Psychotic disorders

Question 1

Discuss the diagnostic criteria for schizophrenia, its prevalence, and usual age of onset.

Answer 1

1% worldwide, early age of onset
Characteristic symptoms, generally 2 required for at least one month: Delusions, Hallucinations, Disorganized speech
Grossly disorganized or catatonic behavior, Negative symptoms such as affective flattening, Social/occupational dysfunction in work, interpersonal relationships, or self care
Duration of symptoms, in full or attenuated form, for at least 6 months
Mood disorder has not played a prominent role in the illness. Illness is not due to a medication or other medical condition or substance abuse Illness is not part of autism or other pervasive developmental disorder

Question 2

Discuss the proposed causes of schizophrenia, including genetic and environmental factors.

Answer 2

Overall, the relationship between genotype and pheno
type in schizophrenia is likely mediated by
multiple genes interacting with each other (gene-gene) and the environment (gene-environment} leading to disruption of normal brain development and maturation.

Question 3

Discuss the proposed role of the Dopamine neurotransmitter and neural circuits involved.

Answer 3

Mesolimbic System:
dopamine neurons from the ventral tegmental area (VTA) release dopamine to the nucleus accumbens. This system regulates reward pathways and emotional processes and is associated with the positive symptoms of schizophrenia
Mesocortical System: dopamine neurons from the VTA and the substantia nigra. The VTA neurons included in the mesocortical system release dopamine to the prefrontal cortex and regulate areas involved in cognitive processing (i.e. the dorsal lateral prefrontal cortex that regulates executive function). The neurons in the substantia nigra release dopamine to the basal ganglia and regulate areas involved with motor control. The mesocortical system is associated with the negative symptoms of schizophrenia.

Question 4

Clozapine

Answer 4

atypical-2nd gen neuroleptic less parkinsonian effects
S/E agranulocytosis
blocks several classes of receptors for
5HT, NE, ACH, and dopamine, has weaker dopaminergic blockade than most other neuroleptics.

Question 5

Discuss the proposed role of the Glutamate neurotransmitter and neural circuits involved

Answer 5

Prolonged exposure to NMDA receptor antagonists such as phencyclidine (PCP) has been associated with chronic, severe psychotic illness displaying both the positive and negative symptoms of schizophrenia. Ketamine, which is also an NMDA antagonist drug, produces transient, mild psychotic symptoms, negative symptoms, and cognitive deficits in normal subjects, mimicking schizophrenia. Glutamate can bind to dopamine neurons and is hypothesized to produce regional hyperactivity and hypoactivity in dopamine neuron release. Chronic NMDA antagonist administration results in persistent elevationof dopamine release in the nucleus accumbens (mesolimbic system) and decreases in dopamine release in prefrontal cortex (mesocortical system). Because NMDA antagonists produce schizophrenic-like symptoms, schizophrenia may be a result of glutamatergic hypoactivity.

Question 6

Other atypical Neuroleptics

Answer 6

risperidone, olanzapine, quetiapine, asenapine, and
ziprasidone have been synthesized to mimic clozapine’s blockade of serotonin 5HT-2 receptors.
Aripiprazole also has an atypical profile, but it is a mixed dopamine agonist and antagonist.
S/E most of the atypical drugs have
enhanced effect on appetite, weight gain, hypercholesterolemia, and diabetes mellitus

Question 7

1st generation neuroleptics

Answer 7

Basic types are phenothiazines (chlorpromazine and perphenazine), thioxanthines (thiothixine), and butyrophenones (haloperidol). All these drugs are highly lipophilic, slowly excreted, t 1/2 over 24 hours after chronic administration. There is no tolerance to therapeutic effects.
dopamine D2 receptor
S/E Parkinsonian syndrome and tardive dyskinesia, became more problematic. Tardive dyskinesia is a choreoathetosis that is associated with increased dopamine neurotransmission. After years of chronic blockade by antipsychotics, dopamine receptors on the caudate and putamen (but fortunately not in the cerebral cortex) increase in number, an example of denervation suspersensitivity, and patients develop tardive dyskinesia.