AP PSYCH

The BrainGone Bad

SCHIZOPHRENIA

Mr. Pustay

Prevention

Schizophrenia is a PSYCHOTIC

DISORDER A severe mental disorder in which

thinking and emotion are so impaired that the individual is seriously out of contact with reality.

*Psychotic symptom is out of touch with reality

Positive SymptomsPositive SymptomsHallucinationsDelusions (bizarre, persecutory)Disorganized ThoughtPerception disturbancesInappropriate emotions

Negative SymptomsNegative SymptomsBlunted emotionsAnhedoniaLack of feeling

CognitionCognitionNew LearningMemory

Mood SymptomsMood SymptomsLoss of motivationSocial withdrawalInsightDemoralizationSuicide

Schizophrenia - symptoms

FUNCTION

What is schizophrenia?

• A chronic severe brain disorder; often they hear voices, believe media are broadcasting their thoughts to the world or may believe someone is trying to harm them.

• In men it usually develops in teen years and early 20s; in women it usually develops in 20s and 30s.

Diagnosis

• Currently there is no physical or lab test (although 2012 genome research is showing some signs of success) that can predict high risk to diagnose schizophrenia. – Cost ($3000-$4000)

• A psychiatrist usually comes to the diagnosis based on clinical symptoms.

GENOME TESTING

• Researchers at the Indiana University School of Medicine have developed a test that can predict how likely an individual is to develop schizophrenia. – The scientists combined data from several different

types of studies in order to identify and prioritize a group of genes most associated with the disease

• "At its core, schizophrenia is a disease of decreased cellular connectivity in the brain, precipitated by environmental stress during brain development, among those with genetic vulnerability."

Early onset schizophrenia: Wave of gray matter loss - begins in parietal cortex and spreads forward STG = superior temporal gyrus; DLPFC=dorsolateral prefrontal cortex

Prevalence of Schizophrenia

• 1-2% of U.S. population

• 2 million diagnosed in U.S.

• Median age at diagnosis = mid-20’s

• Men = Women prevalence– Men earlier diagnosis

Prognosis of Schizophrenia

• 10% continuous hospitalization

• < 30% recovery = symptom-free for 5 years

• 60% continued problems in living/episodic periods

Biological Finding

• The Dopamine Hypothesis– Disturbed functioning in dopamine system

(i.e., excess dopamine activity at certain synaptic sites)

Dopaminergic Pathways

Role of Dopamine

• Original theory proposed that an over activation of DA led to schizophrenic symptoms

• More recently it has been hypothesized that – Positive symptoms are caused by an over

activation of specific DA pathways– Negative symptoms arise from and under

activation of different DA pathways

GABAGamma-aminobutyric acid

• GABA is the chief inhibitory neurotransmitter in the brain

• Primarily has effects in the spine, brainstem and retina--it is responsible for the vast majority of all inhibitory neurotransmission in the CNS

• Between 20-50% of all central synapses use GABA as their transmitter. – The enzyme responsible for the formation of GABA from

the amino acid glutamate

– This chemical messenger is known to aid in relaxation and sleep and regulate anxiety.

GLUTAMATEAMINO ACID

• Glutamate sends chemical messages in the brain by “exciting” neurons that are sensitive to it.

• It plays a vital role in learning, memory, and brain development; too much glutamate can be toxic.

– When a person experiences a head injury or stroke, glutamate floods the injured area and kills the neurons by overexciting them, causing brain damage

– one of the reasons why schizophrenia occurs is because people with schizophrenia have a deficiency or a defect in this receptor and the receptor cannot be properly stimulated by glutamate.

• Resembles those on PCP

SEROTONIN

• Acts by blocking the affects of serotonin at specific receptors in the brain and therefore it can produce amazing changes in the mind and mental processes and behavior– Internal processes in the brains of people with schizophrenia

showed similar behavior and mental processing as if on LSD– Abnormally low levels of the serotonin receptors can cause

psychotic systems in behavior

Schizophrenia and Antipsychotic Treatment

New Antipsychotics 2002-2014• 2002 Aripiprazole (ABILIFY); Nov 15• 2003 Risperidone LAI (RISPERDAL CONSTA); Oct 29• 2004• 2005• 2006 Paliperidone (INVEGA); Dec 19• 2007• 2008 Clozapine• 2009 Iloperidone (FANAPT); May 6

Paliperidone LAI (INVEGA SUSTENNA); Jul 31 Asenapine (SAPHRIS); Aug 13 Olanzapine LAI (ZYPREXA RELPREVV); Dec 11

• 2010 Lurasidone (LATUDA); Oct 28• 2011• 2012• 2013• 2014

AP PSYCH

The BrainGone Bad

SCHIZOPHRENIA

Mr. Pustay

Progression of Schizophrenia

Role of Dopamine

• Original theory proposed that an over activation of DA led to schizophrenic symptoms

• More recently it has been hypothesized that – Positive symptoms are caused by an over

activation of specific DA pathways– Negative symptoms arise from and under

activation of different DA pathways

Cocaine Use

• Cocaine may increase symptoms of schizophrenia by increasing dopamine levels

GLUTAMATEAMINO ACID

• Glutamate sends chemical messages in the brain by “exciting” neurons that are sensitive to it.

• It plays a vital role in learning, memory, and brain development; too much glutamate can be toxic. – One of the reasons why schizophrenia occurs is

because people with schizophrenia have a deficiency or a defect in this receptor and the receptor cannot be properly stimulated by glutamate.

• FLAT EFFECT

SCHIZOPHRENIA

• By definition Schizophrenia is most likely characterized by disorganized and fragmented thinking

Selective Attention

• Selective Auditory Attention

• How people are able to track certain conversations while tuning others out, a phenomenon he referred to as the "cocktail party" effect.

• The "spotlight" model– William James suggested

that this spotlight includes a focal point in which things are viewed clearly.

– The area surrounding this focal point, known as the fringe, is still visible, but not clearly seen.

– Finally, the area outside of the fringe area of the spotlight is known as the margin.

• The “Zoon lens” model

BRAIN AREAS INVOLVED IN ANTIPSYCHOTIC TREATMENT

• The oversimplified version of what brain areas are involved in anti-psychotic medication use is:– Reticular Activating System: the effects on this area

generally moderate spontaneous activity and decrease the patients reactivity to stimuli.

– The Limbic System: the effects on this area generally serves to moderate or blunt emotional arousal.

– The Hypothalamus: the effects on this areas generally serve to modulate metabolism, alertness, and muscle tone.

Thalamus

• Vigorous activity in the thalamus has been found to be associated with hearing voices

• Schizophrenics have smaller than normal thalamus which causes difficulty in focusing attention

Schizophrenia Correlations

• Prenatal viral infections contribute to schizophrenia

• Low birth weight• People born in North

America during the month of February are at increased risk for schizophrenia

Seasonality of Schizophrenia

• One possible reason that researchers believe may explain this seasonality of schizophrenia risk is the association between winter/spring births and schizophrenia may be related to sunlight exposure.

• A lack of sunlight (for example, during the shorter days of winter) can lead to vitamin D deficiency, which scientists believe could alter the development of a child's brain in the mother's womb and after birth.

Genetic Studies

• Twin Studies• Blood

(Family)relatives• Adoption• High-risk populations

(e.g., children of schizophrenic parents)

KH2F090509_05

Percentageof Risk

GeneralPopulation

Offspring ofTwo

Schizophre-nic Parents

Spouse

FirstCousin

Uncleor Aunt

Nephewor Niece

Grand-child Half

SiblingParent

SiblingFraternal Twin

Offspring ofOne

Schizophre-nic Parent

IdenticalTwin

50

40

30

20

10

0

Second-Degree Relative

First-Degree Relative

1% 2% 2% 2%4% 5% 6% 6%

9%

Relationship to Schizophrenic Person

60

Third-Degree Relative

Unrelated Person

13%17%

46%48%

If identical twins have different placentas it is only 1/10 probability versus 5/10

Early Course Schizophrenia

Prodromal Period Post-Psychotic Period

Initiation of Antipsychotic

Psychosis

Positive Sx

Negative SxDepression

Based on Häfner, ABC Schizophreniestudie

5 years 1-2 years*

PsychosisThreshold

Schizophrenia

• Symptoms of withdrawal following the disappearance of hallucinations and delusions are most indicative residual schizophrenia (chronic)

Background

• It is believed that Schizophrenia must be treated in a multifaceted treatment– While medication is the first line treatment

counseling, social and family services should be provided for proper treatment of patients

• Further developments in pharmacological treatments should increase functioning of patients in society by reducing side effects with more selective drugs

Misdiagnosis

• This is a common problem since schizophrenia shares a significant number of symptoms with other disorders.– DDs, Bipolar, Depression, Mania, etc.

• There is an average of 10 years from onset to correct diagnosis & tx.

Two Categories of Symptoms in Schizophrenia

• Positive symptoms

• Negative symptoms

• Positive symptoms are the presence of inappropriate behaviors, and negative symptoms are the reduction of appropriate behaviors

Positive Symptoms• Distortions or excesses of normal functioning

– delusions, – hallucinations, – disorganized speech,– thought disturbances, – motor disturbances

• Positive symptoms are generally more responsive to treatment than negative symptoms

• Auditory hallucinations (particularly "hearing voices") are far more common than visual, with some estimating prevalence of over 70%

Delusions

• False beliefs that are firmly and consistently held despite disconfirming evidence or logic

• Individuals with mania or delusional depression may also experience delusions. – The delusions of patients with schizophrenia

are often more bizarre (highly implausible).

Types of Delusions

• Delusions of Grandeur– Belief that one is a famous or powerful

person from the past or present

• Delusions of Control– Belief that some external force is trying to

take control of one’s thoughts (thought insertion), body, or behavior

Types of Delusions

• Thought Broadcasting– Belief that one’s thoughts are being broadcast

or transmitted to others

• Thought Withdrawal– Belief that one’s thoughts are being removed

from one’s mind

Types of Delusions

• Delusions of Reference– Belief that all happenings revolve around

oneself, and/or one is always the center of attention

• Delusions of (Paranoid) Persecution– Belief that one is the target of others’

mistreatment, evil plots, and/or murderous intent

Hallucinations

• Sensory experiences in the absence of any stimulation from the environment

• Any sensory modality may be involved– auditory (hearing); – visual (seeing); – olfactory (smelling); – tactile (feeling); – gustatory (tasting)

• Auditory hallucinations are most common

Common Auditory Hallucinations in Schizophrenia

• Hearing own thoughts spoken by another voice

• Hearing voices that are arguing

• Hearing voices commenting on one’s own behavior

Disorganized Speech / Thought Disturbances

• Problems in organizing ideas and speaking so that a listener can understand

• Loose Associations (cognitive slippage)– continual shifting from topic to topic without

any apparent or logical connection between thoughts

• Neologisms– new, seemingly meaningless words that are

formed by combining words – “Word Salad”

Negative Symptoms

• Behavioral deficits that endure beyond an acute episode of schizophrenia

• More negative symptoms are associated with a poorer prognosis

• Some negative symptoms might be secondary to medications and/or institutionalization

• An expressionless face is an example of a negative symptom

Types of Negative Symptoms

• Anhedonia– inability to feel pleasure; lack of interest or

enjoyment in activities or relationships

• Avolition – inability or lack of energy to engage in routine

(e.g., personal hygiene) and/or goal-directed (e.g., work, school) activities

Types of Negative Symptoms

• Alogia– lack of meaningful speech, which may take

several forms, including poverty of speech (reduced amount of speech) or poverty of content of speech (little information is conveyed; vague, repetitive)

• Asociality– impairments in social relationships; few friends,

poor social skills, little interest in being with other people

Types of Negative Symptoms

• Flat Affect (Catatonia)– No stimulus can elicit an

emotional response– Patient may stare vacantly, with

lifeless eyes and expressionless face.

– Voice may be toneless. – Echolalia (parrotlike repeating of

another’s speech or movements– Flat affect refers only to outward

expression, not necessarily internal experience.