Schizophrenia

1. Schizophrenia Description and Etiology

2. Symptoms of Schizophrenia • Positive Symptoms • Pathological additions to normal behavior (ie. hallucinations, delusions) • Negative Symptoms • Characteristics that are lacking or are reduced (ie. reduced range of emotion, reduced amount of speech) Psychomotor Symptoms • Odd gestures, excited movement, motionless stupor

3. Hallucinations Perceptions in any sensory modality without relevant or adequate stimuli • Auditory • may hear sounds that other people do not hear • Visual • may see images that are not really there. May also have a difficult time distinguishing relevant from irrelevant information. • Tactile • strange or unusual sensations on the skin. • Olfactory • may smell smells that are not there. • Taste • may have unusual tastes that are not caused by physical objects.

4. DelusionsBeliefs that are unfounded and contrary to reality • Persecution - the belief that others are out to get you. • Grandiosity - the belief that you have special powers or abilities. • Guilt - belief that you have committed some crime or have done something that is unforgivable. • Reference - may attach special meanings to things or the behaviors of others. • Control - beliefs that others are controlling thoughts, feelings or behaviors or that the patient has control over others’ thoughts, behaviors or feelings, or events. • Somatic - something is physically wrong with their body even if the doctor says that nothing is wrong

5. Disorganized Thinking or Speech • Loose associations or derailment - ideas slip off track to matters that are unrelated • Tangentiality, circumstantiality – difficulty reaching answers in a succinct way. • Incoherence - thought patterns do not make sense • Conceptual difficulties - difficult to think in abstract terms • Unusual word use: • Neologisms • Word salad • Perseveration • Clang association

6. Inappropriate Affect • Any range of emotion that does not fit the content of the situation • May laugh when describing serious events • May have unexplainable shifts in mood • May become angry in positive situations • Mood may be inappropriately intense • Might be caused by internal stimuli (hallucination)

7. Disorganized Behavior • People may dress oddly • Act in inappropriate manners • child-like or silly • Collect odd items • Act sexually inappropriate in front of others • masturbating, exposing oneself

8. Negative Symptoms • Avolition - lack of energy or interest in routine activities • Alogia - poverty of speech and poverty of content of speech • Anhedonia - inability to experience pleasure • Flat or blunted affect - little facial expression,patients appear dull • Asociality (social withdrawal) - impairments in social functioning

9. Psychomotor Symptoms • Reduced spontaneous movements • Catatonia • Decrease in reactivity to environment (stupor) • Patients make repeated gestures (excitement) • Catatonic Rigidity and Posturing • Patients will keep odd postures for a prolonged period of time. • Resist efforts to be moved (negativism) • Waxy flexibility

10. DSM Criteria A. Characteristic Symptoms. Two (or more) of the following, each present for a significant portion of time during a 1-month period (or less if successfully treated): 1) delusions 2) hallucinations 3) disorganized speech (e.g., frequent derailment or incoherence) 4) grossly disorganized or catatonic behavior 5) negative symptoms (affective flattening, alogia, avolition) B. Social/occupational dysfunction. One or more major areas of functioning such as work, interpersonal relations, or self-care are markedly below the level achieved prior to the onset. C. Duration. Continuous signs of the disturbance persist for at least 6 months.

11. Incidence • Impacts about 1% of the population • Typically occurs in males between the ages of 18-25 • Typically occurs in females between the ages of 25-30 • Can happen earlier or later than those age groups • There is thought to be a bimodal period in women - another age period where there is a high onset, typically late 30’s early 40’s • About 10-15% may commit suicide • Often more present in cities rather than rural areas • Often more common in lower SES populations

13. Types of Schizophrenia • Catatonic • motor immobility or excessive motor activity • disorganized behavior • Repetition of words or speech • unusual postures held for a long period of time • Paranoid • presence of hallucinations and/or delusions • negative symptoms are not prominent but may be there to a very minor extent. • Disorganized • speech and behavior are disorganized and often not goal-directed • flat or inappropriate affect

14. Types of Schizophrenia • Undifferentiated • meet criteria for schizophrenia but none of the other categories are met (no prominent hallucinations or delusions, catatonic [im]mobility) • Residual • there has been at least one episode of schizophrenia, positive symptoms are not present, negative symptoms are present. • Often seen as a transition period between an episode and remission.

16. Etiology

17. Walker et al (2005) • Schizophrenia is a brain disease • Its etiology involves the interplay between genetic and environmental factors • Multiple developmental pathways eventually lead to disease onset • Brain maturational processes play a role in the etiological process.

18. Genetic Factors

19. Diathesis-Stress Model • But… • Concordance rate is never more than 50% • Unexpressed genetic vulnerability is common • Combination of physiological vulnerability and life stresses may be needed • Adoption studies indicate an interaction between genes and environment • Tienari et al. (1994) adoption study • Rate of schizophrenia significantly higher than in the matched control adoptees • However, genetic vulnerability was mainly expressed in association with disruptive adoptive environments • Elevated rate of schizophrenia was not detected in adoptees reared in healthy family environments

20. Prenatal and Postnatal Factors • Prenatal • Obstetrical complications (OCs) • Pregnancy, labor, and delivery complications • Hypoxia (fetal oxygen deprivation) most strongly linked to Schz • Maternal infection • Flu during second trimester (brain development) • Maternal stress during pregnancy • Effects on HPA Axis • Postnatal (Brain Injury) Do these act independently or interact with a genetic vulnerability (i.e., do genetics increase response to brain damage)?

21. Premorbid Development • What happens prior to onset of symptoms? • Childhood • Lower IQ, grades in school (difference greatest as age increases) • Less responsive in social situations, less positive emotion, and have poorer social adjustment • Delays and abnormalities in motor development, • deficits in the acquisition of early motor milestones such as bimanual manipulation and walking

22. Environmental Stressors • Stressful life events • Family environment predating onset of symptoms increases risk • Neglect/abuse • Institutional settings • HPA Axis (elevated cortisol levels) • Structural brain changes (reductions in hippocampal volume) • More severe symptoms and cognitive deficits • Exacerbate symptoms by augmenting dopamine activity • Increase risk for relapse • Worsen the course of schizophrenia • Number of stressful life events increases in the months immediately preceding relapse • More likely to relapse if they live in homes where family members express more negative attitudes and emotion

23. Family Environment Early Theories • Schizophrenogenic Mother • Mother as rejecting, cold, domineering • Double-bind Theory • Parents present ideas, feelings, and demands that are mutually incompatible. Contemporary Family Studies • Expressed Emotion

24. Camberwell Family Interview • Interview conducted with family member (spouse, parent, sibling). • Broad discussion about ill relative • Coded • Criticism • Hostility • Emotional Overinvolvement • Warmth

25. EE & Relapse(Butzlaff & Hooley, 1998) Meta-analytic effect size r=0.31. HOW IMPORTANT ARE THESE FINDINGS? • For a hypothetical sample of 200 patients (high EE=100; low EE=100), an effect size r=0.30 translates into a high and low EE relapse rate of 65% and 35%, respectively. • In this model, EE is associated with approximately one third of the relapses that do occur and with two thirds of the relapses that do not occur.

26. EE & Relapse • Found across cultures • Not merely a consequence of overall symptoms or illness severity • Not merely a reflection of lower tolerance for symptoms • Some relation to chronicity

27. What gives rise to Hostility/Criticism? • Attributions • If family member believes that patient has control over behavior (internal attribution) they may show greater criticism (Hooley) • Some symptoms may give rise to such attributions Negative symptoms were more frequently criticized than positive sxs. Hi-EE relatives criticized negative Sxs more than Lo-EE relatives (Weisman et al., 1998)

28. Causal Attributions in EE(Yang et al., 2004)

29. Brain Abnormalities • Enlarged brain ventricles, especially increased volume of the lateral ventricles • Decreased frontal, temporal, and whole-brain volume • Reductions in the size of thalamus and hippocampus • Brain abnormalities predate onset of illness • Present in adolescent studies

30. Malfunction of neural circuits • Possible abnormal function of “cortico-striatal circuits” that link various regions of the cortex and the limbic system with the striatus • Brain regions that distinguish these circuits mature at different rates • It is possible that disruption in one or more of the circuits characterized by neuromaturation in adolescence/early adulthood may subserve the onset of symptoms.

31. Neurotransmitters • Dopamine • Enables communication in the circuits that link subcortical with cortical brain regions • Early evidence that • drugs that reduce dopamine activity also serve to diminish psychotic symptoms • drugs that heighten dopamine activity exacerbate or trigger psychotic episodes • antipsychotic drugs have their effect by blocking dopamine receptors

32. Dopamine (continued) • Early studies of dopamine in schizophrenia failed to find evidence of excess dopamine or its metabolites • However, they found some evidence of increased densities in dopamine receptors • Augmented dopamine synthesis and release

33. Glutamate • Excitatory neurotransmitter that connect the hippocampus, prefrontal cortex, and thalamus, all regions that have been implicated in the neural circuitry of schizophrenia • Evidence of diminished activity at glutamatergic receptors among schizophrenia patients in these brain regions • One of the chief receptors for glutamate in the brain is the NMDA receptor • Blockade of NMDA receptors produces negative symptoms and cognitive impairments. • Administration of NMDA receptor antagonists induces schizophrenic-like symptomatology • Conversely, drugs that indirectly enhance NMDA receptor function can reduce negative symptoms and improve cognitive functioning