How Stress Hormones Rewire Our Emotions
From life-saving therapy to unexpected mood swings, the story of ACTH and cortisone reveals a profound link between our body and mind.
Imagine a medication that can save a life by taming a runaway immune system, but as a side effect, plunges the patient into a deep depression or launches them into a state of euphoric mania. This isn't science fiction; it was the puzzling reality doctors faced in the 1950s with the introduction of the "miracle drugs" ACTH and cortisone.
These powerful hormones, our body's natural response to stress, do more than just regulate inflammation—they can fundamentally alter our psychological landscape. This is the story of how scientists began to unravel the complex dialogue between our endocrine system and our mental state.
"A hormone released in response to physical stress could directly manufacture emotions and thoughts that felt every bit as real as those arising from life experiences."
To understand the psychological whirlwind, we first need to meet the key players in the body's central stress response system, known as the HPA axis (Hypothalamic-Pituitary-Adrenal axis).
When your brain perceives a stressor, a region called the hypothalamus sounds the alarm by releasing CRH (Corticotropin-Releasing Hormone).
CRH tells the pituitary gland, a pea-sized organ at the base of the brain, to release ACTH (Adrenocorticotropic Hormone) into the bloodstream.
ACTH travels down to the adrenal glands, sitting on top of your kidneys, and orders them to produce cortisol (in humans) or its close relative, cortisone.
Cortisol is the master stress hormone. In a short-term crisis, it's vital: it boosts energy, sharpens memory, and curbs non-essential functions like digestion. But when this system is constantly activated—or when synthetic versions like prednisone are introduced—the effects on the brain can be dramatic.
While many early reports were anecdotal, a seminal 1951 study led by Dr. William H. Clark and his team sought to systematically document these psychological changes. Their work, "Psychological Investigations of Hormone-Induced Abnormal Behavior," provided one of the first clear windows into this phenomenon .
They selected patients hospitalized for various medical conditions who underwent psychological evaluations before treatment to establish baseline mood, personality, and cognitive function.
Patients were divided into groups receiving ACTH, cortisone, or a placebo. Dosages were therapeutic, similar to what would be used to treat inflammatory diseases.
A double-blind procedure was used, meaning neither patients nor assessing doctors knew who received the real hormone versus placebo, preventing bias in observations.
For weeks, patients were closely monitored by psychiatrists and nurses who conducted regular interviews, cognitive tests, and recorded detailed behavioral notes.
The results were striking and confirmed the wild variability of psychological responses. The data painted a clear picture of a chemical-induced alteration of mind.
| Psychological Symptom | Percentage of Patients (ACTH) | Percentage of Patients (Cortisone) |
|---|---|---|
| Significant Mood Elevation (Euphoria) | 35% | 40% |
| Increased Anxiety & Irritability | 25% | 30% |
| Clinical Depression | 15% | 20% |
| Severe Cognitive Impairment | 10% | 15% |
| Psychotic Symptoms (e.g., Paranoia) | 5% | 8% |
The tables showed that these hormones were far from psychologically neutral. Cortisone appeared to have a slightly more potent effect, producing more frequent and severe psychotic reactions. The most common initial response was a feeling of well-being and euphoria, which often masked the underlying physical illness. However, for a significant minority, the experience was terrifying, leading to profound depression or a break from reality.
| Cognitive Measure | Baseline Performance | Performance After 3 Weeks of Treatment |
|---|---|---|
| Short-Term Memory Recall | 92% | 78% |
| Attention Span (min. focused) | 18 min. | 11 min. |
| Complex Problem-Solving | 85% accuracy | 65% accuracy |
This data was crucial. It demonstrated that the effects weren't just "mood swings." The hormones were directly impairing core cognitive functions, likely by affecting brain regions crucial for memory and executive function, like the hippocampus and prefrontal cortex .
| Daily Cortisone Dose | Incidence of Severe Psychological Reactions |
|---|---|
| Low (≤ 50 mg) | 3% |
| Medium (51-100 mg) | 12% |
| High (> 100 mg) | 35% |
This finding was critical for clinical practice. It established a clear dose-response relationship: the higher the dose, the greater the risk of a severe psychological side effect. This gave doctors a practical guideline, urging caution with high-dose, long-term therapy.
How did researchers like Clark measure these abstract concepts like mood and cognition? They relied on a specific set of tools and reagents.
| Tool / Reagent | Function in the Experiment |
|---|---|
| Synthetic ACTH | Used to directly stimulate the adrenal glands to produce natural cortisol, allowing study of the entire HPA axis activation. |
| Pharmaceutical Cortisone | Used to bypass the HPA axis and deliver the end-product hormone directly, isolating its effects on the body and brain. |
| Placebo Saline Injection | The crucial control. A harmless saltwater injection given to the control group to account for the psychological impact of simply receiving medical attention (the "placebo effect"). |
| Standardized Psychological Batteries | A set of validated tests and questionnaires (e.g., Rorschach Inkblot, IQ tests, mood scales) to quantitatively measure changes in personality, perception, and intellect. |
| Structured Clinical Interviews | Systematic interviews conducted by psychiatrists to ensure consistent and objective recording of symptoms like paranoia, hallucinations, and depressive thoughts. |
The pioneering work on ACTH and cortisone was more than just a medical curiosity; it was a paradigm shift. It provided irrefutable evidence that our mental state is not isolated from our biochemistry. A hormone released in response to physical stress could directly manufacture emotions and thoughts that felt every bit as real as those arising from life experiences.
Today, this research forms the bedrock of psychoneuroimmunology, a field dedicated to understanding the intricate interplay between the nervous system, the endocrine system, and the immune system. It taught doctors to be not just physicians of the body, but guardians of the mind, warning them to monitor patients on corticosteroid therapy for profound psychological changes.
The "chemical weather" brought by these hormones is a powerful reminder that the self is a delicate balance, one deeply woven into the fabric of our biology.