Biological Basis of Nervous System Disorders

Psychological disorders aren't just patterns of behavior — many have identifiable genetic, neurochemical, and structural roots in the brain. This article covers the biological basis of four conditions tested on the MCAT: schizophrenia, depressive and bipolar disorders, Alzheimer's disease, and Parkinson's disease.

Key Takeaways

• Schizophrenia is linked to genetic risk (10x risk to first-degree relatives), birth hypoxemia, and adolescent marijuana use, with excess dopamine (the dopamine hypothesis) as its core biological marker; neuroleptics treat it by blocking dopamine receptors.

• Depression is marked by decreased norepinephrine/serotonin/dopamine (monoamine theory), high amygdala glucose metabolism, hippocampal atrophy, and elevated cortisol; bipolar disorder shows the opposite pattern — increased norepinephrine and serotonin — plus a notable association with multiple sclerosis.

• Alzheimer's disease involves early-onset risk genes (PSEN1, PSEN2, APP) and a late-onset risk modulator (APOE), alongside cholinergic deficits (reduced acetylcholine, ChAT), brain atrophy, and its two histopathological hallmarks: extracellular β-amyloid senile plaques and intracellular hyperphosphorylated tau neurofibrillary tangles.

• Parkinson's disease results from decreased dopamine production in the substantia nigra, impairing basal ganglia function and producing bradykinesia, resting tremor, cogwheel rigidity, masklike facies, and shuffling gait; L-DOPA (a dopamine precursor) partially treats it.

Schizophrenia

Schizophrenia's most probable cause is genetic, though environmental factors also contribute risk. Trauma at birth — especially hypoxemia (low oxygen concentrations) — is a considered risk factor, as is excessive marijuana use during adolescence.

Schizophrenia is partially inherited: if a person has schizophrenia, their first-degree relatives have roughly 10 times the risk of developing the disorder compared to the general population.

Biologically, schizophrenia is highly associated with an excess of dopamine in the brain — the dopamine hypothesis of schizophrenia. It may also involve structural changes in the brain.

Neuroleptics are medications used to treat schizophrenia by blocking dopamine receptors. The name "neuroleptic" (also called antipsychotic) comes from the sedating, psychomotor-slowing side effects of these drugs.

MCAT Callout — Dopamine hypothesis vs. monoamine theory: don't mix up the two major neurotransmitter theories in this chapter. Schizophrenia is linked to an excess of dopamine, which is why neuroleptics work by blocking dopamine receptors. Depression, by contrast, is linked to a deficit of norepinephrine, serotonin, and dopamine (see the monoamine theory below) — the opposite direction, in a different but overlapping set of neurotransmitters.

Depressive and Bipolar Disorders

Depression is associated with several biological markers:

• High glucose metabolism in the amygdala.

• Hippocampal atrophy after a long duration of illness.

• Abnormally high levels of glucocorticoids (cortisol).

• Decreased norepinephrine, serotonin, and dopamine — the monoamine theory of depression. Both the neurotransmitters themselves and their metabolites are decreased, meaning their actual production is reduced (not just their reuptake or breakdown).

Bipolar disorder is associated with a different set of markers:

• Increased norepinephrine and serotonin.

• Higher risk if a parent has bipolar disorder.

• Higher risk for persons with multiple sclerosis.

Alzheimer's Disease

Alzheimer's disease is a type of dementia characterized by gradual memory loss, disorientation in time and place, problems with abstract thought, and a tendency to misplace things. Later stages are associated with changes in mood or behavior, changes in personality, difficulty with procedural memory, poor judgment, and loss of initiative.

The disease is most prominent in patients older than 65, and women are at greater risk. Family history is a significant risk factor, while higher levels of education are associated with a lower risk level.

Genetic Component

• PSEN1 (chromosome 14) and PSEN2 (chromosome 1) — the two presenilin genes — contribute to having the disease when mutated; mutations in PSEN1 account for the majority of early-onset familial cases.

• Apolipoprotein E (APOE) gene mutations on chromosome 19 can alter the likelihood of acquiring the disease.

• β-amyloid precursor protein (APP) gene on chromosome 21 contributes to a higher risk.

• Individuals with Down syndrome are at a much higher risk of Alzheimer's disease.

Biological Factors

• Diffuse atrophy of the brain visible on CT or MRI.

• Flattened sulci in the cerebral cortex.

• Enlarged cerebral ventricles.

• Deficient blood flow in the parietal lobes, correlated with cognitive decline.

• Reduction in acetylcholine levels.

• Reduction in choline acetyltransferase (ChAT), the enzyme that produces acetylcholine.

• Reduced metabolism in the temporal and parietal lobes.

• Senile plaques of β-amyloid — a misfolded protein in beta-pleated sheet form.

• Neurofibrillary tangles of hyperphosphorylated tau protein.

MCAT Callout — Plaques vs. tangles: senile plaques and neurofibrillary tangles are both Alzheimer's hallmarks, but they're built from different proteins in different locations. Senile plaques are extracellular deposits of misfolded β-amyloid. Neurofibrillary tangles are intracellular aggregates of hyperphosphorylated tau protein. If a vignette or image shows a deposit sitting between neurons, that's a plaque; a tangle forms inside the neuron itself.

Parkinson's Disease

Parkinson's disease is characterized by:

• Bradykinesia: slowness in movement.

• Resting tremor: a tremor that appears when the muscles aren't being used.

• Pill-rolling tremor: flexing and extending the fingers while moving the thumb back and forth, as if rolling something between the fingers.

• Masklike facies: a static, expressionless facial expression — for example, staring eyes and a partially open mouth.

• Cogwheel rigidity: muscle tension that intermittently halts movement as an examiner attempts to move a limb.

• Shuffling gait: a stooped posture with a shuffling walk.

Dementia and depression are also commonly associated with Parkinson's disease.

The biological basis of Parkinson's disease is decreased dopamine production in the substantia nigra, a layer of brain cells that normally produces dopamine. Dopamine permits the proper functioning of the basal ganglia, which is critical for initiating and terminating movements and for sustaining and smoothing repetitive motor tasks.

L-DOPA is a dopamine precursor that can be converted into dopamine once it reaches the brain, and it's used to partially treat Parkinson's disease.

Why Biological Basis of Nervous System Disorders Matters for the MCAT

MCAT questions on this material typically test whether a reader can connect a symptom or treatment back to its underlying biological mechanism:

• Direction of neurotransmitter change matters. Schizophrenia = excess dopamine; depression = deficit of norepinephrine/serotonin/dopamine; bipolar disorder = increased norepinephrine/serotonin. Mixing up the direction of change is the most common trap.

• Match the gene to the Alzheimer's onset pattern. PSEN1/PSEN2 and APP mutations cause early-onset, familial disease; APOE modulates late-onset, sporadic risk.

• Plaques are extracellular, tangles are intracellular. Both are built from different proteins (β-amyloid vs. tau) — don't conflate them.

• L-DOPA is a precursor, not dopamine itself. It's given because dopamine can't cross the blood-brain barrier, but L-DOPA can, and gets converted to dopamine once inside the brain.

• Substantia nigra dysfunction connects directly to basal ganglia symptoms. Decreased dopamine production in the substantia nigra explains why basal ganglia function — movement initiation, termination, and smoothing — breaks down in Parkinson's disease.

Common MCAT Mistakes

• Assuming dopamine changes always point the same direction across disorders — schizophrenia involves excess dopamine, while Parkinson's disease involves decreased dopamine production, in different brain regions.

• Treating depression and bipolar disorder as having the same neurotransmitter direction — depression shows decreased norepinephrine/serotonin/dopamine, while bipolar disorder shows increased norepinephrine/serotonin.

• Confusing which Alzheimer's genes drive early-onset familial disease (PSEN1, PSEN2, APP) with the one that modulates late-onset sporadic risk (APOE).

• Treating senile plaques and neurofibrillary tangles as interchangeable, rather than distinguishing extracellular β-amyloid plaques from intracellular hyperphosphorylated tau tangles.

MCAT-Style Concept Check

Question: A patient presents with bradykinesia, cogwheel rigidity, and a resting tremor that diminishes with voluntary movement. Which of the following best explains the biological basis of this presentation?

• A) Excess dopamine activity in the brain

• B) Decreased dopamine production in the substantia nigra, impairing basal ganglia function

• C) Reduced acetylcholine and choline acetyltransferase levels

• D) Increased norepinephrine and serotonin levels

Answer: B

Explanation: Bradykinesia, cogwheel rigidity, and resting tremor are hallmark features of Parkinson's disease, which arises from decreased dopamine production in the substantia nigra. Since dopamine is required for proper basal ganglia function — initiating, terminating, and smoothing movement — this deficit produces the motor symptoms described. Option A describes schizophrenia's dopamine excess, not Parkinson's. Option C describes Alzheimer's cholinergic deficits. Option D describes a biological marker of bipolar disorder, not Parkinson's.

FAQ

What's the difference between the dopamine hypothesis of schizophrenia and the monoamine theory of depression?

The dopamine hypothesis holds that schizophrenia is associated with excess dopamine, which is why neuroleptics treat it by blocking dopamine receptors. The monoamine theory holds that depression is associated with decreased norepinephrine, serotonin, and dopamine — the opposite direction, and a broader set of neurotransmitters.

Are senile plaques and neurofibrillary tangles the same thing?

No. Senile plaques are extracellular deposits of misfolded β-amyloid protein. Neurofibrillary tangles are intracellular aggregates of hyperphosphorylated tau protein. They're both hallmarks of Alzheimer's disease, but they're built from different proteins in different locations.

Why is L-DOPA used instead of dopamine to treat Parkinson's disease?

L-DOPA is a dopamine precursor that can be converted into dopamine once it reaches the brain, allowing it to partially treat Parkinson's disease by replenishing brain dopamine levels depleted by substantia nigra dysfunction.

What's the difference between PSEN1/PSEN2/APP and APOE in Alzheimer's genetics?

PSEN1, PSEN2, and APP mutations contribute to Alzheimer's disease, with PSEN1 mutations accounting for the majority of early-onset familial cases. APOE gene mutations instead alter the likelihood of acquiring the disease, functioning as a risk modulator rather than a direct cause of early-onset disease.