7 thoughts on “On Anxiety

  1. As I was reading your post, I couldn’t help thinking about Obsessive Compulsive Disorder (OCD) and the amount of anxiety that seems to go along with it. Individuals with OCD (most of them, anyway) seem to be comorbid for anxiety, or at least their anxiety causes OCD in order to manage their fears, or the OCD causes anxiety (or perhaps they occur simultaneously?). Either way, I think that it is very interesting that these two disorders would coincide.


  2. First off, this is a random question, but is it considered animal cruelty when we are inducing them with anxiety or depression?

    Secondly, I am curious to why a combination of psycho and pharmaceutical therapy is usually the best bet when dealing with anxiety, depression, eating disorders, etc. Is it that the medication helps “fix the brain chemistry” and the counseling “fixes the mind and thoughts” of the individual?

    In response to Jenn, it is interesting to note OCD as an anxiety disorder, particularly because I always thought it was a personality disorder- symptoms of a REALLY anal personality (then again I really know nothing about OCD).


  3. OCD is always an interesting disorder to think about. I think Oliver Sacks (aka MY HERO) once turned me on this idea. If I go wash my hands, the pleasure areas of my brain get activated and I get this sense of “cleanliness” when I wash my hands. What happens if my pleasure centers never get activated? Do I keep washing my hands because I can never get that sense of “cleanliness?” I think it is an interesting concept.

    Lia’s question on animal cruelty is quite fascinating. It depends on what kind of animals you are talking about. Word on this street is that Rats and Mice are NOT considered animals by the USA. Hamsters and Gerbils are considered animals. So I guess it depends!

    Your answer to the second question sounds correct to me. In some situations, the synergistic effects of both treatments might be better than the individual treatments.


  4. The cruelty question is a good one Lia and I’ll reserve my thoughts on hamsters/gerbils v. rats… this type of research requires rigorous oversight and detailing of all procedures and implications of outcomes. We can definitely discuss that more if you like. Sara, nice overview. There is a fascinating model that describes a crucial role for hippocampus in anxiety. Just sayin’.


  5. It is so interesting to think of cleanliness as a response to the pleasure pathways in the brain- my eyes are starting to open to the Biological sides of things. Thanks Sharonda. I think it is especially interesting because of the possibility that dopamine and the pleasure pathways play a role in depression. Since there is such a close relationship between depression and anxiety it would be interesting to examine this further!


  6. Everytime I learn more about biological bases of behavior or pathology, I am reminded of how interconnected everything is! Sara talked about 5-HT and the serotonin influences, Melissa mentioned the hippocampus… and an article I read about depression mentioned anxiety and focused on the nucleus accumbens. That’s what makes finding the “root” of the problem so tricky- those roots are so connected that I wonder if there is ONE that triggers it all, or if pathology results from the combination of several areas functioning incorrectly a the same time.


  7. Anxiety is such an encompassing and widespread illness. I’m glad that the research on treatment methods was done. I think it’s really important to find what is the best way to treat anxiety.


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