Schizophrenia: Causes and Treatments

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Questions and Answers

Which factor is a prognostic sign for isolated episodes of schizophrenia?

Insidious onset

Family history

Stable premorbid personality (correct)

Poor social adjustment

What is a common treatment approach for managing chronic schizophrenia?

Only psychotherapy

Immediate cessation of medication

Avoiding hospital treatment

Long-term maintenance therapy (correct)

What aspect tends to be preserved in patients experiencing acute episodes of schizophrenia?

Social adjustment

Insight into their condition

Emotional responses (correct)

Relationships

Which factor describes a typical characteristic of persistent schizophrenia?

Loss of initiative and drive Signup and view all the answers

Why is psychotherapy not effective in the early stages of schizophrenia?

Patients lack insight into their condition Signup and view all the answers

What is the relationship between cannabis use and acute psychosis?

Only high THC cannabis can induce acute psychosis. Signup and view all the answers

Which statement accurately reflects the confusion surrounding cannabis and schizophrenia?

Cannabis use is associated with psychosis but does not consistently increase schizophrenia incidence. Signup and view all the answers

How does CBD relate to cannabis-induced psychosis?

CBD may help ameliorate symptoms of cannabis-induced psychosis. Signup and view all the answers

What are the effects of cannabis on individuals with pre-existing vulnerabilities?

Cannabis may precipitate or worsen psychosis in vulnerable individuals. Signup and view all the answers

Which statement about cannabis and psychotic symptoms is inaccurate?

All cannabis use leads to psychosis in every user. Signup and view all the answers

What does psychosis primarily include as symptoms?

Delusions and hallucinations Signup and view all the answers

How has the understanding of schizophrenia evolved historically?

It was previously labeled merely as madness until the early 20th century Signup and view all the answers

What is often incorrectly associated with psychosis, contributing to stigma?

The term 'crazy' Signup and view all the answers

Which of the following is not a symptom of psychosis?

Split personality Signup and view all the answers

What significant contribution did Bleuler make to the understanding of schizophrenia?

He coined the term 'schizophrenia' Signup and view all the answers

Which statement is true about the symptoms of psychosis?

They can include disorganized behavior Signup and view all the answers

What is a common misconception about schizophrenia?

It is a personality disorder Signup and view all the answers

Which aspect is highlighted in the description of psychosis?

It includes a set of symptoms that may differ among individuals Signup and view all the answers

Which factor is not considered an environmental factor contributing to neurodevelopmental issues?

Genetic predisposition Signup and view all the answers

What is the primary focus of the neurodevelopmental model discussed?

Interactions between genetic and environmental factors Signup and view all the answers

In the context of schizophrenia, what effect does mesolimbic dopaminergic hyperactivity have?

Exacerbates positive symptoms Signup and view all the answers

What dilemma is associated with the treatment of schizophrenia regarding dopamine pathways?

Choosing between increasing or not increasing dopamine Signup and view all the answers

Which hypothesis has given rise to novel psychopharmacological agents?

Glutamate hypothesis Signup and view all the answers

How does mesocortical dopaminergic hypoactivity affect schizophrenia symptoms?

Contributes to negative symptoms Signup and view all the answers

What aspect of neurotransmission does the glutamate hypothesis revise?

Secretion and reuptake Signup and view all the answers

Which of the following environmental factors is least likely to contribute to neurodevelopmental outcomes?

High socioeconomic status Signup and view all the answers

What is one effect of reducing mesolimbic dopamine hyperactivity in treating schizophrenia?

It reduces positive symptoms. Signup and view all the answers

What role does 5HT2A antagonism play in the mechanism of atypical antipsychotics?

It reduces EPS by improving dopaminergic tone in specific pathways. Signup and view all the answers

Which atypical antipsychotic is noted for not binding to the 5HT1B and 5HT1D receptors?

Cariprazine Signup and view all the answers

Which side effect is commonly associated with D2 antagonists in patients with schizophrenia?

Weight gain and diabetes Signup and view all the answers

Which receptor does ziprasidone bind more potently to compared to the D2 receptor?

5HT1B Signup and view all the answers

Which atypical antipsychotic is associated with both binding weakly to 5HT1B and 5HT1D receptors?

Aripiprazole Signup and view all the answers

How does blocking serotonin receptors in the cortex impact dopamine levels?

It leads to increased dopamine secretion downstream. Signup and view all the answers

What is a common behavior in people with schizophrenia related to dopamine neurotransmission?

Higher rates of smoking Signup and view all the answers

Which pathway is associated with cortico-thalamic communication?

Cortico-thalamic Glu pathway Signup and view all the answers

What is hypothesized to be a mechanism for schizophrenia pathogenesis?

NMDA receptor hypofunction Signup and view all the answers

How might NMDA receptor hypofunction relate to schizophrenia symptoms?

It can cause psychotic episodes. Signup and view all the answers

What role do GABAergic interneurons play in neurotransmission?

They coordinate excitatory neurotransmission. Signup and view all the answers

What percentage of patients may experience psychosis due to autoimmune responses against NMDA receptors?

6.3% Signup and view all the answers

Which structures are involved in the mesolimbic pathway?

VTA and NAc Signup and view all the answers

What effect does the blockade of NMDA receptors have on glutamate-mediated excitations?

It prevents glutamate-mediated excitations. Signup and view all the answers

Which neurotransmitter is primarily affected in NMDA receptor dysfunction?

Glutamate Signup and view all the answers

Which neurotransmitter system is likely impaired as a result of NMDA receptor hypofunction?

Glutamatergic system Signup and view all the answers

What is the consequence of GABAergic modulation on cortical excitability?

It dampens neuronal excitability. Signup and view all the answers

Study Notes

Psychosis and Schizophrenia

Psychosis is a set of symptoms, not a disorder itself
Schizophrenia is a specific disorder that may or may not be associated with other conditions like mania, depression, or cognitive disorders.
Psychosis includes delusions, hallucinations, disorganized speech, disorganized behavior, and gross distortions of reality.
Schizophrenia is characterized by a set of symptoms that define psychosis.
Schizophrenia was once broadly considered "madness" in the early 20th century. Bleuler (1911) defined the condition.
Schizophrenia does not equal "split personality," a disorder known as multiple personality disorder
The onset of schizophrenia typically occurs in adolescence or early adulthood.

Learning Outcomes

Students should be able to define the distinction between psychosis and schizophrenia.
Students will be able to identify and describe the symptoms of schizophrenia. These include positive and negative symptoms.
Students will get a historical overview of schizophrenia.
Students will gain knowledge on the neuropathology, aetiology, and treatment of schizophrenia.
Students can describe the advantages and disadvantages of different treatments for schizophrenia.

Reference Literature

Stahl online: Chapters 4 and 5

The Scream

Edvard Munch created the piece "The Scream."
His account regarding the creation involved feeling unspeakably tired, extreme fear, and an infinite scream of nature.
Munch depicted a sense of vulnerability and isolation.

Psychosis and Schizophrenia- Meaning of terms

The term "psychosis" is difficult and misused within both the media and by healthcare professionals.
Negative perceptions and stigma associated with psychosis contribute to the use of the pejorative term "crazy"
Psychosis is a syndrome composed of symptoms.

Symptoms of Psychosis

Delusions: fixed false beliefs, not based on reality
Hallucinations: sensory experiences without external stimuli (auditory, visual, tactile)
Disorganized speech: nonsensical or illogical communication
Disorganized behavior: bizarre and inappropriate actions
Gross distortions of reality: profound difficulties interpreting surroundings

Schizophrenia: Aetiology and Pathology

Onset is typically during adolescence/early adulthood
Lifetime risk for schizophrenia is ~1%
Presentation of symptoms and outcome is highly variable across individuals
Multiple contributing factors are responsible for the condition, which is not completely understood. There is no single, definable cause.
Problems of definition: Subgroups exist within schizophrenia that share common symptoms and other characteristics.
Higher incidence in lower socioeconomic groups
Possible correlation with prior, impaired functioning

Genetics

Schizophrenia often runs in families, but no single gene is solely responsible.
It is more likely that multiple gene interactions create vulnerability to developing the condition. Possessing the genes doesn't guarantee development.
Studies with identical twins support the genetic component. If one identical twin is diagnosed, the other has a 1 in 2 chance. This is true even if they have different upbringings.
Non-identical twins with different genetic makeups show less correlation in the development of the disorder.

Schizophrenia: Neuropathology

Cerebral blood flow is often reduced in association with reduced frontal function.
Enlarged ventricles of the brain show up in scans
Volume of the brain's temporal lobes displays reductions in those diagnosed with schizophrenia.
Schizophrenia is not a progressively worsening condition.

Schizophrenia: Symptoms In Brief

Positive symptoms describe new behaviours that were not present before diagnosis. These symptoms include delusions, hallucinations, disorganized speech, disorganized behaviour and agitation.
Negative symptoms describe behaviours that have been lost. These include reduced emotional responsiveness, reduced interest and reduced social drive and poor grooming.

Schizophrenia: Aetiology

Inherited genetic factors play a role, and increased risks are apparent if one family member is already diagnosed.
Studies of twins, both identical and non-identical, indicate a genetic contribution. Identical twins have a higher risk of developing the disorder if one twin is impaired, in comparison to non-identical twins.
Environmental factors are also significant and include birth complications, viral infections, inner-city living, changes in environment and drug abuse.

Aetiology: Dopamine Hypothesis

Dopamine production, degradation, and transmission all form part of the dopamine hypothesis in the etiology of schizophrenia. Chemical processes are important in the production, degradation, and transmission of dopamine.
The hypothesis suggests the hyperactivity of mesolimbic dopamine pathways might trigger cognitive and other positive symptoms.
Conversely, the hypoactivity of mesocortical pathways may induce negative symptoms.

Aetiology: Glutamate Hypothesis

A new hypothesis suggests that there are problems with glutamatergic neurotransmission which may contribute to schizophrenia
The hypothesis states that altered glutamatergic neurotransmission might be associated with symptoms of schizophrenia.

Phencyclidine (PCP) on the NMDA Receptor

PCP and ketamine can block NMDA receptors which have been noted as potentially important in the pathophysiology of schizophrenia.
Blockade might impact glutamate-mediated excitation, contributing to the condition's pathogenesis.

Intracortical Glutamatergic Neurotransmission

Intracortical glutamatergic neurotransmission is facilitated/moderated via GABAergic interneurons.

NMDA-R Hypofunction

Hypofunction of NMDA receptors may lead to positive symptoms of schizophrenia.
This happens when the glutamate pathways are affected.

In other terms

Glutamatergic and GABAergic neurons have interactions that impact dopamine-related processes and cause symptoms of schizophrenia

Schizophrenia: Symptoms (Summary)

Positive symptoms, including delusions, hallucinations, and disorganized speech, represent new behaviours.
Negative symptoms, including reduced emotional responsiveness, reduced interest, and reduced social drive, represent lost behaviours.

Changes in Symptoms With Time

Initially, schizophrenia may present with mild symptoms but as the condition progresses, often towards a chronic state, negative symptoms overpower positive symptoms.
Early detection and intervention are important to better manage the condition.

Schizophrenia Outcomes

Approximately 25% of patients experience a single episode of psychosis and recover.
Factors contributing to successful recovery from a single episode include: no family history or pre-existing conditions; stable premorbid personality; acute onset; and preservation of emotional responsiveness along with early diagnosis and treatment.
Symptoms of persistent schizophrenia frequently correlate with a patient's family history and include persistent, premorbid personality distortions; difficulties in forming relationships; and disrupted social or domestic life. Onset is often insidious, and the patient may experience loss of initiative and drive along with delayed diagnosis and treatment.

Treatments for Schizophrenia

Treatment aims to control acute attacks and resolve underlying social and domestic factors.
Rehabilitative care for patients with schizophrenia is critical due to the repercussions of psychosis. This includes the treatment and monitoring of mood, emotion, and behavior and begins after a comprehensive evaluation.

Schizophrenia: D2 Antagonists

Psychotherapy is potentially helpful
Antipsychotic (neuroleptic) medications, such as haloperidol and chlorpromazine, primarily target positive symptoms.
The onset of action is typically delayed
Approximately 30% of patients might not respond to this class of medication.
Depot formulations of medication can improve compliance in affected individuals.

Treating Schizophrenia

Reducing mesolimbic dopamine hyperactivity reduces positive symptoms.
However, such treatments often increase negative symptoms because mesocortical dopamine tone is also reduced.

Therapeutic and Side Effects

Antipsychotic drugs reduce dopamine hyperactivity, improving positive symptoms but may exacerbate negative symptoms.
Medication can sometimes cause side effects: Extrapyramidal (EPS) such as extrapyramidal side effects, including acute dystonia, pseudo-parkinsonism, akathisia, and tardive dyskinesia.

Side Effects: Extrapyramidal Symptoms

Extrapyramidal symptoms (EPS) represent a common side effect of antipsychotic medications.
These may manifest as involuntary movements affecting various body parts.
Common EPS include acute dystonia, pseudo-parkinsonism, akathisia, and tardive dyskinesia.

Side Effects: Prolactinaemia

High prolactin levels can arise due to interference with dopamine pathways, leading to hormonal imbalances.

Narrow Therapeutic Range

A narrow therapeutic range for certain antipsychotic medications suggests that achieving effective doses for treatment while minimizing side effects becomes challenging.

Other Actions of Conventional Antipsychotics

Conventional antipsychotics may have multiple effects on various neurotransmitter receptors besides dopamine receptors.
M1 antagonism has side effects: constipation, blurred vision.

Treating Schizophrenia: Serotonin Hypothesis and Atypical Antipsychotics

Reducing mesolimbic dopamine hyperactivity leads to reduced positive symptoms.
5HT2A antagonism leads to increased dopamine tone, which reduces extrapyramidal symptoms (EPS).

Blocking 5-HT2A in Schizophrenia

Blocking serotonin receptors in the cortex has been shown to increase dopamine secretion and decrease extrapyramidal symptoms (EPS)

Better Therapeutic Profile

Atypical antipsychotics have a wider margin for treatment success versus side effects.

Binding Properties of Atypical Antipsychotics

Atypical antipsychotics display varying binding affinities to different receptors.
Some medications show strong binding activity, for instance, to 5HT1B/D and D2 receptors.

Atypical Antipsychotic Side Effects

People with schizophrenia who take antipsychotic medications often smoke more.
side effects include weight gain, diabetes and increased smoking, especially amongst those diagnosed with schizophrenia.
The use of atypical antipsychotics can lead to metabolic syndrome.
Older medications, like haloperidol, were often associated with weight loss effects.

Metabolic Syndrome

Metabolic syndrome is closely associated with schizophrenia in certain individuals, mostly those currently taking antipsychotic medication

Treating Schizophrenia: D2 Antagonists/Partial Agonists atypical Antipsychotics

Reducing mesolimbic dopamine hyperactivity reduces positive symptoms using dopamine partial agonists such as aripiprazole
Partial agonist activity on D2 in the mesocortical pathway reduces negative symptoms

D2 Antagonists/Partial Agonists

Partial agonists have different receptor effects than full agonists.
Conventional antipsychotics block dopamine receptors.
Partial agonists have both activating and blocking effects on dopamine receptors.

Antipsychotic Drugs

Antipsychotics were developed in the 1950s and are mainly classified by their chemical structure.
Typical antipsychotics primarily block dopamine receptors to primarily target positive symptoms.
They include chlorpromazine, haloperidol, thioridaxine, and others
Atypical antipsychotics target dopamine AND other receptors (e.g., serotonin).

Summary of Antipsychotic Drug Classes

A summary table provides comparative data on the main types of antipsychotics and their affinities to various receptors.

New Anti-Psychotic Drug Tolerability

A table shows side effect profiles of different antipsychotics, helping in their selection depending on patient needs and risk factors.

Quiz: Side Effects

A quiz using diagrams to assess the knowledge of different side effects and how receptors are affected

How to Manage Side Effects

Pharmacists should understand the pharmacology to predict side effects and implement strategies to minimize negative effects.

Quetiapine

Quetiapine has multiple effects, including hypnotic, antidepressant, and antipsychotic actions, depending on the dosage.

Treatment Strategies

Early intervention and maintenance treatment for acute episodes are often successful
Strategies to manage relapses should be part of a comprehensive treatment plan.

Cannabis Psychosis

Cannabis use can cause short-term psychotic episodes in certain individuals, particularly those with pre-existing mental health vulnerabilities.

Cannabis and Schizophrenia

Cannabis use does not appear to increase the risk of schizophrenia but may induce or worsen psychosis in some individuals who are vulnerable or are already diagnosed with schizophrenia.

Drugs & Psychosis: Context

Several illicit substances and even some prescription medications are associated with inducing or exacerbating psychotic episodes. For example, amphetamines, cocaine, MDMA, PCP.

Schizophrenia - Losing Control

Images depict the experience of profound mental health struggles (a visual aid).

Revision Slides

Revision slides covering previous topics summarized.

Studying That Suits You

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Description

This quiz explores key aspects of schizophrenia, including prognostic signs, treatment approaches, and the complex relationship between cannabis use and psychosis. Test your knowledge on symptoms, historical understanding, and the effectiveness of psychotherapy at various stages of the disorder.