Schizophrenia

Question 1

What are all of the dimensions that Schizophrenia impacts and a way to understand the disorder?

Answer 1

It is a debilitating disorder that involves disturbance in almost every dimension of human function:
perceptions, thoughts, behaviour, emotions and language and impacts on social relationships and occupational functioning

Question 2

In terms of the features of Schizophrenia, what is the prevalence, mean age of onset and how this onset is understood?

Answer 2

~0.2 - 2.0% of general population (lifetime risk ~0.7%)

Mean age of onset:
Males = 26.5 years and females = 30.6 years - early manifestations in childhood

Onset:
either actor, or emerges gradually from prodromal phase; typically adolescence/ young adulthood

Question 3

In terms of the features of Schizophrenia, what is the illness course and data on remission and relapse?

Answer 3

Illness course:
generally, acute episodes of florid illness superimposed upon relatively stable periods with persisting disability

remission and relapse:
83% achieve at least partial remission during first year of treatment - 82% experience at least one relapse after remission

Question 4

What is the life course of schizophrenia?

Answer 4

Episodes become more sever, and speed and extent of recovery less after arch episode; but after several decades, illness tends to wane

Question 5

What are the phases of schizophrenia in terms of the illness course?

Answer 5

Negative symptoms gradually increase from prenatal to prodrome period of development.

Positive symptoms peak at the first-episode of psychosis just after the prodrome phase. This is were treatment is begun, followed by a relapse and then a reduction in the chronic phase of psychosis.

Question 6

What are some factors that contribute to the relapse in schizophrenia?

Answer 6

Treatment discontinuation, substance use and stress

Question 7

How do people generally try to treat schizophrenia prior to the prodromal stage? (before diagnosed illness)

Answer 7

Talk therapy without pharmacological intervetions. Here, schizophrenia is usually benign and there is mixed outcomes for “catching” schizophrenia in this period. There is usually a continuation of symptoms leading to the first-episode. There is usually better outcomes if treatment is begun after the first-epidote.

Question 8

What is the diagnostic criteria of schizophrenia in the DSM5?

Answer 8

at least 2 of the 5 symptoms to be present for a month or longer:
1. delusions
2. hallucinations
3. disorganised speech
4. disorganised or catatonic behaviour
5. negative symptoms
PLUS and impairment in work, interpersonal or self-care functioning

Question 9

What is the diagnostic criteria in the ICD-11?

Answer 9

At least two of the following over a month period.
1. persistent delusions of any kind
2. Persistent hallucinations in any modality
3. Thought disorder
4. Distortions of self-experience (e.g. passivity phenomena, thought intersection or withdrawal)
5. Negative symptoms such as apathy and anhedonia
6. Disorganised behaviour, including odd, eccentric, aimless, and agitated activity
7. Psychomotor disorders
All not due to medication or another disorder

Question 10

The heterogeneity of the clinical presentation of schizophrenia makes it likely that several different pathophysiological processes might contribute to the illness. What are the positive and negative symptoms?

Answer 10

Postive:
Reflect and excess of behaviour not usually seen or the presence of an abnormal mental process (delusions, hallucinations, disorganised speech or behaviour) - most prominent during acute phase of illness

Negative:
Reflect diminution/absence of a mental function that is normally present (apathy, flat affect, social withdrawal, lack of spontaneous movement) - tend to be chronic

Question 11

What is a summary of Positive and negative symptoms?

Answer 11

Positive - symptoms that are not always there
Negative - Always there in the background and cause issues in day to day functioning

Question 12

What are delusions described as clinically?

Answer 12

1. Erroneous/ logically inconsistent beliefs
2. Held with fixed, intense conviction
3. Inconsistent with social, educational, and cultural background
4. Can be transitory or permanent
5. Arise form altered experience of self/external reality

Question 13

What are persecutory delusions?

Answer 13

Most common form - belief that they are being mistreated or that someone is spying or planning to harm them

Question 14

What are grandiosity delusions?

Answer 14

Over-inflated sense of self-worth, talent, power, knowledge or identity

Question 15

What are delusions of control?

Answer 15

belief that thoughts or behaviours are controlled by external forces

Question 16

What are somatic delusions?

Answer 16

Belief of having a physical defect or medical problem

Question 17

What is thought broadcasting?

Answer 17

Belief that other people can read their mind or hear their thoughts

Question 18

What is thought intersection? (type of delusion)

Answer 18

Belief that one’s thought are not one’s own, but rather belong to someone else and have been inserted into one’s mind

Question 19

What is thought withdrawal? (type of delusion)

Answer 19

Belief that thoughts have been ‘taken out’ of their mind, and they have no power over this

Question 20

What is the clinical definition of hallucinations?

Answer 20

False sensory perception, experienced as real, but not based on external stimuli in any sensory modality.

Question 21

Auditory hallucinations are the most common form of hallucinations, how can they be described?

Answer 21

Voices - single words, voices commenting, voices conversing, hearing thoughts aloud
music or other sounds people can’t hear

Question 22

How can visual hallucinations be characterised?

Answer 22

Seeing objects, people, lights or patterns that others can’t see

Question 23

How can somatic hallucinations be characterised?

Answer 23

Sensation occurring in the body (e.g, worms inside intestines)

Question 24

How can tactile hallucinations be characterised?

Answer 24

Sensation involving sense of touch (e.g. burning or itching of skin)

Question 25

How can olfactory hallucinations be characterised?

Answer 25

Smelling odours others can’t smell

Question 26

How can gustatory hallucinations be characterised?

Answer 26

Distortions of taste that occur in the absence of any food or beverage.

Question 27

In formal thought disorders, which is a disorder form and flow of thought (structure, organisation and coherence) - how do they manifest as positive and negative thought disorders?

Answer 27

it is usually a “loosening of associations”

Positive - derailment, tangentiality, incoherence, loss of goal, incoherence, stilted speech, concrete thinking, perseveration circumstantiality

Negative - poverty of speech (alogia); poverty of content of speech

Question 28

In terms of emotional disorder, what are the four ways that we can see this affect in schizophrenia?

Answer 28

1. Blunted affect - decreased responsiveness to emotional issues
2. Depression
3. Inappropriate affect - inappropriate for the circumstance
4. Excitation - irritability, sleeplessness, agitation, and motor overactivity

Question 29

In terms of the motor/behavioural disorder seen in schizophrenia, how can it be characterised?

Answer 29

Subtle disturbances of motor co-ordination is common, catatonic is rare. Seen as:
Hyporeactive (stupor/unresponsive)
Hyperactivity (stereotypic activity, waxy, flexibility, mimicry

Question 30

What are disjointed and weakened volitional/motivational disorder?

Answer 30

Disjointed - poorly organised, ill-judged activates which appear to be prompted to impulse

Weakened - prolonged periods of under activity (lack of drive/motivation)

Question 31

What is a lack of insight?

Answer 31

Failure to accept one is ill and to appreciate that symptoms are due to illness

Question 32

Although the complete aetiology of schizophrenia is unclear, what is the current understanding of its basis? (made of two major factors).

Answer 32

Biological
- Genetics
- abnormalities of brain structures and function
- Neurotransmitter abnormalities

Psychosocial factors (environment)

Question 33

What is the neurodevelopment hypothesis of schizophrenia?

Answer 33

Brain development disruptions during early life contribute to the later onset of psychosis in adulthood, possibly with an additional trigger in adolescence. Various brain functions develop at different stages, and in schizophrenia, the functional consequences may be more disordered as functions come online later in life. This concept is known as the developmental Risk Factor Model.

Question 34

What were the key findings regarding neurodevelopmental brain structure based on analysing changes in cortical thickness? - this is regionally dependent

Answer 34

1. differing levels of complexity of cortical growth, across the cortex
2. Regions with simple laminar architecture (limbic areas) show simpler growth trajectories
3. Polysensory and higher-order association areas (the most complex areas in terms of laminar architecture) have the most complex developmental trajectories

Question 35

What does “cubic” refer to in terms of schizophrenia neurodevelopmental structure?

Answer 35

“Cubic” describes a non-linear pattern of brain development or functioning in schizophrenia, indicating rapid changes or increases in specific neural processes or structures during certain stages of development.

Question 36

What does “quadratic” imply in terms of schizophrenia neurodevelopmental structure?

Answer 36

“Quadratic” suggests a non-linear pattern of brain development in schizophrenia, indicating more pronounced changes or alterations in neural processes or structures during specific periods of development.

Question 37

What does “linear” indicate in terms of schizophrenia neurodevelopmental structure?

Answer 37

“Linear” refers to a steady and predictable progression of neural processes or structures over time without significant deviations or sudden changes in individuals with schizophrenia.

Question 38

What happens during neurodevelopment in relation to brain function, and what are the key characteristics of schizophrenia in terms of onset and affected brain areas?

Answer 38

Neurodevelopment refines brain function as regions mature. Schizophrenia begins in conception and birth, impacting parietal and temporal lobes. Symptoms persist into the “first-episode” in adolescence, progressing to a chronic condition in adulthood. Schizophrenia mainly affects executive functioning and working memory, distorting normal developmental consolidation.

Question 39

In the Developmental Risk Factor Model of Schizophrenia, what are the three major variables that contribute to both onset and course of schizophrenia?

Answer 39

Conception, birth factors
- maternal illness during pregnancy, obstetric complications, psychological factors

Demographic or familial risk factors
- Maternal/paternal age at birth, socio-economic status, urbanity, migration and ethnicity, family factors such as expressed emotion, childhood adversity/trauma

Childhood and adolescent risk factors
- childhood illness, substance misuse

Remember: It is not these experiences in isolation, but rather an accumulation of them with genetic interaction that could lead to schizophrenic vulnerability

Question 40

What is the hypothesis about schizophrenia as a neurodevelopmental disease, and what are the key findings related to neuronal processes and connectivity?

Answer 40

Neurodevelopmental disease due to abnormalities in cortical neuronal migration. Key findings include deficits in neuronal processes, synaptic connectivity, and abnormalities in the limbic system. There is also an abnormally high frequency of aberrant neurons in the white matter underlying the prefrontal cortex, temporal, and Parahippocampal regions, suggesting connectivity issues.

Question 41

The findings in the literature show that schizophrenia is not a neurodegenerative disease but rather a neurodevelopment one. What are the three components of a neurodegenerative disease that are lacking in schizophrenia?

Answer 41

1. Inclusion bodies
2. Dystrophic neuritis
3. Reactive gliosis

Question 42

Why is it that monozygotic twin populations have the largest hereditary component of all mental illnesses and thus schizophrenia concordance?

Answer 42

Because they share 100% of their genes, the likely hood is far higher. It is not 100% schizophrenic concordance due to environmental factors.

Question 43

An adoption and family studies, why are the mental illness rates higher?

Answer 43

Adoption: rates are higher in children of parents than control adoptees but to biological family pattern

Family studies: Risk increases proportionate to familial proximity and number of affected relatives

Question 44

In terms of heritability of schizophrenia, what is important to understand?

Answer 44

What you are inheriting is not schizophrenia, you are inheriting a vulnerability to schizophrenia. You can carry all of the risk however other things might determine if you express the illness.

Question 45

What is the purpose of linkage analysis in studying schizophrenia, and what are some key findings and challenges associated with it?

Answer 45

Linkage analysis in schizophrenia aims to identify genomic regions associated with the disorder, without pinpointing specific allelic variants. Key findings suggest that multiple chromosomal regions may contain susceptibility loci. However, replication difficulties arise due to being underpowered to address genomic loci with small effects.

Question 46

What is the purpose of genome-wide association studies (GWAS) in schizophrenia research, and what are some key findings?

Answer 46

GWAS in schizophrenia aim to identify allele variants more frequent in patients. They have identified over 100 risk loci associated with schizophrenia, including genes related to dopamine receptors, glutamatergic neurotransmission, synaptic plasticity, and central immune functions (DISC1, NRG1, COMT, and DTNBP1). These loci have small individual effects on susceptibility.

Question 47

What is the “common disease, common variants” hypothesis in schizophrenia research, and what are some key aspects related to it?

Answer 47

The hypothesis suggests that schizophrenia is mainly associated with common genetic variants (SNPs). Over 100 risk loci have been identified. Polygenic risk scores, based on thousands of common alleles with small effects, contribute to schizophrenia risk. However, common variants explain only a portion of schizophrenia heritability, cumulatively accounting for about 1/4 to 1/2 of the genetic liability variance.

Question 48

What is the “common disease, rare variants” hypothesis in schizophrenia research, and what are some examples of these variants?

Answer 48

The hypothesis suggests that schizophrenia involves rare genetic variants with larger effects. Examples include rare copy number variants (CNVs), single nucleotide variants (SNVs), and small insertions/deletions (indels). These variants are found in a small percentage of individuals with schizophrenia.

Question 49

In epigenetic mechanisms of schizophrenia, what are the three groups of mechanisms examined?

Answer 49

1. DNA methylation
2. Histone modifications
3. Non-coding microRNA’s

Question 50

In epigenetic mechanisms of schizophrenia, explain DNA methylation?

Answer 50

It blocks the binding of transcription at gene promoters and laters chromatin structure and thereby regulates gene expression and gene silencing.

Question 51

In epigenetic mechanisms of schizophrenia, explain Histone modifications?

Answer 51

This is modifications to the proteins that package and order DNA into nucleosomes; may be transcriptionally permissive or repressive.

Question 52

In epigenetic mechanisms of schizophrenia, explain non-coding microRNA’s

Answer 52

miRNA’s are single-stranded non-coding RNA’s that function in RNA silencing and post-transcritptional regulation of gene expression

Question 53

What is the evidence for epigenetic modulations in schizophrenia, and why is it important for understanding phenotypic expression and medication responses?

Answer 53

Epigenetic modulations occur in genes related to neurotransmission, neurodevelopment, and immune function in schizophrenia. Differential miRNA expression, like miR-137, impacts synaptogenesis and synaptic function. Understanding these modulations helps explain symptom variation and predict medication responses.

Question 54

What are the key features of the dopamine hypothesis in schizophrenia neurochemistry?

Answer 54

The dopamine hypothesis suggests that schizophrenia is associated with elevated dopamine levels in the striatum. This is due to increased dopamine release and an excess of dopamine receptor sites. Antipsychotic medications work by blocking dopamine uptake as D2 receptor antagonists. The exact opposite of amphetamines which can induce psychotic symptoms.

Question 55

What are the key aspects of dopamine function in schizophrenia? (increase in some places, decrease in others)

Answer 55

There is a functional excess of dopamine in the striatum, resulting from increased synaptic release and heightened post-synaptic receptor sensitivity. However, there are regionally specific effects, with decreased dopamine activity in the prefrontal cortex.

“overactivity” in striatum, “under activity” in prefrontal cortex.

Question 56

In relation to dopamine, what are the negative and positive symptoms and where are they located?

Answer 56

Hypodopaminergic function - negative symptoms in the frontal portions of the brain and causes cognitive impairment

Hyperdopaminergic function - the case of positive symptoms such as movement disorders and is in the caudate nucleus.

Question 57

What are the key characteristics of first- and second-generation antipsychotics in terms of neurochemistry and side effects? remember extrapyramidal is effects on motor function.

Answer 57

Antipsychotics act by occupying dopamine D2 receptors, with optimal efficacy at 60-75% occupancy.

First-generation antipsychotics (typicals) are D2 antagonists with a higher risk of extrapyramidal side effects.

Second-generation antipsychotics (atypicals) are 5HT2A/D2 antagonists with a lower risk of extrapyramidal side effects but a higher risk of metabolic side effects.

Both generations show similar effectiveness in treating cognitive and negative symptoms of schizophrenia.

Question 58

What are the key aspects of the “Attribution of Salience” theory in relation to dopamine and psychosis?

Answer 58

Dopamine mediates the conversion of neutral sensory stimuli into attractive or aversive representations. In psychosis, dysregulation of the mesolimbic dopamine system disrupts the normal process of context-driven salience attribution. This leads to the abnormal assignment of salience to external objects and representations, resulting in delusions (efforts to make sense of aberrantly salient experiences) and hallucinations (direct experiences of aberrant salience of internal representations). Antipsychotics help dampen salience in psychosis.

Question 59

What are the key aspects of cognitive deficits in schizophrenia?

Answer 59

Schizophrenia is associated with a generalised cognitive deficit, with specific impairments in episodic memory, working memory, and executive control. These impairments are observed even before the onset of psychotic symptoms and in non-psychotic relatives, indicating a potential liability to the disorder. The deficits primarily represent a vulnerability to the illness rather than the illness itself.

Question 60

What are the key techniques used in structural brain imaging?

Answer 60

Structural brain imaging techniques include Computed Tomography (CT), which uses X-ray measurements to produce cross-sectional images of the brain, Structural Magnetic Resonance Imaging (sMRI), which utilizes strong magnetic fields and radio waves, and Diffusion Tensor Imaging (DTI), an MRI-based technique that maps the connections between brain regions by estimating white matter tract location, orientation, and anisotropy.

Question 61

What are the key techniques used in functional brain imaging?

Answer 61

Functional brain imaging techniques include Positron Emission Tomography (PET) and Single-Photon Emission Computed Tomography (SPECT), which use radioactive tracers to study receptor binding, glucose metabolism, and brain activation. Functional Magnetic Resonance Imaging (fMRI) utilizes the Blood Oxygen Level Dependent (BOLD) technique to infer changes in neural activity.

Question 62

What are some key findings in CT imaging studies regarding structural abnormalities in schizophrenia?

Answer 62

CT imaging studies have identified mild cerebral atrophy and larger lateral ventricles in post-mortem studies and Johnstone et al. (1976) study. The degree of ventricular enlargement varies and cannot be used as a diagnostic marker for individuals. The functional significance of these findings is unclear, as there is no systematic relationship with various clinical measures, except for a possible association with abnormal behavior and involuntary movements.

Question 63

What are the key findings regarding enlarged ventricles in schizophrenia, and what do they indicate about brain tissue?

Answer 63

Enlarged ventricles are observed in schizophrenia, suggesting atrophy or deterioration of brain tissue. However, ventricle size is not a diagnostic marker and does not correlate with positive symptoms or cognitive deficits, providing limited functional information.

Question 64

What are the key MRI findings in schizophrenia?

Answer 64

MRI studies have revealed enlarged lateral ventricles, reduced volume in limbic structures (amygdala, hippocampal-amygdala complex), decreased total grey and white matter volume, and reductions in frontal and temporal volumes. Basal ganglia volume, specifically the globus pallidus, is increased, possibly associated with first-generation medication dosage.

Question 65

What are the key findings regarding structural abnormalities in schizophrenia based on meta-reviews of MRI studies?

Answer 65

Meta-reviews of MRI studies reveal widespread reductions in grey matter structures, including the anterior cingulate, frontal and temporal lobes, hippocampus/amygdala, thalamus, and insula. Some regional alterations are specific to illness stage or medication status, such as increased basal ganglia volume with atypical antipsychotics. These findings suggest the involvement of interconnected brain networks in complex tasks.

Question 66

What are the key findings from diffusion tensor imaging (DTI) studies in schizophrenia?

Answer 66

Grey matter deficits exceed white matter abnormalities in schizophrenia. Reduced fractional anisotropy indicates disrupted white matter integrity in multiple regions.

Question 67

What is the impact of schizophrenia or perception?

Answer 67

it can lead to difficulties in accurately perceiving and interpreting sensory stimuli

Question 68

How does schizophrenia affect attention?

Answer 68

Schizophrenia can impair attention, making it challenging to maintain focus and filter out distractions

Question 69

How is working memory affected in schizophrenia?

Answer 69

It can disrupt working memory, resulting in difficulties in maintaining and manipulating information for fail-directed behaviour

Question 70

What is the impact of schizophrenia on declarative memory?

Answer 70

I can cause impairments in both semantic and episodic memory, affecting the ability to recall and retrieve information

Question 71

How does schizophrenia impact cognitive control?

Answer 71

it can disrupt cognitive control, leading to difficulties in attention, task switching, inhibition, error detection, conflict resolution and cognitive flexibility

Question 72

What causes cognitive impairments?

Answer 72

Dysfunctional coordination among multiple brain regions in schizophrenia leads to breakdowns in various cognitive functions.

Question 73

What are the social cognitive impairments in schizophrenia?

Answer 73

Difficulties in identifying emotions, feeling connected to others, inferring people’s thoughts and reacting emotionally to others.

Question 74

What is the timing and origin of brain changes in schizophrenia?

Answer 74

Brain abnormalities appear when symptoms emerge, with some originating during neurodevelopment and others potentially influenced by stress neurotoxicity in adolescence or early adulthood.