BIOSCI N165 - Unit 7

Schizophrenia

A chronic neuropsychiatric disorder defined as a loss of touch with reality (psychosis). Involves a breakdown in the normal relationship among thought, emotion, and behavior.

Equal incidence in men and women.

Prevalence: 1-2% across cultures. Males have earlier onset (18-25); females later (26-45). Less industrialized countries have better recovery rates.

Treatment note: Occupational Therapy helps with self-care and work options; important for functional rehabilitation

Psychosis

An abnormal condition of the mind involving a loss of contact with reality.

May include:

• Personality changes

• Thought disorder

• Unusual/bizarre behavior

• Difficulty with social interactions

• Impairment in daily activities

A SYMPTOM of schizophrenia, mania, and certain severe depressions — NOT a diagnosis in itself.

Hallucination

Positive symptom of Schizophrenia (added behavior)

A perception in the absence of a stimulus.

In a strict sense: perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception — vivid, substantial, and located in external objective space.

Think: SENSORY disorder.

Most commonly auditory (hearing voices).

Command hallucinations involve voices giving orders; often co-occur with delusions of persecution or being controlled.

Delusion

Positive symptom of Schizophrenia (added behavior)

An idiosyncratic, irrational belief or impression firmly maintained despite being contradicted by what is generally accepted as reality.

Think: THOUGHT disorder.

Three common types:

1. Delusions of persecution — others are spying/plotting

2. Delusions of grandeur — patient is all-powerful

3. Delusions of being controlled — someone controls thoughts/actions.

Over-Inclusion

Positive symptom of Schizophrenia (added behavior)

A type of disorganized thought/speech in which the patient jumps from idea to idea WITHOUT the benefit of logical association.

Also seen in severe mania.

Paralogic Thought

Positive symptom of Schizophrenia (added behavior)

A type of disorganized thought that on the surface appears logical but is actually seriously flawed.

"Para" means "almost" or "next to" — so paralogic = almost logical.

Example: "Jesus was a man with a beard. I am a man with a beard. Therefore I am Jesus!"

Flat Affect

Negative symptom of Schizophrenia (something missing/disruption)

In which the patient has very little reaction to events around them. They display little-to-no emotion physically and may not feel emotions very much either.

Contrasted with INAPPROPRIATE affect (Another negative symptom of Schizophrenia), where displayed mood does not match circumstance (e.g., laughing at serious events).

Catatonic Behavior (Catatonia)

Negative symptom of Schizophrenia (something missing/disruption)

Characterized by unresponsiveness to the environment, usually marked by immobility for extended periods.

Also associated with echolalia and waxy flexibility.

Can also occur in depression, mood disorders, and other neuropsychiatric conditions.

Note: Lack of motivation is also a negative symptom of Schizophrenia

Echolalia

Negative symptom of Schizophrenia (something missing/disruption)

Parrot-like repetition of speech.

Associated with catatonic schizophrenia. Also seen in other neuropsychiatric conditions such as Tourette's syndrome.

Waxy Flexibility

Negative symptom of Schizophrenia (something missing/disruption)

A psychomotor symptom of catatonic schizophrenia which leads to a decreased response to stimuli and a tendency to remain in an immobile posture for a long time.

Paranoid Schizophrenia

Schizophrenia subtype with well-formed, elaborate hallucinations and delusions (typically of persecution and grandeur).

MOSTLY POSITIVE SYMPTOMS / fewer negative symptoms.

Most common subtype.

BEST prognosis. (DSM-4 subtype — removed from DSM-5 but still useful conceptually.)

Disorganized Schizophrenia (Hebephrenic)

Schizophrenia subtype with disorganized speech, silly/childlike behavior (hence "hebephrenic"), and flat affect.

Delusions and hallucinations are LESS pronounced and have little meaning. Patients tend to be incoherent and have issues with daily self-care.

Also called disorganized type.

Residual Schizophrenia

Schizophrenia subtype that primarily displays NEGATIVE SYMPTOMS: flat affect, reduced speech, lack of motivation.

Positive symptoms are absent or minimal.

Catatonic Schizophrenia

Schizophrenia subtype characterized by unresponsiveness to surroundings, echolalia, waxy flexibility, and possible purposeless movement.

RARE.

Treated with ECT in addition to antipsychotics.

Undifferentiated Schizophrenia

Schizophrenia subtype with a combination of hallucinations, specific delusions, and general disorganization — but no SINGLE symptom type is most prominent.

Patients do not fit well into other categories.

Hypofrontality Hypothesis

Biological / Structural cause of Schizophrenia

A theory that problems in the FRONTAL LOBE are associated with schizophrenia. Suggests genetic/environmental changes to frontal lobes may cause schizophrenia.

Evidence:

1. Discordant identical twins — only the affected twin shows decreased frontal blood flow

2. PET scans show reduced frontal activity in schizophrenics

3. Schizophrenics have difficulty with the Wisconsin Card Sorting Task.

Dopamine & Schizophrenia

Neurochemical cause of Schizophrenia

Dopamine may play a role in schizophrenia, especially hallucinations.

Key relationship:

• TOO MUCH dopamine = psychosis (side effect of L-Dopa for Parkinson's disease).

• TOO LITTLE dopamine = movement disorder/tardive dyskinesia (side effect of antipsychotics).

  • Typical antipsychotics block dopamine D2 receptors.

Genetic cause of Schizophrenia

• Risk increases with genetic similarity to a person with schizophrenia

  • Identical twins: ~48–50% concordance

  • Fraternal twins: ~17%

  • Siblings: ~9%

  • General population: ~1%

• Strong genetic links suggest a biological cause

  • Congenital risks — difficult birth (e.g., oxygen deprivation); prenatal viral infection (e.g., flu during gestation)

  • Brain structure changes: enlarged cerebral ventricles, decreased hippocampus and amygdala, loss of temporal and frontal cortex (particularly in adolescence)

  • Hypofrontality hypothesis

Neurochemical causes of Schizophrenia

• Dopamine

• Glutamate — key excitatory neurotransmitter

  • Some evidence that glutamate decreases are correlated with schizophrenia

  • Medications that increase glutamate do not help symptoms and increase seizure risk

• Serotonin — atypical antipsychotics may also affect serotonin pathways

  • Serotonin's exact role is still being studied

Environmental causes of Schizophrenia

• Stress as a trigger or worsening factor

• Historical (incorrect) theory — Symptoms blamed on the mother (Freud)

  • Now understood to involve structural and functional brain differences

Typical Antipsychotics

Treatment for Schizophrenia

Older class of antipsychotic medications; discovered by accident.

DECREASE DOPAMINE brain-wide.

Primarily improve POSITIVE symptoms rather than negative or cognitive ones.

Higher side effect profile than atypical antipsychotics. Risk of tardive dyskinesia with long-term use.

Atypical Antipsychotics

Treatment for Schizophrenia

Newer class of antipsychotics developed to have fewer side effects.

Affect dopamine pathways in complicated ways. May also affect serotonin pathways.

Decrease many positive and SOME negative symptoms.

Cause cognitive slowing and risk of tardive dyskinesia.

Used for schizophrenia, bipolar disorder, and schizophreniform disorder.

Tardive Dyskinesia

Treatment for Schizophrenia

A POSSIBLY PERMANENT disorder of involuntary, repetitive, purposeless movements — a side effect of long-term or high-dose use of dopamine antagonists (antipsychotics).

Facial muscle distortions and limb tremors common.

Progressive (worsens over time).

Compare: L-Dopa for Parkinson's disease INCREASES dopamine and can cause psychosis — the opposite problem.

Schizoaffective Disorder

A schizophrenic spectrum disorder combining SCHIZOPHRENIA SYMPTOMS (hallucinations, delusions) AND MOOD DISORDER SYMPTOMS (depression or mania).

Two types:

1. Bipolar type — includes mania and sometimes major depression

2. Depressive type — includes only major depressive episodes.

Think: schizophrenia + bipolar disorder.

Schizophreniform Disorder

A schizophrenic spectrum disorder with symptoms of schizophrenia present for LESS THAN 6 MONTHS.

May have rapid onset. Often less social dysfunction.

Better prognosis than schizophrenia — however, about 2/3 of patients eventually progress to full schizophrenia.

Treated with atypical antipsychotics plus social supports.

Schizotypal Personality Disorder

A schizophrenic spectrum personality disorder characterized by paranoia, social anxiety, inappropriate/reduced affect, lack of close relationships, MAGICAL THINKING, and vague metaphorical speech.

Resembles the POSITIVE symptoms of schizophrenia.

Patients often described as odd or eccentric.

Magical Thinking

A thought pattern associated with schizotypal personality disorder.

The patient believes that their thoughts by themselves can bring about effects in the world, or that thinking something corresponds with doing it.

Example: fear of performing certain acts because of an assumed calamitous correlation.

Schizoid Personality Disorder

A schizophrenic spectrum personality disorder characterized by lack of interest in social relationships, tendency toward a SOLITARY LIFESTYLE (hermit), secretiveness, and emotional coldness.

Resembles the NEGATIVE symptoms of schizophrenia.

Patients often happily withdraw from society.

Distinguished from schizotypal by the absence of magical thinking and paranoia.

Frontal lobes

The largest lobes of the brain and are associated with complex "human-like" functions.

Prefrontal cortex (PFC)

Highly developed in humans compared to other mammals, and is highly interconnected with the medial temporal lobe, limbic structures, temporal lobe, and parietal cortex

General functions of the frontal lobes

JEWELS:

• Judgement & Decision-making

  • Determining good vs. bad, better vs. best; predicting future consequences of current actions

  • The "Crystal Ball" – weighing risks/rewards

• Execution & Planning

  • Planning, coordinating, controlling, and executing behavior; problem-solving initiation; motor function

  • The "Project Manager" – getting things done

• Working memory

  • Holding information in your mind temporarily to manipulate it (e.g., remembering a phone number while dialing)

  • The "Mental Whiteboard" – temporary sticky notes

• Emotion & Personality

  • Moderating correct social behavior; personality expression; impulse control

  • The "Social Filter" – what makes you "you"

• Language/Speech Production

  • Motor function of speech (Broca's area – getting words out)

  • The "Megaphone" – turning thoughts into spoken words

• Socialization & Inhibition

  • Differentiating between conflicting thoughts; inhibiting inappropriate actions; acting in accordance with internal goals

  • The "Brakes" – stopping yourself from blurting things out

Executive functions

Cognitive tasks such as working memory, cognitive flexibility, planning, inhibition, and abstract reasoning

General function of frontal lobes

Dorsolateral Prefrontal Cortex (DLPFC)

The highest cortical area responsible for motor planning, organization, and regulation

Involved in the integration of sensory and memory information; regulates intellectual function and action (executive function); involved in working memory.

End point for the dorsal (how-to) pathway.

Damage leads to Frontal Convexity Syndrome.

Orbitofrontal Cortex (OFC)

Frontal lobe subdivision involved in sensory integration, affective value of reinforcers, decision making, expectation/anticipation, taste, flavor

Regulates planning behavior associated with sensitivity to reward and punishment; involved in response inhibition.

Damage leads to Orbitofrontal Syndrome.

Anterior Cingulate Cortex (ACC)

Frontal lobe subdivision that subserves primarily executive functions related to emotional control and the reward system

Key roles in decision making, empathy, and reward anticipation; also involved in autonomic functions (blood pressure, heart rate) together with the brain stem.

Damage + MFC damage leads to Medial Frontal Syndrome

Ventromedial PFC

Frontal lobe subdivision associated with emotion; closely related to orbitofrontal functions.

Wisconsin Card Sorting Task

An example of a test that can reveal problems with executive function associated with DLPFC damage.

• Subject is given a pile of cards that vary in 3 dimensions: color, number, and item

• Goal is to sort cards into category piles — the subject does not know what the categories are; they get feedback from the experimenter

• The rules change — piles that were correct become incorrect

• Normal subjects: can learn the rules after a few trials and can learn to switch and test new rules when old ones fail

• With DLPFC damage: tend to perseverate — have significant difficulty testing and applying new rules

Lobotomy

A procedure where ice picks are placed in the orbital sockets, up into the prefrontal cortex, and wiggled around to destroy tissue — used to treat a wide variety of mental illnesses including schizophrenia, depression, anxiety, and mood swings.

• 1930s–1950s: widely used by Dr. Freeman

• Over 40,000 performed in the US

• 1949 Nobel Prize awarded for its development ("prefrontal leucotomy")

• Last performed in the US in the 1980s

• Results ranged from improvement to severe apathy, withdrawal, and catatonia-like states

• Famous case: Rosemary Kennedy

Frontal Convexity Syndrome

Caused by damage to Dorsolateral Prefrontal Cortex (DLPFC)

Key hallmarks: apathy (no motivation), perseveration (gets mentally stuck), working memory deficits (can’t hold instructions in head)

Mental flexibility impaired, but IQ does not lower

“Apathetic Zombie”

Orbitofrontal syndrome

Caused by damage to Orbital Frontal Cortex (OPC)

Key Symptoms:

• Disinhibited & impulsive behavior (pseudo-psychopathic — says/does anything)

• Emotional lability (large/rapid shifts in emotions)

• Poor judgment and insight

• Sexual disinhibition/inappropriate

Patients have problems with moral reasoning and little insight into their condition

Associated with dementia (e.g., frontotemporal lobar dementia)

Thought to be linked to antisocial personality disorder

“The Reckless Party Animal”

Medial frontal syndrome

Caused by damage to Medial Frontal Cortex + ACC (medial wall of the frontal lobe)

Key symptoms:

• Akinetic mutism

• Incontinence (loss of bladder and bowel control)

• Sparse speech

Causes: Creutzfeldt-Jakob (mad cow) disease, stroke, brain tumor

Patients are not paralyzed — they lack the will to move

Treatment: varies by patient; stimulants, L-Dopa (to increase dopamine)

“The Mannequin”

Akinetic Mutism

A paucity of spontaneous movement and gesture, sparse verbal output, lower extremity weakness and loss of sensation

Antisocial Personality Disorder

Symptoms closely resemble orbitofrontal syndrome. An enduring pattern of manipulating, exploiting, or violating the rights of others.

Related terms: psychopathic personality disorder, sociopathic personality disorder.

• Diagnosed only after age 18; juvenile equivalent is conduct disorder

• Juvenile warning signs: bedwetting, animal abuse, pyromania, problems with authority

• Prevalence: ~3% of men, ~1% of women; estimates of 30–95% of felons

• Causes: genetic risk; possibly maternal deprivation before age 5

• No recognized treatment

Tourette’s Syndrome

A common neuropsychiatric disorder defined as part of a spectrum of tic disorders.

• Onset in childhood: typically 5–9 years old

• Prevalence: up to 1 in 100 children

• Boys diagnosed 3–4× more than girls

• Frequently co-occurs with OCD, ADHD, depression, and anxiety

• Most patients experience peak tic severity before mid-teens, with improvement in late adolescence and early adulthood

• Does not adversely affect intelligence or life expectancy

Symptoms of Tourette’s Syndrome

Multiple motor tics AND at least one vocal tic

Tics are stereotypic, temporarily suppressible, non-rhythmic, and often preceded by an unwanted premonitory urge (like the feeling of needing to sneeze)

Tics wax and wane over time — they change in type, frequency, location, and severity

Patients can sometimes suppress tics briefly, but a rebound effect of more tics typically follows

Tics often worsen with stress or excitement and improve during calm, focused activities

Motor Tics

Involuntary, repetitive movements that are stereotypic, temporarily suppressible, and non-rhythmic

Common examples include eye blinking, facial movements, head jerking

Vocal Tics

Involuntary vocalizations such as throat clearing, sniffing, coughing, or words/phrases

Coprolalia

A condition associated with Tourette's in which the patient has a vocal tic consisting of socially inappropriate exclamations

Occurs in only ~10% of patients (unlike the common media portrayal)

Causes of Tourette’s Syndrome

• Genetic — likely genetic cause affecting frontal lobe and basal ganglia development

• Decreased size of the caudate nucleus of the basal ganglia is correlated with increased tic severity

  • Note: OCD also correlates with changes in the caudate nucleus — this explains the frequent co-occurrence of OCD and Tourette's

• Environmental role in severity — tics often worsen with stress; possible role of stress hormone cortisol

Treatments for Tourette’s Syndrome

• Behavioral: Habit reversal training; Cognitive Behavioral Therapy (CBT); CBIT (Cognitive Behavioral Intervention for Tics)

• Deep Brain Stimulation (DBS) — targets the basal ganglia; can have dramatic symptom improvement but is invasive

• Medications (variable effect):

  • Antipsychotics — decrease dopamine; used for tics

  • Antidepressants (SSRIs) — for co-occurring depression/anxiety

  • Blood pressure medications — for other associated symptoms

Klüver-Bucy Syndrome

A rare behavioral disorder characterized by a distinctive cluster of symptoms resulting from bilateral damage to the amygdala and its connections to the frontal cortex and limbic system.

PVSHE:

• Placidity — diminished fear responses; inability to recognize the emotional importance of an event

• Visual agnosia — diminished ability to visually recognize objects

• Sexuality (altered) — compulsive sex drive; sexual interest in inappropriate objects

• Hyperorality — examining objects by putting them in the mouth

• Eating / Hypermetamorphosis — eating inappropriate objects (e.g., non-food items); overeating / reacts to everything

Caused by bilateral damage to the amygdala and limbic-frontal connections

Causes include stroke, surgery, trauma, infection (e.g., herpes encephalitis)

Hypermetamorphosis

The impulse to notice and react to everything within sight; extreme hyper-reactivity and hyper-responsiveness to environmental stimuli; inability to ignore normal distractors.

Treatment for Klüver-Bucy Syndrome

• Symptomatic only — treatments target symptoms rather than the underlying damage

• Antipsychotic medications — act to decrease dopamine via dopamine pathways