Stress & Anxiety Flashcards
1
Q
Types of stress ›
A
Acute Stress
- Helpful stress responses= acute stress e.g. threat to your safety will trigger F/F response.
- This mobilises hormones which prime body to be alert and ready to escape or deal with danger
- Extremes in temperature and O2 content are external stressors, exercise is an internals tressor
- Major stress types: frustration (blocked goal), conflict ( incompatible motivation), change (having to adapt to changes in environment)
- Chronic stress is MALADAPTIVE stress
Maladaptive Stress
- When stressors persist/ become chronic and we are unable to resolve problem, stress becomes maladaptive
- Causes structural and functional changes in brain and body: often deleterious and organ may fail- death, physiological/psychological breakdown
- Importance of stressor activated responses of central neural network (HPA axis, particularly CRH activity)
- Despite behavioural, autonomic, neuroendocrine and immune responses some stressors persist and provide long-term activation of a common stress response network involving the limbic brain and CRH neuronal activity
- Prolonged cortisol= necrotic to hippocampal glucocorticoid receptors, thus reduces ability of cells to “turn off” the stress response
2
Q
The importance of the HPA, CRF and the Limbic system ›
A
HPA Axis
- Amygdala→ fear centre→ stimulates stress response ( corticotropin- releasing hormone neurons in hypothalamus)
- CRH stimulates release release of adrenocorticotropic hormone from anterior pituitary
- ACTH stimulated adrenal cortex to release cortisol
- Amygdala & hippocampus regulate CRH neurons of hypothalamic
- Amygdala→ fear response→ activates the stress response
- Hippocampus contains glucocorticoid receptors (respond to rising levels of cortisol) → suppresses stress response
Limbic System
- Cerebral cortex forms ring (in green) the “limbus” or border around gray matter of corpus callosum: acts as a link beween higher cognitive functions and more primitive emotional responses. Includes insular, cyngulate gyrus, parahippocampal gyrus, hippocampus, hypothalamus, septal nuclei, amygdala, parts of thalamus, midbrain reticular formation and olfactory areas
- Hypothalamus & Pituitary: the neuro- endocirne control of response to maintain homeostasis is needed for survival
Severe stressors
- Causes distress/ stress= a serious disruption when homeostatic mechanisms are unable to restore “steady state”
- Usually when stress extreme, unusual or long lasting= may lead to malfunction → disease or even death
- Physiological stress response is called “general adaptation syndrome” which occurs in 3 stages: Flight or fight response, resistance reaction, exhaustion
3
Q
The 3 stages of the physiological stress response ›
A
- F/F: mass discharge of sympathetic nervous system, short lived
- Resistance reaction: initiated mainly by hypothalamic releasing hormones, longer lasting response, sees us through stressful episode
- Exhaustion: occur if body resources depleted that resistance stage cannot be sustained and fails to combat stressor
4
Q
Stress, the immune response and disease ›
A
- Immunity and the CNS: important bidirectional interaction between brain, behaviour and immune system (i.e. complex interaction of biological, psychosocial and environmental factors causing illness), immune cells are influenced by many hormones(including adrenalin and noradrenaline, ACTH and cortisol), the cortical and limbic forebrain ( hypothalamus, hippocampus, amygdala in particular) are major CNS systems responding to immune signals and regulating outflow to immune system
- Evidence for interaction includeS: SNS via hypothalamo-adreno-medullary axis affects immunity increase adrenalin and noradrenaline levels ( former increases NK activity), SNS also associated with increased Ab production → due to increased firing of hypothalamic neurons, interaction between CNS and immune system releases IL-1 (inflammatory mediator, producing fever and stimulating CHR release, thus increase ACTH and cortisol)
5
Q
The importance of the HPA, CRF and the Limbic system ›
A
HPA Axis
- Amygdala→ fear centre→ stimulates stress response ( corticotropin- releasing hormone neurons in hypothalamus)
- CRH stimulates release release of adrenocorticotropic hormone from anterior pituitary
- ACTH stimulated adrenal cortex to release cortisol
- Amygdala & hippocampus regulate CRH neurons of hypothalamic
- Amygdala→ fear response→ activates the stress response
- Hippocampus contains glucocorticoid receptors (respond to rising levels of cortisol) → suppresses stress response
Limbic System
- Cerebral cortex forms ring (in green) the “limbus” or border around gray matter of corpus callosum: acts as a link between higher cognitive functions and more primitive emotional responses. Includes insular, cyngulate gyrus, parahippocampal gyrus, hippocampus, hypothalamus, septal nuclei, amygdala, parts of thalamus, midbrain reticular formation and olfactory areas
- Hypothalamus & Pituitary: the neuro- endocirne control of response to maintain homeostasis is needed for survival
6
Q
The role of endogenopus opiates
A
Endogenous Analgesia Systems
•Stressful situations stimulate Periaqueductal gray matter which communicates to inhibitory neurons to release enkephalins (endogenous opiates) and suppress pain signals
7
Q
Consider selected stress related conditions ›
clinically relevant examples of stress-related conditions ›
The importance of clinical signs and symptoms ›
Brain circuitry and Anxiety
A
- Anxiety closely linked to fear= involves amygdala (part of limbic system). It coordinates fear response/ stress response
- amygdala= also important in vigilance, threat detection and determining meaning and importance of stimuli (making sense of stimuli)
- Sends message to motor areas, brain stem nuclei controlling autonomic responses and arousal, integrates multiple sensory areas to assess stimuli.
- Cortical areas have reciprocal connections so feedback between amygdala, medial prefrontal cortex, hippocampus and cortico-striato-thalamic circuits
- Cortex can “curb” fear when threat passes
- Hippocampus supplies amygdala with information on context of threat- retrieves explicit information from memory, this may be coloured by the emotional context of the memory
- Dysfunction of hippocampus= poor contextual stimulus discrimination- overgeneralization of fear response
- Enhanced autonomic activity occurs via efferents to lateral hypothalamus→ motor response, including “freezing”, mediated via projections to periaqueductal gray matter (refer to endogenous analgesia)
8
Q
Panic Disorder
A
- Many disabling panic attacks. More women than men ( 2-3% vs 0.5-1.5%). Onset most common after adolescence but before age 50.
- “Exam nerves” a common cause
- Characterised by intense ANS arousal symptoms include: dyspnoea and hyperventilation, associated pCO2 reduction and consequent lightheadedness, numbness and tingling around mouth, racing pulse, palpitations, sweating, trembling, abdominal distress etc
- May develop into agoraphobia and becoming housebound
9
Q
PD- Aetiology & Physiology
A
- Genetic factors important - 20% increase risk with positive family history, only 2-6 % in others
- Brain regions affected are locus coeruleus (LC) (noradrenaline) and hippocampus and amygdala
- LC contains cell bodies of adrenergic neurons (noradrenaline) responsible for innervating all regions of the forebrain- the hypothalamus, cortex, temporo limbic, midbrain, cerebellum
- Hippocampus and LC monier internal and external signals, latter sensitive to changes in respiratory and cardiovascular systems
- GABA- Benzodiazepine (BZ) receptor system involved. BZ increases response in GABA ion channels → increased nt inhibitory effects
10
Q
GABA
A
- GABA- primary inhibitory CNS nt, opens Cl- channels and cause cell to hyperpolarize → reduce firing rate
- Benzodiazepines and barbiturates allosterically enhance affinity of GABA (A) receptor ( at site remote to active site of GABA nt)
- Benzodiazepines enhance ability of GABA to open Cl_ channels, allow more Cl- ions enter cell, prolongs GABA inhibitory effect on CNS functions
- Benzodiazepines are used as Anxiolytic agents and side effects= light headed, drowsy, increase reaction time, decreased motor coordination and cause mental confusion
11
Q
Generalised Anxiety Disorder (GAD)
A
- Excessive and persistent worries, affects 4-6% of population, more women than men
- Usually emerges early 20s, can occur in children
- symptoms= restlessness, motor tension, irritability, fatigue, poor concentration, sleep disturbance, startle easily
- Clinically- chronic exposure to stressful life events may be associated with depressive symptoms
- Severity fluctuates with environmental stressors
GAD- Aetiology & Pathophysiology
- Poorly understood, involves abnormalities in certain nt/receptor systems
- Reduced negative feedback → chronic cortisol→ reduced hippocampal glucocorticoid receptors→ reduced inhibition of stress response
- Alterations in noradrenaline system and reduced a2 receptor binding: presynaptic ( negative feedback control at local level- when excessive adrenergic stimulation occurs, they inhibit nt release at terminal end, prevent over stimulation of effector), postsynaptic: effect on pancreas
- Reduction in serotonin (5-HT) in some subjects and reduced number of BZ (GABA- benzodiazepine) receptors, particularly in left temporal hemisphere (language and speech and coordination of auditory and visual aspects of language), therapeutic effects of BZs may be due to “normalising” BZ receptor alterations
12
Q
Mood Disorders & Depression
A
- Mood disorders/ affective disorders= disordered emotions. Affects >7% population
- Strong comorbidity with GAD
- Getting “blues” common, BUT clinical depression more prolonged, severe and has perception of loss of control
- It is disabling, causes problems with concentration, socialising and appetite, may also involve insomnia, fatigue, lack of self esteem, job loss, guilt, suicidal thoughts etc
- May last 4-12 months up to 2 years but may be chronic
- Due to abnormality. Reduction in monoamine nt- serotonin (5-HT) and noradrenaline
- Treatment with anxiolytics= enhances neurotransmission at the central noradrenergic or serotonergic synapses. Serotonin selective reuptake inhibitors (eg prozac) now widely used. Can also be used for OCD.
- Also possible that effective drugs promote long term adaptive brain changes including HPA axis
13
Q
PTSD
A
- Exposure to terrifying/traumatic events, shell shock, war neurosis, natural disaster, violence, kidnapping, causing chronic debilitating psychiatric disorder
- Characterised= reliving event in dreams, thoughts and cues may trigger flashbacks and panic attacks (e.g. odours, sounds are common triggers- may last hours to days)
- Acute PTSD- symptoms present at least 1 month, chronic PTSD- persist for 3 months and beyond (decades in cases) may be delayed- hours, months, years. Complex PTSD (CPTSD) extend diagnosis - symptom cluster reflect alteration in affect regulation, consciousness, self perception and relation with others, systems of meaning. Closely related - disorders of extreme stress, not otherwise specified (DESNOS)
- May overlap with other anxiety disorders, clinical depression. More women 1-2% (more potentially harmful situations?), men 0.5% (males less likely to disclose thus low rate)
PTSD Atieology
- Predisposition in those with positive psychiatric history, poor socioeconomic status/support
- Persistent symptom= insomnia, irritability, poor concentration, hyperarousal, increased startle response, hypervigilance etc
- Failure to habituate to redundant information over responsive to novel information
- Hypothesis= traumatic reminders in flashbacks play role in maintenance of PTSD
- Involves several structures in neural and neuroendocrine systems due to heterogeneity in posttraumatic psychological distress
PTSD: Pathophysiology
- Dysfunction of neuroendocrine, cardiovascular and GIT system, disturbance of pain sensitivity
- Decrease natural immunity increased activity of cell specific immunity and increase in pro inflammatory cytokines
- Reduction of hippocampal volume, increased blood flow to amygdala but decrease in prefrontal cortex
- These are important in memory of fear responses. Are changes “risk factors for” or a consequence of PTSD
- Also implicated is ineffective top down regulation of amygdala and limbic circuitry by prefrontal cortex
- Note: HPA tone is hyper regulated - basal cortisol at any given time (upward or downwards) depend upon current stressors and coping strategies i.e. degree of emotional engagement or withdrawal to cope
- Cortisol levels are decreased or increased i.e. abnormal in plasma, urine and saliva (a hallmark of PTSD), blunted response to CFR? Or changed HPA tone- thus less able to deal with stress *** recent studies indicate dysregulation of in glucocorticoid signalling before PTSD develops
- In acute studies catecholamine & their metabolite levels increased in rape and child abuse victims
- Combat victims show increased autonomic responses ( increase pulse, increase BP) due to hyper adrenergic activity)
14
Q
Age & Stress
A
- Specific problem with very young or elderly subjects
- Dementias in elderly- major problem with ageing population
- Increased public health/pharmaceutical costs
