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Flashcards in Pyc 211 Schiz W13/1 Deck (21):
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Schizophrenia is NOT a split personality disorder, what it is is?

▪ Schizophrenia means ‘split mind’ but does NOT imply a split or multiple personality.
▪ The term ‘schizophrenia,’ coined by Eugen Bleuler (1857-1939), was intended to describe a separation of function between personality, cognition and perception.
▪ One percent of the worlds population is affected by schizophrenia.
▪ Typically begins in adolescence or early adulthood.
▪ Comorbid with depression, anxiety and substance abuse.
▪ Social problems include long-term unemployment, poverty and homelessness.
▪ Reduced life expectancy and high suicide rate.

1

Positive symptoms of scz include:

Positive symptoms are characterised by their ‘presence.’ They include:

1. Thought disorders - disorganised, irrational thinking:

2. Delusions - a false belief that is held with absolute conviction, is incorrigible and patently untrue.

3. Hallucinations - a false sensory perception in the absence of sensory stimulation.

2

Thought disorders - disorganised, irrational thinking: include

- Loose associations e.g. "The next day when I'd be going out you know, I took control, like uh, I put bleach on my hair in California.”

- Incoherence e.g. the question "Why do people believe in God?" elicits a response like "Because he makes a twirl in life, my box is broken help me blue elephant. Isn't lettuce brave? I like electrons. Hello, beautiful." Word salad

- Neologisms e.g. "I got so angry I picked up a dish and threw it at the geshinker."

Not speech disorders, but thought disorder.

3

Delusions - a false belief that is held with absolute conviction, is incorrigible and patently untrue. They include

- Persecutions - others are plotting or conspiring against him/ her (e.g., “My mother is trying to kill me.”)

- Grandeur - one’s power and importance e.g., “I am god.”

- Control - thoughts controlled by external means (e.g., thoughts are controlled by tiny radio receivers implanted in his/her brain).
- Delusional jealousy; erotomania; love somatic, oddly infected.

4

Hallucinations - a false sensory perception in the absence of sensory stimulation.

- Auditory - hearing voices when no-one has spoken. Often these voices tell the person to perform some act, or they can be quite derogatory.

- Visual - seeing patterns, lights or objects that aren’t there.

- Olfactory, gustatory and tactile hallucinations exist but these types are not common for schizophrenia although they might be related to a particular delusion (e.g. olfactory hallucinations contribute to delusions that others are trying to kill him/her with poison gas).

5

Negative Symptoms of Schizophrenia are?

▪ Negative symptoms are characterised by the ‘absence’ of behaviours that are normally present. They include:

- Flattened affect, emotional blunting
Alogia, poverty of speech
- Avolition, lack of drive
- Anhedonia, no pleasure

- Social withdrawal

- Cognitive symptoms
Failure to sustain attention
low psychomotor speed
deficits in learning and memory
poor abstract thinking
poor problem solving

Negative symptoms also found in PPP with brain damage.

6

People can have an unexpressed ‘schizophrenia gene’

▪ Some people are ‘susceptible’ to schizophrenia but do not express it.

▪ The incidence of schizophrenia is as great in the offspring of a nonschizophrenic member of a discordant monozygotic twin pair as in the schizophrenia member.

7

Discovery of the First Antipsychotic Drugs
***?

▪ Chloropromazine, initially used to reduce surgical shock, was found to have a calming effect on difficult-to-handle psychotic patients.
▪ Chloropromazine had a specific affect on schizophrenia: agitated schizophrenics were calmed by it whereas blunted schizophrenics were activated by it.

Chloropromazine and other antipsychotics (e.g. reserpine; α- methyl p-tyrosine) reduced positive symptoms by
antagonising dopamine transmission (Carlsson and Lindqvist, 1963).
▪ DA agonists (e.g. amphetamine, cocaine, methylphenidate, L- DOPA) lead to the production of positive symptoms which can be alleviated with antipsychotic drugs.

8

The Dopamine Hypothesis of Schizophrenia is..

▪ Positive symptoms of schizophrenia are caused by high levels of activity at dopamine receptors (Carlsson and Lindqvist,
1963).
▪ Dopamine binds to more than one dopamine receptor subtypes.
▪ The potency of haloperidol was due to its ability to bind to dopamine D2 but NOT D1 receptors. D2 high ventral striatum/accumbans. V1 in prefrontal area.
➔ Schizophrenia caused by hyperactivity specifically at dopamine D2 receptors (Snyder, 1978).

9

Relationship between dopamine release and changes in positive symptoms (Laruelle et al., 1996)

▪ Amphetamine causes more dopamine release in striatum in schizophrenic patients, non specific dopamine release.
Esp. More in stratum of scz
▪ Dopamine release is associated with a change in positive symptoms

10

Long-term drug treatment of schizophrenia

▪ Schizophrenic patients on a long-term treatment regimen show Parkinsonian symptoms (e.g. slowness in movement, lack of facial expressions, general weakness).

▪ A third of all patients show tardive dyskinesia; they are unable to stop moving, which is presumably caused by supersensitivity of the dopamine neurons in the striatum. Like pd ldopa issue

▪ Atypical antipsychotic medications (e.g. clozapine, resperidone, olanzapine) are the new class of drugs that help patients who are not significantly helped by the older ‘typical’ class of drugs.

11

The positive symptoms of schizophrenia may be related to the main function of dopamine: Reinforcement.
*****!

Positive symptoms may be caused by overactivity of synapses between dopaminergic neurons of the VTA and neurons in the nucleus accumbens (the mesolimbic pathway)

12

Schizophrenia as a Neurological Disorder

Abnormal Brain Development, sim. Brain injury!

Schizophrenia patients have large ventricles
In MZ twins discordant for schizophrenia, the schizophrenic twin has larger lateral ventricles.

The schizophrenic twin also shows a smaller anterior hippocampus and reduced volume of gray matter in the temporal lobe.

Ventricle size of schizophrenic patients ct scan was twice as great as that of normal control subjects.

13

Abnormal Brain Development associated with scz

Children who subsequently became schizophrenic showed more negative affect in their facial expressions relative to their siblings (Walker et al., 1994; 1996).

▪ Children born to schizophrenic parents who later became schizophrenic showed poor social functioning and adjustment, low psychomotor speed and performed poorly at school (Cannon et al., 1997; Schiffman et al., 2004).

➔ Although schizophrenic symptoms are not seen in childhood, the early brain development of children who later become schizophrenic is not entirely normal.

Review prenatal stuff!!! Toxemia etc. I guess.

14

Role of the Prefrontal Cortex in scz

▪ Schizophrenia is associated with abnormalities in the prefrontal cortex.
▪ Negative symptoms are caused by hypofrontality: decreased activity of the dorsolateral prefrontal cortex (Weinberger, 1988).

• Schizophrenic patients perform poorly on neuropsychological tests of prefrontal function.

15

Hypofrontality is caused by a?

‘decrease’ in dopamine release in the prefrontal cortex

▪ In monkeys, destruction of the dopaminergic input to the prefrontal cortex leads to cognitive dysfunction

▪ Infusing dopamine antagonists directly into the monkey dorsolateral prefrontal cortex produced cognitive impairments similar to those observed following prefrontal lesions

16

Effect of PCP on cognitive symptoms of scz?

▪ Phencyclidine (PCP) and ketamine (NMDA receptor antagonists) elicits the full range of symptoms of schizophrenia.

▪ PCP treated monkeys show ‘barrier reaches’ in the object retrieval task instead of normal detour reaches
(Jentsch et al., 1997). Barrier reach, hit box.
▪ Monkeys with prefrontal lesions also show impairments in this task (Diamond, 1997).
▪ Atypical antispychotics improve performance of PCP treated monkeys.

17

The role of NMDA in schizophrenia

▪ PCP causes hypofrontality.
▪ Dopamine and NMDA receptors are intimately related:
- NMDA receptor activation triggers the insertion of dopamine receptors into the membranes of dendritic spines;
- Activation of dopamine receptors increases NMDA receptor efficacy.
▪ Thus, by inhibiting NMDA receptors, PCP suppresses prefrontal activity either directly or indirectly via dopamine receptors

18

Why does hypoactivity of NMDA and dopamine receptors of the prefrontal cortex, cause positive symptoms of schizophrenia which are due to hyperactivity of the dopamine neurons of the mesolimbic pathway?

Prefrontal hypoactivity causes hyperactivity of the mesolimbic dopamine neurons

Why dealing with negative symptoms first is important, so positive do not arise.

19

The prefrontal cortex has excitatory and inhibitory connections with the VTA

▪ ▪
The prefrontal cortex sends glutamatergic (excitatory) neurons to the VTA which project back to the prefrontal cortex.

The PFC also forms synapses with GABAergic (inhibitory) neurons to the VTA which inhibit the dopamine neurons projecting to nucleus accumbens.

20

There is an inverse relationship between the prefrontal cortex and the nucleus accumbens


Stimulation of the prefrontal cortex inhibits the release of DA in the nucleus accumbens

By contrast, deactivating the prefrontal cortex (by infusing PCP or dopamine antagonists), increases dopamine release in the nucleus accumbens

Hypofrontality causes hyperactivity of the mesolimbic pathway which leads to positive symptoms.