The biology of mood, anxiety, psychosis and ADHD

Transcript

RyanThink about the last time you sat down for a big test. Heart pounding. That jolt of adrenaline before the first question even loads.

SoheeI think every person listening just tensed up a little.

RyanSorry about that. But that reaction is our starting point. Welcome to EPPP Prep, the podcast. I'm Ryan.

SoheeAnd I'm Sohee. Today we connect the body's stress machinery to the biology of the disorders you'll see on the exam: depression, panic disorder, obsessive-compulsive disorder, or OCD, schizophrenia, and attention-deficit/hyperactivity disorder, or ADHD.

RyanSo, that test-day feeling. The OpenStax psychology textbook uses it as an example. You're in no real physical danger, yet your body responds as if you are. That's the sympathetic nervous system.

SoheeQuick map. The autonomic nervous system controls our internal organs and glands. It has two divisions. The sympathetic division prepares the body for stress. The parasympathetic division returns the body to routine, day-to-day operation.

RyanAnd sympathetic activation is the fight or flight response. Pupils dilate, heart rate and blood pressure rise, the bladder relaxes, the liver releases glucose, and adrenaline surges into the bloodstream.

SoheeWhen the threat passes, the parasympathetic system takes over. Heart rate and blood pressure come back down, the pupils constrict, and the liver starts storing glucose again.

RyanHere's why this matters clinically. Fight or flight was adaptive for our ancestors facing physical threats. But many modern threats are psychological, things we can neither fight nor flee. The textbook notes research linking persistent, repeated stress to greater susceptibility to heart disease and impaired immune function.

SoheeNow the slower partner, the endocrine system. Hormones are chemical messengers too, but unlike neurotransmitters, they travel through the bloodstream. Their effects are widespread, slower to start and longer lasting.

RyanAnd they're ultimately controlled through the hypothalamus working with the pituitary gland, which is often called the master gland.

SoheeThe adrenal glands, sitting on top of the kidneys, release stress hormones like epinephrine and norepinephrine. And the thyroid is worth knowing. In hyperthyroidism, too much thyroxine causes agitation, bulging eyes and weight loss. In hypothyroidism, people feel tired and often feel cold.

RyanOkay, depression. The textbook says people with mood disorders often have imbalances in norepinephrine and serotonin, which regulate appetite, sex drive, sleep, arousal and mood.

SoheeAnd it describes a brain circuit. People with depression show elevated activity in the amygdala, which assesses the emotional significance of things, especially when they see negative stimuli like sad faces.

RyanWhat's striking is that this heightened amygdala response happens even when the stimuli are presented outside conscious awareness, and it persists after the stimuli are gone.

SoheeMeanwhile, depressed individuals show less activation in the prefrontal cortex, particularly on the left. And the prefrontal cortex can dampen the amygdala. So the picture is: more reaction to negative emotion, and less capacity to regulate it.

RyanThen there's cortisol, a stress hormone. Researchers have noted abnormal cortisol in depression since the 1950s. Many people with depression show elevated levels, especially those with early life trauma, like losing a parent or childhood abuse.

SoheeAnd the textbook raises the key question. Is high cortisol a cause or a consequence of depression? High cortisol is a risk factor for future depression, and cortisol activates the amygdala while deactivating the prefrontal cortex.

RyanSo high cortisol may play a causal role. But because stress itself increases cortisol, it's equally reasonable to think stress may precipitate depression. Hold that cause-or-consequence question. We'll need it.

SoheePanic disorder next. The textbook points to the locus coeruleus, a brainstem region that is the brain's major source of norepinephrine, the neurotransmitter that triggers fight or flight.

RyanIn research with nonhuman primates, stimulating the locus coeruleus, electrically or with drugs, produces panic-like symptoms. That led to the theory that panic disorder may involve abnormal norepinephrine activity there.

SoheeThen OCD. The region believed to play a critical role is the orbitofrontal cortex, part of the frontal lobe involved in learning and decision-making.

RyanIn people with OCD, it becomes especially hyperactive when they're provoked, for example by a photo of a toilet or pictures hanging crookedly. It's part of a set of connected regions called the OCD circuit, and people with OCD show much higher connectivity within that circuit.

SoheeAnd now the caution, which is pure exam material. The textbook says these imaging findings have limits. They can't explain differences between people's obsessions and compulsions. And the relationship between brain abnormalities and symptoms is correlational, so it cannot imply causation.

RyanPause and think. A study finds the orbitofrontal cortex is overactive in people with OCD during symptom provocation. A newspaper headline says scientists found the cause of OCD. What's wrong?

SoheeThe finding is correlational. Overactivity could contribute to symptoms, result from them, or both. Same logic as cortisol and depression. On the exam, be wary of any answer that turns a brain difference into a proven cause.

RyanSchizophrenia. Interest in dopamine came from two findings. Drugs that increase dopamine can produce schizophrenia-like symptoms. And medications that block dopamine reduce symptoms.

SoheeFrom that came the dopamine hypothesis. Too much dopamine, or too many dopamine receptors, drives the onset and maintenance of schizophrenia.

RyanBut the refined version is more specific, and this is the testable detail. Too much dopamine in the limbic system may be responsible for symptoms like hallucinations and delusions. Too little dopamine in the prefrontal cortex may be responsible mainly for the negative symptoms.

SoheeWhich the textbook lists as avolition, alogia, asociality and anhedonia. And newer antipsychotics also work by blocking serotonin receptors.

RyanStructurally, brain imaging shows people with schizophrenia have enlarged ventricles, the fluid-filled cavities in the brain. That suggests a loss of brain tissue. Many also show reduced gray matter in the frontal lobes and less frontal activity during cognitive tasks.

SoheeAnd environmental factors appear to matter. High rates of obstetric complications. Higher risk if the mother was exposed to influenza in the first trimester. And longitudinal studies suggest marijuana use is a risk factor. In a classic study of over 45,000 Swedish conscripts, those who had used marijuana at least once by the time they were drafted were more than twice as likely to develop schizophrenia.

RyanFinally ADHD, where dopamine shows up again, but in the opposite direction. Genes implicated in ADHD include at least two involved in regulating dopamine.

SoheePeople with ADHD show less dopamine activity in key regions, especially those tied to motivation and reward. And medications like methylphenidate and amphetamine with dextroamphetamine have stimulant qualities and elevate dopamine activity.

RyanImaging studies find children with ADHD tend to have smaller frontal lobe volume and less frontal activation during mental tasks. Since the frontal lobes help inhibit behavior, that fits the uncontrolled behavior seen in ADHD.

SoheeAnd two myths the textbook takes apart. Sugar: a review of 16 studies concluded sugar has no effect on children's behavior and cognitive performance. And poor parenting: the genetic evidence suggests family environment doesn't play much of a role.

RyanWhat does have a significant link? Prenatal exposure to nicotine from cigarette smoke.

SoheePause and think. Dopamine is too high in one disorder and too low in another. Which is which, and where?

RyanIn schizophrenia, excess dopamine in the limbic system is linked to hallucinations and delusions, and low prefrontal dopamine to negative symptoms. In ADHD, it's less dopamine activity in reward and motivation regions, which is why stimulants that raise dopamine help.

SoheeSo, how does the exam use this? Often by matching a structure or chemical to a disorder. Locus coeruleus and norepinephrine with panic. Orbitofrontal cortex with OCD. Amygdala up, prefrontal down, and cortisol with depression. Enlarged ventricles and dopamine with schizophrenia. Frontal lobes and dopamine with ADHD.

RyanAnd the tempting wrong answers usually swap partners. Putting the locus coeruleus with OCD, or calling ADHD a dopamine excess. Or they overstate the science, saying a finding proves a cause.

SoheeRecap. Sympathetic means fight or flight, parasympathetic means rest and restore. Hormones travel in the blood, act slowly and widely, and are controlled through the hypothalamus and pituitary.

RyanDepression: norepinephrine and serotonin, a hyperreactive amygdala, an underactive prefrontal cortex, and elevated cortisol, with cause versus consequence still an open question.

SoheePanic: locus coeruleus and norepinephrine. OCD: the orbitofrontal cortex and the OCD circuit, with correlational evidence. Schizophrenia: dopamine, region by region, plus enlarged ventricles. ADHD: lower dopamine activity and frontal lobe differences.

RyanAnd if that opening scene, the pounding heart before a test, feels familiar, now you know what it is. Your sympathetic nervous system, doing exactly what it evolved to do. It isn't a sign that something is wrong with you. It's a sign that this matters to you.

SoheeYou covered five disorders' worth of biology today, plus the stress response and hormones. That's a lot. Give yourself credit, take a real break before your next study block, and we'll see you next time. Thanks for listening to EPPP Prep.

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