Lecture 15: Stress Part 2 & Mood | BIO178

Lecture 15 Stress Part 2 & Mood  Announcements Office hours: Wed. 11:00am-12pm, Thurs. 2-3pm Wed: In-class review Session (optional); come with questions! Thurs: Gap day Friday: Final Exam 3:30-5:30pm Annotated Bibliography due Wed the 24th by 11:59pm...

Lecture 15 Stress Part 2 & Mood  Announcements Office hours: Wed. 11:00am-12pm, Thurs. 2-3pm Wed: In-class review Session (optional); come with questions! Thurs: Gap day Friday: Final Exam 3:30-5:30pm Annotated Bibliography due Wed the 24th by 11:59pm 2  Announcements Final exam Will heavily emphasize the lecture and discussion material presented since the midterm: – Female sexual behavior – Aggression -- Affiliation – Stress – Parental behavior – Mood Will include major concepts from before the midterm (e.g., organizational/activational, Aromatization Hypothesis, basics of the endocrine system, etc.) 125 points total; will include Multiple Choice, Matching, and Short Answer questions **Same cheat rules apply to the final but don’t rely on them too much!! 3  Outline of Today’s Lecture 1. Adaptive and Maladaptive Consequences of the Stress Response 2. Allostasis, Allostatic Load, and Allostatic Overload 3. Stress and Social Behavior 4. Modulation of the Stress Response 5. Endocrine effects on mood in humans  Learning Objectives 1. Explain how the stress response can be beneficial in the short term but maladaptive in the long term 2. Describe the concepts of allostasis and allostatic load and explain how allostatic overload can lead to pathology. 3. Explain how social interactions can both cause and ameliorate stress. 4. Describe how the stress response can be modulated. 5. Understand endocrine changes associated with varying moods  Adaptive and Maladaptive Consequences of the Stress Response  Adaptive Functions of the Stress Response  Availability of energy (glucose) Enhance  Oxygen intake ability to  Blood flow to muscles cope with  Memory immediate  Sensory function danger  Blood flow to non-essential body regions  Digestion  Growth Inhibit  Immune function non-essential  Reproduction bodily  Perception of pain (analgesia) functions  Inflammation In the short term, the stress response is beneficial 7 (adaptive) for dealing with emergency situations.  Stress, Stressors, and the Stress Response Stimulus Brain If brain Homeostasis / Stress (threat to deciphers perceives psychological response is homeostasis stimulus as stimulus as a well-being is terminated and/or either threat threat, stress restored psychological on non-threat response is well-being) is initiated received and – SAM conveyed to – HPA brain 8  Stress, Stressors, and the Stress Response Stimulus Brain If brain Homeostasis / Stress (threat to deciphers perceives psychological response is homeostasis stimulus as stimulus as a well-being is terminated and/or either threat threat, stress restored psychological on non-threat response is well-being) is initiated received and – SAM conveyed to – HPA brain Pathology! Stress response persists 9  Pathological Effects of the Stress Response  Energy use Fatigue, myopathy (muscle loss)  Cardiovascular tone Hypertension  Growth Psychosocial dwarfism  Reproduction Impotence, anovulation  Immunity, inflammation Impaired disease resistance delayed wound healing  Cognition Accelerated neural degeneration psychopathology In the long term, the stress response, if not terminated, has pathological (maladaptive) consequences. 10  Pathological Effects of the Stress Response  Growth Psychosocial dwarfism 11  Pathological Effects of the Stress Response  Immunity, inflammation Impaired disease resistance delayed wound healing 12  Pathological Effects of the Stress Response  Cognition Accelerated neural degeneration psychopathology Control Stressed Pyramidal cells in monkey hippocampus 13 Allostasis, Allostatic Load, and Allostatic Overload  Homeostasis and Allostasis Homeostasis “Homeo” – similar to; “stasis” – stability Maintenance of a steady state in the internal environment by correcting changes after they happen – e.g., body temperature, blood glucose levels, blood pH Maintains a variable level within a range around an optimal set point Typically involves small responses to a change or perturbation 15  Homeostasis and Allostasis Allostasis “Allo” – different; “stasis” – stability Stability through change Physiological and/or behavioral changes to cope with changes in the environment Can involve resetting the internal environment (e.g., establishing a new set point) Requires expenditure of energy 16  Homeostasis and Allostasis Allostasis Example: Person in desert – undergoes allostatic changes in sweat glands, blood vessels, kidneys, vasopressin secretion, behavior, etc. 17  Allostatic Load Allostatic Load – Energetic costs incurred during allostasis – Accumulates over an individual’s lifetime – “The wear and tear of life” Allostasis (or responding to stressors) increases the energetic demands on organisms. 18  Allostatic Load Allostatic Load 19  Allostatic Overload Allostatic Overload Allostatic load (energetic demand) that exceeds an individual’s ability to cope Two types: Type 1 and Type 2 20  Allostatic Overload Type 1 Allostatic Overload Negative energy balance: not enough energy available to meet energetic demands Triggers Emergency Life History Stage: “Survival mode” Inhibition of normal activities Helps to restore positive energy balance May be common in free-living animals 21  Allostatic Overload Type 2 Allostatic Overload Positive energy balance: Frequent or chronic activation of the stress response by psychological/social factors. May be common in captive animals. Food consumption can increase (stress-induced eating). Energy balance remains positive. Chronically high cortisol not balanced by high energetic demands. Can lead to obesity, type-2 diabetes, atherosclerosis, hypertension, etc. 22 Stress and Social Behavior  Socially Induced Stress Social interactions can be stressful! Social novelty Social density/crowding stress 24  Socially Induced Stress Social interactions can be stressful! Dominance relationships – In some species, subordinates have…  Glucocorticoid levels  Stress-related pathology 25  Stress and Dominance: Male Baboons In free-living male baboons: Basal cortisol tends to be lower in dominant males than subordinate males. Low cortisol is more closely associated with certain personality types and behavioral patterns. 26  Stress and Dominance: Male Baboons In free-living male baboons, low cortisol is associated with… Ability to differentiate between neutral and threatening social situations. Initiation of fights Displacement of aggression after losing a fight Many “friendships” with females (non-sexual social bonding) 27  Stress and Dominance: Male Tree Shrews Place male in another male’s cage → Resident immediately attacks intruder Separate males → Both recover from fight Maintain males in visual contact of each other → Loser dies within 20 days due to constant “threat anxiety” Subordinates show:  Norepinephrine  Cortisol  Testosterone (sterility)  Body weight (emaciation)  Immune function 28  Social Reduction of Stress Social separation Separation from an attachment figure can elicit a stress response. (Also seen in humans, pets, etc.) 29  Social Reduction of Stress Social buffering Social interactions can  the response to a stressor. 30  Stress and Social Behavior 31 Modulation of the Stress Response  Modulation of the Stress Response Determinants of “stressfulness” and the stress response: Novelty Unpredictability Uncontrollability Inability to engage in displacement behaviors 33  Modulation of the Stress Response Determinants of “stressfulness” and the stress response: Unpredictability Control Signaled shock Unsignaled shock Tone followed by Shock alone Tone alone shock (no warning) 34  Modulation of the Stress Response Determinants of “stressfulness” and the stress response: Uncontrollability Controllable Uncontrollable No shock shock (“yoked”) shock 35  Modulation of the Stress Response Determinants of “stressfulness” and the stress response: Personality (including genetics) Early experience (including epigenetics) Environment Genetics Early Experience (Personality, (Stress, Rearing, Neurochemistry) Epigenetics) Vulnerable Phenotype Exercise, Daily Stress, Psychotherapy, Traumatic Event, Antidepressants Life Event Stress-Related 36 Pathology Neonatal Influence of the Stress Response in Rats “Stress Immunization” – Handle pups or separate pups from dam (mother) →  hormonal (CORT) response to stress in adulthood How?? Handle pups or separate pups from dam →  ultrasonic vocalizations by pups →  licking, grooming by dam →  hormonal response to stress in adulthood Early exposure to mild stressor leads to more efficient stress response later in life. 37 Neonatal Influence of the Stress Response in Rats Individual differences in stress responsiveness are associated with naturally occurring differences in maternal behavior received when young. High licking/grooming received from dam →  ACTH, CORT responses to stressors 38 Neonatal Influence of the Stress Response in Rats Individual differences in stress responsiveness are associated with naturally occurring differences in maternal behavior received. How is this effect mediated? High licking/grooming received from dam →  glucocorticoid receptors in hippocampus →  negative feedback of CORT on CRH →  CRH in paraventricular nucleus (PVN) →  ACTH & CORT responses to stressors 39 Neonatal Influence of the Stress Response in Rats The HPA axis revisited: Offspring of Offspring of High LG Mothers Low LG Mothers GR = Glucocort- icoid receptor 40 Neonatal Influence of the Stress Response in Rats Glucocorticoid Receptors CRH mRNA in PVN in Hippocampus Maternal behavior “programs” the HPA stress 41 response in pups Liuthrough et al., 1997 actions on the brain. Neonatal Influence of the Stress Response in Rats Individual differences in stress responsiveness can be caused by epigenetic modification of gene expression. High licking/grooming from mother →  methylation of glucocorticoid receptor gene promoter →  hippocampal expression of glucocorticoid receptors Maternal responsiveness to stress can be transmitted to future generations through epigenetic mechanisms! 42  Glucocorticoid Programming Glucocorticoid overexposure in utero can have permanent effects on… Brain & behavior Cardiovascular, renal, and liver function Endocrine function Etc. 43 Khulan & Drake 2012  Mood: Hormones and Perimenstrual Syndrome  Hormones and Mood Many affective (mood) disorders occur or begin during times of pronounced hormonal changes – Before/during menstruation – Postpartum – During puberty Prevalence of many mood disorders differs between the sexes. Hormones can both influence and be influenced by mood and mood disorders. Animal models may be less useful than for other topics in behavioral endocrinology because “mood” is more subjective than other behaviors. 45  Perimenstrual Syndrome (PMS) Prevalence: ~ 45% of women are affected; most have mild symptoms. ~ 3-5% have debilitating symptoms. Pre-Menstrual Dysphoric Disorder Late Luteal Phase Dysphoric Disorder Symptoms are highly variable among and within women. Several different subtypes of PMS have been described. 46  Perimenstrual Syndrome (PMS) Correlates/Influences: – Length/heaviness of menstrual bleeding – Age – Birth-control pill use – Stress – Affective disorders – Dietary factors (carbohydrates, calcium) 47  Perimenstrual Syndrome (PMS) Physiological/physical symptoms may include… – Abdominal bloating – Body aches – Breast tenderness/fullness – Cramps, abdominal pain – Fatigue – Headaches – Nausea – Swelling of extremities – Weight gain Most physiological/physical symptoms occur during menstruation. 48  Perimenstrual Syndrome (PMS) Psychological/behavioral symptoms may include… – Anger/irritability – Anxiety – Changes in appetite – Changes in libido – Decreased concentration – Depression – Feeling out of control – Mood swings – Withdrawal from usual activities – Tension – Poor sleep, increased need for sleep Most psychological/behavioral/mood symptoms occur before menstruation during the luteal phase (high, declining P and declining E). 49  PMS: Hormonal Hormonal Correlates Correlates 1. Estrogen PMS not consistently correlated with E levels. E treatment does not consistently alleviate mood symptoms of PMS. PMS is not associated with abnormal estrogen levels. 50  PMS: Hormonal Correlates 2. Progestogens (steroids that activate the progesterone receptor) No consistent P differences between women with and without PMS. P treatment does not consistently alleviate PMS symptoms. PMS is not associated with abnormal luteal phase levels of progesterone. 51  PMS: Hormonal Correlates 2. Progestogens GABA (gamma-aminobutyric acid): The major inhibitory neurotransmitter in the brain Benzodiazepines (e.g., Valium, Xanax, Halcion, Ativan) and Ethanol: – Bind to GABAA receptor – Act as allosteric modulators (not agonists; they affect affinity) – Increase inhibitory effects of GABA – Anxiolytic (calming) effects – May be addictive 52  PMS: Hormonal Correlates 2. Progestogens Allopregnanolone: – Metabolite of progesterone – Synthesized by corpus luteum or in brain – Can bind to GABAA receptors and alter GABA activity. Women with severe PMS may be more responsive to GABAA receptor modulation than other women. PMS might reflect “addiction” to and “withdrawal” from anxiolytic (calming) effects of progesterone’s metabolite. 53  PMS: Hormonal Correlates 3. Menstrual cycle dynamics PMS is not associated with any specific E or P abnormalities. P antagonist - block luteal phase → no change in PMS symptoms. Leuprolide (GnRH agonist) – prevents cycling → ameliorates PMS. 54  PMS: Hormonal Correlates 3. Menstrual cycle dynamics PMS seems to involve abnormal responses to normal levels of E & P. Repeated ovarian cyclicity - but not specifically luteal phase events - are associated with PMS. Evolutionarily and comparatively, long-term ovarian cyclicity (not interrupted by pregnancy/lactation) is very rare! Most animals breed often so they don’t get through as many hormone cycling events. 55  Mood: Hormones and Depression  Depression Symptoms: Sadness Low self-esteem/worthlessness Fatigue Guilt Sleep disturbances Reduced sex drive Reduced appetite Anger Absence of pleasure Agitated or retarded motor symptoms 57  Depression: Categories Secondary Depression: Results from other psychological or physical problems. Primary Depression: Doesn’t result from other psychological or physical problems. – Major Depression Severe symptoms Lasts >2 weeks – Dysthymia Less severe symptoms Lasts > 2 years Depressed people may have several hormonal abnormalities, involving thyroid hormones, growth hormone, prolactin, and 58 the hypothalamic-pituitary-adrenal axis.  Depression Evidence for possible influence of gonadal hormones: Lifetime prevalence in USA: 21% in women, 13% in men. Symptoms are generally more severe in women than men. Sex differences emerge during adolescence. Incidence in women declines after menopause, when reproductive hormones stabilize. Estrogen influences the brain’s serotonin system, which is strongly implicated in depression. 59  Depression and the HPA Axis Cortisol in depressed individuals: Elevated baseline levels Altered circadian rhythm Resistance to glucocorticoid negative feedback 60  Depression and the HPA Axis Depression is associated with “central disinhibition” ( negative feedback) and increased “central drive” ( stimulation) of the HPA axis. Elevated CRH may play a prominent role in depression. HPA dysregulation is state-dependent – occurs only during bouts of depression; not a stable “trait” of people prone to depression. Treatment of depression often normalizes HPA function. 61  Depression and the HPA Axis Depression might contribute to HPA hyperactivity. HPA hyperactivity might contribute to depression. Other hormones (e.g., thyroid hormones, estrogen) might also play a role. 62 Androgens and Mood  Androgen Replacement Therapy Androgens may be prescribed to treat impotence, improve libido, or prevent body wasting (e.g., AIDS patients). When used properly (under medical supervision), androgen replacement can elevate mood and improve well-being in: Hypogonadal men Older men people with very low T Ovariectomized women Post-menopausal women 64  Androgen Abuse >1 million males in the U.S. use illicit anabolic steroids, including junior- high and high- school students. Many health risks: Many of these effects are irreversible! 65  Androgen Abuse Most men use 10-100 times the recommended doses. Many men use multiple steroids simultaneously (“stacking”). Many men alternate periods of steroid use and non-use (“cycling”). Illicit steroid use differs dramatically from medically supervised steroid use. 66  Androgen Abuse Controlled studies have found... No psychiatric or behavioral changes in most subjects. but… Mania Euphoria Irritability, mood swings, hostility Distractibility, confusion, impaired memory...in some subjects using lower doses than commonly used by illicit steroid abusers. 67  Androgen Abuse Androgen Abuse Based on non-controlled studies, anabolic steroid abuse appears to be associated with...  Euphoria  Verbal aggression  Provocation to fight (also in rodent studies)  Criminal violence  Homicide  Suicide  Mania  Violent behavior by previously non-aggressive individuals “Roid rage” 68  Androgen Abuse Androgen Abuse Can androgenic anabolic steroids be addictive? Androgens have rewarding properties in rodents. (didn’t die) Wood 2004 Hamsters will work to give themselves i.v. or i.c.v. injections of testosterone or other androgens. 69  Androgen Abuse Can androgenic anabolic steroids be addictive (cont.)? Many men have difficulty terminating steroid use. Cessation of steroid use can cause symptoms characteristic of drug withdrawal. Androgens can change functioning of the brain’s reward pathway. Anabolic steroids may be addictive! 70 End of Lecture 15