1
Q
what is schizophrenia?
A
- split mind - irrational divergence between behavior and thought content
- chronic, debilitating illness associated with deterioration in mental function and behavior
2
Q
what is the hallmark symptom of schizophrenia?
A
psychosis
3
Q
in schizophrenia, impairment in reality testing that may present as:
A
- alteration in sensory perceptions (hallucinations)
- abnormalities in thought content (delusions)
- abnormalities in thought process/organization
4
Q
define illusion
A
misperception of real external stimuli
5
Q
hallucinations?
A
sensory perceptions not generated by external stimuli
6
Q
ideas of reference?
A
- false conviction that one is subject of attention by other people
- feeling as though people are referring to you in their conversations
7
Q
what is delusions?
A
false beliefs not correctable by logic or reason, not based on simple ignorance, and not shared by culture, delusions of persecution most common
8
Q
loss of ego boundaries?
A
not knowing where one’s mind and body end and those of others begin
9
Q
alogia?
A
lack of informative content
10
Q
echolalia (clanging)
A
repeating statements of others/associating words by their sounds, not by their meaning (eg- I’m very sure I’ve got the cure and I’m not pure.”
11
Q
thought blocking
A
abrupt halt in the train of thinking, often because of hallucinations
12
Q
neologisms
A
inventing new words
13
Q
circumstantiality
A
in responding to questions, one presents unnecessary and voluminous details ultimately arriving at an answer to the questions posed
14
Q
tangentiality
A
beginning a response in a logical fashion but then getting further and further away from the point and fail to answer the question initially posed (can understand topic transition)
15
Q
loose association
A
loss of logical meaning between words or thoughts, when asked a question, illogically jumps from one subject to another
16
Q
Neurological abnormalities
A
- Abnormalities of frontal lobes (hypo)
- Lateral and third ventricle enlargement (enlarged)
- Decreased volume of hippocampus, amygdala, parahippocampal gyrus
17
Q
Neurotransmitter Abnormalities
A
Excess dopamine, serotonin, glutamate, norepinephrine
18
Q
what are the good prognostic indicators for schizophrenia?
A
Good prognostic indicators include:
- Female gender
- Older age at onset
- Married
- Have social relationships
- Good employment history
- Presence of mood symptoms
- Presence of positive symptoms
- Few relapses
19
Q
OTC agents for sleep
A
Melatonin
antihistamines
20
Q
Rx agents/habit forming
Benzodiazepines
A
triazolam
temazepam
flurazepam
21
Q
Off Label Options
A
Trazodone is a sedating antidepressant
Quetiapine is a sedating antipsychotic
22
Q
schizophrenia
A
- split mind
2. illness that tends to get worse
23
Q
characteristic of schizophrenia
A
downward drift
24
Q
symptoms of schizophrenia
A
- psychosis is the hallmark symptom
- impairment in reality testing that may present as:
- alteration in sensory perceptions (hallucinations)
- abnormalities in thought content (delusions)
- abnormalities in thought process/organization
25
hallucination is
alteration in sensory perceptions
26
delusion is
abnormalities in thought content (false belief not correctable by logic or reason)
27
schizophrenia also have
abnormalities in thought process/organization
28
idea of reference
1. false conviction that one is subject of attention by other people
2. feeling as though people are referring to you in their converstions
29
alogia
lack of informative content in speech, lacking/poverty of speech
30
inventing new words
neologisms
31
repeating statements of others/associating words by their sounds, not by their meaning (I'm very sure I've got the cure and I'm not pure)
echolalia (clanging)
32
abrupt halt in the train of thinking, often b/c of hallucinations
thought blocking
33
In responding to questions, one presents unnecessary and voluminous details ultimately arriving at an answer to the question posed
Circumstantiality
34
Beginning a response in a logical fashion but then getting further and further away from the point and fail to answer the question initially posed (can understand topic transition)
Tangentiality
35
Loss of logical meaning between words or thoughts; when asked a question, illogically jumps from one subject to another
Loose associations
36
At least one episode of psychosis with persistent disturbances of
thought, behavior, appearance, speech and affect (emotion) as well as impairment in occupational and social functioning
37
In contrast to delirium or substance abuse, patients with schizophrenia do not have clouding of consciousness
- Attention and memory capacity typically intact, when not psychotic
- Alert and oriented, do not fluctuate in/out of consciousness/stupor
38
DSM-5 Diagnostic Criteria for Schizophrenia
A. Characteristic symptoms: 2 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. Grossly disorganized or catatonic behavior
4. Negative symptoms (flat affect, alogia, or avolition)
5. Disorganized speech (frequent derailment or incoherence)
* the DSMIV only req’d 1 symptom
39
Duration: Continuous signs of the disturbance persist for at least
6 months. This 6-month period must include at least 1 month of symptoms (or less if successfully treated) that meet Criterion A (i.e., active phase symptoms) and may include periods of prodromal (symptomatic of the onset) or residual symptoms.
40
Schizoaffective and Mood Disorder exclusion:
Symptoms cannot be due to another illness
41
positive symptoms of schizophrenia
Positive symptoms: are additional to expected behavior (i.e. symptoms that are added to a patient’s normal functioning)
1. Delusions
2. Hallucinations
3. Agitation
4. Talkativeness
5. Thought Disorder
- -> Respond well to most traditional and atypical antipsychotic agents
42
Negative symptoms: are missing from expected behavior (i.e. decreased or loss of usual function)
1. Lack of motivation
2. Social withdrawal
3. Flattened affect/emotion
4. Cognitive disturbances
5. Poor grooming
6. Poor/impoverished speech
- -> Sometimes a better response with atypical antipsychotics.
43
phases of schizophrenia
Three phases:
1. Prodromal: prior to first psychotic break
Avoidance of social activities
Quiet and passive or irritable
Sudden interest in religion or philosophy
May have physical complaints
Anxiety and depression common
2. Psychotic/Active: loss of touch with reality
Associated with positive symptoms
3. Residual: period between psychotic episodes, in touch with reality, but doesn’t behave normally
Negative symptoms, peculiar thinking, eccentric behavior and withdrawal from social interactions
44
Adoption and twin studies support the role of genetics
Concordance rate in twins- 50% vs. dizygotic twins- 10%
Advanced paternal age?
De novo mutations in paternal germ cells
Gender differences
Occurs equally in men and women
Age of onset: 15-25 years in men, 25-35 years in women
Women respond better to antipsychotic medication
Greater risk of tardive dyskinesia (TD) though
Cumulative days of D2 receptor (dopamine) drug blockade can lead to permanent movement disorder
Choreic movts
Athetotic movts
Most often oro-facially
45
environmental factors for schizophrenia
Viral infection and exposure to drugs during development have been implicated in the etiology of schizophrenia
Increased incidence when born in cold-weather months
Due to viral infections that occur seasonally?
Third-trimester maternal use of diuretics
Severe maternal HTN requiring use of diuretics
Anti- NMDA receptor antibodies??? In adults
46
Neurological Abnormalities
1. Abnormalities of the frontal lobes
- -> Decreased use of glucose in prefrontal cortex (hypofrontality)
2. Lateral and third ventricle enlargement
3. Abnormal cerebral symmetry (loss of asymmetry)
4. Changes in brain density
- -> Decreased volume of hippocampus, amygdala and parahippocampal gyrus
5. Decreased alpha waves, increased theta and delta waves and epileptiform activity on EEG
6. Abnormalities in eye movements (ex. poor saccadic smooth visual pursuit)
47
Neurotransmitter Abnormalities
| Dopamine Hypothesis:
- excessive dopaminergic (DA) activity in mesolimbic tract
1. Stimulant drugs, amphetamines and cocaine, can cause psychotic symptoms by amplifying this tract/pathway
2. Negative symptoms; may involve different abnormality of dopaminergic mechanism: hypoactivity of mesocortical dopamine tract/pathway
3. Elevated levels of homovanillic acid, a metabolite of DA in bodily fluids of patients with schizophrenia suggests more DA activity and use in the central nervous system (CNS)
48
in schizophrenia
the frontal is cold and middle is hot
49
pts of schizophrenia have more
light up in the fMRI (their amygdala has a stronger response to stimuli)
50
DA lives in
ventral tegmental area
51
what controls movement where low DA causes EPS, parkinsonism, dystonia, akathisia, neuroleptic malignant syndrome?
nigrostriatal pathway
52
what path is involved in controling prolactin secretion where low DA increases prolactin?
tuberoinfundibular path
53
what pathway is involved in negative and cognitive symptoms (path is inactive)
mesocortical pathway (treatment aim should be increase DA and neurotransmission)
54
what pathway is involved in positive symptoms (path is too active)
mesolimbic pathway (treatment aim should be slow down dopamine)
55
Glutamate Hypothesis
1. Glutamate (GLU) is the major excitatory neurotransmitter in the central nervous system
2. Antagonists of NMDA subtype of GLU receptors aggravate and create psychosis (ie. Ketamine, PCP) while agonists of NMDA receptors may experimentally relieve symptoms
3. In fact a leading hypothesis is the NMDA receptor (NMDAR) hypoactivity hypothesis
- NMDAR proteins, if mutated become ineffective or underactive
- If they sit on GABA interneurons positioned between a cortical GLU pyramidal neuron and its secondary neuron, a loss of inhibition occurs in the secondary GLU allowing excessive firing and ultimately an increase in firing in the VTA which sends extra DA into the limbic system thus causing psychosis
Perhaps the DA hypothesis, is created buy the GLU hypothesis
56
in schizophrenia the glutamate
transporter is hypoactive (loss of stimulatory function in schizophrenia) --> as a result DA spikes up!!!
57
normal function is
glutamate --> gaba --> glu --> DA
58
in schizophrenia what neuron is not working well?
bad receptors in GABA interneuron and hypofunctional NMDA receptors in prefrontal cortex
59
negative symptoms is due to
glu-gaba-glu-gaba-da
60
Differential Diagnosis
1. Psychotic disorder caused by a general medical condition
B12/Folate deficiency, temporal lobe epilepsy, cortico-steroid induced, etc…
2. Manic phase of bipolar disorder
3. Substance-induced psychotic disorder
Cocaine, crystal meth, ritalin/adderall(stimulants), ketamine, PCP, LSD, bath salts
4. Other psychotic disorders
Brief psychotic disorder (1-29 days of schizophrenia symptoms)
Schizophreniform disorder (1 month-6 months of symptoms)
Schizoaffective disorder (schizophrenia + mania and/or depression)
Delusional disorder (delusions, but no other schizophrenia symptoms)
Shared psychotic disorder (one person is delusional and a second person develops same delusion)
61
Brief psychotic disorder
(1-29 days of schizophrenia symptoms)
62
Schizophreniform disorder
(1 month-6 months of symptoms)
63
Schizoaffective disorder
(schizophrenia + mania and/or depression)
64
Delusional disorder
(delusions, but no other schizophrenia symptoms)
65
Shared psychotic disorder
(one person is delusional and a second person develops same delusion)
66
treatment for schizophrenia
All effective antipsychotics block D2 receptors in the mesolimbic DA path
Often a life long treatment
This does not lower DA availability, but blocks neurons from excessively firing even in the face of high DA concentrations
Traditional high- and low-potency (D2 receptor affinity) typical first generation antipsychotics (Prior to 1995)
haloperidol, chlorpromazine, respectively
High potency/affinity drugs are better at binding and sticking to D2 receptors and may cause more side effects in the nigrostriatal and tuberoinfundibular pathway (see above)
67
Treatment for schizo
1. All effective antipsychotics block D2 receptors in the mesolimbic DA path
2. Often a life long treatment
- This does not lower DA availability, but blocks neurons from excessively firing even in the face of high DA concentrations
3. Traditional high- and low-potency (D2 receptor affinity) typical first generation antipsychotics (Prior to 1995)
- haloperidol, chlorpromazine, respectively
- High potency/affinity drugs are better at binding and sticking to D2 receptors and may cause more side effects in the nigrostriatal and tuberoinfundibular pathway (see above)
68
Atypical second generation antipsychotics also block 5HT2a receptors (after 1995)
Clozapine, risperidone, paliperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, asenapine, iloperidone, lurasidone
First line agents due to fewer negative neurological effects such as parkinsonism or tardive dyskinesia
5HT2a blockade allows dopamine to more freely flow in the nigrostriatal path
69
Compliance rate is low due to unpleasant side effects (ex. fatigue, grogginess, sedation) and poor patient insight
Long acting injectable depot forms for noncompliant patients
Haloperidol decanoate, fluphenazine decanoate, (typical)
Risperidone, Paliperidone, and aripiprazole (atypical)
70
why would you use 2nd generation drug as a 1st line?
b/c of the fewer negative neurological effects such as parkinsonism or TD
71
Compliance rate is low due to unpleasant side effects (ex. fatigue, grogginess, sedation) and poor patient insight
Long acting injectable depot forms for
noncompliant patients
72
management of schizo
Provide long-term support for patient and family
Foster compliance with drug regimen
Types of psychotherapy:
Cognitive Behavioral Therapy (CBT)
Improve executive dysfunction
Memory, concentration, planning, prioritizing
Family Therapy
Peer and Mentor support or social skills Group
73
good prognosis of schizo
```
Good prognostic indicators include:
Female gender
Older age at onset
Married
Have social relationships
Good employment history
Presence of mood symptoms
Presence of positive symptoms
Few relapses
```
74
prognosis of schizo
Lifelong impairment, with chronic, downhill course in 90%
Often stabilizes in midlife, however, with more negative symptoms predominating
suicide is common in patients with schizophrenia
>50% attempt suicide, 10% die in the attempt
Post-psychotic depression
“Command” hallucinations
75
negative symptoms is associated with
mesocortical pathway (glu-gaba-glu-gaba-da)
76
positive symptoms is associated with
mesolimbic pathway (glu-gaba-glu-da)
77
in order to be qualified as schizophrenia, At least one episode of psychosis with persistent
disturbances of thought, behavior, appearance, speech and affect (emotion) as well as impairment in occupational and social functioning
78
In contrast to delirium or substance abuse, patients with schizophrenia do not have
clouding of consciousness
Attention and memory capacity typically intact, when not psychotic Alert and oriented, do not fluctuate in/out of consciousness/stupor
79
Women respond better to
antipsychotic medication
| Greater risk of tardive dyskinesia (TD) though
80
Cumulative days of D2 receptor (dopamine) drug blockade can lead to
permanent movement disorder
1. Choreic movts,
2. Athetotic movts
3. oro-facially
81
what are the neurological abnormalities of schizo?
1. abnormalities of the frontal lobes --> Decreased use of glucose in prefrontal cortex (hypofrontality)
2. lateral and third ventricle enlargement
3. abnormal cerebral symmetry
4. change in brain density (Decreased volume of hippocampus, amygdala, and parahippocampal gyrus)
5. decreased alpha waves, increased theat and delta waves and epileptiform activity on EEG
6. abnormalities in eye movements (Poor saccadic smooth visual pursuit)
82
Antagonists of NMDA subtype of GLU receptors
aggravate and create psychosis (ie. Ketamine, PCP) while agonists of NMDA receptors may experimentally relieve symptoms
83
In fact a leading hypothesis is the NMDA receptor (NMDAR) hypoactivity hypothesis NMDAR proteins, if mutated become ineffective or underactive
If they sit on GABA interneurons positioned between a cortical GLU pyramidal neuron and its secondary neuron, a loss of inhibition occurs in the secondary GLU allowing excessive firing and ultimately an increase in firing in the VTA which sends extra DA into the limbic system thus causing psychosis
Perhaps the DA hypothesis, is created buy the GLU hypothesis
84
Atypical second generation antipsychotics also block
5HT2a receptors
85
5HT2a blockade allows dopamine to more
freely flow in the nigrostriatal path
86
Brief psychotic disorder
(1-29 days of schizophrenia symptoms)
87
Schizophreniform disorder
(1 month-6 months of symptoms)
88
Schizoaffective disorder
(schizophrenia + mania and/or depression)
89
Delusional disorder
(delusions, but no other schizophrenia symptoms)
90
Shared psychotic disorder
(one person is delusional and a second person develops same delusion)
91
All effective antipsychotics block
D2 receptors in the mesolimbic DA path (positive symptoms)
BS
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