4/12/2014. Early-Onset Schizophrenia

Size: px

Start display at page:

Download "4/12/2014. Early-Onset Schizophrenia"

Elfreda Fox
6 years ago
Views:

1 Early-Onset Schizophrenia 1

2 Overview History: Conceptualizations Past and Present DSM Model, Symptoms & Subtypes Epidemiology: Prevalence/Onset/Course/Duration Comorbidity Neurobiology Genetic Underpinnings Differential Diagnosis & Assessment Considerations Treatment Recommendations Developmental Risk model 2

History of Schizophrenia Emil Kraeplin: coined the term dementia praecox.

between the mind and the brain (Bleuler, 1911).

3 History of Schizophrenia Emil Kraeplin: coined the term dementia praecox. This term reflects two distinguishing characteristics: being demented (dementia) with an early onset (praecox; Kraeplin, 1896). It was not until 1911 that Eugen Bleuler coined the term Schizophrenia, which refers to the split between the mind and the brain (Bleuler, 1911). DSM-I Schizophrenic Reaction DSM-II Schizophrenia (all childhood psychoses under childhood schizophrenia) DSM-III Same criteria for adults and children DSM-III-R No big changes DSM-IV 2 out of 5 diagnostic categories to be present DSM-IV-TR Same diagnostic criteria 3

4 Criterion A DSM-IV-TR Criteria Characteristic Symptoms: 2 or more of the following, each present for a significant portion of the time during a 1-month period (or less if successfully treated): Delusions Hallucinations Disorganized speech (e.g., frequent derailment or incoherence) Grossly disorganized or catatonic behavior Negative symptoms (i.e., affective flattening, alogia, or avolition) Only one Criterion A symptom is required if delusions are bizarre or hallucinations consist of a voice keeping up a running commentary or the person s behavior or thoughts, or two or more voices conversing with each other. 4

5 Positive vs. Negative Symptoms Positive: Delusions (bizarre vs. non-bizarre) Hallucinations Disorganized Speech Grossly Disorganized or Catatonic Behavior Psychotic Dimension vs. Disorganized Dimension Negative: Affective Flattening Alogia Avolition 5

6 Hallucinations and Delusions Auditory Visual Gustatory Persecutory Hallucinations Referential Somatic Tactile Olfactory Delusions Grandiose Religious 6

7 DSM-IV-TR Criteria Criterion B: Social/occupational dysfunction Criterion C: Symptoms must persist for at least 6 months Criterion D: Schizoaffective and Mood Disorder with Psychotic Features exclusion Criterion E: Substance/general medical condition exclusion Criterion F: Relationship to a Pervasive Developmental Disorder Longitudinal Course Episodic With Interepisode Residual Symptoms Episodic With No Interepisode Residual Symptoms Continuous Single Episode In Partial Remission Single Episode In Full Remission Other or Unspecified Pattern 7

8 Schizophrenia Subtypes Paranoid Type (295.30) Disorganized Type (295.10) Catatonic Type (295.20) Undifferentiated Type (295.90) Residual Type (295.60) 8

9 DSM-IV-TR Model Of Schizophrenia Environmental Factors: Stress Substance use Prenatal Factors Neurobiological Substrate Genetic Predisposition Core Features: 1.Delusions 2.Hallucinations 3.Disorganized speech 4.Disorganized/catatonic behavior 5. Negative symptoms Secondary Features: Sleep Problems Concentration/Attention Problems Occupational/School Problems Interpersonal difficulties Social difficulties Associated Features/Outcomes: Substance Abuse Depression Anxiety Violent behavior Suicide Homelessness 9

10 Epidemiology Adult-Onset Early-Onset (13-18 years old) Very Early-Onset (prior to 13 years old) Incidence 1 in in 10,000 Lifetime prevalence risk = 1% No gender differences Marked increase in schizophrenia during adolescence 0.1-1% of schizophrenic disorders manifest before age 10, 4% before age 15 Later age of onset for women Later age of onset for females Later age of onset for girls, no gender differences after 14 Onset Between 16 and 30 years old; infrequent after 45 Mean age for women = 18; Mean age for men = 25 Can be insidious, higher rates of acute onset Can be insidious, higher rates of acute onset Insidious 10

11 Prodromal Phase Development and Course of Symptoms Onset Acute Phase Complete Remission Course Recovery Residual Chronic weeks to years 1 to 6 months Mild positive symptoms Deterioration in functioning Symptom free Improvement in positive symptoms Prolonged periods between acute phases Continuation of symptoms Mood symptoms Increase in positive symptoms Some continuation of negative symptoms Little impairment due to positive symptoms Worsening of symptoms Cognitive difficulties Impairment/ Distress Depression Social withdrawal Professional Attention Social withdrawal Anxiety symptoms Medication Bizarre behavior Behavior Problems Kodish & McClellan, 2008) 11

12 Epidemiology (Cont.) Course Adult-Onset Moderate Stability Early-Onset (13-18 years old) Very Early-Onset (prior to 13 years old) Earlier onset = worse prognosis Earlier onset = worse prognosis Earlier onset = worse prognosis 21-30% treated for first episode have no symptom relapse over next 5 years About 23% of adolescents (and adults) reach full remission 50% achieve partial remission 25% achieve partial remission 27% show remission 25% show chronic course 52% show chronic course Cognitive deficits and negative symptoms tend to be more stable than positive symptoms Cognitive deficits and negative symptoms tend to be more stable than positive symptoms Cognitive deficits and negative symptoms tend to be more stable than positive symptoms Psychotic symptoms tend to be episodic over time; emergence and worsening related to worse functioning Psychotic symptoms tend to be episodic over time; emergence and worsening related to worse functioning Psychotic symptoms tend to be episodic over time; emergence and worsening related to worse functioning Cognitive deficits and negative symptoms greatly influence functional impairment Mortality due to suicide (5%) Cognitive deficits and negative symptoms greatly influence functional impairment Cognitive deficits and negative symptoms greatly influence functional impairment 12

13 The Epidemiology of onset and Course of Schizophrenia (Heiden & Hafner, 2000) 13

14 14

15 15

16 Developmental Precursors - Premorbid Impairments (Hollis, 2003) 16

17 Stress-Vulnerability Model of Schizophrenia (Mueser & McGurk, 2004) 17

18 Comorbidity Buckley, Miller, Lehrer, and Castle (2009)review of empirical studies: Comorbid Diagnosis Percentile Depression 50% Substance Abuse 47% PTSD 29% OCD 23% Panic Disorder 15% High comorbid substance abuse in adolescents with schizophrenia First psychotic symptoms are associated with substance use in adolescents (not etiological, but may be a possible trigger) (Eisner & McClellan, 1998) 18

19 Early-Onset Comorbidity 82 children, ages % had at least one comorbid psychiatric illness most common comorbid conditions identified: Comorbid Diagnoses Percent ADHD 84% ODD 43% Depression 30% SAD 25% Ross et al., 2006) 19

20 Neurobiological Substrates related to Schizophrenia Time-lapse of brain development of healthy teens from age 5- to 20-years old 20

21 21

22 Early and Late Gray Matter Deficits in Schizophrenia Normal Controls Teens with EOS 22

23 23

24 Enlarged Ventricles in the Brain: Individuals with schizophrenia, including those who have never been treated, typically have enlarged ventricles in the brain, as demonstrated in over 100 studies to date. 24

25 The Dopamine Hypothesis of Schizophrenia Evidence for Dopamine Hypothesis Drugs that block dopamine reduce schizophrenia symptoms Drugs that block dopamine have side effects similar to Parkinson's which is caused by a lack of Dopamine in the Basal Ganglia Evidence Against Dopamine Hypothesis Amphetamines do more than increase Dopamine levels - they alter other neurotransmitters Drugs that block dopamine receptors act on receptors quickly. When used to treat schizophrenic symptoms, they make take several days Best drugs used to treat schizophrenia resemble Dopamine and completely block Dopamine receptors High doses of amphetamines cause schizophreniclike symptoms Effects of Dopamine blockers may be indirect - they may influence other symptoms that have more impact on the symptoms New drugs fro schizophrenia such as Clozapine, block receptors for both Dopamine and Serotonin Amphetamines make schizophrenic symptoms worse Abnormal brain wave patters in childhood-onset and adult-onset schizophrenia can be reduced by drugs that block Dopamine receptors 25

26 Genetics: Concordance Rates (Gottesman, 1991) 26

27 Genetics contd. Schizophrenic Patient Person at Risk Percent at Risk General Population Everybody 0.8%-1.5% Father Each Child 10%-18% Mother Each Child 10%-16% Both Parents Each Child 25%-46% Child Each Parent 5% One Sibling Each Sibling 8%-10% 2 nd degree relative Another 2 nd degree relative 2%-3% MZ twin MZ twin 40%-50% DZ twin DZ twin 12%-15% Adoptive Parent Biological Parent Adoptee reared by nonschizophrenic biological Adoptee reared by nonschizophrenic adoptive 4.8% 19.7% Maxmen, J.S. & Ward, N.G. (1994) 27

28 GENES 28

, family stress and instability) compared 212 children of schizophrenic mothers to 99 children of mothers without Schizophrenia strong environmental effects for those

29 Genetics and Environment 25-year longitudinal study of exposure to environmental risk factors (e.g., family stress and instability) compared 212 children of schizophrenic mothers to 99 children of mothers without Schizophrenia strong environmental effects for those children who had mothers with Schizophrenia (Carter et al., 2002). Tienari and colleagues (2003) compared adopted children of biological mothers with Schizophrenia with adopted children who did not have schizophrenic biological mothers. strong environmental influence (as measured by rearing environment in the adoptive home) for those children with a biological predisposition for Schizophrenia. 29

30 Genetics vs. Environment Prenatal/Perinatal Factors: Exposure to influenza in the 1 st trimester of pregnancy Maternal rubella and respiratory infections during the 2 nd or 3 rd trimester of pregnancy Obstetric complications Premature birth, low birth weight, perinatal hypoxia, and birth in late winter/early spring Family/Social Factors: Urban environment Social disadvantage poverty, racial discrimination, family dysfunction, unemployment, or poor housing conditions Childhood experiences of abuse or trauma Parenting is not held responsible for schizophrenia unsupportive dysfunctional relationships may contribute to an increased risk. Drug use: Stimulants like cocaine and amphetamines are capable of inducing a picture clinically identical to paranoid schizophrenia, and more recent reports have also implicated cannabis. It is suggested that variations in the dopamine metabolising COMT gene influence the vulnerability to develop psychosis in people who use cannabis (Caspi et al, 2005). 30

31 Genetics 31

32 Genetics 32

33 Differential Diagnosis: Medical Neurological Conditions: Huntington s chorea, lipid storage disorders, seizure disorders CNS Lesions: Brain tumors, congenital malformations, head trauma Endocrine and Metabolic Disorders: Addison s and Cushing s diseases, fluid or electrolyte imbalance, hypoxia, hyper/hypothyroidism, hypo/hyperglycemia, pituitary insufficiency Nutritional Deficiencies: Vitamin B12, Niacin, Thiamine Toxins Substance abuse, medications, heavy metals Others: HIV, Encephalitis, Meningitis, Syphilis, 33

34 Differential Diagnosis 34

35 Differential Diagnosis: How do you differentiate??? Nonpsychotic Hallucinations 788 (8%) children in an epidemiological study reported hallucinations (McGee, Williams, & Poulton, 2000) Mood Disorders Children with depression may present with hallucinations or, more rarely, delusions (Calderoni et a;., 2001) Over ½ of the children diagnosed with Bipolar Disorder were incorrectly diagnosed with Schizophrenia (AACAP, 1997; Werry, 1992) Post-traumatic Stress Disorder Hallucinations, cognitive changes, and alertness/suspiciousness related to the trauma Pervasive Developmental Disorders/Autism Developmental abnormalities Obsessive-compulsive Disorder lack insight about their obsessions and compulsions can lead to diagnostic misinterpretation with regard to hallucinations 35

36 Cultural Considerations You should always consider cultural/religious factors! Linguistic variations vs. disorganized speech Visual or auditory hallucinations with a religious content Emotional expression variations across cultures Some evidence of overdiagnosis in some ethnic groups in the UK and US (APA, 2000) African American Asian American 36

37 Assessment You should.. Interview the parents, significant persons in the child s life (as possible), and the child (AACAP, 2001) Determine the specific onset, course, and duration of symptoms as well as any changes in the child s functioning. This is important given the frequency of symptom overlap with other psychiatric diagnoses mentioned above Assess family psychiatric history This is important given the high heritability estimates 37

38 Assessment Semi-structured interviews (e.g., K-SADS-PL) are preferred over structured interviews why?? These should be conducted with the child s parents as well as with the child (AACAP, 2001) Rating scales can be used to supplement the above assessment procedures The Positive and Negative Syndrome Scale (PANSS) (Kay et al., 1987) The Brief Psychiatric Rating Scale for Children (Hughes et al., 2001) A thorough assessment should also include.. a review of the child s school records in order to assess for academic and cognitive functioning IQ testing and an assessment of language skills, particularly if developmental delays are present A review of medical records to rule out the medical causes of psychosis mentioned above.or a referral to a physician in order for medical testing to be conducted 38

39 Treatment Approximately 24% of those with psychosis do not attend treatment as scheduled (Nose et al., (2003) Approximately 30% with psychosis and/or schizophrenia disengage from treatment (O Brien et al., 2009) Treatment disengagement is related to exacerbation of symptoms, increased rates of hospitalization, violence, & suicide (Kreyenbuhl, Nossel & Dixon, 2009) Risk factors for dropping out of treatment being younger, being male, lower SES, social isolation, poor social functioning, greater severity of mental illness, comorbid psychopathology, and substance abuse (Kreyenbuhl, Nossel & Dixon, 2009) 39

40 Medical Treatments 1st Generation (Typical) Antipsychotics Chlorpromazine (Thorazine) Haloperidol (Haldol) Perphenazine (Etrafon, Trilafon) The first antipsychotic medication developed Same effectiveness as adults found with children Reduces hyperactivity, excitability, anxiety, provocativeness Quicker acting than Prolixin Some evidence of reduction in assaultive behavior Fluphenazine (Prolixin) Phenothiazine type drug Rates between 50 and 93% of children showing improvement 40

41 2nd Generation (Atypical) Antipsychotics Clozapine (Clozaril) Does not have "tardive dyskinesia" as a side effect, but there is a 1-2% chance of developing a low white blood cell count (Agranulocytosis) Effective in the treatment of hallucinations Fewer Extrapyramidal side effects Found superior to Haldol and Zyprexa Requires blood monitoring Risperidone (Risperdal) Olanzapine (Zyprexa) Quetiapine (Seroquel) Zipasidone (Geodon) Aripiprazole (Abilify) Paliperidone (Invega) Blocks some serotonin and dopamine receptors Blocks serotonin and dopamine receptors Blocks some serotonin and dopamine receptors; Introduced in 1997 New antipsychotic medication that may work on dopamine and serotonin systems. FDA Approved for children and adolescents FDA Approved for children and adolescents Common Side Effects: dizziness, blurred vision, drowsiness, sun sensitivity, rashes, rapid heartbeat, metabolic changes, weight gain, muscle rigidity, muscle spasms Tardive Dyskinesia = uncontrollable muscle movements 41

42 The main blood tests that should performed routinely at baseline assessment in a young person presenting with a psychosis, their commonly used abbreviations and rationales for their use. 42

43 43

44 44

45 Psychosocial Treatments 45

46 Psychosocial Treatments (cont) 46

47 DSM-IV-TR Model Environmental Factors: Stres s Substance use Prenatal Fac tors Neurobiological Substrate Genetic Predisposition Core Features: 1.Delus ions 2.Halluc inations 3.Dis organiz ed s peech 4.Dis organiz ed/c atatonic behav ior 5. Negativ e s y mptoms Secondary Features: Sleep Problem s Conc entration/attention Problem s Occupational/School Problem s Interpers onal diffic ulties Soc ial diffic ulties Associated Features/Outcomes: Substance Abuse Depres s ion Anx iety Violent behav ior Suic ide Hom eles s nes s 47

Developmental Risk Model of Early Onset Schizophrenia Environmental Stressors: Prenatal Stress Flu, Diabetes, Smoking, Hypoxia Environmental Stressors: Poor relationships with peers and family

48 Developmental Risk Model of Early Onset Schizophrenia Environmental Stressors: Prenatal Stress Flu, Diabetes, Smoking, Hypoxia Environmental Stressors: Poor relationships with peers and family Demands of school Stressful life events Biological Influences Genetics Neurobiological Substrates Tissue loss Grey matter loss Enlarged Ventricles Dopaminergic System Prodromal Phase Disturbances in Mood Social deficits Cognitive deficits Bizarre behavior Withdrawal Behavior problems Secondary Features Sleep problems Academic problems Difficulty concentrating Interpersonal problems Associated Features Substance abuse Depression Anxiety Violent behavior Suicide Active Phase (Core Features) Delusions Hallucinations Disorganized speech Disorganized/catatonic behavior Negative symptoms 48

Schizophrenia and Related Psychotic Disorders

Schizophrenia and Related Psychotic Disorders and Related Psychotic Disorders Anand K. Pandurangi, MD Professor & Chair, Div. of Inpatient Psychiatry Director, Program VCU Medical Center 1 Kraeplin 1896 Dementia Praecox. Single, Homogenous Disorder