Psychopathology Flashcards
Question: What biological discoveries in early 20th-century psychiatry connected mental illness to brain disease, particularly in paralytic dementia?
Key Findings:
• Paralytic Dementia (麻痹性痴呆)
• A severe psychiatric condition marked by delusions, grandiosity, euphoria, and cognitive decline.
• Later discovered to be caused by late-stage syphilis (梅毒晚期), specifically when the infection reached the brain.
• Biological Perspective
• This was one of the first clear cases showing that psychiatric symptoms could result from biological infection.
• It shifted psychiatry toward a biomedical model.
• Postmortem Studies
• Brain examinations after death showed clear damage caused by syphilitic infection (由梅毒引起的感染).
• This led to effective treatment using penicillin (青霉素), proving that some mental illnesses have treatable biological causes.
Key Takeaway:
• The discovery that paralytic dementia was caused by syphilis supported the idea that mental illness can result from biological disease, laying the groundwork for modern biological psychiatry.
How are psychiatric disorders diagnosed, and what does epidemiological research reveal about their prevalence?
Key Findings:
• Diagnosis
• Psychiatric disorders are diagnosed using standardized criteria, mainly from the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 第五版精神疾病诊断与统计手册).
• Diagnosis is based on observable behaviors and self-reported symptoms, not direct biological markers.
• Epidemiology (流行病学研究)
• Studies of population-level data reveal that:
• About 1 in 3 people will experience a psychiatric disorder at some point in life.
• Anxiety disorders are the most common, followed by mood disorders (e.g., depression).
• Schizophrenia is less common but highly disabling.
• Mental illness often begins in adolescence or early adulthood and can be chronic or episodic.
Key Takeaway:
• Psychiatric disorders are diagnosed using behavioral criteria from tools like the DSM-5. Epidemiological studies show they are very common, affecting roughly one-third of the population, with anxiety and mood disorders being most prevalent.
Question: Why do epidemiological studies report higher prevalence of psychiatric disorders in North America compared to other regions?
Key Findings:
• 1. Better Diagnosis & Reporting
• North America has more mental health awareness, access to diagnostic tools, and willingness to seek help, leading to higher reported rates.
• In other regions, stigma and limited healthcare infrastructure may lead to underreporting.
• 2. Cultural Differences
• Cultural norms affect how distress is expressed and whether it’s labeled as a “disorder.”
• Some symptoms may be normalized or expressed somatically (as physical symptoms) in other cultures.
• 3. Lifestyle & Social Factors
• Individualism, high stress, competitive work/school environments, and social isolation in North America may contribute to higher rates of anxiety, depression, and substance use disorders.
• 4. Medicalization of Experience
• There’s a tendency in Western healthcare to label a broader range of behaviors as clinical disorders, which increases diagnostic rates.
Key Takeaway:
• Higher prevalence of psychiatric disorders in North America likely reflects a combination of greater awareness and diagnosis, sociocultural stressors, and healthcare system differences, rather than actual biological differences.
What has genomic screening revealed about the genetic basis of mental illnesses like schizophrenia, bipolar disorder, anxiety, and depression?
Key Findings:
• Genetic Contribution
• Psychiatric disorders show strong heritability, especially:
• Schizophrenia and bipolar disorder have high genetic overlap.
• Depression and anxiety also show genetic correlations, though generally less than psychotic disorders.
• Genome-Wide Association Studies (GWAS)
• These studies scan the entire genome to identify common genetic variants linked to psychiatric conditions.
• Findings:
• No single “mental illness gene,” but many small-effect variants contribute to risk.
• Some variants are shared across multiple disorders, suggesting common biological pathways.
• Shared Risk Loci
• Schizophrenia and bipolar disorder share overlapping genetic risk loci, particularly in genes involved in synaptic function and neurodevelopment.
• Depression and anxiety share loci related to stress response and neurotransmitter regulation.
Key Takeaway:
• Genomic studies show that psychiatric disorders are polygenic (influenced by many genes), with shared genetic risk across conditions like schizophrenia, bipolar disorder, anxiety, and depression—supporting a dimensional view of mental illness.
What is schizophrenia, how common is it, what are its symptoms, and what is the recovery outlook?
Key Findings:
• Definition:
• Schizophrenia is a severe psychiatric disorder characterized by disruptions in thought, perception, emotion, and behavior.
• Prevalence:
• Affects approximately 1% of the population worldwide.
• Core Symptoms:
• Disorganized Thinking:
• Speech may be tangential, incoherent, or loosely connected (“word salad”).
• Difficulty forming logical, goal-directed thoughts.
• Positive Symptoms (addition of of abnormal features):
• Hallucinations (most often auditory)
• Delusions (false, fixed beliefs)
• Disorganized speech/behavior
• Negative Symptoms (absence of normal functions):
• blunted affect (face always stay neutral), social withdrawal, lack of motivation, anhedonia
• Cognitive Symptoms:
• Impaired working memory, attention, and executive function
• Recovery Rate:
• About 50% of patients show improvement or partial recovery with treatment.
• Others may have chronic symptoms, relapses, or require long-term care.
• Early intervention and continued support improve outcomes significantly.
Key Takeaway:
• Schizophrenia affects about 1% of people, with symptoms like disorganized thinking, hallucinations, and social withdrawal. While recovery is possible, especially with early treatment, many require long-term management.
Is schizophrenia genetically caused? What did twin studies find about its heritability?
Key Findings:
Concordant (一致的): Both twins have schizophrenia.
• Discordant (不一致的): Only one twin has schizophrenia.
• Schizophrenia has a strong genetic component, but it is not entirely genetic.
• Twin studies provide key evidence:
• Monozygotic (identical) twins: ~50% concordance rate.
• Dizygotic (fraternal) twins: ~17% concordance rate.
• The large gap between MZ and DZ twins shows high heritability.
• However, since MZ concordance is not 100%, environmental factors must also contribute (e.g., prenatal stress, infections, early trauma).
Key Takeaway:
• Schizophrenia is highly heritable, as shown in twin studies, but not entirely genetic—environmental factors are also necessary for expression.
What is the modern, psychobiological view of schizophrenia, and what challenges remain in treatment?
Key Findings:
• Psychobiological Model
• Schizophrenia is viewed as a disorder involving interactions between genes, brain development, neurochemistry, and environment.
• Emphasizes that no single cause explains it — it’s a complex, multifactorial illness.
• Modern Understanding Includes:
• Genetic vulnerability (polygenic risk, endophenotypes)
• Neurodevelopmental disruptions (e.g., in utero insults, synaptic pruning)
• Brain abnormalities (enlarged ventricles, reduced gray matter, disorganized hippocampus)
• Neurochemical dysfunctions (dopamine, glutamate imbalances)
• Environmental factors (e.g., stress, trauma, paternal age)
• Treatment Limitations:
• Current treatments mainly target dopamine and positive symptoms.
• Negative symptoms and cognitive deficits remain hard to treat.
• There is no cure, and many patients require lifelong management.
• Personalized, multi-target approaches are needed but not yet fully developed.
Key Takeaway:
• The modern view of schizophrenia is that of a complex brain disorder shaped by genetics, development, and environment. Despite progress, we are still far from a complete treatment, especially for negative and cognitive symptoms.
What is an endophenotype, and how is it related to schizophrenia?
Key Findings:
• Endophenotype
• A measurable biological or behavioral trait that is intermediate between a genetic predisposition and a full-blown disorder.
• It is heritable, associated with the disorder, and present even in unaffected family members.
• Examples: eye-tracking deficits, working memory impairment, or reduced prefrontal activation.
• In Schizophrenia:
• Used to identify biological markers that may reflect genetic risk even before clinical symptoms appear.
• Helps researchers study the underlying neural or cognitive dysfunctions in schizophrenia.
• For example, many people with schizophrenia (and some of their relatives) show poor smooth pursuit eye movements, even if they don’t have the disorder themselves. Their eyes may show jerky, discontinuous movements when trying to follow a moving object. Which suggest something in the brain’s coordination systems, especially involving frontal eye fields and related circuits is disrupted.
Key Takeaway:
• Endophenotypes are heritable traits that bridge genes and symptoms. In schizophrenia, they help identify underlying vulnerabilities and clarify genetic risk mechanisms.
Is schizophrenia caused by a single gene, and what role does paternal age play?
Key Findings:
• No Single Gene
• Schizophrenia is polygenic — influenced by many genes, each contributing a small amount of risk.
• Genome-wide studies show complex genetic architecture, with no one gene being solely responsible.
• Paternal Age as an Epigenetic Factor
• Epigenetic factor: influences gene expression without changing DNA sequence (表观遗传因素).
• Advanced paternal age is linked to increased risk of schizophrenia in offspring.
• Likely due to increased de novo mutations (新生突变) in sperm and epigenetic changes in older fathers.
Key Takeaway:
• Schizophrenia is not caused by a single gene. Paternal age is an epigenetic risk factor, with older fathers increasing the likelihood of schizophrenia in children.
Question: What is the relationship between lateral ventricle size and schizophrenia, and what have animal models shown?
Key Findings:
• Larger lateral ventricles are commonly observed in people with schizophrenia.
• Ventricles don’t grow themselves; their enlargement reflects loss of brain tissue (e.g., in hippocampus, amygdala, frontal cortex).
• This suggests reduced brain volume, not an increase in skull or brain size.
• Mouse models of schizophrenia show similar ventricular enlargement, supporting a neurodevelopmental basis for the disorder.
Key Takeaway:
• Enlarged ventricles in schizophrenia reflect brain tissue loss, not skull expansion. Animal studies confirm this structural change, reinforcing the disorder’s biological foundation.
Question: What does human research reveal about the relationship between ventricle size and schizophrenia across sex, age, and genetics?
Key Findings:
• Sex and Age Effects
• Males with schizophrenia show larger lateral ventricles than both healthy males and females with schizophrenia.
• Ventricular enlargement is more pronounced with age, indicating progressive brain tissue loss.
• Twin Studies
• In monozygotic (identical) twins discordant for schizophrenia:
• The affected twin often shows larger ventricles than the unaffected co-twin.
• Suggests ventricular enlargement is linked to the expression of the disorder, not just shared genes.
• Interpretation
• Supports the idea that ventricular enlargement is a marker of disease progression or severity, not merely genetic predisposition.
• Also reinforces that brain structure changes can be observed even before full-blown symptoms, especially in high-risk individuals.
Key Takeaway:
• Larger ventricles in schizophrenia are more common in males and increase with age. Twin studies show the enlargement is linked to disease expression, not just genetics, supporting a progressive neurodevelopmental model.
What structural changes occur in the hippocampus and amygdala in individuals with schizophrenia?
Key Findings:
• Hippocampus
• Often found to be smaller in volume in people with schizophrenia.
• Shows disorganized pyramidal cell layers, indicating abnormal neurodevelopment or cellular migration.
• Linked to memory deficits and disrupted contextual processing.
• Amygdala
• Also shows volume reduction, though less consistently than the hippocampus.
• May contribute to emotional dysregulation and impaired threat detection, both of which are common in schizophrenia.
• These structural abnormalities are seen in MRI studies and postmortem analysis, and may emerge early in the disease course or even before symptom onset.
Key Takeaway:
• Schizophrenia is associated with reduced volume and cellular disorganization in the hippocampus and amygdala, which may underlie impairments in memory, emotion, and cognition.
How is sleep related to depression, and what abnormalities are observed in the EEG of depressed individuals?
Key Findings
• Depression is strongly associated with sleep disturbances, including insomnia, early morning awakening, and non-restorative sleep.
• EEG studies reveal that people with depression often show abnormalities in sleep architecture, especially in REM (rapid eye movement) sleep.
• Depressed individuals tend to enter REM sleep earlier (shorter REM latency) and have more frequent and intense REM episodes.
• They may also experience reduced slow-wave (deep) sleep, which is important for physical and emotional recovery.
• These changes suggest that disrupted sleep regulation may be both a symptom and a contributing factor in depression.
Key Takeaway
• People with depression often show altered sleep patterns on EEG, including early REM onset and reduced deep sleep, highlighting a close link between sleep regulation and mood disorders.
What cerebral abnormalities and corpus callosum changes are found in individuals with schizophrenia?
Key Findings:
• Cerebral Atrophy (大脑萎缩):
• Individuals with schizophrenia often show loss of gray matter, especially in the frontal and temporal lobes.
• May contribute to impaired executive function, planning, and social cognition.
• Corpus Callosum (胼胝体)
• The main fiber tract connecting the left and right hemispheres of the brain.
• In schizophrenia, it may be thinner or abnormally shaped.
• Abnormalities are linked to disrupted inter-hemispheric communication, which may contribute to disorganized thinking and cognition.
• Developmental Timing:
• These abnormalities are believed to arise during early brain development, possibly before symptoms appear.
• Supported by imaging and longitudinal studies.
Key Takeaway:
• Schizophrenia is associated with cortical gray matter loss and corpus callosum abnormalities, both of which may underlie key cognitive symptoms and reflect early neurodevelopmental disruption.
Question: What is the hypofrontality hypothesis in schizophrenia, and what do PET scans show?
Key Findings:
• Hypofrontality Hypothesis
• Proposes that individuals with schizophrenia have reduced activity in the frontal lobes, especially the prefrontal cortex (前额叶皮层).
• The prefrontal cortex is critical for decision-making, working memory, planning, and goal-directed behavior.
• PET Scan Evidence
• Positron Emission Tomography (PET) scans show reduced glucose metabolism in the prefrontal cortex of people with schizophrenia, particularly during tasks requiring executive function (like the Wisconsin Card Sorting Test).
• This supports the idea of functional underactivation, not just structural changes.
• Functional Implications
• Hypofrontality may underlie negative symptoms (e.g., flat affect, lack of motivation) and cognitive impairments.
Key Takeaway:
• PET scans support the hypofrontality hypothesis by showing reduced frontal lobe activity in schizophrenia, helping explain deficits in executive function and motivation.
Question: How has the treatment of schizophrenia evolved historically, and what are the main approaches today?
Key Findings:
• Historical Treatments
• Psychosurgery (精神外科手术) was used in the early 20th century, most notably the lobotomy (脑叶切除术).
• Intended to calm severely disturbed patients but often caused severe side effects like emotional blunting and cognitive impairment.
• In the 1950s, the introduction of chlorpromazine (氯丙嗪) marked the first effective antipsychotic drug.
• Reduced positive symptoms (e.g., delusions, hallucinations) by blocking dopamine receptors, launching the dopamine hypothesis.
• Today’s Treatments
• Psychosurgery is rare today due to ethical concerns and poor outcomes.
• Antipsychotic medications remain the main treatment:
• First-generation: Strong D2 receptor antagonists (e.g., haloperidol).
• Second-generation: Also affect serotonin receptors; fewer motor side effects.
• Psychosocial therapies (e.g., CBT, family education, supported employment) are widely used to improve function and reduce relapse.
Key Takeaway:
• Schizophrenia treatment evolved from invasive and risky procedures like lobotomy to pharmacological and behavioral therapies, with antipsychotics as the primary treatment and psychosurgery now rarely used.
What is the glutamate hypothesis of schizophrenia, and what evidence supports it?
Key Findings:
• Glutamate Hypothesis
• Proposes that schizophrenia is partly caused by underactivation of glutamate signaling, especially at NMDA receptors (一种重要的谷氨酸受体).
• Suggests deficient glutamate transmission leads to symptoms like cognitive dysfunction, negative symptoms, and possibly even positive symptoms.
• Supporting Evidence:
• PCP and ketamine, which are NMDA receptor antagonists, produce schizophrenia-like symptoms in healthy people (including hallucinations and cognitive deficits).
• People with schizophrenia show reduced glutamate activity in brain regions like the prefrontal cortex and hippocampus.
• Broader Implication:
• Helps explain symptoms that the dopamine hypothesis doesn’t fully account for, particularly cognitive and negative symptoms.
Key Takeaway:
• The glutamate hypothesis suggests that NMDA receptor hypofunction contributes to schizophrenia, offering a broader understanding of symptoms beyond dopamine alone.
Question: What is the dopamine hypothesis of schizophrenia, and why are antipsychotic drugs used?
Key Findings:
• Dopamine Hypothesis
• Suggests that overactivity of dopamine transmission, particularly at D2 receptors, contributes to positive symptoms of schizophrenia (e.g., hallucinations, delusions).
• Based on observations that:
• Amphetamines (which increase dopamine) can induce psychosis-like symptoms.
• Antipsychotic drugs that block D2 receptors reduce these symptoms.
• Why Use Antipsychotics?
• First-generation antipsychotics (e.g., chlorpromazine, haloperidol) are D2 receptor antagonists.
• Effective for positive symptoms but can cause motor side effects (e.g., tardive dyskinesia).
• Second-generation antipsychotics also block serotonin receptors (5-HT2A) in addition to D2.
• Lower risk of motor side effects, and may help with negative symptoms.
• Limitation of the Hypothesis
• Doesn’t fully explain negative or cognitive symptoms.
• Led to exploration of other systems, like glutamate (NMDA receptor hypothesis).
Key Takeaway:
• The dopamine hypothesis explains schizophrenia’s positive symptoms as related to excess dopamine activity. Antipsychotics work by blocking D2 receptors, making dopamine signaling a central target in treatment.
What is the role of D2 receptors in schizophrenia, and why are they important in treatment?
Key Findings:
• D2 Receptors (Dopamine Type 2 Receptors)
• A subtype of dopamine receptors located in key brain regions, including the striatum and limbic system.
• In schizophrenia, overactivation of D2 receptors is believed to contribute to positive symptoms, such as hallucinations and delusions.
• Link to Antipsychotic Drugs
• Most effective antipsychotic medications (especially first-generation) work by blocking D2 receptors, reducing dopamine activity.
• The degree of D2 receptor binding correlates with clinical effectiveness — drugs that strongly bind to D2 tend to reduce symptoms better.
• Side Effects
• Blocking D2 receptors, especially in the basal ganglia, can also lead to motor side effects (e.g., tremors, rigidity, tardive dyskinesia), similar to Parkinson’s disease, which is associated with low dopamine.
Key Takeaway:
• D2 receptors are central to the dopamine hypothesis of schizophrenia. Antipsychotic drugs work by blocking these receptors, which reduces positive symptoms but can also cause motor-related side effects.
What are the long-term side effects of antipsychotic drug use, including dyskinesia, tardive dyskinesia, and super-sensitivity psychosis?
Key Findings:
• Dyskinesia (运动障碍)
• A general term for involuntary, erratic movements, often caused by dopamine-blocking drugs.
• Can occur during or shortly after starting treatment.
• Tardive Dyskinesia (迟发性运动障碍)
• A late-onset motor side effect of long-term antipsychotic use, especially first-generation drugs.
• Characterized by involuntary, repetitive movements (e.g., lip-smacking, tongue flicking, facial grimacing).
• Caused by chronic D2 receptor blockade, leading to receptor upregulation and hypersensitivity.
• Super-sensitivity Psychosis (过度敏感性精神病)
• A rebound psychotic episode that can occur when antipsychotic medication is reduced or stopped.
• Thought to result from dopamine receptor supersensitivity after prolonged blockade.
• May cause worsening of symptoms or increased relapse risk despite treatment.
Key Takeaway:
• Long-term antipsychotic use can lead to motor side effects like tardive dyskinesia and worsened psychosis due to receptor supersensitivity, highlighting the need for careful dosing and monitoring over time.
What are first- and second-generation antipsychotics, how do they differ, and what does receptor affinity mean?
First-Generation Antipsychotics (Typical)
• First-generation antipsychotics include drugs like chlorpromazine and haloperidol.
• These drugs primarily block D2 dopamine receptors, reducing positive symptoms such as hallucinations and delusions.
• They carry a high risk of motor side effects, including tardive dyskinesia.
Second-Generation Antipsychotics (Atypical)
• Second-generation antipsychotics include clozapine, risperidone, and olanzapine.
• These drugs block both D2 dopamine and 5-HT2A serotonin receptors, offering broader symptom control.
• They have a lower risk of motor side effects and may help with negative symptoms, but may lead to weight gain and metabolic issues.
Receptor Affinity（受体亲和力）
• Receptor affinity refers to how strongly a drug binds to a specific receptor.
• A drug with higher affinity binds more tightly and is more likely to block receptor activity.
• Some second-generation drugs have weaker D2 affinity, which may reduce side effects while maintaining therapeutic effect.
Key Takeaway
• First-generation antipsychotics block D2 receptors and carry motor side effects; second-generation drugs target both dopamine and serotonin, improving symptom coverage with fewer motor risks. Receptor affinity explains how strongly drugs interact with their targets.
What is phencyclidine (PCP), and how is it related to schizophrenia research?
Key Findings:
• Phencyclidine (PCP)
• A dissociative anesthetic and hallucinogenic drug, also known as angel dust.
• Originally developed as a surgical anesthetic, but discontinued due to severe psychiatric side effects.
• Mechanism of Action
• PCP is a non-competitive NMDA receptor antagonist (NMDA受体拮抗剂), meaning it blocks glutamate signaling in the brain.
• Glutamate is critical for learning, memory, and normal brain function.
• Relevance to Schizophrenia
• In healthy individuals, PCP can produce schizophrenia-like symptoms, including:
• Hallucinations, delusions, disorganized thinking, and emotional withdrawal.
• These effects mimic both positive and negative symptoms, suggesting glutamate dysfunction may be involved in schizophrenia.
Key Takeaway:
• PCP is a glutamate-blocking hallucinogen that induces schizophrenia-like symptoms, supporting the glutamate hypothesis of schizophrenia alongside the traditional dopamine hypothesis.
