Biology of Mental Disorders - Introduction Slides

What is an unhealthy or maladaptive condition known as? Is it sign, etiology, pathology, illness, or symptom?

Illness

What is an abnormal physical or mental process that CAUSES an illness known as? Is it etiology, symptom, sign, or pathology?

Pathology

What are conditions that cause pathology, such as infectious agents (ex. bacteria or viruses), genetic factors (ex. mutations), and lifestyle factors (ex. high-fat diets, which can lead to heart disease) known as? Would a condition like this be called symptom, sign, etiology, or illness?

Etiology

What is a manifestation of pathology reported by the affected person, which is subjective (ex. I feel sad) known as? Is it an illness, symptom, etiology, or sign?

Symptom

What is a manifestation of pathology observable by others, and therefore objective (ex. She is crying) known as? Is it an illness, etiology, symptom, or sign?

Sign

What is the term for an impairment of specific physical or mental functions (objective signs, subjective symptoms) due to a KNOWN pathology? Is it a disease, syndrome, or diagnosis?

Disease

What is the impairment of specific physical or mental functions (objective signs, subjective symptoms) that often “go together” and suggest a common underlying, but UNKNOWN, pathology known as? Is it a disease, syndrome, or diagnosis?

Syndrome

What is determining (through examination) the presence, nature, and circumstances of a disease or syndrome known as? Is it diagnosis or treatment?

Diagnosis

What is reducing or eliminating (objective) signs and (subjective) symptoms of illness by either eliminating pathology, known as curative _____ (which leads to total recovery), or by reducing, known as palliative _____ (which focuses mostly on improving quality of life)? Is it diagnosis or treatment?

Treatment

What are some examples of symptoms of mental illness, bearing in mind that symptoms are reported by the patient and are therefore subjective?

Sadness, anxiety, racing thoughts, loss of energy, euphoria, grandiosity, etc.

What are some examples of signs of mental illness, bearing in mind that signs are observable (by others) and are therefore objective?

Agitation, flushing, slow movement, confused speech, hyperactivity, tics

There is a (sometimes considerable) overlap between signs and symptoms that are still within the range of healthy functioning, and signs and symptoms of major depression. So what do we use to diagnose things and actually define illness, and how is that different from what we would like to do under ideal conditions?

Ideally we would use deductive or forward reasoning, where one “block” builds on the next. In deductive reasoning, etiology (the cause of pathology) comes first. Are there any infectious agents behind the problem? Any genetic causes, environmental stressors, aspects of lifestyle (like diet)?

ex. streptococcus pneumoniae, for the illness of strep throat

Next, we would look at pathology (the cause of illness) - how is the illness developing, progressing, manifesting?

ex. respiratory system inflammation (an abnormal physical process) for strep throat

Finally, we would look at signs and symptoms (how the illness feels to the person, and looks to the outside observer).

ex. cough, for strep throat

However, since we don’t live in an ideal world, we have to progress backwards (from signs and symptoms to pathology to etiology).

Describe how inductive reasoning works to provide a diagnosis of an illness.

Inductive or “backwards” reasoning occurs by looking at signs and symptoms of an illness, which are what a patient comes in with, and going in REVERSE to find the pathology (or cause of that illness) and then the etiology (the cause of the pathology).

For example, for a patient with strep throat, they might report a cough. The underlying pathology might be respiratory system inflammation, but the underlying etiology could be a variety of things. It could be smoking, streptococcus pneumoniae, or the influenza virus.

We have to go through and rule out each of these etiologies until we find the one that the patient has - for example, by doing a chest X-ray.

What are the differences between deductive reasoning (what we’d like to do) versus inductive reasoning (what we actually do) in a clinical context? What is the one similarity?

With deductive reasoning, we have to identify cases with known pathology and controls without it. Looking at signs, symptoms, and historical characteristics is important, but comes as a “final step” or a means of providing a holistic look at a condition.

This is opposed to inductive reasoning, where we identify cases with NON-OVERLAPPING (distinct) clusters of signs and symptoms FIRST, and then search for pathological differences between cases and controls.

However, both involve taking a closer look at the progression/path of etiology towards pathology, and pathology’s connection to specific signs and symptoms.

What are some sources of inductive errors?

When identifying cases with distinct groups of abnormal characteristics, or syndromes…

a) we could misclassify cases based on normal and abnormal characteristics

(meaning that we could either group someone into a syndrome category based on one abnormal trait, or we could wrongly end up taking them out because they have one or two normal traits - even if they DO belong in the syndrome category)

b) we might define syndromes themselves incorrectly, mixing cases with non-cases

When searching for pathological (how a disease develops and what effects it has on the body) differences between cases and controls…

a) we might look in the wrong place for pathology

b) we might not have the technology to look in the right place

What is descriptive psychiatry? What is its goal and primary assumption?

Descriptive psychiatry’s goal is to identify reliable syndromes through CAREFUL OBSERVATION of signs and symptoms.

The underlying assumption here is that the common underlying etiology and/or pathology will produce SIMILAR abnormal signs/symptoms and respond to similar treatments.

Descriptive psychiatry offers a practical approach to reliable diagnosis (since we are using what the patient gives us, in terms of signs and symptoms, and working backwards from there), and consequent treatment.

What are some limitations of descriptive psychiatry?

a) Syndromes use binary model of pathology which is not correct. The binary model says that you either have a pathology or you don’t, whereas it’s much more like a spectrum. Diseases also develop gradually - it isn’t all or nothing.

b) It can get confusing when the same symptoms arise from different etiologies. For example, you might see a symptom of “laziness” or lack of ability to get much done in a patient, but the etiology could be a mood disorder (depression) or a neurodevelopmental disorder (ADHD).

In other words, there is overlap between the range of healthy functioning and the range of diseases (schizophrenia, major depression), which doesn’t even get into the overlap between just these diseases.

How does biology constrain definitions and causal theories of mental illness?

Biology tells us that a lot of things reflect brain-based problems - through biomarkers, they provide us with observable biological signs of pathology AND components of a plausible etiologic pathway.

Other characteristics of biomarkers include that they are reliably observed in a majority of cases (high sensitivity), and reliably absent in a majority of unaffected (high specificity).

What are some potential biomarkers of mental illness?

a) genetic profiles

b) response to neurotransmitter-altering medication (signaling the presence of an issue that likely had something to do with that neurotransmitter)

c) decreased hippocampal volumes in PTSD

d) decreased frontal lobe activity in schizophrenia

e) in-vivo imaging of amyloid-beta/lipid profile for Alzheimer’s disease

Are biomarkers sufficient to determine the presence of illness? Look at something like CTE.

cTBI = traumatic brain injury

pTau = phosphorylated (abnormal) tau protein, responsible for stabilizing neurons and acting as scaffolding. If the tau protein is phosphorylated it can start clumping together, leading to cell death

A movie about a football player who committed suicide and had CTE might show a straightforward path between the original injury (the cTBI) to pTau to suicide, but it is obviously a lot more complex than that. This is why biomarkers are NOT sufficient to determine the presence of illness or making out the cause of suicide to be CTE (inferring a causal link)

What are some inconvenient truths related to CTE?

• positive cases are selected based on outcome. For example, you can’t assume that CTE leads to suicide based on cases where patients who were found to have CTE in an autopsy committed suicide. There are a lot of other risk factors for the outcome present as well.

• No dose-response effect: a more significant brain injury/more neurodegeneration related to the TBI doesn’t necessarily mean someone is at higher risk for suicide

• No defined syndrome (signs or symptoms that go together and suggest an underlying, but unknown, pathology): some cases with CTE are behaviorally normal

• NFL players, who have higher exposure to head trauma than the general population, have LOWER RATES of suicide than non-players. So we can’t assume that traumatic head injuries are linked to suicide.

Can you demonstrate the difficulty of establishing a causal link between repetitive head trauma/CTE and suicide by outlining pathways that could arise from other causes? Hint: many of them involve pTau as an intermediate step.

family history of bipolar —> amygdala dysfunction, potentially pTau or phosphorylated/abnormal Tau proteins —> suicide

life stress —> suicide; life stress —> pTau —> suicide

substance abuse —> pTau —> suicide; substance abuse —> prefrontal cortex dysfunction —> suicide

So repetitive head trauma isn’t the only pathway involving pTau and suicide, which means that it is difficult to establish a causal relationship between the two (likely due to the lack of longitudinal and cross-sectional studies on the topic)