CNS_L12_Anxiety_Update.pdf

Neurochemical disorders III: Anxiety Dr. Jose Sapien, MD. Lecturer Anxiety is a normal emotional reaction to threatening or potentially threatening situations, and is accompanied by sympathetic overactivity. Anxiety is a state of increased vigilance and responsiveness that results in a range of meas...

Neurochemical disorders III: Anxiety Dr. Jose Sapien, MD. Lecturer Anxiety is a normal emotional reaction to threatening or potentially threatening situations, and is accompanied by sympathetic overactivity. Anxiety is a state of increased vigilance and responsiveness that results in a range of measurable defensive behaviors. 2 Amygdala It integrates information from cortical and thalamic sensory inputs to generate fear and anxiety-related behavioral outputs. Information processing within the amygdala is heavily dependent on inhibitory control (GABAergic hypothesis). The amygdala consists of multiple subdivisions, of which the basolateral amygdala (BLA) and central amygdala (CeA) are particularly important in anxiety processing. 3 Baselotareal amygdala = Lateral amygdala and Basal amygdala = Excitatory pathways Central nucleus of the Amygdala = Centromedial and Centrolateral = GABAergic pathways. 4 Amygdala Cortex (+Prefrontal cortex) & Thalamus → BLA → the lateral nucleus (LA) → BA (it processes this information in the basal nucleus (BA)) → the lateral subdivision of the CeL (centrolateral amygdala) and CeM (centromedial amygdala) → it may undergo additional processing → periaqueductal gray (PAG), bed nucleus of the stria terminalis (BNST), hypothalamus and dorsal vagal complex (DVC) → autonomic and motor responses → brainstem nuclei (the rostral ventrolateral medulla (RVLM)) = sympathetic preganglionic neurons → increase of sympathetic outflow. 5 6 7 Experience-dependent neuroplasticity: every experience we expose to someone has the capacity to change and strengthen their brain. The emotional memories stored in the central part of the amygdala may play a role in anxiety disorders involving very distinct fears, such as fears of dogs, spiders, or flying. The hippocampus is the part of the brain that encodes threatening events into memories. 8 Anxiety becomes pathological when: Fear is greatly out of proportion to the risk/severity of threat Response continues beyond the existence of threat or becomes generalized to other similar or dissimilar situations Social or occupational functioning is impaired Often comorbid with substance use and depression 9 Anxiety disorders are subdivided into five main types: Generalized anxiety disorder Panic disorder Stress reactions Obsessive compulsive disorder (OCD) Phobias (i.E. Agorafobia). The categorization of anxiety disorders was subsequently divided into anxiety, obsessive–compulsive, and trauma- and stressor-related disorders in the fifth edition, DSM-5. → 10 Categorization of anxiety, obsessive–compulsive, and trauma-related disorders in DSM-5. Anxiety disorders Separation anxiety disorder Selective mutism Specific phobia Social anxiety disorder (social phobia) Panic disorder Panic attack (specifier) Agoraphobia Generalized anxiety disorder Substance/medication-induced anxiety disorder Anxiety disorder due to another medical condition Other specified anxiety disorder Unspecified anxiety disorder 11 Obsessive–compulsive and related disorders Obsessive–compulsive disorder Body dysmorphic disorder Hoarding disorder Trichotillomania (hair-pulling disorder) Excoriation (skin-picking) disorder Substance/medication-induced obsessive–compulsive and related disorder Obsessive–compulsive and related disorder due to another medical condition Other specified obsessive–compulsive and related disorder Unspecified obsessive–compulsive and related disorder 12 Trauma- and stressor-related disorders Reactive attachment disorder Disinhibited social engagement disorder Posttraumatic stress disorder Acute stress disorder Adjustment disorders Other specified trauma- and stressor-related disorder Unspecified trauma- and stressor-related disorder 13 Based on American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. DSM-5. Arlington, VA: American Psychiatric Publishing; 2013.4 Epidemiology 1 yr prevalence: 1-4%, lifetime prevalence 6% (some studies 28%); M:F = 1:2 Age of onset: before 20 or middle adulthood 14 Etiology Many transmitters seem to be involved in the neural mechanisms of anxiety, the evidence being especially strong for γ-aminobutyric acid (GABA) and 5hydroxytryptamine (5-HT). Genetic studies suggest that generalized anxiety disorder and major depression may have a common genetic basis. The main brain structure involved is the amygdala. There is evidence for decreased GABA binding in the left temporal pole, an area concerned with experiencing and controlling fear and anxiety. 15 16 Treatment Treatment of mild anxiety disorders may only require simple supportive psychotherapy. Lifestyle: avoid caffeine and sleep hygiene. Psychological: CBT (cognitive restructuring), relaxation techniques, mindfulness. 17 Treatment Biological 1st line anti-depressants: SSRIs (escitalopram, sertraline, paroxetine), SNRIs (venlafaxine XR, duloxetine) → Their mechanism of action in anxiety is unclear. Pregabalin? Benzodiazepines considered 2nd line (short-term, lowest effective dose, helpful while titrating antidepressant) B-blockers not recommended 18 https://www.youtube.com/watch?v=2S21LH2Cqq0 (Endocrine system –Cortisol suggestion) https://www.youtube.com/watch?v=QAeBKRaNri0 (Endocrine system suggestion) https://www.youtube.com/watch?v=0IDgBlCHVsA (Sympathetic NS reminder video suggestion) 19 Additional bibliography Lee, S., Kim, S.-J., Kwon, O.-B., Lee, J. H., & Kim, J.-H. (2013). Inhibitory networks of the amygdala for emotional memory. Frontiers in Neural Circuits, 7. https://doi.org/10.3389/fncir.2013.00129 Babaev, O., Piletti Chatain, C., & Krueger-Burg, D. (2018). Inhibition in the amygdala anxiety circuitry. Experimental & Molecular Medicine, 50(4), 1–16. https://doi.org/10.1038/s12276-018-0063-8 20