Psychological Disorders

Understanding Psychological Disorders

Priority labels: Must know = cold; Know the logic = mechanism not names; Passage-level = recognize, don't memorize; Optional = skippable.

Must know

A psychological disorder is a clinically significant disturbance in cognition, emotion regulation, or behavior that causes distress and/or impairment in functioning.

The "4 D's":

• Deviance — deviates markedly from cultural norms
• Distress — subjective suffering
• Dysfunction — impairs daily functioning
• Danger — risk of harm to self or others

No single criterion is sufficient alone. Deviance without distress or impairment is not a disorder (e.g., eccentricity). Distress and dysfunction are the most central; danger is the least common.

The Role of Culture

Passage-level

Behavior must be judged relative to cultural context: the DSM-5 recognizes cultural syndromes that don't map onto Western categories. On the MCAT, behavior that is culturally sanctioned or normative does not by itself constitute a disorder.

Stigma, Labeling, and the Rosenhan Experiment

Must know

In David Rosenhan's "On Being Sane in Insane Places," healthy confederates feigning hearing voices were admitted to psychiatric hospitals (mostly diagnosed schizophrenia); once labeled, their normal behavior was reinterpreted through the diagnosis (note-taking became "writing behavior"). It demonstrated the unreliability of diagnosis and the power of labeling — once labeled "disordered," behavior is read to confirm the label — connecting to stigma and labeling theory of mental illness.

Quick check: A student scores in the top 1% on intelligence tests, has no friends, and prefers isolation — but reports that life feels meaningful and satisfying, and she holds a steady job she loves. Does she have a psychological disorder?
Answer: No. Deviance alone does not define a disorder. She lacks distress and impairment — the two most critical criteria — so no diagnosis is warranted.

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Biomedical vs. Biopsychosocial Approaches

The Biomedical Model

Must know

The biomedical model views disorders as biological malfunctions of the brain (neurotransmitter imbalance, genetics, structural abnormalities) treated biologically (pharmacotherapy, ECT). Its strength is empirical precision; its weakness is neglecting life experience and social context.

Passage-level

Biomedical/somatic treatments target the brain directly (drugs; ECT for treatment-resistant depression; TMS, DBS). Psychotherapies target thoughts/behaviors/relationships, each following from a theory of disorder:

Therapy school	Core idea
Psychodynamic (Freud)	Symptoms from unconscious conflict; insight via free association/transference
Humanistic (Rogers)	Distress from incongruence; unconditional positive regard
Behavioral	Maladaptive behavior is learned; conditioning (desensitization, exposure)
Cognitive / CBT (Beck, Ellis)	Distorted thoughts drive distress; restructure cognitions

The Biopsychosocial Model

Must know

The biopsychosocial model (Engel) — the dominant modern framework the MCAT endorses — holds that disorders emerge from interacting biological (genes, neurochemistry, brain structure), psychological (cognition, coping, learning history), and social (SES, family, culture, stress) factors. It explains why two people with the same genes can have different outcomes. Combining biological and psychosocial treatment often outperforms either alone.

The Diathesis-Stress Model

Must know

The diathesis-stress model is the high-yield biopsychosocial application: a pre-existing vulnerability (diathesis — genetic, cognitive, or trauma-based) becomes a disorder when sufficient stress is imposed. High vulnerability needs little stress; high resilience needs a lot. It explains why not everyone exposed to trauma develops PTSD and why schizophrenia runs in families but isn't inevitable.

Quick check: A woman has a family history of major depression (biological diathesis) and recently lost her job and her long-term partner in the same month. She now meets criteria for major depressive disorder. Which model best explains her case, and what are the three contributing dimensions?
Answer: The biopsychosocial (or diathesis-stress) model. Biological: genetic predisposition; Psychological: possibly a ruminative cognitive style; Social: job loss and relationship dissolution as stressors.

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Classifying Psychological Disorders

DSM-5 vs. ICD

Must know

The DSM-5 (American Psychiatric Association) is the US psychiatric classification the MCAT tests. It is categorical: disorders are defined by symptom criteria meeting duration/impairment thresholds. (In DSM-5, OCD and PTSD each sit in their own chapters, separate from anxiety disorders.) The ICD (WHO) covers all medical conditions and is used internationally — do not call the DSM international.

Reliability and Validity

Know the logic

• Reliability: different clinicians reach the same diagnosis for the same patient (a major criticism of early DSM editions).
• Validity: the category captures a real, coherent entity.

Quick check: A researcher finds that two experienced clinicians agree on a diagnosis of generalized anxiety disorder for the same patient only 55% of the time. Is this a reliability or validity problem?
Answer: Reliability. The clinicians are not consistently arriving at the same conclusion — this is an inter-rater reliability issue, not a question of whether GAD is a real entity.

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Rates of Psychological Disorders

Must know

Two terms:

• Prevalence = proportion of a population that has a disorder at a given time (lifetime prevalence = ever met criteria).
• Incidence = number of new cases over a time period.

Know the logic

Rough magnitudes (don't memorize exact percents): anxiety disorders are the most common category (~30% lifetime), then depression (~17%); schizophrenia and bipolar I are each ~1%.

Comorbidity (two or more disorders in one person) is the rule, not the exception — depression and anxiety frequently co-occur. Sex differences (classic angle): mood/anxiety disorders are ~2x more common in women; substance use and antisocial PD more common in men; schizophrenia has equal prevalence but earlier onset in men.

Quick check: A study reports that 3 out of 100 adults in a city currently have generalized anxiety disorder. Is this a prevalence or incidence figure?
Answer: Prevalence (specifically, point prevalence — the proportion with the disorder at one moment in time). Incidence would require tracking who newly developed the disorder over a period of time.

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Types of Psychological Disorders

The following sections cover each major disorder category the MCAT tests. For each, focus on: core features, DSM-5 criteria highlights, relevant neurobiology, and classic MCAT scenarios.

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Anxiety Disorders

Must know

Anxiety is the anticipatory response to a perceived future threat (mediated by the sympathetic nervous system and HPA axis). It becomes a disorder when persistent, disproportionate, and impairing. Anxiety disorders are the most prevalent class. The distinctions:

• Generalized anxiety disorder (GAD): excessive, uncontrollable worry across many domains, more days than not — the hallmark is the breadth and uncontrollability, not one specific fear.
• Panic disorder: recurrent unexpected panic attacks (sudden surge of intense fear peaking within minutes — palpitations, shortness of breath, chest pain, fear of dying/losing control) PLUS persistent anticipatory anxiety or avoidance about future attacks. The anticipatory worry is what makes it a disorder beyond the attacks.
• Specific phobia: intense, recognized-as-excessive fear of a specific object/situation. Know the logic the blood-injection-injury subtype is unique — it triggers a vasovagal response (bradycardia, BP drop, fainting) rather than the usual sympathetic surge.
• Social anxiety disorder: fear of social scrutiny/embarrassment.
• Agoraphobia: fear of situations where escape/help is difficult (crowds, open spaces, public transit); separate from panic disorder in DSM-5.

Neurobiology of Anxiety

Know the logic

The amygdala is central to fear; anxiety involves amygdala hyperactivation, reduced prefrontal regulation, and low GABA tone (the main inhibitory neurotransmitter — less GABA → more anxiety; benzodiazepines potentiate GABA). SSRIs/SNRIs are first-line maintenance.

Quick check: A 28-year-old man has been terrified of dogs since being bitten at age 5. He reports significant distress and won't visit friends who own dogs, but is otherwise functioning well. Which anxiety disorder fits?
Answer: Specific phobia (animal subtype). The fear is of a specific stimulus, is recognized as excessive, and causes behavioral avoidance/impairment.

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Obsessive-Compulsive Disorder

Must know

OCD sits in its own DSM-5 chapter, separate from anxiety disorders. Obsessions are recurrent, intrusive, unwanted thoughts/urges/images; compulsions are repetitive behaviors or mental acts performed to reduce the distress an obsession causes (e.g., contamination fear → washing; doubt → checking). The compulsion temporarily relieves anxiety (negative reinforcement) but isn't realistically connected to the feared outcome.

Optional

Related disorders (recognize, don't memorize): body dysmorphic disorder, hoarding, trichotillomania (hair-pulling), excoriation (skin-picking).

Neurobiology of OCD

Know the logic

OCD involves hyperactivity in the cortico-striato-thalamo-cortical loop (orbitofrontal cortex and caudate) — an "error signal" that never habituates, hence the relentless sense something is wrong. First-line: SSRIs and exposure and response prevention (ERP) (confront the trigger without performing the compulsion).

Quick check: A woman spends 3 hours each morning checking the stove, locks, and electrical outlets before leaving her home. She knows intellectually that she checked them thoroughly but cannot resist repeating the process. She is embarrassed and has been late to work 20 times this month. What disorder and which specific feature (obsession/compulsion) drives each behavior?
Answer: OCD. The intrusive doubt that she may have left something on/unlocked is the obsession; the repeated checking is the compulsion. The compulsions are maintained by temporary anxiety reduction (negative reinforcement).

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Trauma- and Stressor-Related Disorders

This DSM-5 chapter is defined by disorders etiologically linked to a specific external event — unlike anxiety disorders, which need no external trigger.

Post-Traumatic Stress Disorder (PTSD)

Must know

PTSD follows exposure to a traumatic event (actual/threatened death, serious injury, or sexual violence) and persists >1 month with four symptom clusters:

1. Intrusion: flashbacks, nightmares, intrusive memories
2. Avoidance: of trauma reminders
3. Negative cognition/mood: negative beliefs, detachment, numbing
4. Hyperarousal: hypervigilance, exaggerated startle, irritability

Know the logic

Neurobiology: amygdala hyperactive; hippocampus reduced (trauma feels ongoing); prefrontal cortex underactive (impaired fear extinction). First-line: SSRIs and exposure-based therapy.

Acute Stress Disorder

Passage-level

Same symptom domains as PTSD but lasting under one month after trauma; if it persists beyond a month, it becomes PTSD.

Adjustment Disorder

Know the logic

Adjustment disorder is an out-of-proportion emotional/behavioral response to an identifiable, non-traumatic stressor (divorce, job loss, illness) — a "subthreshold" stress response that resolves once the stressor ends.

Quick check: A combat veteran has nightmares about his deployment, avoids watching war movies, feels emotionally numb and detached from his family, and startles violently at loud sounds — all persisting for 8 months. What is the most likely diagnosis?
Answer: PTSD. The Criterion A event (combat), intrusion (nightmares), avoidance (avoiding war movies), negative mood alterations (numbing, detachment), and hyperarousal (exaggerated startle) are all present for >1 month.

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Somatic Symptom and Related Disorders

Must know

These disorders bridge psychology and medicine. The highest-yield aspect is distinguishing them (see the table below).

• Somatic symptom disorder: distressing physical symptom(s) PLUS disproportionate thoughts/anxiety/behavior about them. The symptoms may or may not have a medical cause — diagnosis rests on the dysfunctional response, not the absence of organic cause.
• Illness anxiety disorder (formerly hypochondriasis): high anxiety about having a serious illness with minimal or no actual symptoms, persisting despite reassurance.
• Conversion disorder (functional neurological symptom disorder): neurological symptoms (paralysis, blindness, seizures) incompatible with known neurology and not intentionally produced. MCAT cue: symptoms that don't follow anatomical patterns (e.g., non-dermatomal sensory loss).
• Factitious disorder (Munchausen): symptoms intentionally produced to assume the sick role, motivation internal (no external gain). Imposed on another = inducing illness in a dependent.
• Malingering (NOT a disorder): faking for clear external gain (money, avoiding legal trouble).

Disorder	Aware of faking?	External gain?
Somatic symptom disorder	No (symptoms are real)	No
Illness anxiety disorder	No	No
Conversion disorder	No	No
Factitious disorder	Yes	No (internal motivation)
Malingering (NOT a disorder)	Yes	Yes

Quick check: A hospitalized man is found to have been secretly injecting himself with bacteria to stay in the hospital. When confronted, he denies any secondary gain — he simply "likes the attention from the nurses." Is this factitious disorder or malingering?
Answer: Factitious disorder. He is intentionally producing symptoms (aware), but the motivation is internal (sick role, attention) — not external gain like money or legal avoidance.

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Bipolar and Related Disorders

Must know

Bipolar disorders involve episodes of elevated mood alternating with depressive periods. Mania vs. hypomania:

• Manic episode: abnormally elevated/irritable mood with increased energy, lasting ~1 week, causing marked impairment (may include psychosis or require hospitalization). Features: grandiosity, decreased need for sleep, pressured speech, flight of ideas, distractibility, impulsive/reckless behavior.
• Hypomanic episode: same features but shorter, milder, no marked impairment, no psychosis.

The diagnoses:

• Bipolar I: at least one full manic episode (depression common but not required) — the most severe.
• Bipolar II: a hypomanic episode PLUS a major depressive episode, never full mania (full mania → upgrade to Bipolar I).
• Cyclothymic disorder: chronic (≥2 yr) subthreshold hypomanic and depressive symptoms.

Treatment

Know the logic

Cornerstone is mood stabilizers (classically lithium). High-yield caution: antidepressants alone can trigger mania in bipolar patients.

Quick check: A 25-year-old woman has a 3-year history of weeks feeling "on top of the world," needing only 3 hours of sleep, spending recklessly, and being extremely productive, alternating with weeks of profound sadness, hypersomnia, and hopelessness. During the "up" periods she was never hospitalized and maintained her job. What is the most likely diagnosis?
Answer: Bipolar II disorder. Her elevated episodes do not cause marked impairment and no hospitalization occurred (hypomanic, not manic). The major depressive episodes are also present.

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Depressive Disorders

Depression is the leading cause of disability worldwide and the single most-tested mood disorder on the MCAT.

Major Depressive Disorder (MDD)

Must know

A major depressive episode is depressed mood and/or anhedonia (loss of interest/pleasure — a core feature) plus several additional symptoms for at least 2 weeks, causing impairment. The standard symptom set (mnemonic SIG E CAPS) is: Sleep changes, Interest loss (anhedonia), Guilt/worthlessness, Energy loss, Concentration difficulty, Appetite/weight changes, Psychomotor agitation/retardation, Suicidal ideation. (Know the concept; you don't need to count exact criteria.)

Persistent Depressive Disorder (Dysthymia)

Must know

Chronic depressed mood lasting at least 2 years — less severe than MDD but more persistent.

Seasonal Affective Disorder (SAD)

Passage-level

A seasonal pattern (usually fall/winter onset, spring remission) tied to reduced light → reduced serotonin and disrupted melatonin/circadian rhythms. Treatment: morning light therapy, SSRIs.

Psychological Theories of Depression

Must know

Two named theories:

• Beck's cognitive triad: negative views of the self, the world, and the future, maintained by cognitive distortions. Basis for CBT.
• Seligman's learned helplessness: dogs given inescapable shock later failed to escape when they could — having learned their actions don't affect outcomes. In humans, perceiving responses as independent of outcomes → helplessness → depression. The reformulation adds attributional style (internal, stable, global attributions for bad events increase vulnerability).

Suicide: Risk Factors

Know the logic

Women attempt suicide more often, but men die by suicide more often (men use more lethal means). The single strongest predictor is a prior attempt; other risk factors include mood/substance disorders, isolation, recent loss, and hopelessness.

Neurobiological Basis of Depression

Must know

The monoamine hypothesis (detailed below) proposes deficiency in serotonin, norepinephrine, and/or dopamine. Neuroanatomy: reduced prefrontal activity, amygdala hyperactivity, reduced hippocampal volume.

Quick check: Using Beck's cognitive triad, describe the thought patterns of a college student with MDD who says, "I'm a failure, this school is set up for people smarter than me, and no matter what I do I'll never graduate."
Answer: Negative self ("I'm a failure" — self), negative world ("the school is set up against me" — world), and negative future ("I'll never graduate" — future). This captures all three corners of Beck's cognitive triad.

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Schizophrenia

Must know

Schizophrenia is a chronic psychotic disorder affecting ~1% of people, with onset in early adulthood (earlier in men).

Diagnosis and Course

Must know

Schizophrenia requires two or more of: delusions, hallucinations, disorganized speech, grossly disorganized/catatonic behavior, negative symptoms (with continuous disturbance over time). It progresses through a prodromal phase (gradual withdrawal, declining function, odd beliefs before frank psychosis), an active phase (florid positive symptoms), and a residual phase. It is a textbook diathesis-stress disorder — genetic vulnerability plus environmental insults.

Passage-level

Risk factors: prenatal stressors, adolescent cannabis use, and high family expressed emotion (predicts relapse). The downward drift hypothesis explains lower SES as a consequence of the illness, not a cause.

Positive vs. Negative Symptoms

Must know

"Positive" = added to normal experience; "negative" = normal functions lost.

Positive (excesses)	Negative (deficits)
Delusions (fixed false beliefs)	Avolition (no motivation)
Hallucinations (most often auditory)	Alogia (poverty of speech)
Disorganized speech/thought	Affective flattening (blunted affect)
Disorganized/catatonic behavior	Anhedonia, asociality

Positive symptoms respond better to antipsychotics; negative symptoms are more treatment-resistant and predict long-term outcomes. Delusions are false beliefs (persecutory, grandiose, referential); hallucinations are false perceptions (auditory most characteristic). Disorganized speech shows as derailment/loosening of associations, tangentiality, or word salad.

Dopamine Hypothesis

Must know

The dopamine hypothesis holds that excess mesolimbic dopamine underlies positive symptoms. Evidence: dopamine-boosting drugs (amphetamines) can induce psychosis, and typical antipsychotics work by blocking D2 receptors. It doesn't fully explain negative/cognitive symptoms (which may involve glutamate), so atypical antipsychotics (dopamine + serotonin) address those better. Other findings: strong genetic component and enlarged cerebral ventricles.

Optional

EPS aside: typical antipsychotics also block dopamine in the nigrostriatal pathway, mimicking Parkinson's and producing extrapyramidal symptoms and, long-term, tardive dyskinesia.

Quick check: A 22-year-old man is brought to the ER believing that his food is being poisoned by his neighbors and that he can hear his neighbors talking about him through the walls at night. He has had these experiences for 7 months and has become increasingly withdrawn and stopped attending school. Identify the symptom type (positive/negative) for each feature described.
Answer: Beliefs about poisoning = persecutory delusion (positive). Auditory hallucinations (hearing voices through walls) = hallucination (positive). Withdrawal and school cessation = asociality and avolition (negative symptoms).

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Dissociative Disorders

Must know

Dissociation is a disruption in the normally integrated experience of consciousness, memory, identity, and perception. The three disorders:

• Dissociative identity disorder (DID) (formerly multiple personality disorder): two or more distinct identity states that take control, with amnesia between them; strongly linked to severe childhood trauma. Distinguish from schizophrenia (psychosis, not split identity) and BPD (identity instability without discrete alters).
• Dissociative amnesia: inability to recall important autobiographical (often traumatic) information beyond ordinary forgetting; subtype dissociative fugue adds travel/new identity.
• Depersonalization/derealization disorder: detachment from self (depersonalization — "watching myself from outside") or from surroundings (derealization — world feels unreal). Reality testing stays intact, which rules out psychosis.

Quick check: A patient reports that she sometimes feels as if she is watching herself from outside her body, as though she were a character in a movie — but she knows this is an unusual experience, not literally true. Which dissociative disorder fits, and what feature rules out psychosis?
Answer: Depersonalization/derealization disorder. Intact reality testing (she knows it's not literally true) rules out psychosis.

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Personality Disorders

Must know

Personality disorders are enduring, pervasive, inflexible patterns of experience/behavior that deviate from cultural expectations and begin by early adulthood. Their defining feature is being ego-syntonic — the person sees the traits as normal/acceptable (contrast OCD, which is ego-dystonic and distressing). DSM-5 groups 10 into three clusters:

Cluster A — "Odd, Eccentric"

Know the logic

Share features with schizophrenia; more common in relatives of people with schizophrenia.

• Paranoid PD: pervasive distrust/suspiciousness (no psychosis).
• Schizoid PD: detachment; genuinely prefers to be alone.
• Schizotypal PD: eccentricity, magical thinking, ideas of reference; genetically related to schizophrenia.

Cluster B — "Dramatic, Erratic"

Must know

• Antisocial PD: disregard for and violation of others' rights, deceit, impulsivity, lack of remorse (preceded by conduct disorder; diagnosed at ≥18). More common in men.
• Borderline PD: instability of self-image, relationships, and affect; impulsivity; fear of abandonment; splitting (all-good/all-bad); self-harm. Treated with dialectical behavior therapy (DBT).
• Histrionic PD: excessive emotionality, attention-seeking.
• Narcissistic PD: grandiosity, need for admiration, lack of empathy (with fragile self-esteem).

Cluster C — "Anxious, Fearful"

Know the logic

• Avoidant PD: social inhibition; wants relationships (unlike schizoid) but fears rejection.
• Dependent PD: excessive need to be cared for; submissiveness.
• Obsessive-Compulsive PD (OCPD): rigid perfectionism and control; ego-syntonic. Distinct from OCD — a personality style, not intrusive thoughts/compulsions.

Quick check: A 35-year-old woman frequently shows up at her ex-boyfriend's workplace, believes he is secretly sending her messages through song lyrics on the radio, and has no other psychotic symptoms. Her friends describe her as always suspecting people of plotting against her. Which cluster and personality disorder fits?
Answer: Cluster A, Paranoid Personality Disorder. The referential thinking (song lyrics as messages) and pervasive suspiciousness fit, but the absence of full psychosis rules out a psychotic disorder. (Note: schizotypal PD could also fit given the ideas of reference and magical thinking — the MCAT would need to specify further.)

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Biological Bases of Nervous System Disorders

This section bridges psychology and biology — one of the MCAT's signature integration moves.

Depression — Neurobiological Basis

Must know

The monoamine hypothesis proposes depression results from deficient monoamines — serotonin, norepinephrine, dopamine. Antidepressant classes raise monoamine availability: SSRIs (block serotonin reuptake), SNRIs (serotonin + norepinephrine), TCAs, and MAOIs (block monoamine breakdown).

Know the logic

The lag: antidepressants raise synaptic monoamines within hours, but clinical response takes 2–4 weeks, implying the real therapeutic mechanism is downstream neuroplasticity (e.g., hippocampal neurogenesis) — so the simple monoamine deficit story is incomplete. Neuroanatomy: reduced prefrontal activity, amygdala hyperactivity, reduced hippocampal volume.

Quick check: Why does it take 2–4 weeks for SSRIs to relieve depression if they block serotonin reuptake immediately?
Answer: The immediate biochemical effect (increased synaptic serotonin) triggers downstream adaptations — including downregulation of presynaptic autoreceptors, changes in postsynaptic receptor sensitivity, and BDNF-mediated neuroplasticity — that take weeks to develop and may be the actual therapeutic mechanism.

Alzheimer's Disease

Must know

Alzheimer's disease (AD) is the most common dementia. Two pathological hallmarks:

1. Amyloid (senile) plaques: extracellular deposits of β-amyloid peptide.
2. Neurofibrillary tangles: intracellular aggregates of hyperphosphorylated tau (normally stabilizes microtubules).

Neurotransmitter deficit: loss of cholinergic neurons → low acetylcholine in cortex and hippocampus. Clinical course: begins with episodic memory loss (hippocampus affected earliest), progressing to global cognitive decline.

Optional

People with Down syndrome develop AD pathology early (amyloid precursor protein gene is on chromosome 21).

Quick check: A 68-year-old man with progressive memory loss has a brain biopsy showing extracellular protein deposits and intracellular fibrillary tangles. What are these structures, what proteins compose them, and what neurotransmitter system is most depleted?
Answer: Extracellular deposits = amyloid (senile) plaques, composed of β-amyloid peptide. Intracellular tangles = neurofibrillary tangles, composed of hyperphosphorylated tau protein. Most depleted neurotransmitter system = acetylcholine (cholinergic deficit).

Parkinson's Disease

Must know

Parkinson's disease (PD) results from loss of dopaminergic neurons in the substantia nigra, which normally supplies dopamine to the striatum via the nigrostriatal pathway (basal ganglia / extrapyramidal motor system).

Classic motor signs (TRAP): resting Tremor ("pill-rolling," improves with movement), Rigidity (cogwheel), Akinesia/bradykinesia, Postural instability. Pathological hallmark: Lewy bodies (intracellular α-synuclein). Treatment restores dopamine, classically with levodopa (L-DOPA).

PD vs. AD: PD = motor disorder (dopamine, substantia nigra); AD = cognitive disorder (acetylcholine, cortex/hippocampus). Both are neurodegenerative with abnormal protein aggregation (α-synuclein vs. β-amyloid/tau).

Quick check: A neurologist notes that a patient's tremor disappears when she reaches to pick up a glass of water. What type of tremor is this, and what disorder does this pattern suggest?
Answer: Resting tremor (present at rest, suppressed with voluntary movement) — this is classic for Parkinson's disease. By contrast, essential tremor worsens with action/intention.

Stem Cell-Based Therapy to Regenerate CNS Neurons

Must know

The adult CNS has very limited self-repair: dead neurons (stroke, spinal cord injury, AD, PD) are largely not replaced. Stem cell therapy aims to overcome this.

Stem cell types:

• Embryonic stem cells (ESCs): pluripotent; high potential but ethical (embryo destruction) and rejection concerns.
• Induced pluripotent stem cells (iPSCs): somatic cells reprogrammed to pluripotency (Yamanaka). Avoid the ethical issue; autologous use avoids rejection.
• Neural stem cells (NSCs): multipotent CNS cells persisting in a few niches (notably the hippocampus) — sites of the limited adult neurogenesis.

Passage-level PD is the leading target because the deficit is focal (replace substantia nigra dopamine neurons); AD is harder because degeneration is diffuse.

Key challenges (common distractors):

• Functional integration: transplanted cells must survive, migrate, differentiate correctly, and wire into existing circuits — not just fill space.
• Immune rejection: donor/ESC cells can be attacked; autologous iPSCs sidestep this.
• Tumorigenicity: residual undifferentiated pluripotent cells can form teratomas.
• Ethics: ESCs require embryo destruction; iPSCs avoid this.

Quick check: A research team wants to treat a Parkinson's patient by generating dopaminergic neurons from the patient's own skin cells, avoiding both immune rejection and embryo destruction. What cell type are they using, and what is the principal safety risk they must control for?
Answer: Induced pluripotent stem cells (iPSCs) — reprogrammed autologous somatic cells, so they avoid immune rejection and the ethical issues of ESCs. The principal safety risk is tumorigenicity: any residual undifferentiated pluripotent cells can form teratomas, so the graft must be fully differentiated and screened before transplantation.

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Common Confusions & Tricks

1. Biomedical vs. biopsychosocial. Biomedical = biological causes alone; biopsychosocial adds psychological + social/cultural factors (the dominant framework). The diathesis-stress model is a specific biopsychosocial idea: a vulnerability triggered by environmental stress.

2. DSM vs. ICD. DSM-5 (APA) = US psychiatric diagnosis. ICD (WHO) = all medical conditions, international. Don't call the DSM international.

3. Bipolar I vs. II. I = at least one full manic episode (depression not required). II = hypomania + a major depressive episode, never full mania.

4. OCD/PTSD are no longer anxiety disorders. In DSM-5 they have their own chapters, separate from anxiety disorders.

5. Obsessions vs. compulsions. Obsessions = intrusive thoughts; compulsions = repetitive behaviors done to relieve the obsession's anxiety.

6. Schizophrenia ≠ DID. "Split mind" trap — schizophrenia is psychotic, not multiple personalities. Multiple identities = DID (dissociative).

7. Positive vs. negative symptoms. Positive = added (hallucinations, delusions, disorganization); negative = lost (flat affect, avolition, alogia). "Positive" ≠ good.

8. Delusion vs. hallucination. Delusion = false belief; hallucination = false perception.

9. Conversion vs. factitious vs. somatic symptom vs. malingering. Conversion = unintentional neurological symptoms, no medical cause. Somatic symptom = real distress/worry about physical symptoms. Factitious = intentional symptoms for the sick role (no external reward). Malingering = faking for external gain (not a disorder). Key axes: intentional vs. not, internal vs. external motivation.

10. MDD vs. dysthymia. MDD = discrete episodes (≥2 weeks). Dysthymia = chronic low-grade mood (≥2 years).

11. Parkinson's vs. Alzheimer's. PD = dopamine loss, substantia nigra (motor; α-synuclein/Lewy bodies). AD = acetylcholine loss (cognitive; β-amyloid plaques + tau tangles).

12. Personality clusters. A = odd/eccentric (paranoid, schizoid, schizotypal); B = dramatic/erratic (antisocial, borderline, histrionic, narcissistic); C = anxious/fearful (avoidant, dependent, OCPD). OCPD ≠ OCD (ego-syntonic rigid personality style).

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Key Theories & Terms

Term / Concept	What it means
Biomedical model	Views disorders as arising from biological causes alone (genes, neurochemistry, brain structure); treated biologically
Biopsychosocial model	Dominant framework: disorders result from interacting biological, psychological, and social/cultural factors
Diathesis-stress model	A biological/genetic vulnerability (diathesis) is expressed as a disorder when triggered by environmental stress
Rosenhan experiment	"Being sane in insane places"; demonstrated unreliability of psychiatric diagnosis and the power of labeling/context
DSM-5	American Psychiatric Association's classification of mental disorders; standard for US psychiatric diagnosis
ICD	WHO's International Classification of Diseases; covers all medical conditions and is used internationally
Generalized anxiety disorder (GAD)	Excessive, uncontrollable worry about many domains, most days for ≥6 months
Panic disorder	Recurrent unexpected panic attacks plus persistent fear of future attacks
Specific phobia	Marked, irrational fear of a specific object or situation
Social anxiety disorder	Intense fear of social scrutiny or embarrassment
Agoraphobia	Fear of places/situations where escape is difficult (e.g., crowds, open spaces)
Obsessive-compulsive disorder (OCD)	Intrusive obsessions (thoughts) and compulsions (rituals) that reduce anxiety; linked to cortico-striatal-thalamic circuits
PTSD	Re-experiencing, avoidance, negative mood/cognition, and hyperarousal lasting >1 month after trauma
Acute stress disorder	PTSD-like symptoms occurring within 1 month of trauma (3 days–1 month)
Adjustment disorder	Emotional/behavioral symptoms in response to an identifiable stressor, out of proportion to it
Somatic symptom disorder	Excessive thoughts/distress about real physical symptoms
Illness anxiety disorder	Preoccupation with having a serious illness despite minimal/no symptoms
Conversion disorder	Neurological symptoms (e.g., paralysis, blindness) with no medical cause, not intentionally produced
Factitious disorder (Munchausen)	Intentionally produced symptoms to assume the sick role, without external reward
Bipolar I	At least one full manic episode (± depression)
Bipolar II	Hypomanic episode plus major depressive episode; no full mania
Cyclothymic disorder	Chronic (≥2 yr) fluctuating hypomanic and depressive symptoms below threshold for full episodes
Major depressive disorder (MDD)	Discrete episodes (≥2 weeks) of depressed mood/anhedonia plus somatic and cognitive symptoms
Persistent depressive disorder (dysthymia)	Chronic low-grade depressed mood lasting ≥2 years
Seasonal affective disorder (SAD)	Depressive episodes with a seasonal (typically winter) pattern
Monoamine hypothesis	Depression linked to deficient serotonin, norepinephrine, and dopamine; basis for SSRIs/SNRIs/TCAs/MAOIs
Schizophrenia	Psychotic disorder with positive symptoms (hallucinations, delusions, disorganization) and negative symptoms (flat affect, avolition, alogia)
Dopamine hypothesis	Schizophrenia linked to excess dopaminergic (mesolimbic) activity; antipsychotics block D2 receptors
Dissociative identity disorder (DID)	Two or more distinct identity states; a dissociative — not psychotic — disorder
Dissociative amnesia	Inability to recall important personal information, often after trauma
Depersonalization/derealization	Persistent detachment from self (depersonalization) or surroundings feeling unreal (derealization)
Personality disorder clusters	A = odd/eccentric; B = dramatic/erratic; C = anxious/fearful (enduring, pervasive, inflexible patterns)
Alzheimer's disease	Dementia with β-amyloid plaques + tau neurofibrillary tangles; cholinergic deficit (nucleus basalis)
Parkinson's disease	Loss of dopaminergic neurons in the substantia nigra; resting tremor, rigidity, bradykinesia; α-synuclein Lewy bodies
Stem cell therapy	Use of ESCs, iPSCs, or neural stem cells to replace lost CNS neurons; key challenges are integration, immune rejection, and tumorigenicity