Schizophrenia Flashcards
1
Q
Why are males more susceptible to schizophrenia?
A
- Males tend to have a more severe form of schizophrenia, with brain-imaging studies demonstrated more severe sz-associated brain anomalies. Females also tend towards a better clinical outcome.
- This may be due to sex hormones providing a protective role – declining levels of oestrogen often coincides with worsening of psychotic symptoms.
- Declining levels of oestrogen around menopause may also explain rates of late-onset sz in women. This late onset sz is also associated with more severe clinical presentation.
2
Q
Outline the controversy in diagnosing schizophrenia between DSM-IV and DSM-5.
A
The DSM-IV ignored cognitive symptoms despite:
- Decreased IQ
- Loss of recall
- Recognition memory
- Working memory
- Impairments in executive control (planning cognitive actions).
- Problems with attention
- Information processing
- Eye movements (altered smooth pursuit).
This is due to the idea that cognitive symptoms do not distinguish schizophrenia from other “boundary” disorders.
Removed subtypes
- Lack of clear distinctions between the various subtypes Issues with DSM-IV Criteria.
- These have poor diagnostic stability over time, people shift between subtypes.
- <5% research looked at subtypes.
- Hierarchical structure for those fitting >1 subtype, this was arbritary, narrow conception for a heterogeneous disorder.
- Subtypes not genetic.
- Can’t measure diagnostic features of subtypes.
3
Q
Outline hallucinations in schizophrenia.
A
Hallucinations:
- A sensory experience that seems real to the person having it, but occurs in the absence of any external perceptual stimulus.
- They can occur in any modality, but auditory hallucinations are by far the most common- being found in 75% of schizophrenic patients sampled (compared to 39% visual, and 1-7% tactile, olfactory, and gustatory).
- Patients can become emotionally involved in their hallucinations, often incorporating them into their delusions.
- People who consider themselves socially inferior perceive their voices to be more powerful and compelling than they are, and so behave accordingly (Paulik, 2011).
- Voices are often of people they know, but may be from God or the Devil.
- Most patients report hearing more than one voice, and that their hallucinations are worse when they’re alone.
- Most commonly, hallucinated voices utter vulgarities and expletives, were critical, bossy, or abusive, while others were pleasant and supportive.
4
Q
Outline delusions in schizophrenia.
A
Delusion:
- An erroneous belief that is fixed and firmly held despite clear contradictory evidence.
- People with delusions believe things that others who share their social, religious, and cultural backgrounds do not believe.
- 90% of schizophrenics experience delusions at some point.
- Certain types of delusions are more characteristic than others:
- Beliefs that their thoughts, feelings, or actions are being externally controlled.
- Thought broadcasting
- Thought insertion
- Thought withdrawal.
- Delusions of reference (some neutral environment such as a TV program is believed to have a special person or meaning).
- Delusions of bodily changes (e.g. removal of organs).
5
Q
Outline disorganised speech and behaviour in schizophrenia.
A
- Disorganised speech is the external manifestation of a disorder in thought form.
- Failure to make sense (despite conforming to semantic and syntactic rules) is not attributable to low intelligence, poor education, or cultural deprivation.
- This process has been referred to as “cognitive slippage”, “derailment”, “loosening” of associations, or even “incoherence”.
- Formal thought disorder refers to problems in the way that disorganised thought is expressed in disorganised speech.
- Disorganised behaviour manifests in many way:
- Goal-directed behaviour is almost universally disrupted, and is impaired in routine daily functioning. For example, they may not maintain minimal standards of personal hygiene.
- May be attributable to impairments in the PFC, disrupting executive functioning.
- Catatonia: Virtual absence of all movement and speech in what is called a catatonic stupor. May otherwise hold an unusual posture for an extended period of time without any seeming discomfort.
6
Q
Outline negative symptoms in sz.
A
- Negative symptoms reflect an absence or deficit of behaviours normally present, such as flat affect, alogia, avoliton, and anhedonia.
- In the case of flattened affect, while sz patients may not look as if they are experiencing as much emotion as controls when watching very positive or very negative film clips, as observed by researchers, they tend to report experiencing just as much emotion (Kring & Neale, 1996).
7
Q
Where do sz hallucinations stem from?
A
- Neuroimaging studies found that auditory hallucinations seem to stem from Broca’s area, rather than Wernicke’s area or the temporal lobe. T
- his pattern of activity is also seen when healthy volunteers are asked to imagine another person talking to them.
- This suggests that auditory hallucinations occur when patients misinterpret their own self-generated and verbally mediated thoughts.
8
Q
Outline and evaluate what twin studies have shown about sz..
A
- Being a twin does not increase one’s risk of developing sz, but there is a higher concordance for sz among MZ twins (28%) than among DZ twins (6%; Torrey et al. 1994). This suggests that a reduction in shared genes from 100% to 50% reduces sz risk by nearly 80%. MZ concordance has never been close to 100%. Two conclusions can be drawn from this:
- Genes undoubtedly play a role in sz.
- Genes themselves are not the whole story.
- Fischer (1971) reasoned that genetic influences, if present, would be just as likely to show up in the offspring of the twins without sz in discordant pairs, as they would be to show up in the offspring of twins with sz.
- This is indeed the case. Gottesman and Bertelsan (1989) reported an age-corrected incidence rate for sz of 17.4% for the offspring of MZ twins without schizophrenia, which was not significantly different from those with schizophrenia.
- Important to bear in mind that around 2/3 MZ embryos are monochorionic. 1/3 MZ embryos and all DZ embryos are dichorionic.
- As a result, because most MZ twins and DZ twins have differing prenatal environments, MZ concordance rates are likely to be vastly overestimated. Monochorionic MZ twins are much more likely to share infections, and are much more likely to develop sz than DZ twins.
9
Q
Outline and evaluate what adoption studies have shown about sz.
A
Twin studies assume that the MZ twin environment is equally as similar to the environment of DZ twins. However, it is reasonable to expect that the MZ twin environment will be more similar, and so to the extent that this is true, twin studies will overestimate concordance rates.
Adoption studies can overcome this limitation.
- Heston (1966) followed up 47 children born to hospitalised sz mothers who were fostered within 72 hours of birth. 16.6% of these children were later diagnosed with sz, compared to none of the 50 control children (residents of the same foster home). They were also more likely to be diagnosed as mentally retarded, neurotic, or psychopathic, had more criminal activities and spent more time in criminal institutions.
- This suggests that a genetic liability by the mothers was not specific to sz. HOWEVER, information about the fathers of the children was not provided.
10
Q
What has molecular genetics shown about schizophrenia?
A
- Likely that hundreds of genes could be implicated for sz.
- Researchers use DNA markers to learn where aberrant genes lie. DNA markers are known locations of some important genes associated with observable traits (e.g. colour blindness, blood group, human leukocyte antigen). Researchers can see whether schizophrenia co-occurs with any known DNA marker traits- this is linkage analysis.
- One example of a candidate gene is the COMT gene. This is located on no. 22 and is involved in dopamine metabolism. Children who have velocardiofacial syndrome, which involves deletion of material from no. 22 are at high risk of sz through adolescence. Furthermore, a particular variant of the COMT gene is implicated in increased likelihood of developing cannabis-induced psychosis.
- Other potential candidate genes are neuregulin 1, the dysbindin gene, the DISC1 B (Disrupted in Schizophrenia) gene, and several dopamine receptor genes. Genetic findings are frustratingly non-replicable and inconclusive.
11
Q
Why should we study endophenotypes in sz?
A
- Instead of focusing on less complex and more homogenous phenotypes (e.g. symptom clusters), researchers are beginning to explore endophenotypes- discrete, stable, and measurable traits thought to be under genetic control.
- Endophenotypic risk markers for sz include magical ideation, perceptual aberrations, and abnormal performance on measures of cognitive functioning. By studying these traits as opposed to the disorder of sz itself, research can be speeded up.
12
Q
Outline prenatal exposure risk factors in sz (viral infection, Rh pregnancy and birth complications, early nutritional deficiency, maternal stress).
A
Viral Infection
- In 1957 there was a major influenza epidemic in Finland.
- Elevated rates of sz were found in children born to mothers who were in their 2nd trimester at the time of the epidemic.
- Risk of sz seems to be highest in mothers who are infected with flu in the 4th-7th months of gestation.
- Small effect size.
- One possible explanation is that mother’s antibodies somehow disrupt foetal neurodevelopment as they cross the placenta. O
- ther viruses such as rubella and toxoplasmosis have been implicated.
Rhesus Incompatibility
- Rh incompatibility seems to be associated with increased risk for sz. Hollister, Laing, and Mednick (1996) found a 2.1% rate of schizophrenia in males who were Rh incompatible with their mothers, compared to 0.8% who were compatible.
- A possibility is that the mechanism involves hypoxia, increasing risk of brain abnormalities and birth complications.
Pregnancy and Birth Complications
- Patients with sz are much more likely to have been born following a pregnancy/delivery that was complicated in some way, for example, breech delivery, prolonged labour, wrapped umbilical cord, will affect the oxygen supply of the newborn.
Early Nutritional Deficiency
- The Hungervinter occurred at the end of WWII in the Netherlands. The population was severely malnourished, with many dying of starvation.
- Fertility levels and birth rate dropped precipitously.
- The children who were born during this time were at a 2x increase of sz.
- Early prenatal nutritional deficiency appears to have been the cause- it is unclear whether this was general or specific to nutrients like folate or iron.
Maternal Stress
- The death of a close relative during the 1st trimester was associated with a 67% increase in the risk of sz in the child (Khashan et al. 2008).
- May be that stress hormones passed to the foetus may negatively affect brain development, but this is not well understood.
13
Q
Outline the seasonality effect in sz.
A
- More schizophrenic births in winter effect, small effect but robust (birth dates of siblings show this is not a bias to procreate in summer).
- Seasonal Perinatal Risk Factors
- Link with winter births and viral events.
- Stress in pregnancy
- 67% increased risk of schizophrenia in offspring exposed to more stress in utero (Khashan et al, 2008)
- Risk signs include low birth weight, pre-eclampsia (hypertension in late stages of pregnancy).
- Perinatal complications
- Cannon et al (1993;2002) 3 classes of complications associated with increased risk of schizophrenia (but some evidence that only when a parent has schizophrenia):
- Complications of pregnancy.
- Abnormal foetal growth.
- Complications of delivery.
- Perinatal effect remains after socioeconomic status is accounted for.
- Birth complications more common in schizophrenic member of discordant twin.
- Cannon et al (1993;2002) 3 classes of complications associated with increased risk of schizophrenia (but some evidence that only when a parent has schizophrenia):
- Dutch famine study.
14
Q
Outline and evaluate the neurodevelopmental perspective of sz (prodromal stage).
A
- Current belief is that sz is an illness that develops early, but symptoms do not become apparent until early adulthood- when the brain finally fully matures.
- Some genes implicated in schizophrenia are known to play a role in brain development and neural connections.
- Cell migration may be impaired, resulting in abnormal internal connectivity in the brain. This occurs in the second trimester (when maternal influenza is most devastating).
- There are even early indications of schizophrenia in children. Family home movies made during the childhoods of 32 people who eventually developed sz. Trained observers made “blind” ratings of certain dimensions such as emotion and facial expressions, motor skills, and neuromotor abnormalities of these children and their healthy outcome sibling in the same clips. Pre-schizophrenic children had significantly more motor abnormalities (especially hand movements), and showed more negative facial emotion and less positive. In some children, signs were seen as early as age 2.
- Other evidence of prodromal signs of schizophrenia has come through prospective research (both with high genetic risk and normal risk children).
- Erlenmeyer-Kimling et al (1998) reported that of an initial group of 51 high-risk children, 10 developed sz or sz-like psychosis as adults. Of these, 80% showed unusual motor behaviour when they were between 7-12 years old.
- Mittal et al. (2008) found that high-risk adolescents showed more motor abnormalities (facial tics, blinking, tongue thrust) than either nonclinical controls or adolescents with personality or behavioural problems. Motor abnormalities is how schizotypal brain abnormalities may first manifest.
15
Q
What do szs show in neuropsychological measures. Evaluate these measures.
A
- Szs perform much worse on neuropsychological tests than do controls, implicating a wide range of brain regions. This is not due to the effects of extended hospitalisation/medication (recent patients tested perform the same).
- Szs have a deficit in reaction time.
- They also show deficits on the Continuous Performance Task, demonstrating impairments in attention.
- There are also problems with working memory (Barch, 2005), displaying less prefrontal activity than healthy controls.
- 54-86% of szs show eye-tracking dysfunction, and are deficient in their ability to smoothly pursue a moving target such as a pendulum (Cornblatt et al. 2008). 50% of first degree relatives of szs show this deficiency too.
- The psychophysiological measure P50 (Heinrichs, 2001) presents two clicks heard in close succession. Normally, the brain will produce a positive electrical response 50ms after each click. In normal controls, the response to the second click is dampened, or “gated” as the brain habituates. Many patients with schizophrenia, however, display poor P50 suppression. First degree relatives of szs are more likely to have this as well. This may be due to compromise in the hippocampus (one of the areas most susceptible to early hypoxic damage).
- Some szs exhibit hypofrontality when involved in tasks like the WCST. In others, hyperactivity of the frontal lobe is displayed- showing they have to work harder to be successful at the WCST. In both circumstances, the brain is not functioning optimally. Again, neither unique nor universal. Most important problem is the way activity in different brain regions is coordinated. Schizophrenics appear to have difficulty disengaging from the “default mode network” (Guerrero-Pedrazza et al. 2011).
