Exam Three: Stress and Psychiatry

How does schizophrenia risk relate to living in a big city?

much higher for those in big cities than small cities/rural. higher in small cities than in rural areas

diathesis stress model

when there is a negative environment, vulnerable indiviuals will have a negative outcome whereas resilient individuals will remain stable. In positive environments, both resilient and vulnerable people thrive

diathesis

vulnerabilities that predispose individuals to mental health issues when environmental stressors are also present (ie. weak brain structure)

symptoms of depression

anhedonia, feelings of sadness and despair, weight/appetite changes, tiredness, difficulty focusing, psychomotor agitation/retardation, suicidal ideation, worthlessness or excessive guilt

anhedonia

the loss of feelings of pleasure, or loss of enjoyment in normally pleasurable activities

psychomotor agitiation/retardation

agitation: itching, fidgiting, rubbing

retardation: moving or taling slowly so that other people notice

symptoms of anxiety

feelings restless, sleep issues, difficulty focusing, irritability, fatigue, feeling tired, excessive worry about many things

lifetime prevalence of anxiety

33%

which is more common, depression or anxiety?

MDD is more common than GAD, however, mood disorders are less common than anxiety disorders

how oftenis someone diagnosed with both anxiety and depression?

60% of people with GAD also have MDD. 55% of people with MDD also have an anxiety disorder (including social, panic, and general)

How genetically similar are MDD and GAD?

75%-100% similar genetic correlation!

shared mechanisms between MDD and GAD

overactive stress response, hyper-responsive to negative stimuli, mind wandering, and impaired top-down regulation

overactice stress response

HPA-axis hyperactivity. this leads to elevated cortisol

hyper-responsive to negative stimuli

overactive amygdala

mind wandering

Default Mode Network (DMN) hypperactivity

Impaired top down regulation

reduced lateral Pre-Frontal Cortex function

reduced connection of the ventral-medial Pre-Frontal Cortex and the amygdala (decreased vmPFC inhibition of amygdala)

what are monoamines

serotonin, norepinephrine, and dopamine

Monoamine Deficiency Hypothesis

an explaination for depression that states that the symptoms involved in MDD are due to a lower amount of neurotransmitters like dopamine, serotonin, and norepinephrine

drugs to treat monoamine deficiency hypothesis

SSRIs, Tricyclics, MAOIs

Monoamine Imbalance

hypothesis to explain anxiety that states that there is an unusual ratio of neurotransmitters like serotonin, dopamine, and norepinephrine as compared to neurotypical individuals

Tricyclics

drug that increases norepinephrine, serotonin, and acetylcholine

MAOIs

drug that inhibits the breakdown of monomines by catalysts

SSRIs

inhibit serotonin reuptake, leaving more serotonin in the synapse to bind to the post-synaptic neuron

how is HPA-axis abnormality different between depression and anxiety?

depression: chronically active HPA → high basline cortisol

anxiety: cortisol surges abnormally high in response to stressful events

Neurological issues unique to depression

hippocampal and reward system abnormalities

hippocampus issues

atrophy (smaller in size). Could either be a cause or a result of depression

reward system abnormalities

underactive reward system

overactive Habenulae (known as the anti-reward center)

neurological issues related to anxiety (in theory)

fear conditioning and GABA receptor deficiency

fear conditioning and anxiety

are people with anxiety more prone to have an increased conditioned fear response? More easily correlate stimuli with fear response

GABA receptor deficiency

GABAa receptors decrease neuronal excitability. people with less of these receptors are bound to have racing thoughts/pent up brain activity and anxiety. an easrly theory for the cause of anxiety

Cognitive Behavioral Therapy (CBT)

gold standard treatment for GAD and MDD. Aims to improve mental health by changing negative thoughts, beliefs, and behaviors. Based on theory that thoughts, feelings and actions are connected

what are some other first line therapies for depression? (not CBT)

interpersonal therapy - focusing on improving relationships

Behavioral activation - increases engagement in pleasurable/meaningful activities

how does behavioral activation work?

it helps motivate people to do healthy activities by prompting them to make one small step towards that goal (ie. putting on your gym shoes can motivate you to follow through with going to the gym)

what are some first line pharmacotherapies for MDD and GAD?

SSRIs and SNRIs

what’s the difference between psychotherapies and pharmacotherapies?

one is tranditional, clinical therapy, the other is drugs

How do SSRIs work?

inhibits reuptake of serotonin by blocking serotonin 5-HT receptor on pre-synaptic neuron

how long will it take for symptoms to improve with SSRIs?

2 weeks. The HT1A receptors have to become desensitized, and BDNF proteins have to be built/rewire the brain.

what are some cellular level downstream effects of SSRIs?

5-HT1A receptor desensitization and increased expression of BDNF protein

How do 5-HT1A receptors complicate SSRI function?

when more serotonin bind to these receptors throughout the body, they start a negative feedback loop that then decreases serotonin production. It takes the body a while to acclimate to the new levels of serotonin

what is BDNF?

BDNF stands for brain-derived neurotrophic factor. It’s a protein that helps neurons grow and survive

How does BDNF contribute to SSRI function?

SSRIs increase serotonin, which increases activation of signalling pathways, which upregulate BDNF gene expression, causing more of them to crop up. This promotes neuroplasticity and strengthens neural connectivity, promoting resilience and alleviating depression/anxiety

Therapies that eveolved from CBT

acceptance and commitment therapy (ACT)

mindfulness-based Stress Reduction (MBSR)

mindfulness-based Cognitive Therapy (MBCT)

Acceptance and Commitment Therapy (ACT)

Focuses on helping clients develop values and live in accordance with them, despite their thoughts and feelings

Mindfulness-Based Stress Reduction (MBSR)

8-week program focusing on reducing stress, improving overall well-being, and managing pain through mindfulness practices like meditation and body scanning

Mindfulness-Based Cognitive Therapy (MBCT)

Builds on the MBSR framework. Combines mindfulness practices with CBT to reduce anxiety and depression. Includes a focus on recognizing and breaking out of harmful thought patterns

Mindfulness based stress reduction vs. SSRIs

mindfulness interventions led to reductions of anxiety that were not signifigantly worse than reductions in stress due to SSRIs. Also, the mindfulness interventions had better attrition and less adverse events

Brain-Derived Neurotrophic Factor (BDNF) is also increased by exercise, and might be a good indicator of CBT effectiveness. What could this mean?

overall brain health (indicated by neuroplasticity and strong neural connections) could play a huge role in overall resilience to mental health issues

breakthrough/investigational pharmacotherapies

opiod receptor modulators

psychedelics

esketamine

psychedelics

LSD, MDMA/Ecstasy

not FDA approved

hypothesized to help with neuroplasticity

esketamine

FDA approved! for treatment-resistant depression with history of suicidal ideation/behavior

works within hours (no wiat time like SSRIs)

also hypothesized to help with neuroplasticity

what does it mean to be a second generation antidepressant?

these types of antidepressants were developed later, after the og SSRI. All of them act on monoamine reuptake or signaling. Only one of them (SNRIs) is also a first line therapy

SNRIs

Serotonin and Norepinephrine Reuptake Inhibitors

NDRIs

Norepinephrine and Dopamine Reuptake Inhibitors

SARIs

Serotonin Antagonist Reuptake Inhibitor

NaSSAs

Noradrenergic and Specific Serotonergic Antidepressants. Acts by imitating norepinephrine and serotonin, binding to their respective receptors and blocking their functioning

rTMS

high frequency stimulation of the left dorsal-lateral PFC is FDA approved for treatment-resistent people with depression (but NOT anxiety). 40% response rate, 20% remission rate.

LEFT dorsal-lateral Pre-Frontal Cortex

tends to support positive emotions, goal-directed behaviors, and cognitive control. It is linked to appraoch behaviors (steps towards healthy habits) and is typically underactive in people with depression.

which brain stimulation approaches are still under investigation?

personalized rTMS (specified approach)

deep brain stimulation (shot gun approach)

What are the DSM-5 criteria for someone to be diagnosed with PTSD?

you have to have a trauma, and have symptoms for each of the four different categories

what are some side effects of SSRIs?

decreased libido, headaches, stomach aches

what drug can help with numbing?

Opiod receptor antagonist. Stops NT from being able to bind to the natural brain painkillers and allows you to feel something again

cannabis

mixed results. Some people it stresses out more. However, may help reduce pain and overstimulation

if a treatment is helpful, and solves a brain issue, does that mean that particular issue is the cause of these mental health problems?

NO! These disorders are complex and caused by a lot of different abnormalities/experiences

deep brain stimulation

going in and implanting electrodes in the brain which will then stimulate the brain

What are some treatments you could offer if CBT did not work?

rTMS, psychadelics

what are the four different symptom categories for PTSD?

Intrusive, Avoidance, negative cognition and mood, hyperarousal

intrusive (at least 1)

recurring, involuntary trauma related memories.

recurrent, distressing, dreams

dissociative reactions

prolonged physiological responses

Avoidance (need at least 1)

avoidance to discussing internal triggers (memories)

avoidance to external triggers (men, locations, other vets)

Negative cognition/mood (need at least 2)

amnesia for parts of trauma

persistent, negative beliefs about self, others, or world

negative emotional state, anhedonia

detached from others

Hypearousal (at least 2)

needless irritability and angry outbursts

reckless/self destructive behavior

concentration issues

sleep issues

trauma definition

actual or threatened violent death, serious injury or accident, or sexual violence. Can be directly or indirectly exposed via family members or job.

dissociative subtype (DSM-5)

a subtype of PTSD with augmented dissociative symptoms such as depersonalization, derealization, amnesia, and altered perceptions of time

Complex PTSD (ICD-9)

another subtype of PTSD. involves extreme difficulties in eotion regulation, self-concept, and interpersonal relationships. Associated with prolonged or repeated traumas

lifetime prevalence of ______ is low, but prevalence of a _______ is about 80%

PTSD; potentially traumatic event

the genetic makep of _______ disorader is highly positively correlated with the genetic makeup of ______ disorder

schizophrenia; bipolar

MDD; Anxiety disorder

the genetic makeup of _____ is moderately positively correlated to the genetic makeup of ______

PTSD; MDD/ADHD

MDD; ADHD, Bipolar, Schizophrenia

are there any genes that predict PTSD?

not really. GWAS found marginal effects for many different genes, which doesn’t help to narrow it down. Even in monozygotic twins, only 30% of the time do both twins end up with PTSD.

which genes did predict PTSD, and what implications does this have?

the genes that were linked were related to general nueral functioning and brain health. this likely means that those with weaker brain health in general are more suseptible to disorders like PTSD

how does PTSD fuck up stress repsonses?

Hyperactive locus coeruleus, blunted cortisol stress response, hyperactive amygdala, increased mindwandering (DMN), impaired top-down regulation

blunted cortisol stress response (PTSD)

elevated negative feedback due to enhanced GR sensitivity and HPA-axis hyperactivity

what does having a hyperactive amygdala mean?

hyperactive response to negative stim

impaired top-down regulation

reduced lPFC function and reduced connectivity of vmPFC and amygdalaw

hat does having an overactive locus coeruleus mean?

increased adrenaline response!

key brain circuits for PTSD

Emotion regulation and executive function, threat and salience detection, contextual processing, fear learning (amygdala)

brain regions involved in emotion regulation and executive function?

lPFC and mPFC

Threat and Salience Detection brain regions

anterior cingulate cortex, insula, amygdala

contextual processing meaning and brain regions

patient fails to recognize context and will react to a firework as if it is a gunshot on the fourth of july

mPFC, Hippocampus, thalamus, locus coeruleus

first line psychotherapies for PTSD

prolonged exposure, eye movement desensitization and reprocessing, cognitive processing therapy

Prolonged Exposure Therapy (PE)

repeatedly engageing with trauma memories (imagined exposure) and triggers (real life exposure). Works by way of fear extinction, where you use repeated, safe exposures to create new memories and associate the trauma with neutral or positive experiences

what are some pro and cons to trauma related vs. non-traume related therapies?

truama focused therapies can have really low attrition, because people with PTSD are avoidant. However, some people view non-trauma related as being irrelavant to their issues and would rather have a more related therapy option

Eye Movement Desesitization and Reprocessing Therapy (EMDR)

repeatedly recalling distressing images while recieving sensory inputs.

Cognitive Processing Therapy (CPT)

correcting trauma-related cognitive biases (the world is dangerous, untrustworthy, unpredictable) to reframe negative worldviews

therapies for PTSD with sufficient evidence to recommend

present-centered therapy, written exposure therapy, ehlers and clark cognitive therapy for PTSD

present-centered therapy (PCT)

focus on current relationships and challenges rather than trauma. As effective as first-line treatments in the short term, but less effective over time (1-4 months posttreatment).

written exposure therapy

5 sessions of writing about trauma and very breifly processing with therapist. less time and resource consuming bc only 5 sessions

ehlers and clark cognitive therapy for PTSD

3 goals: modify negative appraisals, correct autobiographical memory, remove problematic coping strats

what are some other psychotherapies for PTSD?

interpersonal therapy, reconsolidation therapy, third wave therapies

third wave therapies for PTSD

often used to compliment trauma-focused therapies. Meta-analysis found medium to large effects

what are the only FDA approved first line pharmacotherapies for PTSD?

SSRIs

what are a few other drugs that could help with PTSD?

MDMA, SNRIs, Ketamine, rTMS, Cannabis