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  1. 1. Slide 1 Working on the Inside Stress, Depression, and Anxiety HEA 325 Slide 2 Remember what stresses us out! Slide 3 A Circle of Influence NOTE THAT THESE THREE REALLY CAN’T BE SEPARATED Slide 4 Depression • What is depression? • How is it identified? • What appears to cause it? • What is the relationship between stress and depression? • What are some techniques to manage it? • What are the relationships between depression and anxiety? Slide 5 DSM-IV-TR Criteria • Major depression is present when the patient has had at least 5 of the 9 following persistent symptoms for a minimum of two weeks. One of the symptoms must be either: • 1. Depressed mood (most of the day, nearly every day) or • 2. Markedly Diminished Interest or Pleasure (anhedonia) (in almost all activities) Slide 6 • 3. Significant change in weight or appetite • 4. Insomnia or hypersomnia • 5. Psychomotor agitation or retardation • 6. Fatigue or loss of energy • 7. Feelings of worthlessness or guilt • 8. Impaired concentration or ability to make decisions • 9. Thoughts of suicide or self-harm Slide 7 Types of Depression • Major Depression: the most severe and frequent type of depression. • You do not need to feel suicidal to have a major depression. • There is no official diagnosis of "moderate depression“ or “mild depression.” • Dysthymic Disorder: a low to moderate level of depression that persists for at least • two years. The symptoms are not as severe as a major depression, though are more • resistant to treatment • Unspecified Depression: • people with a serious depression, but not quite severe enough to have a diagnosis of • a major depression • people with chronic, moderate depression, which has not been present long enough • for a diagnosis of a Dysthymic disorder • Adjustment Disorder with Depression: This category describes depression that • occurs in response to a major life stressor or crisis • Bipolar Depression: This type includes both high and low mood swings, as well as a • variety of other significant symptoms not present in other depressions
  2. 2. Slide 8 Bipolar Disorders • History of at least 1 MD Episode • Presence of 1 manic or hypomanic episode (3 or more) – Abnormally elevated mood – Grandiosity – Decreased need for sleep – Talkativeness/ Flight of ideas – Distractibility – Psychomotor agitation – Excessive involvement in pleasurable activities Slide 9 Statistics • Spending on antidepressants jumped 150% from 1997 to 2004; • Depression affects approximately 18.8 American adults (9.5% of the adult population); • 15% of the population of most developed countries suffers severe depression; • 15% of depressed people will commit suicide; • The World Health Organization forecasts depression will be the second largest killer after heart disease by 2020; • Nearly two-thirds of depressed people do not get proper treatment. Slide 10 Prevalence of Mental Illness reported10-19-09 Slide 11 Famous People with Depression • Woody Allen (film director) • • Ingmar Bergman (film director) • • Albert Camus (writer) • • Jim Carrey (actor) • • Sheryl Crow (musician) • • Fyodor Dostoevsky (writer) • • Vincent Van Gogh (painter) • • Ernest Hemingway (writer) • • Abraham Lincoln (16th President of US) • • Martin Luther (priest and theologian) • • Michelangelo (painter and sculptor) • • Isaac Newton (physicist) • • Friedrich Nietzsche (philosopher) • • Mark Twain (writer) Slide 12 Famous People with Anxiety • • Anthony Hopkins (actor) • • Barbra Streisand (singer) • • Abraham Lincoln (president) • • David Bowie (singer) • • Edvard Munch (artist) • • Eric Clapton (musician) • • Johnny Depp (actor) • • Nicholas Cage (actor) • • Nicole Kidman (actress) • • Oprah Winfrey (host) • • Sigmund Freud (psychiatrist) • • Sir Isaac Newton (scientist) Slide 13 A disorder with a high rate of relapse. 50% of Individuals who have had an episode of major depressive disorder will have another episode. Of those who have had two episodes, 75% will have a third. Slide 14 Same pattern in samples from France, Germany, and Canada. US sites included white and non-white groups. AGE
  3. 3. Slide 15 Gender Differences Slide 16 Seasonal Affective Disorder Slide 17 Is Depression “in your genes”? NOT EXACTLY…. Slide 18 Genetic heritability for depression is substantial… (This means that our genes do make some contribution to depression, but….) Genes don’t do this alone! Slide 19 Two Buckets v. Mud Pie View NATURE Versus NURTURE Slide 20 Slide 21 Epigenetic Modification • This means a change in gene expression that is caused by something other than a change in the underlying DNA sequence
  4. 4. Slide 22 HOW GENES WORK Transcription Translation Folding DNA mRNA Polypeptides Proteins Impact of transacting factors, Influenced by other enhancers and genes and cell silencers (all made up environments of DNA) } Genetic influences Environmental influences and chance effects Gene Expression Slide 23 • Genes just don’t operate by themselves – they get activated (turned-on) or de- activated (silenced) by environmental influences! Slide 24 What’s the process? • Most well-studied epigenetic mechanism = methylation of cytosine on the DNA; • If methylation occurs in an active stretch of DNA, especially a promoter region, gene expression will likely change. Slide 25 Slide 26 Slide 27 This phenomenon is called: • Epigenetics • Gene - Environment interaction • GXE What’s new about this? – It does not only occur during basic fetal development, when cells are specializing……it can continue after birth and be influenced by the broader environment! Slide 28 What’s the news? Nature Versus Nurture Nature X Nurture Gene-Environment Genes versus Environment Interaction
  5. 5. Slide 29 Relation to Early Experience Meaney et al • Low Maternal Care – Higher and more prolonged CORT responses in adulthood – Higher CRF activity – Higher brain NE activity – Less Brain production of stress modulators: e.g natural opiates – More fearful/anxious behavior – Poorer memory; effects on learning/memory systems Maternal Care in Adult Outcomes of Rodents Poor Maternal Care Slide 30 Maternal behaviour, methylation and pup behavior • Some rat pups inherit a gene variant for cortisol that can make them anxious. At birth it is unmethylated. • If the rat pup is licked a lot in the first six days, a single methyl group (CH3) becomes attached at one specific location on the DNA in brain cells. • This makes it impossible for the gene to be transcribed. The gene is silenced by the mother rats behaviour and the rat pup is placid. • Remove the methyl group (can be done chemically) and the rat pup reverts to being anxious, consistent with its genotype. Slide 31 Licking and stress response • The pups with the gene predisposing them for a more anxious response but who are nursed in this way are less fearful. • They produce less stress hormones when provoked. • Their heart rate doesn't go up as much. • The licking/arch back nursing had to have occurred in the first six days of life. This is now known to be an example of epigenetics Slide 32 GENE-ENVIRONMENT INTERACTION IN LIABILITY TO ANTISOCIAL BEHAVIOR (From Cadoret, Cain & Crowe, 1983) 5 5 4 4 Average number of 3 3 antisocial behaviors 2 2 1 1 0 0 GENETIC FACTOR: Absent Absent Present Present ENVIRONMENTAL: Absent Present Absent Present FACTOR Slide 33 Gene-Environment Interaction: SCHIZOPHRENIA SPECTRUM DISORDER: with CANNABIS USE (Caspi et al., 2005) 20 COMT genotype Met/Met %schizophreniform disorder Met/Val 15 Val/Val 10 5 0 No adolescent use Adolescent use Slide 34 What gene is important to stress and depression? 5-HTT Serotonin Transporter Slide 35 Important Neurotransmitter Systems Movement Ideation Pleasure
  6. 6. Slide 36 Slide 37 The Long and Short of It Combinations: Long-Long (BEST) Long-Short Short-Short (WORST) Slide 38 Gene-Environment Interaction: EFFECT OF LIFE STRESS ON DEPRESSION MODERATED BY 5-HTT GENE (from Caspi et al., 2003) .50 s/s = short allele homozygous s/s l/l = long allele homozygous .40 s/l = heterozygous Probability of major depression episode .30 s/l .20 l/l .10 .00 0 1 2 3 4+ Number of stressful life events Slide 39 GxE: Interaction of HTTLPR and stress in depression Caspi et al, Science 2003 Slide 40 The Interaction Between Genetics and Experience: The case of early abuse Depression Risk .70 SS S = short allele L = long allele .50 SL .30 LL No Abuse Moderate Abuse Severe Abuse Early Childhood Experience Source: Caspi (2003) Slide 41 Predictors of depression Kaufman J et al. PNAS 2004;101:17316-17321 ©2004 by National Academy of Sciences Slide 42 Early Childhood Adversity Can Influence a Range of Lifelong Outcomes Research on the biology of stress helps explain some of the underlying causal mechanisms for differences in learning, behavior, and physical and mental health.
  7. 7. Slide 43 The Adverse Childhood Experiences (ACE) Study: • Recurrent physical abuse • Recurrent emotional abuse • Contact sexual abuse • An alcohol and/or drug abuser in the household • An incarcerated household member • Someone who is chronically depressed, mentally ill, institutionalized, or suicidal • Mother is treated violently • One or no parents • Emotional or physical neglect Slide 44 Risk Factors for Adult Depression are Embedded in Adverse Childhood Experiences 5 4 Odds Ratio 3 2 1 0 1 2 3 4 5+ ACEs Source: Chapman et al, 2004 Slide 45 Risk Factors for Adult Heart Disease are Embedded in Adverse Childhood Experiences 3.5 3 Odds Ratio 2.5 2 1.5 1 0.5 0 1 2 3 4 5,6 7,8 ACEs Source: Dong et al, 2004 Slide 46 How does early life stress “get under the skin” to affect life-long health? Slide 47 The Stress System CORTISOL feedback to the Brain Slide 48 Influence of Cortisol • Steroid hormone goes through the cell wall into the cytoplasm where it binds to receptor. Then these complexes go into the nucleus, attach to DNA and tell DNA to increase or decrease the gene expression. • Gene for cortisol receptor gets TURNED DOWN (Thermostat is off, and it doesn’t give the signal to the body that there is too much cortisol.) • Inflammatory processes stay high. Slide 49 Influence of Cortisol • Cortisol actually damages the hippocampus causing cell death. • Hippocampus is smaller in depressed people (average is 10-18% smaller than in non- depressed people) • When you start losing hippocampal cells, you have less regulation of the HPA axis. • The hippocampus is actually like a “brake” on the system. Loss of cells is like your car’s brakes getting worn down. • The HPA axis is more reactive.
  8. 8. Slide 50 This figure shows data reported by Bunney et al (1969) who found very high cortisol levels in depressed patients who subsequently committed suicide. Slide 51 Institutionalization and Neglect of Young Children Disrupts Their Body Chemistry 35% Percent of Children 30% with Abnormal 25% Stress Hormone 20% Levels 15% 10% 5% Middle Class US Toddlers Neglected/Maltreated Toddlers in Birth Families Arriving from Orphanages Overseas Source: Gunnar & Fisher (2006) Slide 52 Stress gets under your skin • Stressors trigger the first few episodes. • Subsequently, depression can occur regardless of the presence of stressors. • Called “stress-sensitization” or “kindling- sensitization.” Slide 53 Example of Seizure Study with Animals • Animals – initially given a drug that could cause a seizure – have no seizure; • But if you keep giving the low dose, eventually the brain get “sensitized”; • There is a seizure; • This is a MODEL FOR DRUG SENSITIZATION Slide 54 The depressed brain Kindling-Sensitization Theory With each episode of depression, the neurotransmitter systems become more easily dysregulated. FIRST STRONG STRESSOR EPISODE MILDER SUBSEQUENT STRESSORS EPISODES Slide 55 Antidepressant Info • Normally it takes 14-30 days for the patient to benefit from the drug, called “Therapeutic lag”. • During this time, risk of suicide is high. • All drugs have side effects. • Effectiveness differs for severe v. moderate cases – Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ, et al. (2008) Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration. PLoS Med 5(2): e45 doi:10.1371/journal.pmed.0050045 Slide 56 How effective is medication? • Protect the hippocampus against further cell damage. • Relieves moderate/severe depression for some people. Prozac, Serzone, Wellbutrin, Zoloft, Remeron, Celexa, Effexor, Lovox, Paxil
  9. 9. Slide 57 How effective is medication? According to testimony given in the fall of 2004 to the Congressional Energy and Commerce Committee, about half of all studies of anti- depressants have not shown in adults that the SSRI drugs are significantly more effective than a placebo alone. Even worse, insignificant results were found in two thirds of the studies in which children were given anti-depressants and compared to children given a placebo. Slide 58 How effective is medication? On September 10, 2004, testimony was given at a congressional meeting that two internal FDA analyses showed that anti- depressants, given to children and teens, were associated with increased suicidal thoughts, actual self-harm, and hostile behavior. Slide 59 Some conclusions • The chemical imbalance theory of depression has not been proven. The “cause” of depression is unknown. • Stress is clearly related to depression. • Medication can change the brain, but so can thinking and acting. • Antidepressant medication is ineffective for 40 to 50% of people. • Therapies and cognitive-behavioral changes have been shown to be more effective with moderate to mild cases. In severe cases, medication plus therapy is most effective. Slide 60 Views of Depression and Treatments for Depression and Depressogenic Thinking • Cognitive Approaches (Target the thinking) • Mindfulness Approaches (Letting go) • Exercise (Reducing the stress response) • Diet (Reducing inflammatory processes) • Social Support Slide 61 Anxiety Negative HPA axis Thinking Chronic Stress Helplessness Response Sad Mood Cytokine Activation OVERLOAD Hopelessness Lowered Motivation Sickness Cortisol Behavior Goes Up Sleeping/ Eating Problems Slide 62 What am I doing to deserve Why can’t this? I handle Why do things I always better? react this way? Why do I have What else is problems other going on in people don’t have? my life? Slide 63 Learned Helplessness A theory of depression that states that people become depressed when they perceive that they 1) no longer have control over the rewards and punishments in their life 2)they are responsible for this helpless state.
  10. 10. Slide 64 Learned Helplessness: Martin Seligman Slide 65 Beck’s Negative Cognitive Triad SL EF H ow Dpre d e sse Individuals Think about … W RD OL F TU E U R Slide 66 Rumination Triggers the Brain’s Network of Associations Unloved Uncaring Hopeless Mean Cold Sadness Unattractive Worthless Awkward Failure Clumsy Stupid Slide 67 What to Avoid: Cognitive Distortions • Thought (or pattern of thoughts) that contributes to our unhappiness and undermines mental health; • Thought (or pattern of thoughts) that colors perceptions of what happens to us in our life; • Thought (or pattern of thoughts) that affects our moods and behaviors; Slide 68 Albert Ellis Aaron Beck Rational-Emotive Cognitive Therapy Therapy (RET) (CT) Slide 69 Aaron Beck’s Model of Emotional Disturbance OR – HOW THOUGHTS MAKE US SICK! Activating Automatic Emotional Event Thought Consequence Slide 70 My date I bore yawns Sad Everybody! A B C
  11. 11. Slide 71 Different Interpretation, Different Feeling! Slight My date she doesn’t yawns sympathy sleep well for date Slide 72 Another Example- Let’s Include Behavior Turned down I’m a freak; I’ll die single Despondent for date Sleeps all weekend Slide 73 A healthier interpretation Turned down that’s the Slightly for date dating world disappointed for you I’ll try! Slide 74 Some Types of Automatic Thoughts: Cognitive Distortions • All-or-nothing thinking • Overgeneralization • Mental Filter • Disqualifying the Positives • Mind Reading • Catastrophizing • Magnification or Minimization • Emotional reasoning • “Should” statements • Labeling/Mislabeling • Personalization • Maladaptive Thoughts • Compensatory Misconceptions Slide 75 Identify the distortions • Michelle is upset that Richard is late. Her thoughts are: • “What a jerk! He’s never on time. If he cared about me, he wouldn’t be so late. He should be home by now.” Slide 76 Identify the distortions 2 • Brenda has been trying to diet. This weekend, she’s been nervous and, because she doesn’t have anything to do, has been nibbling. After her 3rd candy bar, she thinks “I just can’t control myself. My dieting has gone down the drain. I must look like a balloon after what I’ve done! I can’t stand this. I’m just going to pig out all weekend.” Slide 77 Identify the distortions 3 • Jennifer, a depressed student trying to study for finals, thinks: • “What’s the use in trying to study? My mind will just wander like yesterday. I can’t remember anything I read. I can’t possibly read 200 pages this week, so what’s the point?”
  12. 12. Slide 78 Daily Thought Record Automatic Distortions Rational Thoughts: Response My mind will just wander like yesterday. I can’t remember anything I read. I can’t possibly read 200 pages this week… Slide 79 Really getting to the bottom • Understanding and identifying core beliefs. Slide 80 Self-Schema • The cognitive structure that is hypothesized to contain a person’s knowledge about himself or herself • Your own personal collection of core beliefs Slide 81 Core Belief Activating Automatic Emotional Event Thought Consequence Slide 82 I’m Incompetent ( Core Belief ) Difficulty I’ll never Feeling Understanding get this! Miserable Math Text ( Activating ( Automatic ( Emotional Event ) Thought ) Consequence ) Slide 83 Helpless Core Beliefs • I am powerless • I am inadequate • I am weak • I am incompetent • I am trapped • I am a failure Slide 84 Unlovable Core Beliefs • I am unwanted • I am unworthy • I am bad • I am different • I am undesirable • I’ll be abandoned
  13. 13. Slide 85 Kyle: What is his core belief? • Situation 1: Talking to other students about advanced courses – Automatic Thought: “They’re all smarter than me.” • Situation 2: Thinking about required research paper for a course – Automatic Thought: “I won’t be able to do it.” • Situation 3: Reflecting on the difficulty of a math text – Automatic Thought: “I’ll flunk this course.” Slide 86 Beth: What is her core belief? • Situation 1: Thinking of suggesting group trip to the beach – Automatic Thought: “No one ever likes my ideas.” • Situation 2: With friends who are ordering another pitcher of beer – Automatic Thought: “They’ll all be annoyed if I say I don’t want another beer.” • Situation 3: Declining invitation to dance – Automatic Thought: “Everyone here can dance. I’m such a loser.” Slide 87 Low Frustration Tolerance • Rational belief: “I don’t like existing conditions.” • Irrational belief: “Existing conditions must change to give me what I like, otherwise I can’t stand it and I can’t be happy at all!” • Rational belief: “I would like immediate gratification.” • Irrational belief: “I must have immediate gratification, or else my life is awful!” • Rational Belief: “I find frustrations and hassles inconvenient.” • Irrational Belief: “I can’t stand hassles!” Slide 88 Some Ways to Working with Irrational Beliefs & Cognitive Distortions • Examine the Evidence for Plausibility • Reattribution • Challenging Absolutes (Disputation) • Semantic Method • Labeling Distortions • Self-Monitoring Techniques Slide 89 Another DTR Form Situation Emotion Automatic Core Rational Outcome Thought Belief Thought/ Response Slide 90 Different perspectives • Cognitive Therapy • Mindfulness Intervention Intervention Slide 91 Challenging the Challenging Specific Thoughts Nature of thought AWARENESS In service of Degree of belief changing is not the degree something to of Belief worry about
  14. 14. Slide 92 “It’s not about changing the degree of belief... Not saying that if you change the degree of belief in a thought it will no longer be a problem. To the extent that you can see your thoughts as objects that arise in a context dependent on moods and events, you can hold them in a different way than if you were tied into propositions.” Z. Segal Slide 93 Slide 94 Allow you r thou ghts to be like w riting on w ater.