Anxiety and Stress.

More About Anxiety and Stress.

On a neuroendocrine level, anxiety and stress symptoms arise from an interplay of (1) the threat detection system, (2) subcortical activation, (3) autonomic nervous system activation, (4) cortico-striato-thalamo-cortical (CSTC) loop, and (5) the hypothalamic-pituitary-adrenal (HPA) axis.

• Threat detection system: utilizes the senses (sight, see, smell, feel, taste) and the brain’s capacity to monitor the internal environment (interoception) and external environment (neuroception) for threat.

• Subcortical Activation: Lower brain regions are then activated, including the amygdalae and associated network projections. This system can overwhelm the capacity of the executive brain (prefrontal cortex) to manage the threat.

• Autonomic Nervous System: The sympathetic (fight-flight) and parasympathetic (connect, immobilize, freeze) systems activate to mobilize energy in the body to neutralize the threat. The first thing that happens is the activation of the ventral vagal complex (part of the parasympathetic nervous system) to connect and attach to others in order to neutralize the threat. If significantly overwhelmed or if a safe other is not recognized quickly, then the sympathetic nervous system is activated. The sympathetic nervous system prepares us to fight or flee. If the threat is not quickly neutralized by this system, then the most primitive system is activated (the dorsal vagal complex of the parasympathetic nervous system). In response to threats, this system will induce freezing, numbing, and submitting.

• Cortico-striato-thalamo-cortical (CSTC) Loop: This system carries the stressor beyond the actual stressful encounter when activated. This is the “worry” or “obsession” loop. Often here you’ll experience generalized avoidance or repetitive behaviors (e.g., compulsions) aimed at neutralizing the threat.

• Hypothalamic-pituitary-adrenal (HPA) Axis: This system also carries the stressor beyond the actual stressful encounter. This system releases a stress hormone (cortisol) that aims to mobilize energy in a chronically “activated” body. Think of it as an ongoing energy manager that tries to keep the energy going when there is a persistent threat. This system, while helpful to a degree, can cause damage to the amygdalae (making them chronically hyperactive, making them overly responsive to events), hippocampus (shrinkage, impairing memory), and prefrontal cortex (disconnection, impairing the executive functioning of the brain i.e. planning, organizing, prioritizing, focusing, etc.).

There is considerable overlap in these brain and endocrine changes among anxiety disorders, phobias, obsessive-compulsive disorders, somatoform disorders, trauma disorders, and other stress disorders. I like to conceptualize these as being similar in “process”, or how they arise but differ in “content”, or where the focus of things lies (e.g., obsessions, intrusive thoughts, phobias, bodily sensations, physical symptoms, etc.). That being said, there are some additional neurologic differences among these.

Signs and Symptoms.

There are two syndromic clusters that often arise in the context of an event that produces anxiety or a bodily stress response:

(1) The sympathetic overdrive symptoms (PANICS):

• Papliptations

• Abdominal pain

• Nausea and slowed gastrointestinal motility (e.g., constipation)

• Intense fear (of death or losing control among other things)

• Chest tightness and difficulty breathing

• Sweating

(2) The parasympathetic underdrive or HPA axis symptoms (MISERAble):

• Muscle tension

• Irritability

• Sleep impaired

• Energy decreased

• Restlessness

• Attention impaired

Oftentimes these two symptom clusters overlap and a mix of symptoms is present.

Causes and Contributions.

Anxiety and stress are caused by changes in the way threats are perceived, overactivity of the neural systems previously described, and overactivity of the hypothalamic-pituitary-adrenal (HPA) axis. While identifiable stressors are typically identified as the “cause” of stress and anxiety, it is really the way we perceive threat… Below I’ve listed several factors contributing to altered threat perception:

Biological Factors:

• Impaired genetic abnormalities (e.g., MTHFR or COMT abnormalities)

• Impaired immunity (i.e., inflammatory anxiety/stress)

• Altered endocrine function (e.g., hypothyroid or hyperthyroid, hypercortisolemic/adrenal, and glycemic dysregulation anxiety)

• Post-partum and peri-menopausal changes

• An imbalance of key brain chemicals (serotonin, norepinephrine, and dopamine)

• An imbalance of brain growth and development hormone (e.g., neurotrophins such as brain-derived neurotrophic factor).

• Imbalanced cofactors, methylation, and nutritional factors (e.g., vitamins and minerals)

• Impaired receptor responsiveness (i.e., reception and response to brain chemicals)

• Impaired gut health (i.e., gut dysbiosis)

• Substance-induced dysregulation (e.g., withdrawal from downers such as alcohol, benzodiazepines and opioids as well as intoxication with uppers such as cocaine and methamphetamine)

• Medication-induced anxiety (certain medications can cause anxiety such as steroids, contraceptives, inhalers and beta blockers)

Lifestyle/Environmental Factors: traumatic experiences (single incident, multiple incidents, developmental, or transgenerational), adverse childhood experiences, stressful events (accumulation of small stressors and/or large stressors), socioeconomic strain, impaired or dysfunctional relationships, separation or loss, sedentary lifestyle or impaired ability to exercise, nutritional imbalances and food intolerances/sensitivities, inadequate or impaired sleep, substance use at al. addictions, and nature deficit.

Psychological Factors: coping skills and resources, stress responsivity, perception of self (including a mismatch between ability and performance), interpretation bias, negative emotionality, learned responses to stressors, attachment style, and personality structure.

Screening.

Screening depends on what “content” is associated with the syndromal features. Therefore, the screening tools used will depend on whether or not the concern is for Generalized Anxiety Disorder, Panic Disorder, Obsessive-Compulsive Disorder, Phobic Disorder, Post-traumatic Stress Disorder, etc. For instance, in generalized anxiety (i.e., chronic worry with several triggers) the GAD-7 is a standard tool. On the other hand, if the content is more consistent with obsessions as seen in obsessive-compulsive disorder, then the Y-BOCS is a gold standard tool. Screening and further evaluation are often tailored by the provider.

Diagnosis.

The following sets of conditions have been found to include similar underlying neuroendocrine changes. Each condition differs in terms of the overall “content” of anxiety/stress as well as some individual nuances:

• Obsessive-Compulsive Disorders: Includes obsessions and/or compulsions and includes disorders such as obsessive-compulsive disorder, hoarding disorder, and body dysmorphic disorder, among others.

• Normal life changes: Sometimes anxiety and stress are not pathological, but related to naturally occurring life adjustments. It’s important to note that life adjustments can sometimes lead to significant changes in the body and a hyperactive stress response may be contributable to one of the aforementioned causes/contributing factors.

• Somatoform: These are conditions where anxiety and stress carry the theme of physical symptom presence and concern. These conditions include pain disorder, somatization disorder, conversion disorder, and illness anxiety disorder among others.

• Trauma: Anxiety and stress symptoms in the setting of trauma. Please see my trauma section for further details.

• Attributable: Attributable anxiety and stress conditions include a particular theme. For instance, social anxiety disorder carries the theme of social triggering and specific phobias stem from particular things that induce fear. Anxiety and stress can also be attributable to depression, executive impairment or ADHD, psychotic illness, and personality disorders.

• Generalized: When anxiety and stress stem from several sources not explained by the above categories, as occurs with generalized anxiety disorder.

• Episodic: When anxiety and stress occur in distinct episodes not explained by the above categories and takes on the form of panic attacks as seen in panic disorder.

In the specialty of integrative psychiatry, we expand the syndromic labels used in conventional psychiatry to identify particular phenotypes (subtypes) indicative of specific root causes. Then, the focus becomes exploring the root causes of anxiety so that a more individualized plan of care can be developed for you.

Treatment.

In the treatment of anxiety and stress, likely a combination of treatments is likely to yield positive results and this combination depends on the individual’s experience.

Medications.

Common medications used in the treatment of anxiety include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), bupropion (Wellbutrin), tricyclic antidepressants (TCAs), and several adjunctive treatments.

Some medications are used on a more “as needed” basis when symptoms arise including propranolol, hydroxyzine, clonidine, and benzodiazepines.

Nutraceutical.

There are several nutraceutical options that will help with anxiety. The most appropriate nutraceutical option(s) depends on your specific experiences but may include 5HTP, ashwagandha, Lavendar oil capsules, L-theanine, inositol, Ginkgo biloba, and Saint John’s Wort among others. A focused exploration into the impact of the hypothalamic-pituitary-adrenal (HPA) axis may indicate a need for a regimen aimed at calming the stress response.

Lifestyle.

Several lifestyle modifications can help improve depressive symptoms:

• Habits: Reducing and eliminating substance use and other addictions. Although easier said than done, this often involves multimodal treatment and exploration of root causes.

• Sleep: Stabilization of sleep routines and patterns (e.g., reducing blue light exposure from screens 4 hours prior to bed, avoiding stimulating activity prior to bed, etc.) with a goal of 6-7 hours per night (sometimes medication or nutraceutical options are helpful here).

• Exercise: Moderate intensity exercise (e.g., walking) with a goal of 3-4 times per week has the best evidence basis for improving upon anxiety and stress. Interestingly, exercise works as a form of “exposure” therapy for anxiety by way of training your brain to monitor physical symptoms and neutralize the associated threat perception. It’s recommended to start with something you enjoy and build upon a routine and habit from there.

• Nutrition: Dietary adjustments such as sugar reduction (<10% added sugar in products) and a goal of a Mediterranean diet with healthy fats and high fiber have been shown to improve anxiety symptoms.

Therapy.

Therapy for anxiety involves a combination of techniques to relax the body and improve upon executive functioning. You cannot experience stress and anxiety in a relaxed body, therefore stress reduction techniques (e.g., body scanning with muscle relaxation, breathing techniques, etc.) are an essential part of treatment. As you begin to experience more of a relaxed body, executive functioning tends to come “back online”, though therapy may also involve problem-solving-related assistance and navigating through several issues. Several techniques aim to remove some of the excessive burden on the executive part of the brain to make working through problems and issues a little easier. Depending on your unique circumstances, deep-rooted issues may arise in therapy that require more exploration and work.

Common therapy modalities used in the treatment of anxiety include cognitive-behavioral therapy (CBT), dialectical behavioral therapy (DBT), positive psychotherapy (PPT), and solution-focused or problem-solving therapy (SFT/PST) among others.

If I were to recommend one thing to start with, I would encourage actively checking your body multiple times throughout the day (e.g., via scanning head-to-toe) and noticing where you are tensing muscle groups. As you notice these tensed muscle groups, actively release this tension. When I say multiple times a day, I mean 20, 30, or 60 times a day for a few weeks. The more you do this, the more this will become reflexive. You cannot experience stress and anxiety in a relaxed body. Set reminders in some way to cue you to relax muscle groups. Where there’s tension, pay attention.

Additional Treatments.

Targeting biological derangements with treatments such as thyroid supplementation, B12/folate supplementation, iron, magnesium, zinc, and vitamin D can reduce symptoms of anxiety. A multi-ingredient formula (MIF) such as EmPower+ or Daily Essential Nutrients may also be beneficial. A more novel treatment in psychedelic-assisted and psychedelic integration therapy for anxiety.