Week 3 Topic 3 Flashcards
What is neurotransmission and what is the process of neurotransmission?
When two nerve cells need to communicate, they can’t just tap each other on the shoulder. These neurons pass information from one end of their “body” to the other as a tiny electrical signal. But one cell doesn’t actually touch another. To cross those tiny gaps, called synapses, they rely on chemical messengers. These chemicals are known as neurotransmitters. And their role in cell talk is called neurotransmission.
When an electrical signal reaches the end of a neuron, it triggers the release of tiny sacs that had been inside the cells. Called vesicles, the sacs hold chemical messengers.
Then, the vesicles move to — and merge with — their cell’s outer membrane. From there, they spill their chemicals into the synapse.
Those freed neurotransmitters then float across the gap and over to a neighboring cell. That new cell has receptors pointing toward the synapse.
A neurotransmitter docks into the proper receptor like a key into a lock. And as a messenger chemical moves in, the receptor’s shape will change. This change can open a channel in the cell, allowing charged particles to enter or exit. The shape change can trigger other actions inside the cell as well.
If the chemical messenger binds to a certain type of receptor, electrical signals will flow down the length of its cell. This moves the signal along the neuron. But neurotransmitters also can bind to receptors that will block an electrical signal. That will stop a message, silencing it.
What is the role of neurotransmitters?
They are essential for the transfer of electrical information between neurons.
Neurotransmitters modulate the flow and rate of information transfer within a network, effectively gating synaptic plasticity.
This process is subject to very tight regulation at several levels.
What is schizophrenia?
Schizophrenia is a severe psychiatric disorder characterised by major disturbances in thought, emotion, and behavior.
When schizophrenia is active, symptoms can include delusions, hallucinations, disorganized speech, trouble with thinking and lack of motivation.
What is active schizophrenia like?
When the disease is active, it can be characterized by episodes in which the person is unable to distinguish between real and unreal experiences. As with any illness, the severity, duration and frequency of symptoms can vary; however, in persons with schizophrenia, the incidence of severe psychotic symptoms often decreases as the person becomes older. Not taking medications as prescribed, the use of alcohol or illicit drugs, and stressful situations tend to increase symptoms.
How is schizophrenia diagnosed?
There is no diagnostic pathology for schizophrenia and diagnosis is currently based on clusters of symptoms.
These are described as positive, negative, and cognitive.
What kind of symptoms do schizophrenic patients suffer from?
Positive symptoms: (those abnormally present) Hallucinations, such as hearing voices or seeing things that do not exist, paranoia and exaggerated or distorted perceptions, beliefs and behaviors.
Negative symptoms: (those abnormally absent) A loss or a decrease in the ability to initiate plans, speak, express emotion or find pleasure.
Disorganized symptoms or cognitive symptoms: Confused and disordered thinking and speech, trouble with logical thinking and sometimes bizarre behavior or abnormal movements.
When does schizophrenia begin?
The onset of schizophrenia is typically in late adolescence or in early adulthood.
It typically happens earlier in male patients than in female patients.
It affects approx. 1% of the UK population.
What are the positive symptoms of schizophrenia?
Positive symptoms are described as additional features that are not ordinarily present. These include delusions, hallucinations that maybe auditory or visual, and thought disorder.
Delusions occur in 90% of patients and represent an idiosyncratic belief or impression which is maintained despite being contradicted by reality or rational argument - for example, I’m being watched by an alien force.
Hallucinations are generally auditory– for example, hearing voices– and occur in 70% of patients. Patients may feel as though these voices come from the outside and they often think they’re being criticised by them. Hallucinations may also, however, been visual or related to smell, taste, or touch.
Thought disorder may show up as disordered speech, including rapid changes of subject, the use of invented words, or in an inappropriate emotional response to other people in a particular situation.
What are the negative symptoms of schizophrenia?
Negative symptoms in contrast refer to a loss or reduction in a normal function.
alogia - the function of being reduced speech
affective flattening - lack of emotional facial expression
avolition - a diminished ability to begin and sustain an activity which is related to motivation
anhedonia - the inability to find pleasure in something you used to enjoy
asociality - social withdrawal
What are the cognitive symptoms of schizophrenia?
Cognitive symptoms refer to specific impairments in certain cognitive domains and affect the patient’s general quality of life and ability to hold down a job.
These include working memory, spatial memory, the ability to pay attention, and executive functions which may be defined as planning and decision making.
The combination of these symptoms make it difficult for patients to interact with other people and may severely affect their work depending on the severity of each domain.
What are the possible life courses following a diagnosis of schizophrenia?
Group 1 – a single episode of psychosis that recovers with no lasting impairment (20% of patients)
Group 2 – repeated episodes of psychosis (also referred to as relapse-remit) with no lasting impairment (35% of patients)
Group 3 – repeated episodes of psychosis without full recovery to pre-symptomatic levels of functioning. (about 8%).
Group 4 –repeated episodesof psychosis whichincrease in severityand are associated withno recovery to pre-symptomatic levels. ( 35% of all cases on average)
What are the causes of schizophrenia?
It’s a combination of environmental and genetic factors.
It is the interaction between these environmental factors and genetic factors that determine the clinical outcome in terms of symptom severity, long-term outcome, and the life course.
What are the environmental factors that may contribute to schizophrenia?
Some examples of environmental factors include
- obstetric complications
- pre-term birth
- hypoxia
- exposure to infection or inflammation, either in utero or in early post-natal life
- exposure to social stress, particularly during adolescence
- particularly childhood trauma is a common risk factor
- drug use, particularly addictive drugs such as cannabis, particularly during vulnerable periods of brain development
What are the genetic factors that may contribute to schizophrenia?
On the genetic side, schizophrenia is clearly highly heritable, but the genetics are complex and they break down into rare variants that have large effect and are highly penetrant.
And examples of this include the DISC1 gene and deletions of the gene known as neurexin-1, although there are others.
More common are variants of small effect, which together interact. And this is often referred to as the polygenic score, meaning the number of these small mutations that you have in your genome.
It is the interaction of these environmental factors and the genetic risk factors that define the clinical outcome.
What are the steps to be looked at in dopamine neurochemistry?
uptake
synthesis
storage
release
re-uptake
How is dopamine synthesised?
Dopamine itself is synthesised from the amino acid tyrosine, which enters the neuron by active transport.
1. Tyrosine is first converted to dihydroxyphenylalanine, or DOPA, by an enzyme called tyrosine hydroxylase.
(DOPA is a useful marker of how much dopamine a cell is producing and releasing.)
2. Then DOPA is converted into dopamine by DOPA decarboxylase.
3. Then dopamine is actively transported into vesicles by monoamin transporter 2.
What are the three primary pathways with dopaminergic neurons that use dopamine in the human brain?
- The nigrostriatal pathway: Projects from the substantia nigra to the striatum. Critical for the control of movement.
- The mesolimbic and mesocortical pathways: Project from the ventral tegmental area —>> nucleus accumbens, amygdala, hippocampus (mesolimbic). Ventral tegmental area —>> prefrontal cortex (mesocortical). This pathway is involved in both limbic and cognitive functions, such as memory, motivation, emotional response, reward, desire, and addiction.
- The tuberoinfundibular pathway: Projects from the A8 dopaminergic nucleus via the hypothalamus to the pituitary gland. It is involved in hormonal regulation and secretion of the hormone prolactin.
What is the basic premise of the dopamine hypothesis in schizophrenia?
An increase in dopaminergic neurotransmission in the mesolimbic pathway (VTA–>Nucleus Accumbens) leads to abnormally high levels of dopamine in the nucleus accumbens and the striatum, which are thought to underlie the positive symptoms of schizophrenia.
The mesolimbic pathway is overactive with dopamine (positive symptoms) whereas the mesocortical pathway (projecting to the prefrontal cortex) is underactive with dopamine (negative symptoms).
The increase of the DOPA synthesis capacity correlates positively with the severity of the positive sypmtoms.
