L11 Distorted reality: psychotic symptoms across disorders Flashcards
What is the first article about?
Psychosis as a State of Aberrant Salience: A Framework Linking Biology, Phenomenology, and Pharmacology in Schizophrenia
The paper tries to integrate the neurobiology (brain), phenomenological experience (mind), and pharmacological aspects of psychosis in schizophrenia into a unified framework
Structure:
1. The dopanime hypothesis of psychosis
2. Dopamine as a mediator of motivational salience
3. Psychosis as a Disorder of Aberrant Salience
4. Dampening of Aberrant Salience by Antipsychotics
5. Implications of this model and its links to other models
6. Limitations of the framework
What is a broad overview of the main argument in the article?
Psychosis involves an overactive dopamine system which causes an aberrant assignment of salience to experiences, leading to delusions as the mind tries to make sense of these unusual sensations, and hallucinations as direct experiences of this misassigned importance to internal thoughts. Antipsychotics dampen this aberrant salience to alleviate symptoms.
What are the two ideas in the dopamine hypothesis?
- dopamine hypothesis of antipsychotic action
- dopamine hypothesis of psychosis
How has the dopamine hypothesis of the antipsychotic action developed and what did this lead to?
- Developed from the observation that antipsychotics increase the turnover of dopamine
- It led to the discovery of the dopamine D2 receptor - plays a central role in the action of these medications
- Neuroimaging studies using PET and SPECT have confirmed the importance of D2 receptor occupancy for antipsychotic effects
What is evidence that supports the dopamine hypothesis of psychosis?
- Psychostimulant drugs that release dopamine can induce de novo psychosis and worsen psychotic symptoms in partially remitted patients
- Early postmortem studies showed dopaminergic abnormalities (but their interpretation is complicated by drug effects)
- Most compelling evidence - neuroimaging studies demonstrating heightened dopamine synthesis, increased dopamine release in response to stimuli, and elevated synaptic dopamine levels in psychotic patients with schizophrenia
- There is lot of evidence for heightened dopaminergic transmission, likely involving presynaptic dysregulation rather than changes in the number of dopamine receptors
What is important to consider when suggesting the role of dopamine in psychosis?
- Dopaminergic abnormality is likely not exclusive or primary in schizophrenia, as other neurochemical systems are also involved
- The dopamine disturbance is likely a “state” abnormality associated with the dimension of psychosis within schizophrenia rather than a fundamental abnormality of the illness itself
- “Dopamine [is] the wind of the psychotic fire” - while dopamine plays a role, it’s not the primary underlying cause
↪ dopamine acts as an exacerbating factor, intensifying or driving the symptoms of psychosis rather than being the fundamental origin of the condition itself
What hypothesis proposes dopamine’s role in behaviour? What observations led to a development of alternative ideas?
Dopamine has been widely linked to reward and reinforcement - but it’s unclear how dopamine contributes to those:
- The anhedonia hypothesis - dopamine mediates pleasure derived from rewarding experiences
Observations leading to alternative ideas:
- dopamine is involved in aversive events
- dopamine activity precedes pleasure consummation
- dopamine changes the ‘wanting’ without necessarily changing the ‘liking’ - change in drive to obtain food and sex but not the extent of liking these
What were the alternative ideas proposed?
- Dopamine neurons are important for predicting rewarding events and coding outcome expectancies - doesn’t explain dopamine’s role in aversive events and its long-term modulatory role in behaviours
- Incentive/motivational salience hypothesis
What is the Incentive/motivational salience hypothesis
- Most plausible framework for understanding psychosis
- This hypothesis builds on earlier work on incentive motivation and the role of dopamine in motivated behaviours
- Dopamine mediates the conversion of a neural representation of an external stimulus from something neutral into something attractive or aversive
- In particular, the mesolimbic dopamine system is crucial in the “attribution of salience” where events and thoughts become attention-grabbing and drive goal-directed behaviour due to their association with reward or punishment
- In simple terms: dopamine does not create pleasure but instead assigns importance (salience) to stimuli, making certain objects, thoughts, or events stand out and drive motivation. This system helps organisms focus on rewards and threats, guiding behavior toward beneficial outcomes (e.g., food, social interaction) and away from dangers.
- The concept of motivational salience provides a bridge between brain activity and the subjective experience of psychosis
How does the dopamine mediation differs in normal circumstances and psychosis?
- Under normal circumstances, stimulus-linked dopamine release mediates the acquisition and expression of appropriate motivational saliences
- In psychosis, however, there is stimulus-independent release of dopamine, meaning that dopamine is dysregulated, causing random stimuli to feel intensely important (aberrant salience)
- Thus, dopamine in the psychotic state becomes a creator of aberrant saliences rather than a mediator of contextually relevant ones
What do patients often experience before they experience psychosis?
- Patients may experience an exaggerated release of dopamine, out of sync with the context, leading to inappropriate salience and motivational significance being assigned to stimuli
- This induces a heightened awareness, emotionality, anxiety, and a drive to make sense of the altered perceptions
- Patients report a heightened awareness of insignificant things, increased sensory keenness, and a feeling that something in the world is changing, leading to perplexity and a search for explanation
- These abberant saliences in psychosis are unique due to their persistence in the absence of sustaining stimuli so patients go days or weeks without an explanation for this hightened awarness
According to this framework how do delusions develop?
- Delusions are “top-down” cognitive explanations that individuals develop to make sense of these experiences of aberrant salience
- Reaching a delusional explanation can provide a sense of relief or “psychotic insight” and guides further thoughts and actions, driving the patient to seek confirmatory evidence (e.g. glances from strangers, headlines in newspapers)
What explains the differences in delusions in patients?
Since the delusions are constructed by the individual to make sense of the heightened experience, the content of delusions is influenced by the individual’s psychodynamic themes and cultural context
- This explains how the same neurochemical dysregulation leads to variable phenomological expression
According to this framework how do hallucinations develop?
- Hallucinations arise from a conceptually similar and more direct process: the abnormal salience of internal representations of percepts and memories (e.g. a normal background noise might suddenly feel deeply meaningful)
- This can explain the varying severity of hallucinations, from internal thoughts to external voices (aliens intercepting your brain)
- Psychotic experiences become a clinical illness when shared with others or when they significantly affect the individual’s behaviour
What may further support the development of delusions and hallucinations?
- Pre-existing abnormalities in cognitive, interpersonal, and psychosocial functioning in patients with schizophrenia
- These include biases in probabilistic reasoning, a tendency to “jump to conclusions”, altered attributional styles, differences in “theory of mind”, and abnormal levels of perceptual aberrations and magical ideation
- These factors interact with the aberrant neurochemistry to shape the diverse phenomenology of psychosis
What things remain unclear when it comes to the effects of antipsychotics?
- Although dopamine receptor blockade by antipsychotics reaches a steady state within days, the improvement in psychotic symptoms is slow and cumulative
- A common early improvement reported by patients is that their symptoms “don’t bother me as much anymore” - The core belief in the delusion or the reality of the hallucination may persist even after it stops interfering with thought and function
- Patients often dislike taking antipsychotics due to dysphoria or a “deficit-like state”.
- Antipsychotics provide symptomatic control, as symptoms typically return upon discontinuation of treatment
How do antipsychotics work?
- All antipsychotics share the common property of dampening salience by blocking the underlying aberrant dopaminergic drive
- While antipsychotics differ in their physical properties, their psychological effect of dampening salience is the final common pathway of improvement
- Antipsychotics provide a platform of attenuated salience, allowing for further psychological and cognitive resolution of symptoms
- In summary, antipsychotics, when administered to a patient who works under aberrantly salient
ideas (delusions) or aberrantly salient perceptions (hallu-cinations), block the underlying aberrant dopaminergic drive, and given the critical role of dopamine in salience, this leads to an attenuation of the salience of these ideas and perceptions
Where does the concept of dampening salience originate from?
Very first behavioural studies of anti-psychotics in aminals and humans in the 1950s
- Rats who had come to associate a ringing bell with a shock would try to avoid the mere sound of the bell. However, when these rats received an antipsychotic they stopped avoiding the bell, even though they were motorically capable of doing so and still re-sponded to the shock. This led to the suggestion that antipsy-chotics induce “a forgetfulness of motive” (more recently… ‘‘impair incentive salience attributions’’)
- Early clinical observations noted a désintéressement in surroundings and a state of indifference in patients treated with these drugs
How does this view help explain why there is a slow, gradual response to the drugs?
- Despite antipsychotics blocking the dopamine system at onset, the response is slow and gradual
- By attenuating the salience of delusions and hallucinations, antipsychotics do not primarily change the content of thoughts or perceptions but make them less likely to form and more likely to extinguish
- Patients don’t immediately abandon the idea or percept rather they report that it “doesn’t bother me as much”
- This is implictly understood in the field since rating scales for psychosis often assess the degree to which symptoms preoccupy the mind and affect behaviour rather than solely focusing on the content
- Over time, the content of delusions and hallucinations may be deconstructed and recede from awareness
How can then symptom reduction be explained as a dynamic process?
Symptom resolution is a dynamic process where antipsychotics reduce salience, and the patient “works through” their symptoms towards psychological resolution, possibly involving processes of extinction, encapsulation, and belief transformation
Why does relapse occur?
- Because antipsychotics block the expression of abnormal dopaminergic transmission but do not fundamentally alter the underlying dysregulation
- When antipsychotic treatment is stopped, the endogenous dopaminergic dysregulation gets reinstated
- When in remission, the thoughts are not erased but recede to the background of consciousness and the resurgence of an abnormally heightened dopa-minergic state, whether due to drugs, stress, or endogenous dysregulation, reinvests these dormant symptoms with salience, making them clinically relevant again - often the same content as previously experienced by the patient
How could this framework lead to psychological treatment?
- Psychosis is viewed as a dynamic interaction between a bottom-up neurochemical drive and a top-down psychological process
- This suggests that specific psychotherapies for psychosis should be feasible and synergistic with pharmacotherapies
- Currently, treatment mainly focuses on biological modification without specific help for cognitive-psychological resolution
- Understanding and implementing psychological processes in therapies could enhance antipsychotic effects
- Early studies of cognitive therapies for psychosis show additional efficacy beyond drug effects
- The model suggests that an “overnight” treatment for psychosis is implausible because patients incorporate psychotic beliefs into their cognitive schemas over time
- Blocking neurochemical abnormalities quickly will not immediately dismantle these schemas - Improvement requires psychological strategies with longer timelines
What is an explanation for the unpleasant subjective effects of antipsychotics?
- effects: “neuroleptic-induced dysphoria” and decreased motivational drive
- These may be an unavoidable consequence of dampened salience, affecting both aberrant and normal motivations
- This might explain the higher incidence of substance abuse as self-medication in patients with schizophrenia
- Selectively dampening aberrant salience without affecting normal drives remains a challenge
How can this framework add to other already existing models?
- The aberrant salience hypothesis can complement other models of psychosis that focus on primary neurochemical abnormalities (e.g., mesolimbic dopamine, hypofrontality, glutamate deficit, neurodevelopmental disorder) by providing a link to symptomatic expression
- It differs from ideas focusing on deficient “filtering” of information by conceptualising salience at a cognitive-motivational level rather than a preattentive sensorimotor or electrophysiological level