Schizophrenia - Cognitive Changes (P1)

Time-Course of Cognitive Deficits

Overall, deficits seem to be pretty stable over the lifespan, though become more apparent over time and may get worse late in life:

  • Subtle deficits appear early on in childhood

    • The subtle deficits manifest as neurological soft signs like clumsiness

  • Deficits are visible at the first diagnosis

  • Deficits are seen before the first diagnosis

  • There is little change over time

    • E.g., people don’t generally become better/worse over time

    • However, some people may show increasing cognitive deficits late in life

Pre-Existing Cognitive Deficits

Bilder (2008): A Follow-Back Study

Overview and Premise of the Study

This study sought to identify potential pre-existing cognitive deficits in people who later received a diagnosis of SZ. This was a follow-back study, the idea was to take people who already have a diagnosis of SZ and to go back in time by looking at their cognitive function prior to the development of symptoms.

Bilder took advantage of the fact that in many places in the U.S., children took standardized academic tests every year through grade school and high school.

So, Bilder analyzed the results of these tests (taking results as a measure of global cognitive function) in:

  • Individuals who later developed SZ

  • Controls with the same age and SES

Results of the Study

For the grade school/high school test comparison:

  • Overall, individuals who later developed SZ were on average about 1.5 grades below their peers in terms of performance on these tests

    • These differences/deficits were present as early as grade 1, and persisted over time.

    • It doesn’t seem that this cognitive deficit seemed to be getting larger (i.e., it was relatively stable) but there is some evidence to suggest that this might be the case

For the college admissions tests and IQ scores after onset:

  • Prior to onset of symptoms, IQ scores were 11 points lower than would have been predicted by the college admissions test

    • For instance, I might have gotten a particular score that would predict an IQ of 140, but following the onset of symptoms, I actually have an IQ that is 11 points lower

      • Thus indicating that the onset of the disease is accompanied by additional cognitive decline

Reichenberg (2002): More Evidence of Early Cognitive Decline

Sample: People in the Israeli army who later developed SZ (in israel, army service is obligatory — ppl we’re looking at are representative of the population).

Tested before entering the army at 16-17 (specifically tested on verbal and non-verbal global cognitive function:

  • Compared to SZ-A (schizoaffective disorder) and Bipolar Individuals

Showed that those who later developed SZ showed larger differences in performance on these cognitive tests compared to other groups:

  • SZ patients (N=536) showed poorer performance on all measures

  • SZ-A patients (N=31) only showed deficits on Raven’s progressive matrices and small deficits in the other tests

  • Non-psychotic Bipolar disorder people (N=68) didn’t show differences in these cognitive tests compared to controls

    • STRONG EVIDENCE THAT PEOPLE WHO LATER DEVELOP SZ SHOW CHANGES/DECLINE IN COGNITIVE FUNCTION EVEN BEFORE THE ONSET OF SYMPTOMS

Lam (2018): A Study of High-Risk Individuals

Overview and Premise of the Study

Lan (2018) examined individuals considered to be at a high risk of developing SZ.

The advantage of such a study design is that you can look at high-risk individuals in real time to see what happens to them, rather than trying to look backwards at individuals who already have the disorder.

Here is some important information about the study:

  • Took place in Singapore, which has a good public health system that does a lot of tracking in terms of physical and mental health issues.

  • Sampled Singaporeans aged between 14-29

  • Sampled individuals at ultra-high risk for SZ:

    • (i) low-level psychotic symptoms

    • (ii) history brief psychotic symptoms

    • (iii) family history of psychotic disorder plus persistent low functioning

  • Tested individuals at a two-year interval (once; and then again in two years)

  • Tested…

    • Verbal fluency

    • General cognitive function (like IQ)

    • Social cognition (like theory of mind tasks)

    • Attention

    • Perceptual function (basic perception)

  • Compared controls, those whose symptoms improved (remitter), and those whose symptoms did not (nonremitter)

Results of the Study

Overall, the results of the study showed…

  • At the baseline, all of the people in the ultra-high-risk group performed more poorly compared to controls on every cognitive task

  • At follow-up, remitters showed improved scores whereas non-remitters showed no improvement (i.e., cognitive deficits did not get worse nor better

Changes Over the Course of the Disorder

McCleery (2014)

Overview of the Study

Many studies look at the same individuals over time; however, this can be difficult to do without the time and resources to do so.

McCleery (2014):

  • Compared three groups on a wide range of cognitive tests (e.g., speed, attention, working memory, verbal learning, visual learning, and so on):

    • SZ individuals who had their first episode of the disease

    • SZ individuals with a chronic version of the disorder

    • Healthy controls

Results of the Study

Here are the important takeaways from the study’s results:

  • Both SZ and chronic SZ individuals performed more poorly on cognitive tests compared to healthy controls

  • There are few differences between SZ and SZ chronic individuals:

    • The only significant differences observed were in working memory and social cognition — SZ individuals seemed to be less impaired in these cognitive areas compared to chronic SZ individuals

    • (less impaired first timers than chronics)

Dickenson (2007): Global or Specific Deficits?

Another important question regarding the cognitive deficits seen in SZ patients is whether these deficits are global or more specific.

In Dickenson’s (2007) meta-analysis comparing SZ and controls (N=2000):

  • There is a large IQ deficit (i.e., 1.5 SD difference in global IQ)

  • Also poorer performance on different tasks (e.g., timed finger-tapping, memory, fluency, and matching objects/numbers)

  • It seems to be a global impairment, but…

    • Many of these tasks require executive functions such as attention, basic perceptual processes

    • A big emphasis for SZ is trying to identify whether there are specific deficits within these global functions that are at the root of the congitive problems of SZ

      • If we can identify more specific functions, we can determine if certain medications have a positive effect on those specific functions, or we could develop cognitive training to help them

      • However, it’s harder to design a medication that could change global IQ

      • Moreover, we have put a large emphasis in neuroscience to tie specific functions to particular brain regions; if we were to narrow down specific functions responsible for the cognitive deficits seen in SZ, we could identify specific structural changes in the brain and thereby develop treatments targeting those regions specifically AND it would allow us to elucidate a little more the nature of the genetic side of SZ

Executive Functions

A Quick Refresher on Executive Functions

  • Selecting and inhibiting responses

    • I.e., choosing to perform an action and choosing not to perform an action

  • Working memory

    • I.e., holding onto information and then using it

  • Goal-directed behaviours

    • Planning

    • Organizing a task

    • Staying on task

    • Shifting between tasks

    • Evaluating outcomes (reward)

  • Associated with fronto-parietal network

    • Important for attention in particular

  • Linked to temporal lobe memory network

    • Location of the hippocampal/temporal memory systems

    • Executive functions are closely tied to memory functions

Wisconsin Card Sorting Task

The Wisconsin Card Sorting Task (WCST) is one of the main tests that looks at frontal lobe function, specifically at particular aspects of executive functioning.

The task involves matching a series of cards to one of four key cards:

  • Feedback is only “correct” or “incorrect”.

  • After a set of correct trials, tester switches the rule, and participant must learn the new “correct” card matching pattern.

Essentially, the point of the task is to measure strategizing, feedback, learning, ignoring relevant information, set shifting, inhibition of prepotent responses, as well as retrieving and monitoring working memory.

The scores are measured as such:

  • # of categories in 128 trials

  • “perseverative” errors

  • rule-breaking

Typical Task Results

Patients with frontal lobe lesions perform poorly:

  • Complete fewer categories

  • More perseverative errors

  • Lose track of the rules

SZ patients show similar profiles:

  • Consistent finding

  • Suggests impaired frontal lobe function

Weinberger (1986): Brain Imaging and WCST

Overview of the Study

This was one of the first brain imaging studies looking at SZ:

  • Sampled 20 people with SZ; 25 controls

  • Made participants inhale Xenon 133

    • Could measure the uptake of that Xenon in the brain — Xe113 travels in the blood and crosses the blood brain barrier, and emissions can be detected over the scalp

    • Regions that are more active have more Xe133 uptake

  • They compared task performance between the SZ and control group

Results of the Study

So they looked at various regions of the brain while participants performed the WCST, and they compared this to (1) rest and (2) performing a simplified version of the task (e.g., number matching task). Here are the results:

  • Controls showed more frontal lobe activation while completing the WCST compared to the simplified version

  • SZ individuals did not show a difference in frontal lobe activation between the WCST and the simplified task

    • This indicates that basic activity in the frontal lobe is not engaged to the same degree as it is in controls (i.e., impairment in frontal lobe function)

Verbal Fluency

Overall Task Description

The verbal fluency task is also used to measure executive functioning, because it requires you to retrieve information from memory, hold onto it, remember rules, and inhibit incorrect answers.

Essentially, you are asked to generate as many words as possible in a short period of time, with progressively harder rules to follow:

  • E.g., “that start with the letter ‘p’”, to “that are animals”, to “that begin with ‘m’ and only have 4 letters”

  • No repeats of the same word

  • No forms of the same word (i.e., “park” and “parking”)

  • No proper names (i.e., “Paul” or “Paris”)

Typical Task Results

Generally, people with frontal lobe damage do poorly on these tests:

  • Come up with few words

  • Have trouble retrieving specific information from memory

  • Repeat words (perseverative errors)

  • Break rules (e.g., use similar words)

SZ individuals also show a similarly poor performance.

Memory

Weschler Memory Scale

Tasks like the WCST test memory, but there is also another battery of tasks — known collectively as the Weschler Memory Scale (WMS) — that measures memory more thoroughly (i.e., measures different types of memory). Note that people with SZ perform poorly on all forms of memory measured with this task.

Here are some of the different types of memory assessed with the WMS:

  • Auditory Memory

    • Being told a story and telling the story back to the examiner

    • Memorizing number pairs

  • Visual Memory

    • Being show scenes (“family pictures”) and memorizing faces, environment, and what is happening in the image

  • Immediate Recall and Recognition

    • Involves remembering things immediately after being told/shown them

  • Delayed Recalled and Recognition

    • Involves remembering things after a 20-minute delay

Nester et al. (2008): Memory and Executive Function

This study assesses memory and executive functioning in SZ individuals using an IQ tests, the WMS, and the WCST to assess global cognitive function, memory, and executive function. The main reason for this study was…

  • To determine if the structural connections between the temporal and frontal lobes (e.g., memory system in the temporal lobe and the executive control system in the frontal lobe) are intact or similar/different from controls’

  • They found that SZ individuals performed more poorly on global cognition task and the memory task, and made more perseverative errors in the WCST

  • They looked at the volume (i.e., how many fibres there are) in the uncinate fasciculus (connecting temporal memory areas for objects with the frontal lobe):

    • Found that higher neuronal volume in the uncinate fasciculus was associated with a better performance on the WMS

    • Larger cingulum bundle (more fibres connecting the memory system to executive function/planning areas) associated with fewer errors are made on the WCST (and vice versa)…

      • Useful finding that indicates that SZ is not just about damage to the temporal and frontal lobes, but damage to the connections between them

The study’s controls were matched to SZ participants for age, SES, and parental SES, but not education. People with SZ did more poorly on the global cognitive function task and the test of memory function, and although they don’t statistically perform worse on the Wisconsin Card Sorting Task, although they do make more perseverative errors (which is characteristic of SZ).