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Adult Psychopathology

Adult Psychopathology. Mood Disorders. Depression Major depression Dysthymia Postpartum depression Bipolar disorder Bipolar I Bipolar II Cyclothymia. Major Depression. Marked change in mood Diagnosis entirely behavioural

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Adult Psychopathology

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  1. Adult Psychopathology

  2. Mood Disorders • Depression • Major depression • Dysthymia • Postpartum depression • Bipolar disorder • Bipolar I • Bipolar II • Cyclothymia

  3. Major Depression • Marked change in mood • Diagnosis entirely behavioural • Persistent sad mood, loss of appetite, insomnia, restlessness, feelings of: worthlessness, guilt, helplessness, pessimism, cognitive difficulties, social withdrawal, decreased energy, etc. • Behaviours must persist at least 2 weeks • Isolated or recurrent, mild, major, or severe

  4. Epidemiology • Affects 8-17% of population at least once • Over 1 million Canadians; over 120 million world wide • Projected to be second-leading cause of disability worldwide by 2020

  5. Comorbid Conditions • Anxiety disorders • Attention-deficit hyperactivity disorder • Suggest roles of serotonin, norepinephrine, and dopamine in depression • (More on this later)

  6. Numbers • Heritable • Family risk about 9% vs. 3% in controls • Concordance of 0.43 for MZ and 0.28 for DZ twins • Adoption studies mixed, but sample sizes quite small • No shared environmental effect to speak of

  7. Dysthymia • Less severe condition than major depression • Chronic • Altered eating patterns, insomnia or hypersomnia, low energy, low self-esteem, poor concentration, feelings of hopelessness • Heritable, 2-3 times more common in females

  8. Postpartum Depression • Form of clinical depression • Can affect men too post-childbirth • 5-25% prevalence rate in women • Typically lasts hours to days • Wide range of symptoms • Sadness, hopelessness, low self-esteem, guilt, sleep disturbance, exhaustion, social withdrawal, etc. • Some interesting correlations

  9. Meta-analyses • Predominately environmental factors have been examined • SES is significant, but even when controlled, higher prevalence in African-American • Heritability and ethnicity PredictorCorrelation Prenatal depression 0.44-0.46 Low self-esteem 0.45-0.47 Childcare stress 0.45-0.46 Life stress 0.38-0.40 Low social support 0.36-0.41 Marital difficulty 0.38-0.39 Single parent 0.21-0.31 Low socioeconomics 0.19-0.22 History of depression 0.38-0.39 <Beck (2001)> EthnicityPrevalence of PPD Overall 15.7% African-American 25.2% Native American 22.9% Caucasian 15.5% Hispanic 15.3% Asian/Pacific 11.5% <Segre et al. (2006)>

  10. Hormones and PPD • Has been suggested that post-childbirth hormonal changes are causative factor • Not supported (e.g., O’Hara, 1995) • Also, fathers can experience PPD… • Diathesis-stress models, gene-environment interaction • Some women are susceptible to stress of childbirth and/or hormonal shifts • Hormones simulating pregnancy and parturition induce PPD-like symptoms, but only in some women

  11. Bipolar Disorder • Not a single disorder; category of mood disorders characterized by abnormally elevated mood (mania), sometimes followed by depressive episodes, generally interspaced with normal periods • Affects about 1% of world’s population; 17% lifetime risk for suicide • Bipolar I • At least one or more manic episodes; may be episodes of major depression as well • Bipolar II • At least one manic and one major depressive episode

  12. Affect • Mania • Euphoria, grandiosity, increased energy, increased irritability, decreased need for sleep, rapid speech, risk taking • Depression • Low mood, low energy and motivation, insomnia, feelings of hopelessness

  13. Cyclothymia • Milder form of bipolar II • Recurrent mood disturbances between hypomania and dysthymic mood • Ranging from mild elation to mild depression • Generally goes through cyclic periods • Typically unrelated to life events (from self-reports), although may be triggered by general stress levels • Lifetime prevalence of 0.4-1% • Equal in sexes, but women seek treatment more

  14. Numbers • Heritable • Family risk of 9% vs. 1% in controls • Concordance of 0.4-0.65 for MZ and 0.05-0.07 for DZ twins • Adoption study (Mendlewicz & Rainer, 1977) found 7% of biological parents vs. 0% of adoptive parents show bipolar disorder

  15. Bipolar Linkage • Early linkage studies inconsistent • Suggestions of autosomal dominant loci largely rejected • Polygenic effect • Possible loci: 4p, 5q, 10q, 12q, 13q, 18p, 21q, 22q, Xq (and more!)

  16. Kelsoe et al. (2000) • 443 microsatellite markers • 20 families (San Diego and Vancouver) • Have proband and at least two additional affected members (either bipolar I or II)

  17. Loci • 12 yielded LODs greater than 2.0 across genome • Highest scores for 22q13 (GRK3 gene) • Also high LODs at 5p15 (dopamine transporter gene), 10q, and 13q • Some overlap with loci reported for schizophrenia on these chromosomes • Suggests many susceptibility genes are common for the two disorders • Could be nonspecific susceptibility or different mutations in the same gene may predispose to different disorders

  18. GRK3 Gene • GRK3 widely expressed in brain • Regulation of G protein-coupled receptor signaling • Brain neurotransmission effects, including dopamine and corticotropin-releasing factor receptors (and others) • GRK3 expression induced by amphetamine in rats (animal model of mania) • Unclear if GRK3 is a candidate gene in non-Northern European descended Caucasians

  19. Selling bipolar genetic tests to public over the internet for $399 as of March 2008 • Receive cup, spit in cup, mail cup to Psynomics • Psynomics mails results to client’s doctor indicating likelihood of developing bipolar disorder • Two mutations on GRK3 gene • Kelsoe argues that this moves away from behavioural diagnosis • However, only usable for whites of Northern European ancestry who show some behavioural symptoms and have at least one other bipolar family member • As of yet, APA has no policy on genetic testing • Currently not taking new patients

  20. Bipolar Disorder and Schizophrenia • Similar clinical features • Mood disturbance, cognitive impairment, psychosis • Both about 1% prevalence rate • Both have about 10% risk in first-degree relatives • Some evidence that schizophrenia occurs at increased frequency in relatives of probands with bipolar disorder and vise versa • Loci on chromosomes overlap for disorders • Problem has been identifying specific genes and/or biochemical pathways

  21. Chotai, Serretti & Lorenzi (2005) • 114 schizophrenics and 416 bipolar disorder • Interaction between tryptophan hydroxulase (TPH; involved in serotonin synthesis), serotonin transporter (5-HTTLPR), and dopamine receptor (DRD4) genes • Interaction between alleles of TPH and 5-HTTLPR genes constitute susceptibility to schizophrenia but not to bipolar disorder

  22. Silberschmidt & Sponheim (2008) • COMT gene, 22q11 • Enzyme degrading dopamine, epinephrine, norepinephrine • Valine for methionine SNP affects cognitive tasks by reducing dopamine at four times the regular rate • Differentiated relatives of schizophrenic and bipolar disorder patients on various personality dimensions • Valine allele linked to low narcissism, rejectionability, and stimulus seeking; seen in relatives of schizophrenics, but not relatives of bipolar disorder patients • COMT associated with schizophrenia, but not bipolar disorder

  23. Anxiety Disorders • Wide range of types • Panic disorder, generalized anxiety disorder, phobias, obsessive-compulsive disorder • Either involve anxiety or attempt to reduce anxiety • Most common form of mental illness; lifetime prevalence of 29% • May lead to other disorders, like depression

  24. Panic Disorder • Fear of specific situation that can cause more panic attacks • Lifetime risk of 5% • Morbidity risk in first-degree relatives of 13%; concordance of 31% for MZ and 10% for DZ twins

  25. Generalized Anxiety Disorder • Chronic state of diffuse anxiety; excessive and uncontrollable worrying • Runs in families; 10% for first-degree relatives • Contrasting twin studies • Two show no heritability • Three show about 20% • Little shared environment

  26. Phobias • Fear related to specific stimulus • Predisposition to fear something; specific stimulus from learning • 30% familial risk for general phobias (vs. 10% controls), 20% for social phobias (vs. 5% controls) • Somewhere around 30% heritability

  27. OCD • Different diagnostic criteria; gives different results in studies • On average, 7% risk for family members (vs. 3% controls) • Early onset OCD more familial • Two of three twin studies failed to find heritability

  28. Co-Occurrence of Disorders • Diagnostic criteria behaviourally based • Overlap • Should we separate mood disorders? • Relatives of (unipolar) depressives are not at increased risk for bipolar depression, but relatives of bipolar depressives are at a 14% risk (vs. 1% controls) • Individuals with one disorder have close to 50% chance of having 1+ other disorders in the same year

  29. Bipolar & Schizophrenia • Badner & Gershon (2002) find overlapping linkage for bipolar depression and schizophrenia in 13q and 22q • Under DSM-IV, bipolar can only be diagnosed if patient is not schizophrenic • So clinically, can’t be comorbid • But…

  30. Anxiety Disorder Co-occurrence • Hettema et al. (2005) • Significant overlap between generalized anxiety disorder, panic disorder, agoraphobia, and social phobia • Non-shared environmental effects primarily responsible for differences • Should we have some sort of overarching anxiety measure (e.g., a?), like g for cognitive ability?

  31. Anxiety and Depression • Genetically speaking, anxiety and depression are largely the same thing • Kendler et al. (1992) • Major depression and generalized anxiety disorder • No significant shared environment effects ra = 1.0 ru = 0.51 Additive Unique Unique Additive 31% 42% 58% 69% Major Depression Generalized Anxiety

  32. A New Model • Internalizing disorders • Depression and anxiety disorders • Externalizing disorders • Alcohol and drug abuse, and antisocial adult behaviour • Based on behavioural genetics, not traditional clinical behavioural diagnostics

  33. Internalizing Externalizing Anxious/misery Fear Alcohol dependence Other drug abuse or dependence Adult antisocial behaviour Conduct disorder • Genes associated with an internalized disorder will be associated with other internalized disorders; genes associated with externalized disorders will be associated with other externalized disorders • Genetic effects may be broad in their effects on psychopathology • “Generalist genes” Major depression Generalized Anxiety disorder Panic disorder Animal phobia Situational phobias Disorder- Specific factors Disorder- Specific factors

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