Neuropsych Schizo

5/19/2018 Neuropsych Schizo

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Psychosis

A symptom of severe psychiatric and non-

psychiatric (medical) disorders that may be short

lived or chronic

It is often misunderstood

The individual suffers a break in reality that

influences all aspects of their life


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Differential Diagnosis of

PsychosisPrescription medications causing symptoms-anticholinergic medications

Illicit drugsintoxication from

methamphetamines, cocaine, PCP,hallucinogens, or withdrawal from alcohol, orbenzodiazapenes - xanax, ativan

Medical conditions like seizure, CNS infections,

neurosyphilis, brain tumors

Metabolic abnormalitiesthyroid disease,nutritional deficiencies


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Definition of Psychosis:

Mental StatusBreak from reality evidenced by delusions,hallucinations, illusions, disordered thinking, loss

of ego boundaries, or failed reality testing

Affects thought contentor thought process

A symptom of various disorders, but not a

disorder in itself

Lifetime prevalence of 3% in the US


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On the mental status

exam: Thought ContentDelusions: fixed, false beliefs based on anincorrect reference about an external reality that

fail to correct with reasoning & are inconsistent

with patients education/cultureTypes include bizarre, delusional jealousy,

erotomanic, grandiose, persecutory, somatic, of

being controlled, thought broadcasting, thought

insertion

Ideas of reference: words or actions that have

personal, special meaning but not full delusions


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On the mental status

exam: Distorted

perceptionsHallucinations: a sensory perception that has thecompelling sense of reality of a true perception

but that occurs without external stimulation of the

relevant sensory organ.May or may not have insight

Mood congruent versus incongruent

Illusions: actual external stimulus is misperceivedor misinterpreted


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What about during

Dreams?Hypnagogic: when falling asleepHypnopompic: when awakening


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Illogical Thought Process

CircumstantialityTangentiality

Derailment

Loose associations

Thought blocking

Neologismsmade up words


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Schizophrenia

Serious and lifelong mental disorder

Affects 1% of population

Men >Women

Onset: Men 18-25, women 25-mid 30s

Urban born > rural born

Striking disturbances in mental functioning

Positive & negative signs and symptoms

Disruption in experience of reality


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Schizophrenia

Functionally impaired patients with at least 2

characteristic symptoms (delusions,

hallucinations, disorganized or catatonic

behavior, or negative symptoms) with effectslasting at least 6 months.


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Positive symptoms

an excess or distortion of normal functions

Delusions, hallucinations

Disorganized speech

Catatonic behavior: motoric immobility, excessive

motor activity, extreme negativism, mutism,

pecularities of voluntary movement, echolalia

Disorganized thinking (formal thought disorder)

that impairs effective communication


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Negative Symptoms

A diminution or loss of normal function

Decreased emotional expressivity (affective

flattening)

Restricted speech fluency

Alogiarestricted thought production

Avolitiondecreased goal directed behavior


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Dopamine Hypothesis

Thought that schizophrenia is by product of

dopamine dysregulation

Evidence from work in 1960s

Administering Dopamine agonists

amphetamine, produces symptoms like

schizophrenia

Most important Dopamine receptor is D2


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Neuroimaging and

DopamineRelated to dopaminergic toneNewer hypothesis states the there is a hyper-

dopamine state in the nigrastriatal D2 system

that causes the positive symptoms & hypo-dopamine state in prefrontal D1 system with

negative symptoms (cognitive problems)


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Limitations

Dopamine hypothesis does not account for

negative symptoms

Dopamine blockers (antipsychotics) not effective

in treating negative symptoms

Dopamine agonists do not induce negative

symptoms


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Glutamate

May be associated with pathophysiology of

schizophrenia

People intoxicated with glutamate receptor

agonists (PCP, ketamine) exhibit behavioralsigns like schizophreniaincluding positive &

negative symptoms

These drugs bind to the NMDA class of glutmate

receptors


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GABA

The effects of NMDA antagonists thought to be meditatedthrough GABA release

NMDA receptors are found on GABAergic inhibitoryinterneurons

Activating NMDA receptors causes increased GABAreleasesuppression of glutmate release

In schizphrenia: binding of antagonist on NMDA receptoron GABA inhibitory receptor causes increasedglutamatergic state which is thought to cause symptoms of

psychosis

Higher order cognitive deficits in schizophrenia thought tobe linked to GABA dysregulation


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Antipsychotics

Typicals: Older, Motor side effects, more potent

Atypicals: Newer, metabolic side effects, lesspotent


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Typical Antipsychotics

Haldol

Developed in the 1950s

Was the most widely used antipsychotic for

schizophreniaIncreases neuronal activity throughout the basal

ganglia

No linear relationship between dose and

antipsychotic action


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Atypicals

Risperdone: higher risk of EPS than other

atypicals (especially akathesia) & dose

dependent. Weight gain, and prolactin elevation

Olanzapine (Zyprexa): there is no increasedDopamine blockade after a certain dose, very

sedating, significant weight gain

Quetiapine (seroquel): Low EPS incidence, need

very high doses to get D2 blockade, otherwise

mostly sedation. Associated with hypotension


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Atypicals

Aripiprazole (Abilify): clinically less effective for

positive symptoms, lower risk of weight gain or

EPS

Ziprasidone (Geodon): clinically less effective forpositive symptoms, can have cardiac side effects

Clozapine: effective in otherwise poorly

responsive patients, requires strict monitoring

because of blood count effects, not associated

with TD


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D2 Receptor Affinities

Receptor Seroquel Zyprexa Risperda

l

Abilify Haldol

D2 + ++ +++ ++++ ++++


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Neurotransmitter Location of

Synthesis

Associated With

Acetylcholine Basal Nucleus of

Meynert

Dopamine Substantia nigra Schizophrenia,addiction

Norepinephrine Locus Ceruleus Depression, anxiety

Serotonin Raphe Nuclei Depression, chronic

pain


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Extrapyramidal side effects

Directly related to D2 receptor blockade innigrostriatal pathway, balanced by excitatorycholinergic activity

Acetylcholine works in conjunction withdopamine to produce movement.

Smooth muscle control requires a balance ofdopamine & acetylcholine

High potency, typical antipsychotics > lowpotency, typical antipsychotics > modern, atypicalantipsychotics at modest doses


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Takeaway Point

In psychosis, Dopamine INCREASED

Antipsychotic medications DECREASEdopamine

Side effects of antipsychotic medications cancause DOPAMINE DEPLETION, & movementdysfunction (like Parkinsons disease, which is amovement disorder)

To treat side effects, we use medications thatDECREASE acetylcholine (which effectivelyINCREASES Dopamine & restores balance)


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EPS symptom

Acute dystonia Intermittent but

sustained muscle

spasms leading toinvoluntary

movements

Treated with

anticholinergic

medication in IV form

Akathesia Sensation of motor

restlessness

associated with a

strong desire to move

lower extremity

Treated with beta

blocker

Parkinsonism Rigidity, bradykinesia,

tremor, masked

facies, shuffling gait

Treated with

anticholinergic

medication

Tardive dyskinesia Movement disorderinvolving involuntary

movements of mouth,

tongue and upper

extremities after

chronic antipsychotic

use

Treated withclozapine, reducing

antipsychotic dose


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Video of Bipolar &

schizophrenia


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References

The American Psychiatric Publishing Textbook of

Psychiatry, 5thedition

GabbardsTreatment of Psychiatric Disorders, 4th

edition

Documents

Neuropsych Schizo