Medial And Lateral Prefrontal Cortex
Both medial and lateral prefrontal cortices have direct connections with limbic structures involved in anxiety including dense reciprocal connections with the amygdala and HPC .
The mPFC is a complex cortical structure with different subregions that may contribute to anxiety and stress responses. In general, lesions of the mPFC decrease anxiety in rats exposed to the EPM and the social interaction test . The prelimbic mPFC preferentially inhibits HPA axis responses to psychogenic stressors . It also regulates glucocorticoid secretion, particularly its duration. Inhibition of the prelimbic mPFC or local injection of NE enhances heart rate responses to psychological stimuli . The infralimbic PFC is involved in initiating autonomic and HPA responses to psychogenic stimuli . Electrical stimulation of the ventromedial mPFC increases blood pressure in awake rats, while lesions or inactivation of the ventromedial PFC inhibits conditioned cardiovascular responses without affecting baseline heart rate or blood pressure, suggesting that it may be selectively involved in stressinduced cardiovascular regulation . In a recent study using multisite neuronal recordings with terminal optogenetic stimulation, it was shown that inhibition of the vHPC inputs to the mPFC induces anxiolytic effects .
What Is The Stress Response System
Imagine how you would feel if you encountered a bear in the woods. Your heart might start racing and you might start breathing heavily. You might freeze in place, unable to move out of fear. You might feel the urge to run away. These are all symptoms of stress. Stress is the mental and physical state humans feel when they experience something difficult or threatening. Stress can come from many different sources. Normal stressors are things that make you feel nervous or scared for a short time, like talking in front of a large group of people. Bigger, long-lasting stressors make you feel sad or scared for a long time. The death of a close family member is one example. The good news is that your brain is a superhero! Every day it keeps you safe from too much stress.
Even Superheros Sometimes Need Help
Even though our bodies have these super stressresponse systems, humans are best at dealing with stress when they have a little help. This help is called social support, which refers to the ways that other people can help us feel safe, loved, and cared for . Your friends and family may provide social support by hugging you when you are sad or scared, hanging out with you when you feel lonely, or celebrating with you when you are excited. We especially need social support when we are very young. Remember earlier when we mentioned that the amygdala shares a special connection with the prefrontal cortex? This connection does not mature until you are a teenager therefore, infants and children rely on their parents to help them calm down.
- Figure 2 – This study compared the brains of children and teenagers while they viewed emotional faces.
- When looking at negative emotional faces you can see that the childrens amygdala activity was decreased when their mothers were present. This tells us that the moms were buffering stressresponse systems in the children by providing social support. The teenagers amygdala activity increased when they viewed the emotional faces even though their mothers were present.
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Age Distribution For Anxiety Disorders
Most anxiety disorders begin in childhood, adolescence, and early adulthood . Separation anxiety is an anxiety disorder that commonly begins in childhood and often includes anxiety related to going to school. This disorder may be a precursor for adult anxiety disorders, most commonly panic disorder. According to the DSM-5, separation anxiety disorder can begin in adulthood.
Panic disorder demonstrates a bimodal age of onset in the NCS study in the age groups of 15-24 years and 45-54 years. The age of onset for OCD appears to be in the mid 20s to early 30s.
Most social phobias begin before age 20 years .
Agoraphobia usually begins in late adolescence to early adulthood .
In general, specific phobia appears earlier than social phobia or agoraphobia. The age of onset depends on the particular phobia. For example, animal phobia is most common at the elementary school level and appears at a mean age of 7 years blood phobia appears at a mean age of 9 years dental phobia appears at a mean age of 12 years and claustrophobia appears at a mean age of 20 years. Most simple phobias develop during childhood . and eventually disappear. Those that persist into adulthood rarely go away without treatment.
New-onset anxiety symptoms in older adults should prompt a search for an unrecognized general medical condition, a substance abuse disorder, or major depression with secondary anxiety symptoms.
Conflict Of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
References
Hostinar, C. E., Sullivan, R. M., and Gunnar, M. R. 2014. Psychobiological mechanisms underlying the social buffering of the hypothalamicpituitaryadrenocortical axis: a review of animal models and human studies across development. Psychol. Bull. 140:25682. doi:10.1037/a0032671
Gee, D. G., Gabard-Durnam, L., Telzer, E. H., Humphreys, K. L., Goff, B., Shapiro, M., et al. 2014. Maternal buffering of human amygdala-prefrontal circuitry during childhood but not during adolescence. Psychol. Sci. 25:206778. doi:10.1177/0956797614550878
Guassi Moreira, J. F., and Telzer, E. H. 2016. Mother still knows best: maternal influence uniquely modulated adolescent reward sensitivity during risk taking. Dev. Sci. 111. doi:10.1111/desc.12484
Gee, D. G., Gabard-Durnam, L. J., Flannery, J., Goff, B., Humphreys, K. L., Telzer, E. H., et al. 2013. Early developmental emergence of human amygdalaprefrontal connectivity after maternal deprivation. Proc. Natl. Acad. Sci. U.S.A. 110:1563843. doi:10.1073/pnas.1307893110
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Genetic Contribution To Posttraumatic Stress Disorder
The heritability for PTSD has an estimated range of 30% to 40%, probably resulting from a variety of genes, each with relatively small contributions to the genetic predisposition for this disorder.â Because of the importance of the environmental impact for this disorder, linkage studies in pedigrees cannot be conducted easily. Candidate gene association studies also are confounded by the problem of matching for environmental exposure and largely have been limited by small sample size therefore these studies would able to detect only large genetic effects.
Other genes interacting with early-life stress also are strong candidates for influencing susceptibility for PTSD. Preclinical studies indicate that the persistent hyperactivity of the HPA axis associated with ELS is mediated by a hyperactive CRF1 system, with chronic overactivity of CRF1 in limbic brain regions., In fact, the authors have shown that a haplotype within the gene encoding CRF1 interacts with child abuse to predict depression severity in adults. These polymorphisms, however, did not interact with ELS to predict PTSD symptoms.
Uncertainty Triggers Specific Brain Activity
Dr. Monosov came to his findings by studying the brains of rhesus monkeys, which have many brain structures similar to those of humans.
He focused on the anterior cingulate cortex of the brain, a region in the prefrontal cortex that previous studies have shown plays a role in behaviors associated with uncertainty a key driver of anxiety.
For his study, Dr. Monosov trained two monkeys to associate three different geometric patterns with three different outcomes. One pattern was associated with receiving an irritating puff of air in the face , one pattern was associated with a 50-50 likelihood of getting a puff of air in the face , while the third pattern was associated with no outcome.
As the monkeys were shown each geometric pattern, Dr. Monosov used MRI to measure neuronal activity in the ACC of their brains.
The researcher identified brain cells in the ACC that were activated in response to the geometric design associated with an uncertain outcome. However, when the monkeys were shown patterns associated with a certain outcome or no outcome, these brain cells showed no activity.
We found a population of neurons that activated specifically when monkeys thought something bad or annoying like a puff of air to the face might be coming, but not when they knew for certain it was, explains Dr. Monosov.
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Bed Nucleus Of The Stria Terminalis
The BNST is a component of the extended amygdala, which plays a critical role in the integration of autonomic and behavioral responses to stress . Earlier studies suggested that the CeA may be involved in processing explicit cue information associated with fear, while less explicit information associated with anxiety may activate the BNST . As stated earlier, given the vast evidence suggesting a role for both areas in anxiety, this view has begun to be contested .
Several studies have tested the effects of overall BNST modulation of different neurotransmitters in anxiety and in anxiety induced by acute or chronic stress. Changes in anxiety levels can be induced by intraBNST manipulation of CRF , glutamatergic AMPA receptors , serotonin 1A , calcium channel blockers , GABA synthesis , calcitonin generelated peptide , orexin A and B , and noradrenergic activity .
In awake animals, pharmacological activation of BNST elicits a rapid pressor response followed by bradycardia , whereas inactivation exacerbates restraintinduced increases in heart rate . This indicates that BNST signaling is necessary for inhibiting cardiovascular responses to stress. Modulation of heart rate by BNST stimulation or inhibition seems to be mediated by the parasympathetic nervous system .
Chronic stress and chronic corticosterone both increase BNST volume and modulation of cholinergic activity and galaninmediated signaling in the BNST can block the anxiogenic effects of restraint stress .
Let Us Help Manage & Treat Your Anxiety
Here at StoneRidge Centers, we combine brain science with compassionate care. We know just how taxing anxiety can be on your brain. But we also know that with treatment and support, you can learn to manage anxiety. We created our mental health treatment program for that very reason.
Anxiety doesnt have to take over your life. You dont have to live in fear of the world or constantly worry about potential dangers. We can customize our comprehensive program to meet your needs. Contact us today at 928-583-7799 for a free and confidential conversation about managing your anxiety in a healthy way.
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Neurotransmitters In The Amygdala Involved In Anxiety
Given that stress induces anxiety, stress mediators in the brain, such as CRF, norepinephrine , and glucocorticoids can all induce anxiety when microinjected into the amygdala. Other neurotransmitters and modulators known to be involved in anxiety include serotonin, dopamine, GABA, acetylcholine, endocannabinoids, neuropeptide Y , and orexins. Evidence of their role in anxiety while acting in the amygdala will be summarized succinctly.
Anxiety Caused By Anxiety
Anxiety is also self-sustaining. Earlier we mentioned panic attacks, and how they can often be caused by periods of stress that become overwhelming. But once youve had your first panic attack, you may get them again and again because of a fear of panic attacks, or because your body becomes more attuned to how it feels, which ultimately triggers them in the future.
We see this in other ways too:
- If you found yourself nervous about a plane ride, you might be fearful on future plane rides.
- If you find yourself worried about a negative thought, you may have that thought more often.
- If you experienced severe anxiety symptoms, you may be anxious about experiencing them again.
Essentially, anxiety and a fear of anxiety symptoms can create more anxiety in the future. They become their own self-sustaining cycle. So even justifiable anxiety can lead to unprompted anxiety.
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What Areas Of The Brain Are Involved In Anxiety
Anxiety starts when the central emotional processor known as the amygdalaor the so-called extended amygdala, which encompasses the bed nucleus stria terminalis interprets incoming stimuli from the inner or outer world as a threat. A distress signal is sent out to many other parts of the brain, including the hypothalamus, which in turn relays the signal to the rest of the body by switching on the sympathetic nervous system. The release of epinephrine from the bodys adrenal glands jolts the brain into alertness, sharpening senses and demanding hypervigilance of the environment. The amygdala also communicates with the hippocampus, repository of memory, which can put the threat signal into comforting contextor not.
Normally, through their many interconnections, the prefrontal cortex, seat of executive functioning, exerts control over the emotional output of the amygdala. But the negative emotional signals emanating from the activated amygdala, amplified by the excitatory neurotransmitter glutamate, disrupt cognitive functioning, including decision-making, and keep the prefrontal cortex from switching to other matters. Anxiety short-circuits the decision-making process by literally suppressing the normal activity of specific populations of neurons in the prefrontal cortex.
Finding Help For Social Anxiety Disorder
Undiagnosed and untreated social anxiety disorder is a devastating condition that can severely limit daily functioning. Even when social anxiety sufferers realize they have a serious problem they may have difficulty asking for help, since therapists are authority figures and people with social anxiety disorder generally avoid interactions with authority figures if they can.
But social anxiety disorder is highly responsive to treatment, and when sufferers do summon the courage to ask for help they often achieve terrific results, both short-term and long-term.
While antidepressants and anti-anxiety medications are often prescribed for people with social anxiety disorder, psychotherapy is the core of social anxiety treatment. Cognitive-behavioral therapy in particular has been found to be effective against social anxietys most disabling symptoms, and is almost always recommended by mental health professionals who see social anxiety disorder patients.
Most treatment for social anxiety takes place on an outpatient basis. But people whove struggled with social anxiety disorder for many years can gain great benefit from inpatient stay in a mental health treatment facility, where all the focus is on recovery.
Social anxiety disorder is difficult to endure, but with the help of treatment services and mental health professionals its symptoms are manageable. Even though social anxiety sufferers sometimes have trouble asking for help, once they do they never regret it.
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The Mind And Mental Health: How Stress Affects The Brain
Stress continues to be a major American health issue, according to the American Psychological Association. More than one-third of adults report that their stress increased over the past year. Twenty-four percent of adults report experiencing extreme stress, up from 18 percent the year before.
Its well-known that stress can be a detriment to overall health. But can stress actually change the physiology of the brain? Science says yes.
Panic Attacks And The Brain
Panic attacks are a particularly distressing form of anxiety, and these may be due to the health of the brain too. Researchers have found that those with panic attacks often have an overactive amygdala. While it’s not clear what creates this over activity, the fact that that area of the brain appears to contribute to panic attacks indicates that some aspect of the brain is in control of the panic attack experience.
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