PSY 183 Depressive and Bipolar Disorders 2024 PDF

Introduction to Psychopathology Alan J. Fridlund, Ph.D. NOTICE: These Lecture Notes © Copyright 2014, 2019, 2020, 2023, by Alan J. Fridlund, Ph.D. All Rights Reserved. They May Be Copied Freely for Internal Use by Students Currently Registered in UCSB Psych 183. For-Profit R...

Introduction to Psychopathology Alan J. Fridlund, Ph.D. NOTICE: These Lecture Notes © Copyright 2014, 2019, 2020, 2023, by Alan J. Fridlund, Ph.D. All Rights Reserved. They May Be Copied Freely for Internal Use by Students Currently Registered in UCSB Psych 183. For-Profit Reproduction in Whole or In Part Without Written Permission of the Instructor Is a Violation of U.C. Regulations and the DMCA and Is Expressly Prohibited.  Notice All Course materials (class lectures and discussions, handouts, examinations, Web materials) and the intellectual content of the Course itself are protected by United States Federal Copyright Law, and the California Civil Code. UC Policy 102.23 expressly prohibits students (and all other persons) from recording lectures or discussions and from distributing or selling lectures notes and all other course materials without the prior written permission of the Instructor (See http://policy.ucop.edu/doc/2710530/PACAOS-100). Students are permitted to make notes solely for their own private educational use. Exceptions to accommodate students with disabilities may be granted with appropriate documentation. To be clear, in this class students are forbidden from completing study guides and selling them to any person or organization. The text has been approved by UC General Counsel. For Latest Mental Health News (free one-time login) www.medscape.com/psychiatry  Depressive Disorders Bipolar and Other Disorders (DSM-5-TR)  Robert Burton*, The Anatomy of Melancholy (1621) “Melancholy, the subject of our present discourse, is either in disposition or in habit … which causes anguish, dulness, heaviness and vexation of spirit, any ways opposite to pleasure, mirth, joy, delight…” *Burton was a mathematician at Oxford University. He hanged himself in the chambers at Christ Church Cathedral at Oxford.  Novelist William Styron on Depression “In depression this faith in deliverance, in ultimate restoration, is absent. The pain is unrelenting, and what makes the condition intolerable is the foreknowledge that no remedy will come—not in a day, an hour, a month, or a minute.” “Soon evident are the slowed-down responses, near paralysis, psychic energy throttled back close to zero. Ultimately, the body is affected and feels sapped, drained.” “The pain of severe depression is quite unimaginable to those who have not suffered it, and it kills in many instances because its anguish can no longer be borne.”  The Soul-Searing Pain of Depression: “Hurt”* Music Video by Johnny Cash I hurt myself today To see if I still feel I focus on the pain The only thing that's real The needle tears a hole The old familiar sting Try to kill it all away But I remember everything What have I become My sweetest friend Everyone I know goes away In the end And you could have it all My empire of dirt I will let you down I will make you hurt https://youtu.be/8AHCfZTRGiI *Song by Trent Reznor, Orig Performed by Nine Inch Nails  Clinical Features of Major Depressive Disorder (MDD) Cognitive: ⚫ Pervasive sadness, tearfulness, excessive or inappropriate guilt, feelings of helplessness, emptiness, worthlessness. ⚫ Recurrent thoughts of death (not just a fear of dying), suicidal ideation, or a suicide attempt or plan. Motivational: ⚫ Pervasive anhedonia. Neurovegetative: ⚫ Significant change in weight due to decreased or increased appetite (females likelier to experience increased appetite). ⚫ Sleep disturbance: insomnia or hypersomnia (females likelier to experience hypersomnia). ⚫ Psychomotor agitation (“can’t sit still”) or retardation (inertia, leaden paralysis, “can’t get going”) (females likelier to experience retardation). ⚫ Pervasive fatigue or loss of energy. ⚫ Difficulty thinking, concentrating, or making decisions. Not Due To: ⚫ Bereavement, normal reaction to serious loss, or drug/medication effects. These signs and symptoms may result in social withdrawal and isolation, and in irritability (esp. in adolescents, and males across the lifespan).  Prevalence of Major Depressive Disorder (MDD) (Pre-Covid) ⚫ Point prevalence: about 5% of U.S. population are diagnosably depressed. ⚫ One-Year prevalence: about 7% in U.S., but varies widely across geographic regions. ⚫ Lifetime prevalence, 20.1% (26% of females, 12% of males), mostly moderate or severe depression. Females are likelier than males to suffer from hypersomnia, inertia, and increased appetite; males are likelier to show insomnia, agitation, and decreased appetite. ⚫ 15-20% of U. S. population at any time may suffer from subsyndromal depression, with nearly equal disability (where to set the bar?). ⚫ Depressions in less-Westernized societies differ from those in more Westernized countries: – all people show neurovegetative and cognitive signs. – in more Westernized societies, there is predominance of feelings of guilt and “wretchedness.” – in less-Westernized societies, there is more reference to physical complaints (“somatization”). – The differences may relate to early views of depression among Western religions.  Risk Factors for Major Depressive Disorder ⚫ Genetic predisposition (evid. from adoption/twin studies, animal models) ⚫ Adverse Childhood Experiences (“ACES”: abuse, neglect, isolation, inconsistent/incompetent parenting, violence/conflict in home) ⚫ Grief, job or property loss, or other personal loss - or gain ⚫ Prolonged psychological stress (Depression = collapse?) ⚫ Being in an industrialized nation (although lifespans are longer!) ⚫ Being female: F:M ratio is 1:1 until puberty, but 2:1 after puberty. ⚫ Being LGBT: LGBT youth 16-21 are ~ 3–4 X likelier than cis-gendered, heterosexual counterparts to suffer depression and suicidal thinking. ⚫ Overall, race/ social class does not predict first episodes of Major Depression, but minorities are likelier to have recurrences. ⚫ Average age of first onset in latter 20’s. ⚫ Physical illness/chronic pain (must exclude undiagnosed other illnesses) ⚫ Giving birth – 10-20% of females are depressed during pregnancy, and up to 40-% if there is a prior history of depression – 50-80% of females who give birth have “baby blues” (weepiness, lethargy); usually resolves by 2 weeks. – 10-20% have persistent post-partum depression, and 1-2 per 1000 have psychotic symptoms that may be lethal to mother and child; rates of post-partum are declining due to improved depression screening before and during pregnancy, and increased use of antidepressant medication in pregnancy (CDC, 2017). ⚫ History of previous depressive episodes: “kindling”  “Kindling”: Each Major Depressive Episode Increases the Risk of Later Depression, Regardless of Life Stress Why Are Females Often Diagnosed with Major Depression Twice as Much as Males? Some Possibilities: ⚫ Male depression often masked by alcohol / drug abuse (1980s Study of Old Order Amish by Janice Egeland, Ph.D.); among OOA people, prevalences of Major Depression were 1:1 M:F ⚫ Other exceptions to 2:1 F:M ratio include Western university students, several non-Western societies, and some surveys of the elderly. Explanations offered to explain the 2:1 ratio: ⚫ X-linked depression gene(s) ⚫ Premenstrual symptoms concurrent with MDD surveys (why would this be?) ⚫ Quality of female vs. male life in Western societies ⚫ Female masochism (Freud) ⚫ Cognitive style – Females tend to dwell on problems, which may perpetuate their depression. – Males tend to ignore or escape their problems, with drug/alcohol use or impulsive acts.  Some Varieties of Depression (DSM-5-TR) ⚫ Major Depressive Disorder (MDD; Mostly Episodic) ⚫ MDD with Seasonal Pattern: episodes that typically recur in the dark months of the year. ⚫ Persistent Depressive Disorder (MDD that lasts >= 2 yrs). ⚫ One can have dramatic worsening of Persistent Depressive Disorder that is sometimes called “double depression,” or the overlay of an MDD episode on the Persistent Depressive Disorder. ⚫ Premenstrual Dysphoric Disorder (Females only) – signs and symptoms in the majority of menstrual cycles, which begin the week before menstruation and improve within a few days afterward: – Mood swings and other MDD signs and symptoms. – Marked irritability/anger, interpersonal conflict, feeling on edge. – Depressed mood, hopeless, self-deprecating thoughts. – Physical symptoms, e.g., breast tenderness, joint/muscle pain, weight gain and “bloating”  1st-Line Depression Treatments ⚫ Psychotherapy, especially: – Cognitive Behavior Therapy (CBT) – Interpersonal Therapy (IPT) ⚫ Antidepressant medication. ⚫ Phototherapy for MDD with seasonal patterns. ⚫ For Treatment-Refractory Depression (TRD): – Multiple Medications. – Electroconvulsive Therapy (ECT). Psychotherapy for Major Depression depressiontreatmenthelp.org  Cognitive Behavior Therapy (CBT) (sometimes, “Cognitive Therapy”) ⚫ Main task in CBT - uncovering automatic self-defeating thinking patterns. ⚫ Developing new ways to interpret setbacks (normalization, analyzing logically, de-catastrophizing). ⚫ Replacing old “automatic” thoughts with new ones. ⚫ Focus is on the patient’s view of: – him- / her- self. – important life events. – the future. Aaron Beck, M.D. Optional: Primitive vs. Mature Thinking in CBT Nondimensional and global I am fearful. Absolute and moralistic I am a despicable coward Invariant I have always been and will always be a coward. Self-denigrating Something about me is seriously defective. Irreversible Nothing can be done about it. versus Multidimensional I am moderately fearful, quite generous, and fairly intelligent. Relativistic and I am more fearful than most people I know. nonjudgmental Variable My fears vary from time to time and situation to situation. Self-describing I avoid situations too much. and I have many fears. Reversible I can learn to master many situations and overcome my fears.  “Third-Wave” Cognitive Therapies ⚫ Acceptance and Commitment Therapy (ACT) ⚫ Mindfulness-Based Cognitive Therapy (MBCT) ⚫ Unlike standard CBT, both use Zen-like “mindfulness” meditation to teach patients to become transcending “witnesses” to depressive (and anxious) thoughts rather than trying to banish those thoughts. ⚫ Insufficient evidence of superior effectiveness compared to standard CBT Interpersonal Therapy (IPT): Central Themes (Sources of Insufficient Social Connection & Support) ⚫ Grief – Delayed mourning, developing replacement relationships. ⚫ Fights – Building skills in communication, negotiation, and assertiveness. ⚫ Role Transitions (e.g., leaving home, divorce, retirement) – Reevaluating the lost role, building a new role, developing new social supports. ⚫ Social Deficits (e.g., failure patterns in past relationships) – using role playing to learn new behavior in relationships.  Problems for All Psychological Models of Depression Causation ⚫ Although first episodes of Major Depression are somewhat related to life events, social support, etc., recurrences seem weakly related or not at all. ⚫ Most first episodes of Major Depression remit with no treatment within 3-4 months. ⚫ Despite very different explanations of causation, and different kinds of therapies based on those explanations, the different depression therapies appear equally effective.  Neurochemical Theories of Depression ⚫ Neurotransmitters theories – insufficient “turnover” in brain These are now discredited as primary cause of depression. ⚫ Norepinephrine, Epinephrine ⚫ Dopamine ⚫ Serotonin (5HT) ⚫ Endocrine theories – Hypothalamus-Pituitary Dysfunction (HPA-axis overactivity; equates depression with reaction to stress) ⚫ Thyroid dysfunction ⚫ Adrenal gland dysfunction ⚫ Inflammatory theories - over-secretion of substances related to stress and inflammatory responses in brain: ⚫ Substance P (neuropeptide involved in pain transmission and responses to stress) ⚫ Glutamate and Glycine, through NMDA (N-methyl-D-aspartate) receptors in brain ⚫ (Newest) Neurotrophic Theory – Death of neuronal connections due to reduced activity of neuronal growth factors (e.g., BDNF, or Brain- Derived Neurotrophic Factor) that promote neuronal growth and axonal and dendritic sprouting. ⚫ More recently, the Neurotrophic and Inflammatory theories are seen as complementary.  Neurochemical Disturbances in Depression ⚫ Neurotransmitter abnormalities in depression represent just one part of the neurobiological changes in depression. They probably account for the side effects of antidepressant medications more than the main effects. ⚫ Evidence for Neurotrophic Theory – Depression is associated with: – reduced Brain-Derived Neurotrophic Factor (BDNF) and other growth factors. – altered levels of activity in the limbic system, prefrontal area, and other brain regions, observable by neuroimaging. – Reduced gray matter volume in neocortex is seen in chronic depression, and appears to be restored with successful antidepressant therapy. People with lower amounts of gray matter in the right-hemisphere neocortex carry a greater risk of later depression. ⚫ Evidence for Inflammatory Theory: People with higher levels of the inflammatory blood marker C-Reactive Protein (CRP) are likelier to develop depression within 5 yrs. Also neurosteroids in the brain are reduced in depression, and these normally inhibit signals of brain inflammation. ⚫ Regardless of the mode of action, remission of depression with antidepressant medication results in return to normal levels of BDNF and neurosteroids and the return of normal neural activity. Some Physical Conditions That Can Masquerade as Major Depression ⚫ Hypothyroidism ⚫ Low Testosterone or Estrogen levels ⚫ Undiagnosed illness (e.g., infectious mononucleosis, anemia) ⚫ Chronic Fatigue Syndrome ⚫ Various systemic illnesses (e.g., pulmonary disease, anemia, arthritis, cancer). Antidepressant Medication  Antidepressant Medications: General Use ⚫ Are not euphoriants. ⚫ Are effective for both anxiety and depression. ⚫ Work best for moderate-to-severe depression; explains meta- analyses used to show “ineffectiveness.” ⚫ Do not cure depression; only hold it in check for so long as they are taken (depression may relapse afterward). ⚫ Take 2-3 weeks after first dose to produce an antidepressant response (fast response may = mania if depression is actually phase of Bipolar Disorder). ⚫ Not addictive or habit-forming, but must be tapered slowly to avoid rebound symptoms. ⚫ All have some unpleasant side effects (mostly on sleep and sexual response). ⚫ No known “time bomb” effects or damage to fetus (can be taken for life). ⚫ Recovering patient must be watched for suicidal or other violent behavior – risk is greatest during recovery. ⚫ Can precipitate manic episodes in up to 10% of undiagnosed Bipolar disorder patients. Antidepressant Medications Are in Wide Use Throughout the United States ⚫ Antidepressants are the most frequently prescribed medications in the U.S. ⚫ About 13% of people in the United States (ages 18+) took antidepressants “in the past month” (years 2015-2018), females (~18%) 2 x the rate of males (~8%). ⚫ Highest usage group is females ages > 60; 24% took antidepressant medications. ⚫ The highest-usage state is Utah, at 18.4%, and the lowest- usage state is New York at 9.1%. ⚫ California’s usage rate is 9.9% ⚫ ¼ of all U.S. citizens now taking antidepressant medications have taken them for at least 10 years. ⚫ Antidepressant use increased ~20% during Covid. CDC Nat’l Center for Health Statistics, 2017, 2022 The U.S. Leads the World in Per Capita Antidepressant Use  Suicidality and Antidepressants ⚫ 40% of people with major depression make at least one suicide attempt, and 50-60% have suicidal ideation. ⚫ As of 2004, all antidepressants in U.S. must now carry warnings about suicidality. ⚫ Although some studies show that suicidal ideation is increased with antidepressant medication, various studies have shown no link between antidepressant medication and actual suicides. ⚫ Suicidality is associated with improvement from depression, regardless of the presence of antidepressant medication. Recovery from severe depression is period of greatest concern for suicide! ⚫ How do you know if someone is suicidal? Ask them.  Modern Classes of Antidepressant Medication (Know Classes, Not Individual Med Names) ⚫ Selective Serotonin Reuptake Inhibitors (SSRI’s) – Prozac/Serafem, Zoloft, Celexa, Lexapro, Paxil, Luvox, Viibryd, Brintellix. – 30-40% of patients on SSRI’s suffer from sleep & sexual symptoms. – Children on Paxil may develop suicidal ideation (but not suicide). ⚫ Atypical Antidepressants (Effexor, Cymbalta, Wellbutrin, Pristiq, Remeron, Trazodone) – Together, the most-prescribed class of current antidepressants. – Fewer sexual side effects; varied in actions and side effects. ⚫ People who do not respond to one SSRI have a 40-70% chance of responding to a second one, or one of the atypical antidepressants, or a combination. Predicting which antidepressant is best for a patient may be assisted by family hx. of response to medication. ⚫ Genesight© test: uses combinatorial pharmacogenomics to narrow down medication choices, by matching 12 genes of a patient’s genotype to the pharmacology of 56 depression-related medications.  Special-Use Antidepressants ⚫ Wellbutrin (NDRI*) is stimulating and is used to treat adult ADHD and nicotine cravings (sold as Zyban) ⚫ Cymbalta (SNRI**) is the current best-selling antidepressant. Especially effective at treating chronic pain along with depression; often allows chronic pain patients to reduce dependence on opiate meds. ⚫ Trazodone (SARI†) and Remeron (TTCA††) are both sedating and are used widely for insomnia. Remeron also promotes appetite and is used especially in elderly patients with excessive loss of appetite and excessive weight loss. ⚫ Zulresso is an intravenous treatment for the rapid treatment of post-partum depression. It is a neurosteroid that inhibits signals of inflammation in the brain. Optional Info: * Norepinephrine-Dopamine Reuptake Inhibitor ** Serotonin-Norepinephrine Reuptake Inhibitor † Serotonin Antagonist and Reuptake Inhibitor †† Tetracyclic Antidepressant (Action Uncertain)  How Long Should People Take Antidepressant Medication? ⚫ Most depressions remit with no treatment in 3-4 months. ⚫ However, odds are >50% of 1st recurrence, >75% of 2nd recurrence, etc. ⚫ Each recurrence tends to be longer and leaves the person with greater disability, i.e., depression is often progressive. ⚫ Depression that is aggressively controlled early (by high doses and multiple, or multiple-action, medications) predicts less recurrence. ⚫ Medication can be tapered and then resumed if depression re-emerges, but there is a slight risk of acquired medication immunity if the medication is tapered then resumed. This means finding another medication that was as effective as the original. ⚫ Medication for life? Medication is “unnatural,” but so is depression.  Increased Risks Associated with Antidepressant Medications ⚫ Overall, modern antidepressants are quite safe, but: – SSRI’s may be associated with slightly elevated risks of heart and lung defects in infants, but the evidence is weak and is under investigation. – There is also weak evidence that SSRI’s may slightly increase premature birth complications. However, there are drastic risks to pregnancies when pregnant mothers are depressed. – Serotonin syndrome (e.g., confusion, hallucinations, fever, seizures) can occur rarely in people who are taking multiple SSRI’s, or SSRI’s along with other serotonin-raising drugs. ⚫ Abruptly stopping any antidepressant can result in a Discontinuation Syndrome: dizziness, tremor, “zaps”, anxiety and panic, nausea and vomiting, and confusion. Any antidepressant discontinuation or changing should typically be tapered or cross-tapered over weeks to months. Conditions Associated with Major Depression and Often Treated with Antidepressant Medication ⚫ Chronic pain ⚫ Compulsive shopping ⚫ Binge Eating ⚫ Compulsive gambling Disorder ⚫ Hypochondria ⚫ Bulimia nervosa ⚫ Sexual addiction ⚫ Migraine headache ⚫ Premature ejaculation ⚫ Misc. anxiety ⚫ Premenstrual disorders (e.g., Panic dysphoric disorder disorder, OCD) ⚫ Trichotillomania ⚫ Compulsive zit- popping Alternative Depression Treatments Routine Alternative Depression Treatments ⚫ Medications – St. John’s Wort, Sam-e (over the counter, expensive, weak potency) – Thyroxin (thyroid hormone) supplementation – Testosterone supplementation (M / F) – Estrogen therapy (F, in menopausal and sometimes post- partum depression) ⚫ Phototherapy (for Major Depression w/ Seasonal Pattern) ⚫ Exercise (typically works on only mild forms of depression) ⚫ ECT (Electroconvulsive Therapy) –delivery of intense shocks to patient’s head and induction of seizure  Electroconvulsive Therapy (ECT) ⚫ Works fastest of any standard therapy for major depression. ⚫ Mechanism of action unknown. ⚫ Has fewest side effects of any standard therapy for depression (very high satisfaction ratings). ⚫ BUT: very expensive in time and personnel costs, and sometimes causes spotty memory losses (episodic >> semantic memory losses). ⚫ Usually applied only to right hemisphere to minimize speech disturbance ⚫ Abused in past, and (IMHO regrettably) now used only as a last resort, and for most severe cases. Modern Electroconvulsive Therapy (Muscle Relaxants + Light Anesthesia) Claire Danes in Homeland S07E10  ECT – Before and After Post-ECT Pre-ECT  Comparative Efficacy of Traditional Major Depression Treatments ⚫ ECT works fastest, for most people, and with fewest side effects. BUT it’s time-consuming and expensive, and used mainly for very severe depressions. ⚫ Medication and psychotherapy (esp. Cognitive Behavior Therapy or Interpersonal Therapy) work equally well for most adults, but medication works faster. Also, sometimes patients are too depressed for psychotherapy. ⚫ Some research suggests that psychotherapy may result in fewer remissions, but that evidence is inconclusive. ⚫ For adults, research suggests that a combination of therapy and medication seems no more beneficial than either one alone, but practically they are often synergistic. ⚫ For adolescent depression, current recommendation is an SSRI (by 2009, two were FDA-approved for adolescents: Prozac and Lexapro) plus cognitive-behavior therapy. ⚫ Medication is the least expensive single mode of treatment.  “Treatment-Resistant Depression” (TRD; also see Text Addendum) ⚫ Up to 40% of patients do not respond adequately to standard treatments. ⚫ Strategies: – Switching antidepressants or adding a second one. – Medication augmentation (usually with a second antidepressant med, or a range of other meds) – Medication + ECT – Alternative Treatments: ⚫ TMS, MST & Vagal Nerve Stimulation ⚫ Ketamine by Infusion or Intranasally ⚫ Unproven but promising: Psychedelic therapy (esp. psilocybin) ⚫ Highly experimental: Direct Brain Stimulation (DBS) using implanted brain electrodes and external stimulator  Alternative Therapies for Treatment-Resistant Depression (TRD) ⚫ Magnetic seizure therapy (MST) – Replaces shock electrodes of ECT with a magnetic field sufficient to produce seizures, with shorter seizures than ECT. – Results suggest equivalent efficacy to ECT. ⚫ Vagal Nerve Stimulation (VNS) – FDA Approved for TRD in 2005 – Delivers ~20 pulses per sec to electrodes wrapped around vagus nerve in back of throat, stimulator implanted in chest. – Arose from findings that depressed epileptic patients treated with VNS showed improvement in depression. – Exact mechanism is unknown. ⚫ Transcranial magnetic stimulation (TMS) – Uses weak magnetic field sufficient to produce twitches in fingers. – Standard treatment is 1-2 weeks of short daily sessions. – Only weakly effective as usually given, BUT new treatment protocol, Stanford Neuromodulation Therapy (10 sessions per day for 5 days), shows high rates of depression remission (~80%) for TRD. ⚫ Ketamine Infusion Therapy Ketamine Therapy for Treatment-Resistant Depression Ketamine Infusion Esketamine Nasal Spray (SpravatoTM, Johnson & Johnson)  Ketamine Infusion (also see Text Addendum) ⚫ Widely used “off-label” throughout U.S. in “ketamine clinics” and now hotly researched; most exciting depression news in 50 years. ⚫ Patient: – Is placed in recliner and blindfolded. – receives slow infusion of ketamine (a “dissociative anesthetic” and party drug – “special K”) at sub-anesthetic dose, but sufficient to place in twilight state, accompanied by mild hallucinations and experience of depersonalization and derealization. – has typical course of treatment of 6-12 sessions @45 min each over 10-14 days. Side effects are confusion, hangover hallucinations, fuzzy vision; no driving for 24 hrs. – experiences antidepressant effect within hours, lasting days to weeks; booster infusions provided as needed. ⚫ The mechanism by which it operates is unknown. ⚫ Nasal-spray version containing esketamine approved March 2019 (Spravatotm). Patients receive med, wait 2 hrs in doctor’s office before being driven home, and agree not to drive or use heavy machinery for 24 hrs. ⚫ Experts warn against over-hyping ketamine: not everyone benefits, treatments sometimes lose effectiveness, and the long-term effects are uncertain. ⚫ Other hallucinogenic compounds (esp. psilocybin) are being explored for rapid treatment of Major Depression; early evidence shows promise, but safety is biggest current concern. Mania and Bipolar Disorder  Clinical Features of Manic Episode (DSM-5-TR) ⚫ Euphoria or irritability; increased energy and purposeful behavior; or purposeless/reckless behavior, including impulsive suicidality and assaultiveness). ⚫ Inflated self-esteem / grandiosity. ⚫ Persistent insomnia (historically lethal). ⚫ Racing thoughts, “pressured” speech. ⚫ Poor insight; sometimes frank psychosis. ⚫ Involvement in damaging activities (unrestrained buying, foolish investments, sexual indiscretions. ⚫ Sometimes, if accompanied by substance abuse, impulsive assaultiveness or suicidality. ⚫ Hypomanic episode – More restrained than Manic Episode, does not cause severe impairment or require hospitalization. Mania in the Cinema: Mr. Jones (1993)  Major Varieties of Bipolar Disorder (DSM-5-TR) NOTE: Predominant aspect of Bipolar Disorder is mood instability, moods that shift without any discernible explanation. Bipolar Disorder episodes are most often random and not cyclical, may last from a few hours to many months, and may include intervening stable periods. ⚫ Bipolar I Disorder = History of at least one Major Depressive Episode and at least one Manic Episode. ⚫ Bipolar II Disorder = History of at least one Major Depressive Episode and at least one Hypomanic Episode. ⚫ Bipolar I or Bipolar II Disorder with Mixed Features: Coexistence of Bipolar and Major Depressive signs/symptoms. Sometimes this reflects slow or stalled switches from Depression to Mania/Hypomania, or vice versa. ⚫ Cyclothymic Disorder – History of numerous periods of depression signs and symptoms that are not severe enough to diagnose Major Depressive Disorder, and manic or hypomanic signs and symptoms that are not severe enough to diagnose Bipolar I or II Disorder.  Bipolar Disorder ⚫ One-year prevalence of Bipolar I Disorder ~ 1.5%, and Bipolar II Disorder ~ 0.8 %. About 10% of people with Bipolar II Disorder may change to Bipolar I in their lifetimes. ⚫ Probably no sex difference in prevalence. ⚫ Associated with high rates of alcohol / drug abuse (40-50%, higher than any other major mental disorder), criminal behavior, and anxiety disorders (~40%). Abuse may reflect self-medication and/or impulsivity. ⚫ Age of first diagnosis ranges from 15 to 45, with most people diagnosed in their 20’s. ⚫ BUT sometimes seen in children (pediatric bipolar disorder), even infancy. ⚫ Runs in families: – 65% concordance rate in MZ twins, 14% in DZ twins. – 10% concordance rate in 1st-degree relatives. – Family history of Bipolar Disorder in 30% of Bipolar patients. – In 20% of MZ twins in which one has BPD, the other will have Major Depression, suggesting some common inheritance. – Multiple routes of genetic involvement, some shared with other mental disorders.  Bipolar Depressions vs. Major Depressive Disorder ⚫ Bipolar depressions last longer, recur more frequently, are more likely to reach psychotic levels, and can take twice as long to obtain remission with treatment. ⚫ Most cases of Bipolar Disorder first appear as depressed phase; 40% of persons with Bipolar Disorder are initially misdiagnosed with Major Depression. ⚫ Average age of onset is below age 25, compared to late 20’s for Major Depression. ⚫ ~1:1 sex ratio of diagnosis, as opposed to ~2:1 F:M ratio in Major Depression. ⚫ Depression is the more problematic state in Bipolar Disorder. People with Bipolar Disorder spend up to 1/3 of their adult lives in depression. As people age, depressed periods become worse and more frequent and Manic episodes lessen. ⚫ More than 10% of people with Bipolar Disorder eventually suicide, mostly in depressed phase.  Genetic and Brain Mechanisms in Bipolar Disorder ⚫ Many genes are involved in Bipolar Disorder, among them some that regulate calcium-channel regulation in neurons, the release of neuroprotective proteins, circadian rhythms, and estrogen release. ⚫ There may be defects in the metabolism of Protein-Kinase C (PKC), an enzyme involved in the calcium metabolism of neurons in specific brain areas. The result is unstable levels of neurotransmitter release by these neurons. ⚫ PKC activity is increased in manic patients and is thought to be normalized by anti-manic medications. ⚫ Many other hypotheses are under investigation.  Pediatric Bipolar Disorder ⚫ Occurs in about 1% of children, sometimes as early as infancy. ⚫ Manifested by: mood instability (e.g., rages, despondency), hyper-sexuality, pressured speech, racing thoughts, impaired judgment, delusions and hallucinations. ⚫ Up to ½ of severe childhood depressions become adult Bipolar Disorder. ⚫ About ½ of children treated for Major Depression with SSRI’s develop manic or hypomanic episodes, and this is strong indication (but not foolproof) that child is suffering from Bipolar depression. ⚫ Typically a 10-year lag between occurrence of first signs/sx and onset of treatment. ⚫ Often confused or co-morbid with Attention Deficit Hyperactivity Disorder (ADHD) due to shared sx of distractibility, impulsivity, hyperactivity, irritability.  Mixed Episodes (Mania and Depression Are Not Opposites) Signs/Symptoms May Include: And May Also Include: ⚫ Crying ⚫ Euphoria or Irritability ⚫ Feelings of emptiness, ⚫ Unwarranted risk- worthlessness, taking (physical, helplessness, financial, sexual) hopelessness ⚫ Racing thoughts or ⚫ Irritability / anger flight of ideas ⚫ Suicidal ideation ⚫ Severe insomnia ⚫ Fatigue / loss of energy ⚫ Auditory hallucinations 40% of People with Bipolar Disorder experience a Mixed Episode at least once. Many mixed episodes are actually “switches,” or manias emerging out of depressions.  Treatments for Bipolar Disorder ⚫ Medication is 1st-line treatment, but med compliance only ~30% – Acute management (typically with sedating antipsychotic medications), followed by introduction of a mood stabilizer for chronic management. ⚫ Psychotherapy: – usually requires prior medication response to be valuable – builds compliance to medication – helps patient (and family) understand impact of disorder – no effect on disorder itself ⚫ ECT (effective for both mania and bipolar depressions, as well as mixed episodes; used as adjunct to ongoing medication) ⚫ Induced Sleep for Mania (very rarely used, result typically temporary) Medications for Chronic Management of Bipolar Disorder Standard of Care: Polypharmacy Antimanic Action Antimanic Medications (Mood Stabilizers): ⚫ Lithium carbonate (strong antimanic but weak antidepressant actions; may be best anti-suicide treatment; requires careful dosing and close blood-level monitoring; long-term use may be toxic to kidneys) ⚫ Anticonvulsants (moderate antimanic and overall weak antidepressant actions) – Lamictal – currently preferred Bipolar I/II medication; has moderate antidepressant properties, fewest side effects, and is typically weight-neutral. – Also Neurontin, Tegretol* – For rapid-cycling Bipolar Disorder, Depakote* and Topamax* ⚫ “Antipsychotic” agents (moderate antimanic and overall weak antidepressant actions) – Abilify (mostly weight-neutral), Latuda (greatest antidepressant properties of antipsychotics), Seroquel, Zyprexa, Risperdal Antidepressants: ⚫ Proper function is to normalize mood once mood is stable. Can increase risk of “switching” into mania or mixed states unless mood stabilizer is already in place. Antidepressant Action * Should not be taken while pregnant. Affective Disorders May Be Associated with Creativity “No one has ever written, painted, sculpted, modeled, built, or invented except literally to get out of hell” - Artaud Bipolar Disorder and Creativity Likely Historical Sufferers of Bipolar Disorder ⚫ Alvin Ailey ⚫ Sylvia Plath ⚫ Honoré de Balzac ⚫ Edgar Allan Poe ⚫ Hector Berlioz ⚫ Jackson Pollock ⚫ Winston Churchill ⚫ Robert Schumann ⚫ Vincent van Gogh ⚫ Anne Sexton ⚫ Georg F. Handel ⚫ Nina Simone ⚫ Ernest Hemingway ⚫ Frank Sinatra ⚫ Vivian Leigh ⚫ Leo Tolstoy ⚫ Abraham Lincoln ⚫ Norbert Weiner ⚫ Robert Lowell ⚫ Virginia Woolf ⚫ Edvard Munch ⚫ Johann W. von Goethe Some Recent Celebrities with Bipolar Disorder ⚫ Russell Brand ⚫ Sinead O’Connor ⚫ Mariah Carey ⚫ Jane Pauley ⚫ Aaron Carter ⚫ Charlie Sheen ⚫ Kurt Cobain* ⚫ Sting ⚫ Carrie Fisher ⚫ Kanye West ⚫ Steven Fry ⚫ Brian Wilson ⚫ Mel Gibson ⚫ Amy Winehouse* ⚫ Jimi Hendrix* ⚫ Jean-Claude van Damme ⚫ Demi Lovato ⚫ Catherine Zeta-Jones * Now deceased, from likely drug overdose On Having Bipolar Disorder "I have often asked myself whether, given the choice, I would choose to have manic- depressive illness. If lithium were not available to me, or didn't work for me, the answer would be a simple no... and it would be an answer laced with terror. But lithium does work for me, and therefore I can afford to pose the question. Strangely enough, I think I would choose to have it. It's complicated... I honestly believe that as a result of it I have felt more things, more deeply; had more experiences, more intensely; loved more, and have been more loved; laughed more often for having cried more often; appreciated more the springs, for all the winters... Depressed, I have crawled on my hands and knees in order to get across a room and have done it for month after month. But normal or manic I have run faster, thought faster, and loved faster than most I know. - Kay Redfield Jamison - Touched with Fire (1993)  The Upside of Bipolar Disorder ⚫ The “well” relatives of people with Bipolar Disorder appear to have higher rates of achievement, success and creativity. ⚫ Thus, “the ‘dilute’ genotypes of the illness may have evolved to subserve adaptive functions such as exploration and risk taking. Such an evolutionary perspective represents the ultimate theoretical underpinnings of the concept of bipolar spectrum. The temperaments themselves, particularly the cyclothymic and hyperthymic, may further subserve such functions as interpersonal charm and sexual selection, and territoriality.” Akiskal, 2008  Suicide (Optional Slides: Will Not Be on Exam) ⚫ Appropriate terminology: to “die by suicide”, not to “commit suicide.” (Crimes are committed.) ⚫ Suicide attempts should not be described as “failed” or “successful” but as “uncompleted” or “completed.” ⚫ Inappropriate to describe suicide attempts as “manipulative.”  Demographic Factors in Suicide ⚫ 30% increase in completed suicides over the past decade. Rates are increasing most in: – Military veterans. – Active members of military. – Youth belonging to sexual/gender minorities. ⚫ Increasing age: Rates are highest in middle-aged adults, second-highest is people >85 years old. ⚫ Being male: M:F rates run of completed suicides run 3:1 to 4:1, although the rates for females are now increasing faster than those for males. ⚫ Being Caucasian or American Indian. ⚫ Second-highest cause of death in adolescence, next to accidents. - CDC - CDC  Risk Factors in Suicide ⚫ The presence of mental disorder: – Mental Severe Major Depression or Bipolar depression is present in ¾ of people who attempt suicide. Co-morbid Alcohol Abuse or Dependence increases risk of an attempt. – Eating disorders (anorexia nervosa or bulimia nervosa) – Other predisposing disorders include Post-Traumatic Stress Disorder, Schizophrenia (with command hallucinations, especially). – Chronic pain disorder (usually itself co-morbid with Major Depression). ⚫ Personal history of previous attempts (but ~50% of people who attempt suicide complete on first attempt). ⚫ Family history of suicides or suicide attempts (may be associated with genetic abnormality: short allele of serotonin transporter gene). ⚫ Early history of sexual/emotional/physical abuse and/or neglect. ⚫ Current oppressive environment: harassment, bullying, shaming, unemployment, relationship rejection, divorce and loss of child custody. ⚫ Religious/philosophical/cultural values that consider suicide heroic (although many traditions consider suicide sinful). ⚫ Knowledge of recent deaths by suicide by friends, family, acquaintances, celebrities, etc. (suicide contagion). ⚫ Exposure to social media, especially for adolescents. ⚫ Ready availability of means of completion (drugs, prescribed meds, guns): the most common suicide in the U.S. is a Caucasian male in his 60’s who completes suicide by handgun.  Warning Signs of Suicidality ⚫ Talking about suicide, sometimes as a solution. ⚫ Withdrawing from normal activities, becoming secretive, increased drinking or drug use, failure to do schoolwork or go to work. ⚫ Not talking about the future, giving away important possessions or memorabilia. ⚫ Looking unhappy and making statements like, “what’s the point,” “I might just be better off dead,” “I’m no good to anybody anyway.” ⚫ Obtaining weapons, hoarding medicine instead of taking it as prescribed. ⚫ Making plans. (Ask person, “Have you thought about suicide?” “Have you thought how you would do it?” “Are you planning to take your life?”) Express concern and open a dialog about person’s thinking. ⚫ If friend or family is planning to die by suicide or “thinking about it,” ask person if he/she would be willing to get help. If yes, accompany person to nearest mental health center or ER. If not, phone police, nearest mental health center, or ER for guidance. Do so after telling person that you’re concerned for them and plan to seek guidance.  Prevention Strategies ⚫ Social level (may curtail personal freedoms): – reduce glamorization of suicide. – reduce chance of obtaining lethal means. – control harassing/bullying, or access to it, on social media. – construct barriers to suicide at “hotspots” like bridges and cliffs. – promote opportunities for “connection” for people who may be isolated. ⚫ Relationship level: couples or marital therapy for relationship/marital issues. ⚫ Personal level: promote awareness of mental-health signs and symptoms, and where treatment can be obtained. ⚫ Therapeutic level: – continual monitoring for suicidality in high - risk patients. – aggressive treatment of depression and issues of isolation, rejection, etc. – building of coping skills for handling crises. – formulation of “safety plan” with patient in case of crisis and imminent suicidality. Such a plan may include the number of a “hotline” or the local ER, or the admission # to the local psychiatric facility if there has been a prior admission. End