| What are myths regarding schizophrenia? | People with Schizophrenia have “split personalities”…
Intellectually disabled
Dangerous
Are addicted to their drugs
Schizophrenia is caused by bad parenting
Due to a weakness in character
It is a hopeless disorder |
| How is epidemiology of schizophrenia? | 1% of the worlds population has schizophrenia
•Costs billions of USD annually due to hospitalization, lost wages, disability benefits, lost of productivity…
•High risk for physical illness & suicide: 15% suicide.
•Prevalence same for men & women; onset age 16-25
•In men begins earlier & may be > severe; women > favorable outcome
As age increases, above 30 females become more susciptible.
All economic groups but is concentrated in poor populations
Downward drift theory:
Lower socioeconomic status →stress→ disease ?
OR
The disease→ dysfunction→ lower socioeconomic status ? |
| What are DSM-V diagnostic criteria of schizophrenia? | Characteristic symptoms; 2 or > of the following: Delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, negative symptoms
Social/occupational dysfunction
Duration of at least 6 months
Schizoaffective or mood disorder has been excluded
Disorder is not due to a medical disorder or substance abuse |
| How is phenotype of schizophrenia? | Positive symptoms (delusions, hallucinations)
Negative symptoms (Apathy, anhedonia, cognitive blunting, neuroleptic dysphoria)
Schizophrenia is a mixture of positive and negative symptoms (positive symptoms reflect loss of touch with reality and negative symptoms reflect loss of interest in things and not being able to experience pleasure) |
| What are main positive symptoms of schizophrenia? | Distortions or excesses of normal functioning
Delusions
Hallucinations
Disorganized thinking and speech
Inappropriate affect
Positive symptoms are generally more responsive to treatment than negative symptoms |
| What is schizo delusion? | False beliefs that are firmly & consistently held despite disconfirming evidence or logic. Individuals w/mania or delusional depression may also experience delusions.
However, the delusions of patients with schizophrenia are often > bizarre (highly implausible).
Types (control, grandeur, persecution, reference) |
| What is delusion of control? | external force is trying to take control of
one’s thoughts (thought insertion), body, or behavior.
Thought insertion : believing that thoughts that are not your own have been placed in your mind by an external source
Thought withdrawal: belief that one’s thoughts are being removed from one’s mind
Thought broadcasting: belief that one’s thoughts are being broadcast or transmitted to others |
| What are other types of delusions? | Delusions of Grandeur: belief that one is a famous or powerful person from the past or present.
A 35 year old woman informs her family that she is the virgin Mary who has come to give birth to an new savior who will save the world.
Delusions of reference: belief that all happenings revolve around oneself, and/or one is always the center of attention.
Delusions of persecution: belief that one is the target of others’ mistreatment, evil plots,
&/or murderous intent |
| What is hallucination? | Hallucinations
Sensory perception experiences in the absence of any stimulation from the environment
Any sensory modality may be involved:
auditory (hearing) olfactory (smelling) tactile (feeling) gustatory (tasting) visual (seeing) auditory hallucinations are most common |
| What are negative symptoms of schizo? | . |
| How do we describe negative symptoms? | Symptoms that are deficits in normal thought, behavior, or emotions
Endure beyond an acute episode
More negative symptoms are associated w/ a poorer prognosis
Some might be secondary to medications &/or
institutionalization
Key symptoms on observation (reduced speech, poor grooming/hygiene, limited eye contact)
Key symptoms after questions (reduced emotional response, reduced interest, reduced social drive) |
| What are the 4 main domains of psychopathy of schizo? | Positive Symptoms (Hallucinations, Delusions, Paranoia, Thought disorganization)
Negative symptoms (affective flattening, improvershid speech, ambivalence and anhedonia)
Affective symptoms (dysphoria, suicidality, helplessness)
Neurocognitive (distractability, learning defects, memory deficits, abstract thinking impairment) |
| What are cognitive symptoms of schizo? | . |
| What is the basis of symptoms and malfunctioning brain circuits? | The different symptom domains of schizophrenia are hypothesized to be regulated by unique brain regions. Positive symptoms of schizophrenia are hypothetically modulated by malfunctioning mesolimbic circuits, while negative symptoms are hypothetically linked to malfunctioning mesocortical circuits and may also involve mesolimbic regions such as the nucleus accumbens, which is part of the brain’s reward circuitry and thus plays a role in motivation. The nucleus accumbens may also be involved in the increased rate of substance use and abuse seen in patients with schizophrenia. Affective symptoms are associated with the ventromedial prefrontal cortex, while aggressive symptoms (related to impulse control) are associated with abnormal information processing in the orbitofrontal cortex and amygdala. Cognitive symptoms are associated with problematic information processing in the dorsolateral prefrontal cortex. Although there is overlap in function among different brain regions, understanding which brain regions may be predominantly involved in specific symptoms can aid in customization of treatment to the particular symptom profile of each individual patient with schizophrenia. |
| What are phases of schizo? | 3 phases:
Prodromal phase = the beginning: symptoms
not obvious but person begins to deteriorate.
Active phase = the middle: symptoms are
obvious; may be triggered by stress.
Residual phase = the leftovers? Symptoms
return to prodromal-like phase of functioning. Positive symptoms gone but negative symptoms remain. |
| What are etiologies of schizophrenia? | Genes
Neuro-developmental
Structural abnormalities
Dopamine hypothesis
Glutamate hypothesis
Exogenous toxins |
| What are genetics of schizophrenia? | Identical twins: if one twin develops the disorder, there is a 48% chance that the other twin will
Biological relatives of adoptees with schizophrenia are more likely to display schizophrenic symptoms than are their adoptive relatives
First degree relatives (dizygotic twins and siblings of schizo parents 17%, others 6-13% |
| What are neurodevelopmental abnormalities in schizophrenia? | Subtle molecular abnormalities and schizophrenia.
The "subtlety" of molecular abnormalities may vary, with some leading to psychiatric symptoms in the presence of minimal environmental stress and others requiring multiple major stressors to cause mental illness. For example, the aggregate of symptoms that make up the schizophrenia syndrome may be more biologically determined than that of other psychiatric illnesses.
In this case, perhaps only minor
stressors acting on very high risk circuits would be enough to activate symptoms of schizophrenia. |
| What is stress-diathesis model of schizophrenia? | Schizophrenia may ccur as the result of both genetic (nature) and epigenetic (nurture) factors. That is, an individual with multiple genetic risk factors, combined with multiple stressors causing epigenetic changes, may not have sufficient backup mechanisms to compensate for inefficient information processing within a genetically “biased” circuit. The circuit may be unsuccessfully compensated by overactivation, or it may break down and not activate at all. In either case, the abnormal biological endophenotype would be associated with an abnormal behavioral phenotype, and thus with psychiatric symptoms such as hallucinations, delusions, and thought disorder. Such abnormal circuit activation would be potentially detectable with functional brain scanning, and psychiatric symptoms would be manifest on clinical interview. |
| Describe the neurodevelopmental theory of schizo | 2 X the risk for schizophrenia than those without complications affecting the oxygen supply to the newborn extended labor, breech position, prolapsed umbilical cord or cord around the neck
Preeclampsia
Affects 5-8% of all pregnancies and typically occurs after 20 weeks gestation; characterized by high blood pressure and the
presence of protein in the urine
Other factors: small head circumference |
| What are structural abnormalities in brain of schizo? | Type II schizophrenia recently linked to brain abnormalities.
CAT and MRI reveal enlarged ventricles.
People with enlarged ventricles usually have Type II (negative symptoms) rather than Type I (positive symptoms)
Studies also show Type II people have smaller amount of cortical gray matter, smaller frontal and temporal lobes, and less blood flow in certain areas of the brain |
| What are gross anatomical abnormalities of schizophrenia? | Increased size of ventricles ((lateral and 3rd) and decreased brain volume is the most replicated finding, Ventricular enlargement is found in affected twins of monozygotic pairs discordant for schizophrenia, This enlargement appears to be stable when patients are followed up prospectively)
Decreased cortical gray matter (Especially evident in superior temporal gyrus, dorsal prefrontal cortex and limbic areas such as the hippocampal formation and anterior cingulate cortex. These abnormalities may be present in first-episode, never-medicated patients) |
| What is dopamine theory of schizophrenia? | . |
| How is dompamine hypothesis? | Amphetamine (very high doses) ? paranoia, delusions, auditory hallucination, also exacerbates symptoms of schizophrenia.
Effects blocked by DA antagonist chlorpromazine
Phenothiazines & all other typical neuroleptics block D2 receptors and alleviate (+) symptoms.
Can be seen by 5 dopamine pathways (nigrostriatal [control motor function, parkinsonism, tremor, rigidity], mesolimbic [pleasure sensation, euphoria of drugs, delusions], mesocortical [cognitive symptoms and affective symptoms negative symptoms], tuberoinfundibular [ant pituitary and PRL, normal in schizo], multiple site pathway unknown) |
| Figure of dopamine pathway in schizo. | . |
| How is dx of schizophrenia? | Based on psychiatric interview of the patient and a close relative
Laboratory workup and brain imaging for differential diagnostic issues
Importance of DSM5 as a reference
Workup (CBC, urinanalysis, endocrine test, LFT, EEG, CT, MRI, neuropsycho test, projective tests)
DD (mania w/psychotic features, depression w/psychotic, extreme OCD, schizoaffective disorder, temporal lobe epilepsy, tumor, stroke, endocrine disorder, infection, MS, autoimmune) |
| What are other psychotic disorders? | . |
| What is brief psychotic disorder? | One or more positive symptom (that is not a“culturally sanctioned response pattern”) that
lasts at least 1 day
but less than 1 month
with an eventual return to premorbid functioning
Be careful to rule out intoxication or other effects of drugs |
| What is schizophreniform disorder? | Same as schizophrenia, but lasts less than 6 months (but still at least 1 month)
Therefore, must differentiate from Schizophrenia & Brief Psychotic Disorder |
| How is difference in time frame of different psychotic disorders? | . |
| What are shizoaffective disorders? | Constant schizophrenia with periods of depression, mania, or both
Must be at least 2 weeks during which hallucinations and delusions exist in the absence of prominent mood symptoms
Mood symptoms must be prominent for a
substantial portion of the illness
Two types: depressive or the bipolar type
Difficult to differentiate from Mood Disorder with Psychotic Features and
from the “normal” mood symptoms that accompany schizophrenia |
| What is delusional disorder? | Non bizarre delusions IRL situations for at least 1 month, w/no criterion A schizophrenia met, functioning or behavior not markedly impaired and mood episodes occurred and brief and not related to substance use.
Specific types (erotomanic, grandiose, jealous, persecutory, somatic, mixed, unspecified)
Persecutory is most common. Erotomanic, jealousy, and somatic are also common. Some hallucinations are acceptable (i.e. does not imply schizophrenia) if they are restricted to the context of the delusion
Occurs in 0.3% of population
Onset usually after age 30
Course is variable
Rare and heterogeneous, very difficult to characterize or treat:
Antipsychotics work to some extent
Cognitive therapy ineffective |
| How is medical model in tx of schizophrenia? | Pharmacotherapy – mainly anti-psychotic (neuroleptics) drugs
ECT: for highly resistant cases Individual therapy, family therapy &
psychoeducation, group therapy by professionals – inpatient and outpatient
Antipsychotics (conventional - anti dopamine[Haloperidol (Haldol), Fluphenazine (Fluanxol), Chlorpromazine (Largactil), Thioridazine (Melleril), Perphenazine, Pimozide (Orap), Zuclopenthixol (Clopixol)]
Atypical anti dopamine and serotonin (b3allo l dopamine) [Risperidone (Risperdal), Olanzapine (Zyprexa), Quetiapine (Seroquel), Ziprasidone (Zeldox), Paliperidone (Invega), Asenapine, IMP Clozapine (Leponex) for resistant schizophrenia)
3rd Gen ( Aripiprazole (Abilify)) |
| How are the mechanisms of actions of antipsychotics of shizophrenia? | Atypical antipsychotics block dopamine and serotonin, block dopamine in places with alot of dopamine receptors, and block serotonin and activate dopamine in places with alot of serotonin receptors (b3alli) so in limbic dopamine is low less hallucination, in frontal dopamine a3la solves negative and affective symptoms
Typical (block M1, H1, a1 and D2 effects and side effects)
Atypical (all receptors + 5HT2A receptors and increase dopamine ->dopamine neuron have these receptors that brake the dopamine, so when this receptors is stopped dopamine will increase giving the atypical antipsychotics
Its a matter of concentration of receptors whether dopamine or serotonin is blocked
Tubuloinfundibular no effect on last two pathways which are normal
Non treated pt with new gen all gets resolved |
| What is hit and run pathway of atypical antipsychotics? | activity on dopamine receptors, first generation is very stable with the receptor (very low dopamine) while second gen will hit, block receptors and runs which lowers dopamine to lower hallucinations and less side effects to stop frontal and tubuloinfundibular pathways |
| What are 3rd gen smart agonists dopamine partial agonist? | If low activation of dopamine increases it to the half, and if high activation decreases it to the half so in places with high dopamine removes psychosis and frontal with too low dopamine increases it and decrease negative and affective symptoms
Capable of treating psychosis without side effects
Many drugs, amisulpride, aripiprazole (most used) and bifeprunox
Problem is obesity (metabolic problems, cholesterol high, diabetes) |
| How is the sift of risks of antipsychotic meds? | Past (Tardive dyskinesia, hyperlipidemia, prolactin)
Current (diabetes, weight gain, TD, prolactin, hyperlipidemia, CAD, insulin resistance, sedation) |
| What are limitations of typical antipsychotics? | EPS (blocking nigrostriatal symptoms) and TD in 20-50% of patients
Prolactin elevation
30% of patients remain psychotic
Minimal improvement in negative symptoms
Failure to improve cognitive function
Limited effect on depression and suicidality
Poor compliance and increased relapse
Minimal improvement in overall function |
| What are neuro effects of antipsychotics? | . |
| What are extrapyramidal effects of antipsychotics? | . |
| What is neuroleptic malignant syndrome? | An idiosyncratic, life-threatening illness associated with antipsychotic therapy
Clinical manifestations include
hyperpyrexia
autonomic instability,
“board-like” rigidity |
| How is risk of metabolic syndrome for different antipsychotics? | . |
| How is monitoring of antipsychotic meds? | At baseline, 1 month, 3 months
weight, BP, fasting glucose, fasting lipid panel
Yearly
weight, BP, fasting glucose
Every three years
fasting lipid panel
Looking for:
> 5-7% increase from initial weight or BMI > 25
Fasting glucose > 126
– BP > 140/90
Cholesterol thresholds depends on risk factors |
| What are the effects of multiple relapses on days to remission? | First relapse: remission in 47 days
Second relapse : remission in 76 days
Third relapse : remission in 130 days
Relapse after discontinuation of antipsychotics in remitted subjects after 1 year continuous tx is 94% w/median time in 15 weeks.
Outcome is variable (chronic deteriorating, episodic w/interepisodic deficits (common) or w/out deficit |
| When to treat schizophrenia? | . |
| What are psychosocial interventions for schizophrenia? | Supportive therapy
Behavioral family therapy
Family education
Social skills training
Community support
– Lower relapse; improved functioning, compliance and social adjustment |
