· illnesses and somatic symptoms. health psychology 2019 (38)172-181. • nyberg j, henrikssonm,...

Joint CommissionNational Quality Approval

LOCATED IN ATLANTA, nationally recognized nonprofit mental health treatment organization serving adults ages 18+ with a primary psychiatric diagnosis

www.skylandtrail.org

Back to the FutureDifferentiating anxiety from anxiety disorders and their

ramifications

Raymond J. Kotwicki, MD, MPH, DFAPACharles B. West Chief Medical OfficerSkyland Trail

Critical Issues Facing Children & AdolescentsOctober, 2019

© 2016 Skyland Trail

► Understand that anxiety per se is not necessarily maladaptive, but anxiety disorders may result in systemic problems that can result in severe disability.

► Describe the psychodynamic underpinnings of anxiety, particularly a temporal focus on future events.

► Detail evidence-based treatments for anxiety disorders including behavioral interventions, pharmacological interventions, and physical interventions including exercise.

Learning Objectives


Working Definitions

Anxiety

Worry about future events with uncertain outcomes

Fear

Emotional response to real or perceived threat; vital to survival

Stress

Adaptive response to a challenge or demand which includes physiological changes


Not all Anxiety is a Disorder

Yerkes-Dodson Curve


• Exposure to chronic stress in itself does not necessarily result in anxiety disorders

• Experience, understanding of meaning, management of stress also determines if disability develops

• When anxiety disorders emerge, physiologic changes occur in the brain, endocrine systems, which determine neuropsychiatric illnesses

Chronic, Disabling Anxiety


Introducing the Amygdala

• Fight• Freeze• Flee

AMGYDALA

PRE-FRONTALCORTEX

THALAMUS

HIPPOCAMPUS

RELAY INFO

RELAY INFO

MEMORY RELEVANCE

CONTROLS

CONTEXTUALIZES

REGULATESHypothalamic – pituitary – adrenal systemDopamine tone in brain, esp. PFCPhysiological / metabolic control• Immune system• Metabolic system• Cardiovascular system

SENSORY STIMULI


• Smaller hippocampal volumes (avg. 18%)– May redevelop via BDNF, Brain-Derived

Neurotrophic Factor

• Decrease BDNF

• Decrease serotonin tone

• Loss of dendrites, spines in PFC (cognitive impact)

Physiological Implications


• Reduction in threshold to activate amygdala

• Exaggerated activity in amygdala

• Failure of cortex, hippocampus to dampen amygdala

• Overdrive of HPA axis

When Trouble Emerges


► Glucose metabolism

► Blood pressure regulation

► Immune system regulation

Roles of Cortisol

Macrophage

Local

Systemic

Local Effects- Increased vascular permeability- Vasodilation - Chemokine production- Expression of adhesion molecules- Pain

Effects on Brain- Fever- Fatigue- Anorexia- Anhedonia- Altered sleep

Innate Immunity/Inflammation

Acute Phase Response- C-reactive protein- serum amyloid A- haptoglobin- alpha 1-antichymotrypsin

Effects on Liver

Chemokines

Stromal cell

Endothelial cell

TNF, IL-1, IL-6 IFN-alpha

Adhesion molecules

Leukocyte Diapedesis

Toll-like receptors (TLRs)

Pathogen(e.g. bacteria),

Cellular Debris

TNFIL-1IL-6IFN-alpha

NF-κB

sickness behavior

tumorruborcalor dolor

Conservation of energy resources to promote increased metabolic demands of fighting infection and mounting a fever

SOURCE: MILLER AH 2013


Accelerated Aging!

And maybe worst of all…


• Epigenetics = reversible alterations in gene expression that are not part of the DNA sequence which may be heritable

• Exposure to stress may result in epigenetic changes (early worse than late)

Anxiety Disorders Also Change Genetics


• Epigenetic changes further alter neurotransmitter tone, regulation of HPA axis, and amygdala reactivity

• KIT gene and methylation of FKBP5 gene peripherally increase risk of anxiety disorders

Anxiety Disorders Also Change Genetics


Inextricable Link Between Anxiety & Physical Health

• Bidirectional Link– Biological impacts through cortisol

dysregulation (fluid volume regulation, gastric hypersecretion, etc.) as well as influence on inflammation and the ANS (adrenaline)

– Behavioral impacts such as avoidance of activity, medication hypersensitivity / non-adherence


All Things Considered

Anxiety is associated with:• Diabetes

(Farvid et. al. 2014)

• Heart Disease (Eaker et. al. 2005)

• Arthritis and other autoimmune diseases(Aguilar-Gaxiola et. al. 2016)

• High Blood Pressure (Jonas et. al. 1997)


The Case of Panic

Panic Disorder Symptoms:• Shortness of breath• Chest pain• Numbness• Sweating• Trembling• Chills / hot flashes• Nausea• Psychological fear of losing control or dying

PHYSICAL SYMPTOMS!


Chronic Physical Illnesses Predispose to Anxiety

• Pain may cause worry and anxiety

• Immobility and deconditioning limit exercise

• Anxiety part of certain syndromes– Hyperthyroidism– Pheochromocytoma– Stroke

• Rumination over health

• “Mimicry”


Comparing Anxiety & Depression with Obesity

Niles A, O’Donovan A. Comparing Anxiety and Depression to Obesity and Smoking as Predictors of Major Medical Illnesses and Somatic Symptoms. Health Psychology 2019 (38)172-181.


Comparing Anxiety & Depression with Smoking

Niles A, O’Donovan A. Comparing Anxiety and Depression to Obesity and Smoking as Predictors of Major Medical Illnesses and Somatic Symptoms. Health Psychology 2019 (38)172-181.


Treatment Implications

• Medical workup essential (psychiatrists are MDs!)

• Underutilized beta-blockers when anxiety related to physical symptoms.

• Short course of benzodiazepines as a bridge to interrupt anticipatory anxiety.

• Long-term use of SSRIs with a specific dosing

• Start low - Go high


Non-Pharmacologic, Biological Interventions• MOVE!!

Meta-analysis including 75,831 people showed significantly reduced odds of developing any anxiety disorder with high physical activity ((OR=0.74; 95% CI=0.62; 0.88) Schuch et. al. 2019)

• Mindfulness

• Regulate Gut Bacteria?– British Medical Journal, May 20, 2019,

BeiBei Yan, et. al.

– Non-probiotic > Probiotic– Fecal implantation?


• Stress, anxiety and fear are not inherently bad.

• When the fear neurocircuitry falls out of balance and disability ensues, anxiety may be a disorder.

• Anxiety disorders are associate with well-established physical and neuroanatomic changes.

• Physical, neuroanatomic changes offer many possible points of intervention! Very treatable illness!

Summary


Summary

• Anxiety is inherently a future-focused phenomenon (depression is in the past). Here-and-now focus critical.

• People with anxiety disorders require service connections with primary care providers (just one!) and a medical work-up.

• Discuss HEAL at every appointment!

• Don’t forget beta-blockers, meditation; assume treatment non-adherence.


► Perna G, Iannone G, Alciati A, Cldirola D. Are Anxiety Disorders Associated with Accelerated Aging? A Focus on Neuroprogression. Neural Plasticity 2016; (2016)8457612.

► Mah L, Szabuniewicz C, Fiocco A. Can anxiety damage the brain? Current Opinion Psychiatry 2016; (29) 56-63.

► LeDoux J, Pine D. Using Neuroscience to Help Understand Fear and Anxiety: A Two-System Framework. American Journal of Psychiatry 2016; (173)1083-1093.

► Makavac E, Meeten F, Watson D, Herman A, Garfinkel S, Critchley H, Ottaviani C. Alterations in Amydgala-Prefrontal Functional Connectivity Account for Excessive Worry and Autonomic Dysregulation in Generalized Anxiety Disorder. Biological Psychiatry 2016; (80)786-795.

► Andreescu C, Tudorascu D, Sheu L, Rangarajan A, Butters M, Walerk S, Berta R, Desmidt T, Aizenstin H. Brain structural changes in late-life generalized anxiety disorder. Psychiatry Research 2017 (2017)15-21.

► Nieto S, Patriquin M, Nielsen D, Kosten T. Don’t worry; be informed about the epigenetics of anxiety. Pharmacology Biochemistry and Behavior 2016 (2016)146-147.

References


• Niles A, O’Donovan A. Comparing Anxiety and Depression to Obesity and Smoking as Predictors of Major Medical Illnesses and Somatic Symptoms. Health Psychology 2019 (38)172-181.

• Nyberg J, Henriksson M, Åberg D, Wall A, Eggertsen R, Westerlund M, Danielsson L, Kuhn H, Waern M, Åberg M. Effects of exercise on symptoms of anxiety, cognitive ability and sick leave in patients with anxiety disorders in primary care: study protocol for PHYSBI, a randomized controlled trial. BMC Psychiatry 2019 (19)172.

• Schuch F, Stubbs B, Meyer J, Heissel A, Zech P, Vancampfort D, Rosenbaum S, Deenik J. Physical activity protects from incident anxiety: A meta-analysis of prospective cohort studies. 17 June 2019

• Yang B, Wei J, Ju P, Chen J. Effects of regulating intestinal microbiota on axneity symptoms: A systematic review. General Psychiatry 2019 (32) e100056 DOI: 10.

• El-Gabalay R, Mackenzie C, Pietrzak R, Sareen J. A longitudienal examination of anxiety disorders and phsycialhealth conditions in a nationally representative sample of U.S. older adults. Experimental Gerontology 2014(2014) 46-56.

References

· illnesses and somatic symptoms. health psychology 2019 (38)172-181. • nyberg j, henrikssonm,...

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