Onset and Initial Presentation

Question 1

What are the two measures in epidemiology?

Answer 1

The method used to find the causes of health outcomes and diseases in populations

Question 2

What does prevalence refer to?

Answer 2

Prevalence refers to the proportion of persons who have a condition at or during a particular time period

Question 3

Why is prevalence important?

Answer 3

It is important for understanding the burden of a disease on society at any given time

Question 4

What does incidence refer to?

Answer 4

Incidence refers to the proportion or rate of persons who develop a condition during a time period

Question 5

Why is incidence important?

Answer 5

It is important for understanding changes in the expressions of disease in individuals

Question 6

Why is the prevalence of schizophrenia spectrum disorders difficult to obtain?

Answer 6

Precise prevalence estimates are difficult to obtain due to clinical and methodological factors such as the complexity of diagnosis, overlap with affective disorders, and variation in diagnostic methods

Question 7

What are the best estimates of the prevalence of schizophrenia spectrum disorder?

Answer 7

The best estimates we have suggest:
- Prevalence of schizophrenia and other psychotic disorders in the U.S. ranges between 0.25% and 0.64%

• International prevalence ranges from 0.33% to 0.75%
• Prevalence has been increasing…

Question 8

Is the incidence of schizophrenia spectrum disorder higher in males or females?

Answer 8

Incidence is higher in males vs females (1.4-1.0) so the ratio of M/F is higher

Question 9

What is the prevalence of schizophrenia spectrum disorder by age and sex?

Answer 9

• Males tend to be diagnosed earlier than females so the ratio is much higher in younger age groups
• Mortality rates in females in lower over time and thus, the male to female ratio changes over time

Question 10

What is the global prevalence per 100,000 people for schizophrenia spectrum disorder?

Answer 10

• The newest estimates suggest that from 1990 to 2019, the raw prevalence of schizophrenia increased from 14.2 to 23.6 million people
• These increases have been consistent in both males and females
• These prevalence estimates vary dramatically by region of the world

Question 11

Why might the prevalence of schizophrenia be increasing?

Answer 11

• Due to an increase in incidence
• Life expectancy is increasing
• Mental health is becoming less taboo (at least in some places…)

Question 12

Is incidence hard to calculate?

Answer 12

It is hard to calculate accurately

Question 13

What was believed about the incidence of schizophrenia spectrum disorders?

Answer 13

For many years the belief was that the incidence of schizophrenia was constant both geographically and temporally (over time)

But this is NOT so

Question 14

What is the incidence of schizophrenia spectrum disorders geographically?

Answer 14

The incidence of schizophrenia ranges from 7.7 to 43.0 per 100,000 - depending on the geographic region studied

Question 15

What is the incidence of schizophrenia spectrum disorders temporally?

Answer 15

The newest data (Somi et al 2023) found that from 1990-2019, global incidence increased from 941,000 to 1.3 million

Question 16

Is the incidence of schizophrenia higher in men or women?

Answer 16

It is higher in men early but higher in women later

Question 17

What is the incidence of schizophrenia spectrum disorder by sex and age?

Answer 17

Women tend to be diagnosed later in life than men
- Modal age of onset is ~21 for males and ~26 for females
- Females have a second peak of onset occurring around menopause

Question 18

What has the earlier age of onset in men been attributed to?

Answer 18

The earlier age of onset in men has been attributed to the male brain’s greater susceptibility to neurodevelopmental disorders

Question 19

What could the bump in the incidence of schizophrenia in women be because?

Answer 19

The bump in incidence in women could be secondary to the loss of the antidopaminergic action of estrogens

Question 20

Does the incidence of schizophrenia increase or decrease with age in the sexes?

Answer 20

The incidence of schizophrenia spectrum disorder decreases with age in both sexes

Question 21

Is cannabis use contributing to the increase in the incidence of schizophrenia?

Answer 21

• Cannabis use and potency of cannabis have increased during the past 2 decades

The Population-Attributable Risk Fraction (PARF) is an estimate of the proportion of cases of schizophrenia that would have been prevented if no individuals had been exposed to cannabis use disorder

• About 8%

Question 22

How can/is urban living contributing to the increase in the incidence of schizophrenia?

Answer 22

• Urban areas have a higher population density and higher levels of poverty, which are both risk factors for schizophrenia
• More immigrants tend to live in urban environments, which also increases risk for schizophrenia
• Poor air quality, low levels of sun exposure, daily life stressors are also associated with increased risk for schizophrenia

Question 23

How much of the world’s population lives in cities?

Answer 23

54%

Question 24

What is the burden of schizophrenia?

Answer 24

• Despite its relatively low prevalence, schizophrenia is associated with significant health, social, and economic concerns
• Approximately half of individuals with schizophrenia have comorbid psychiatric diagnoses
• It is one of the top 15 leading causes of liability worldwide
  • Co-occurring medical conditions, such as heart disease, liver disease, and diabetes, contribute to higher premature mortality rates
  • An estimated 4.9% of people with schizophrenia die by suicide vs. 1.4% in the general population, with the highest risk in the early stages of illness
  • The estimated average potential life lost for an individual with schizophrenia in the U.S. in 28.5 years

Question 25

What does DALYs mean?

Answer 25

Disability-adjusted life years

Question 26

What is the global DALYs per 100,000?

Answer 26

- One DALY equals one lost year of healthy life - DALYs allow us to estimate the total number of years lost due to specific causes and risk factors at the country, regional, and global levels

Question 27

True or False: There are high rates of subclinical psychotic symptoms in children.

Answer 27

True

Question 28

True or False: The onset of schizophrenia in children 12 years or older is common

Answer 28

FALSE It is very rare

Question 29

How many patients with affective or other atypical psychotic symptoms are misdiagnosed as COS?

Answer 29

Approximately 30 to 50%

Question 30

How many of the referrals to the NIMH study of COS receive alternate diagnoses?

Answer 30

Over 90%

Question 31

What is the incidence of Childhood-Onset Schizophrenia (COS)?

Answer 31

It is generally accepted that the incidence is less than 0.04%

Question 32

Is Childhood-Onset Schizophrenia (COS) a special diagnosis?

Answer 32

This is not a “special” diagnosis - Possibly reflects a more homogeneous disease - More severe - Worse outcome - Likely linked to genetics

Question 33

How many children with confirmed schizophrenia had premorbid disturbances in social, motor, and language domains and were often diagnosed with learning disabilities?

Answer 33

67%

Question 34

How many children with confirmed schizophrenia had comorbid mood or anxiety disorders?

Answer 34

More than half

Question 35

How many children with confirmed childhood onset schizophrenia met the criteria for autism spectrum disorder prior to the onset of their psychotic symptoms?

Answer 35

27%

Question 36

What are the outcomes and prognoses for Childhood-onset schizophrenia correlated with?

Answer 36

They are positively correlated with the presence and severity of these developmental abnormalities

Question 37

When is it considered late-onset schizophrenia (LOS)?

Answer 37

Typically defined after the age 45

Question 38

What is the prevalence of late onset schizophrenia (LOS)

Answer 38

The prevalence is ~0.6%

Question 39

When is it considered very late onset schizophrenia? What is the prevalence?

Answer 39

Defined after the age 60 The prevalence is 0.1%-0.5%

Question 40

What is late onset schizophrenia (LOS) associated with?

Answer 40

- high levels of occupational functioning - being married - more severe paranoid delusions - more visual, tactile, and olfactory hallucinations - less severe disorganization - less severe negative symptoms

Question 41

What does evidence suggest that risk factors for late-onset include?

Answer 41

- negative life events - history of psychotic symptoms - poor social networks - cognitive impairment - functional limitations

Question 42

What is the average age of onset of schizophrenia?

Answer 42

The average age of onset is late adolescence to early adulthood - Between age 18 and 25 for men and 25 and 35 for women

Question 43

Why is adolescence considered the age of opportunity?

Answer 43

Some areas of the brain may be especially malleable, or “plastic,” in adolescence. - Plasticity: The capacity of the brain to change in response to experience. - The brain’s malleability in response to experience enables us to learn and strengthen abilities. - It is more easily and reliably accomplished before adulthood. - A brain with plasticity learns new skills easier, but it also is more sensitive to disruptions...

Question 44

What are the pre to post-adolescent changes?

Answer 44

Most brain regions undergo very substantial changes during adolescence; particularly in cortical regions (I.e., parietal, temporal, frontal lobes) It includes synaptic pruning and myelination

Question 45

What is synaptic pruning?

Answer 45

The clearing away of underutilized synapses; reflected in the thinning of the cortex

Question 46

What is myelination?

Answer 46

The development and extension of axons; reflected in increases in white matter

Question 47

What does all the pruning and myelination accomplish?

Answer 47

- Child and adult brains are organized generally in the same way - Child brains show more diffuse, less focused activation - Early in life there is higher connectivity in adjacent regions, which transitions to stronger long range connections in adulthood - These changes are very strongly impacted by experience.

Question 48

What is the importance of early intervention?

Answer 48

The end goal of most efforts directed at the study of disease is prevention Theoretically, if you can identify cases early in their emergence, you can do things to prevent their full development or at least provide some protection from the worst outcomes - This is referred to as early intervention

Question 49

What is suggested to the first stage of schizophrenia? Why?

Answer 49

The psychosis prodrome Occurs before noticeable psychotic symptoms appear Characterized by changes in behavior and cognition

Question 50

Do all people with schizophrenia experience the psychosis prodrome?

Answer 50

No, only ~75%

Question 51

What is the initial presentation of schizophrenia spectrum disorders?

Answer 51

There is no “typical” presentation - Often most noticeable is social withdrawal and impaired functioning but the reasons for this are variable

Question 52

Why is there no typical presentation of schizophrenia spectrum disorders?

Answer 52

Onset may be: - Progressive: over months or years - Acute: over days or weeks May be preceded by: - Other psychiatric symptoms (i.e. anxiety, mood, substance abuse) - No history of psychiatric symptoms

Question 53

What is the initiation of treatment for schizophrenia?

Answer 53

Even with all of the efforts of scientists to identify cases early in their course ~84% of those diagnosed between the ages of 15 to 29 are diagnosed in the emergency department ~19% of those diagnosed between the ages of 30 to 59 are diagnosed during general medical outpatient visits Initiation of treatment is extremely variable Longitudinal studies consistently find a delay in receipt of effective treatment

Question 54

How is the Duration of Untreated Psychosis (DUP) usually defined?

Answer 54

DUP: Generally defined as time from first psychotic symptom to first psychiatric hospitalization

Question 55

What is the duration of untreated psychosis?

Answer 55

Essentially reflects the delay to receive treatment after the onset of psychotic symptoms Average DUP ranges from between 22 weeks and over 150 weeks!! These long periods without treatment arise from several sources: - Intrinsic factors (e.g., symptom severity, patients’ attitudes) - Extrinsic factors (e.g., access to care, insurance, culture)

Question 56

What is the impact of short vs. long DUP?

Answer 56

The vast majority of work suggests that longer DUP is associated with more severe illness and worse treatment outcome This may be due to: - Toxicity of psychosis - An early insidious onset However, recent data from the SCMHP suggests that maybe its just an artifact of the way that we look at the data - Jonas et al argued that DUP actually reflects differences in illness stage - Specifically, she argued that DUP does not predict a worse illness trajectory, but merely indicates that an individual is farther along in their illness – This is what she refereed to as the “Lead Time Bias”

Question 57

What is lead time bias?

Answer 57

She found that those with longer DUP experience greater losses of psychosocial function before their first hospital admission than those with shorter DUP. - However, those with shorter DUP experience greater psychosocial function after their first hospital admission than those with longer DUP