Schizophrenia 1

Question 1

What did Emile Kraepelin say about schizophrenia?

Answer 1

First to identify it in 1887, characterised by ‘cognitive disintegration’. Called it ‘dementia praecox’ (early dementia) to distinguish from other dementia.

Question 2

What did Eugen Bleuler say about schizophrenia?

Answer 2

Thought term ‘dementia praecox’ was misleading, as was different from dementia, so in 1908 coined term ‘schizophrenia’ to indicate the splintering of the psyche. Also classified symptoms as ‘positive’ or ‘negative’.

Question 3

What are non-affective psychotic disorders (DSM)?

Answer 3

Schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, brief psychotic disorder, psychotic disorder not otherwise specified.

Question 4

What are affective psychoses (DSM)?

Answer 4

There is a component that overlaps with mood disorders: bipolar disorder with psychotic features, major depressive disorder with psychotic features.

Question 5

What are substance-induced psychotic disorders (DSM)?

Answer 5

Alcohol-induced, other substance-induced. Psychotic disorder due to a general medical condition.

Question 6

What are positive symptoms of schizophrenia?

Answer 6

Delusions, hallucinations, illusions, disorganised thinking (speech) - leads back to definition of ‘split brain’, grossly disorganised or abnormal motor behaviour. Considered positive because the individual is showing something that would not appear in ‘normal’ individuals.

Question 7

What are negative symptoms of schizophrenia?

Answer 7

Diminished emotional expression, avolition (decrease in motivation), alogia (poverty of speech), anhedonia (the inability to feel pleasure), asociality (people who isolate themselves). Two most prominent negative symptoms are diminished emotional expression and avolition.

Question 8

What is the DSM-5 diagnostic criteria for schizophrenia?

Answer 8

2 or more of following signs and symptoms present for a significant portion of time during 1-months. At least 1 must be 1, 2, or 3.
1. Delusions 2. Hallucinations 3. Disorganised speech 4. Grossly disorganised behaviour or catatonic motor behaviour 5. ‘Negative’ symptoms. Impaired functioning in one or more major areas (e.g., work, interpersonal relations, self-care). Continuous signs of the disturbance for at least 6 months (including at least 1 month of symptoms listed in A). Exclusion of other possible causes of the above symptoms (e.g., drugs, medical conditions, schizoaffective disorder, depressive or bipolar disorders). There are some substances that can stimulate a psychotic episode out of the blue.

Question 9

What are delusions?

Answer 9

Fixed beliefs not amendable by conflicting evidence. Fixed beliefs about something you experience in reality.

Question 10

What are the themes of delusions?

Answer 10

Persecutory (one of more frequent, e.g. believing someone is trying to harm you), referential (also frequent, actions and gestures of strangers believed to have special relevance to patient), grandiose, erotomatic, nihilistic (distractive delusions), somatic (delusions about body), religious.

Question 11

What are hallucinations?

Answer 11

Abnormal perceptual-like experiences that occur in the absence of external stimuli. Can be sensory, auditory more common. Similarities in voice hearing in individuals - loudness, location, number of voices, personification, gender, identity, underlying brain activity. Differences - not everyone has distress, varying pitch, some do not exert power on the individual.

Question 12

What are illusions?

Answer 12

Disturbances in perception that are less intense than hallucinations. Something in reality that is actually there, but the perception is not right, e.g. something louder/sharper, colours appear brighter, objects seeming closer/further away, own voice/reflection seem threatening.

Question 13

What is disorganised thinking?

Answer 13

Reflects disorganised speech, with flight of ideas, preservation, and loose associations to the point of incoherence (word salad) - sentences / phrases loosely connected, devoid of overall meaning. Reflected in speech production.

Question 14

What is grossly disorganised/abnormal motor behaviour?

Answer 14

Tics, mannerisms (ordinary movement that becomes abnormal through exaggeration or repetition), stereotypies (frequent repetition of action that serves no obvious purpose), catatonia (psychomotor immobility to reduced mobility), grimacing, posturing (assuming unusual position or contortions), and echopraxia (meaningless repetition or imitation of the movements of others).

Question 15

What is diminished emotional expression (negative symptom)?

Answer 15

Reduction in the expression of emotions in the face, eye contact, intonation of speech, and movement of the hand, head, and face that give an emotional emphasis to speech.

Question 16

What is avolition (negative symptom)?

Answer 16

Decrease in motivation, self-imitated purposeful activities. The individual may sit for long periods of time and show little interest in participating in work or social activities.

Question 17

What is alogia (negative symptom)?

Answer 17

Diminished speech output.

Question 18

What is anhedonia (negative symptom)?

Answer 18

Decreased ability to experience pleasure from positive stimuli and/or degradation in the recollection of past pleasurable experience.

Question 19

What is asociality (negative symptom)?

Answer 19

Reduced social interactions for lack of interest (evolution) and/or for reduced opportunity to meet others.

Question 20

What is cognitive impairment?

Answer 20

Despite Kraepelin’s original terms ‘dementia praecox’, for a long term cognitive impairment has been a neglected component. Impairments seen across all domains of learning and memory, with a disproportionate involvement of semantic memory, working memory and attention (1-2 SD below average). Also the IQ is reduced.

Question 21

What are depressive symptoms?

Answer 21

Often associated especially during the Prodrome Phase. Depressive symptoms may be an integral part of schizophrenia, or a response to the post-psychotic phase, or even a side-effect of medications.

Question 22

What is olfactory dysfunction?

Answer 22

A number of parents exhibit a deficit in the ability to identify odours and to memorise them.

Question 23

What is water intoxication?

Answer 23

A few patients with chronic schizophrenia drink excessive amounts of water (even from unsuitable sources) and develop ‘water intoxication’, leading to hyponatraemia, cerebral oedema, seizures, coma, and even death.

Question 24

What is pain insensitivity?

Answer 24

A few patients with schizophrenia exhibit diminished sensitivity to pain, sometimes to an extreme degree.

Question 25

What are difficult diagnostic issues?

Answer 25

There are no exact boarders for schizophrenia relative to other mental disorders. There is overlapping of other disorders. Some question the term ‘schizophrenia’ - it being a single condition. Because can see delusions etc. in ‘normal’ individuals, it leads to doubts in the diagnosis.

Question 26

What is the prevalence of schizophrenia?

Answer 26

Can begin at any stage of life, usually between 15 and 54 years, with a peak in the mid-twenties for men and broader range of age for women (who have a second peak in their mid-forties). Can fluctuate between periods of remission and periods of psychosis.

Question 27

What are environmental risk factors?

Answer 27

Obstetric complications (e.g. low birth weight and blood type incompatibility) double the risk, maternal influenza/other infections increase the risk, maternal malnutrition (mothers who experience famine early in pregnancy) twice as likely, winter birth (slightly more frequent), paternal age (risk increases with paternal age, but only for 1st born, 50% increase for each 10-year increase), urbanisation (2x risk in urban areas), and migration (risk 2-5 times higher in immigrants).

Question 28

What are antipsychotic drugs?

Answer 28

All antipsychotic drugs block dopamine receptors. If drugs work, this is highly correlated with affinity with D2 receptors - prevent dopamine from binding to receptor - these are clinically affective. D2 is a sub-type of dopamine receptors.

Question 29

What are dopaminergic alterations?

Answer 29

Effectiveness of drugs discovered by chance. Lead to discovering of dopaminergic receptors. Dopaminergic neurones exist between 2 main areas - substantia nigra and VTA, and they protect to the cortex and subcortical region, especially in the striatum. The striatum can be divided into different regions - ventral striatum and dorsal striatum. Dopamine in VTA projects primarily to ventral striatum, dopamine in the substania nigra project mainly to the dorsal striatum.

Question 30

What has PET imagine of dopaminergic alterations shown?

Answer 30

Antipsychotic receptors bind to receptor and prevent dopamine from binding.

Question 31

What are main dopaminergic alterations in SZ?

Answer 31

Increased DA synthesis and release in the striatum (even though dopaminergic innervation is normal). Most prominent in the associative striatum, effect size 0.70, which includes the dorsal striatum. Less prominent in the sensorimotor striatum: effect size 0.34, and in the limbic system: effect size 0.14. DA release in the prefrontal cortex and other extra-striatal regions is decreased or normal. Striatal post-synaptic D2 receptors are upregulated in individuals receiving antipsychotic treatment. Upregulation of post-synaptic beta receptors. Results not consistently reproduced, but general agreement that there is a reduced dopamine release in the prefrontal cortex. Excessive dopamine levels in the striatum reduce dopamine levels in the cortex.

Question 32

What did Lindsröm et al. 1999 find?

Answer 32

Aim to investigate dopamine synthesis not just in the striatum but also in the prefrontal cortex. Results indicate that the synthesis of dopamine is elevated within the striatum and parts of medial prefrontal cortex in schizophrenia. Dopamine synthesis in the striatum is elevated in schizophrenia.

Question 33

What did Seeman and Kapur (2000) find?

Answer 33

More dopamine, more D2 receptors. Found an increased occupancy of dopamine D2 receptors in schizophrenia.

Question 34

What are dopaminergic alterations and symptoms of SZ?

Answer 34

Excess DA release correlated with the intensity of psychotic symptoms and with the effectiveness of antipsychotic drugs in the reduction of the disease. Excess DA release not observed during remission - very mild symptoms mean see much less dopamine release – symptoms fluctuate with dopamine released. More dopamine in the striatum of people with schizophrenia, more dopamine receptors, this is associated with more symptoms and more successfulness of antipsychotic meds.

Question 35

What are key dopaminergic pathways?

Answer 35

Evidence for the dopaminergic hypothesis. Projection from striatum to VTA, and then VTA to NAcc, and to the prefrontal cortex. Also projections that are completely separate from this, e.g. from the hypothalamus to the pituitary gland.

Question 36

What pathway causes positive symptoms?

Answer 36

Projection from the substantia nigra - striatum, and VTA - NAcc. Much more dopamine in the striatum, because dopamine system is hyperactive, which leads to positive symptoms.

Question 37

What pathway causes negative symptoms?

Answer 37

Another pathway - VTA to the prefrontal cortex, in particular the dorsal lateral prefrontal cortex and the ventral medial prefrontal cortex. Less dopamine in those with schizophrenia, which is responsible for the negative, cognitive, and affective symptoms = hypoactivity (less activity).

Question 38

What is the dopaminergic Hypothesis of schizophrenia?

Answer 38

Both mesolimbic and nigrostriatal pathways lead to positive symptoms - hyperactive. Administer anti-psychotic drugs that block beta receptors, so that dopamine cannot bind. Lead to improvement in symptoms. Antipsychotics don’t work for negative symptoms - mesocortical pathways to DLPFC and VMPFC.

Question 39

What does dopamine do in schizophrenia?

Answer 39

James Olds and Peter Milner discover electrical brain stimulation (1954) - discovered when place electrodes in rat brain, they self-stimulate (press things to activate electrodes). Positioning of electrodes critical - increases release of dopamine. Rewarding effect linked to dopamine release in the striatum, in particular the ventral striatum. Found if you impair dopamine system, you impair the reward system.

Question 40

What is the Michigan model of motivation (traditional view)?

Answer 40

Concieved of reward as a unitary phenomenon - found the effect pleasurable, so the lever became an incentive salience. The two things went together - the pleasure and the lever.

Question 41

What is the Michigan model of motivation (Berridge and Robinson)?

Answer 41

Distinguished various components of reward: pleasure aspect, and incentive salience attributer. The two processing are separated. Incentive-salience attributer leads to incentive CS, to wanting, which leads to subjective craving attraction, and elitict consumption. Please integrator leads to pleasant UCS, to liking, to subjective pleasure.

Question 42

How is the incentive salience attributor linked to the dopaminergic system (the Michigan model of motivation)?

Answer 42

The incentive salience attributor coincides with the dopaminergic system. The attributor of this depends on dopamine transmission (more leads to excessive salience to certain stimuli). Therefore, if have schizophrenia, delusion is a cognitive scheme to explain the excessive salience of normal stimuli (e.g. of a stranger) caused by high dopamine transmission. Anti-psychotic reduces the incentive salience because it blocks dopamine, and this therefore reduces delusions.

Question 43

What is the explanation of hallucinations (the Michigan model of motivation)?

Answer 43

Schizophrenia have an abnormal internal monologue. If have hyperactivity of dopaminergic system, have full-blown auditory hallucinations, which are salient as you pay lots of attention to it, until you take anti-psychotics: hear voices, but don’t pay much attention to it. Dopamine doesn’t create the hallucination, but creates its salience: anti-psychotics reduce this salience, make them less distressing. Same with visual hallucinations.