Neurocognitive deficits in bipolar disorders

Question 1

What does the list learning test consist of

Answer 1

> List learning task to examine immediate verbal recall and learning

> Part 1: list 1

• listen and repeat
• trial repeated 5 times
• subject learns as baby words from list as he/she can

> Part 2: list 2 - distractor list

• listen and recall
• short-delay recall of list 1

> Part 3:

• after 20 min performing non-verbal tasks, subject recalls words of list 1
• > examines long-delay recall

Question 2

What does the digit span exercise measure?

Answer 2

Attention and working memory

• forward condition: subject repeats digits in same order as presented
• backward condition: subject repeats digits in reverse order

Question 3

What are the different bipolar disorders classified in the DSM-5?

Answer 3

• Bipolar I
• Bipolar II
• Cyclothymic disorder

Question 4

What are the hallmarks of bipolar disorder?

Answer 4

Mania and hypomania

Question 5

Why are mania and hypomania the hallmarks of bipolar disorder

Answer 5

> Diagnosis of bipolar disorder is possible in absence of current or past major depressive episode
- for bipolar I, not bipolar II

> Diagnosis IS NOT possible in absence of current or past manic or hypomanic episode

Question 6

What is the paradox in the diagnosis of bipolar disorder?

Answer 6

• History of a major depressive episode is not a necessary condition for diagnosing the most severe form of bipolar illness (bipolar I)
• However, in practice, most individuals with bipolar disorder spend more time being depressed than being manic or hypomanic

Question 7

What was the major influence of our understanding of bipolar disorders during the 20th century?

Answer 7

Emil Kraepelin: dichotomy of psychosis

• ‘Dementia praecox’: schizophrenia
• ‘Manic depression’: bipolar disorder

Question 8

How did Emil Kraepelin differentiate “dementia praecox” (schizophrenia) from “manic depression” (bipolar disorder)?

Answer 8

> ‘Dementia praecox’ - schizophrenia

• deteriorating disease
• irreversible loss of cognitive functions

> ‘Manic depression / depressive psychosis’ - bipolar disorder

• episodic disorder
• no brain function becomes permanently impaired

Question 9

How does Kraepelin’s distinction between ‘dementia praecox’ and ‘manic depressive psychosis’ reverberates through current theories of psychosis?

Answer 9

Pr Sir Robin Murray’s research group:
- schizophrenia: lower IQ

• bipolar disorder: little evidence of trait neuropsychological deficits
• 2 conditions share genetic predispositions BUT differ: schizophrenia has additional genes or early environmental hazards causing neurodevelopment impairment

Question 10

How can neurocognitive abilities be preserved in bipolar disorder?

Answer 10

> Episodic illness:
- different possible mood states across and within episodes (Kraepelin’s ‘mixed states’)

> Different stages:

• pre-morbid stage
• high-risk state
• first episode
• chronic phase

-> It’s important to examine neurocognitive functioning at different stages of bipolar disorder

Question 11

What does the evidence suggest on the neurocognitive functioning in pre-morbid bipolar disorder and schizophrenia?

Answer 11

• Intelligence is not impaired before clinical onset of bipolar disorder
• Normal or even higher IQ in pre-bipolar individuals compared to controls
  (measure several years before clinical symptoms = unbiased estimates of pre-morbid IQ)
  -> young people who will develop bipolar disorder do not show intellectual deficits
• Established IQ deficits in pre-schizophrenic individuals

Question 12

How does bipolar disorder differ from schizophrenia in the way that intelligence relates to the risk of clinical onset (McCabe et al., 2010)?

Answer 12

Incidence rate of schizophrenia and bipolar disorder by grade-point average at 16 years old:

• Inverse linear relationship between school grades and risk of schizophrenia
• > worse grades = more likely to develop schizophrenia in adulthood
• Non-linear relationship between school grades and risk of bipolar disorder
• > both lower IQ and higher IQ are risk factors for bipolar disorder

Question 13

What is the reported prevalence linking creativity to bipolar disorder?

Answer 13

8-43%

Question 14

From the existing evidence, can we conclude that neurocognitive functioning is preserved in the premorbid stage, before the clinical onset of bipolar disorder?

Answer 14

No

• large population-based studies use general measures of neurocognitive functioning using IQ
• Hypothesis: only specific domains are impaired at premorbid stage
  BUT data is insufficient

Question 15

What does the evidence suggest on the influence of bipolar genes on cognition?

Answer 15

Meta-analyses of cognitive test performance differences between first-degree relatives vs. normal controls:

• non-bipolar first-degree relatives of patients with bipolar disorder show mild deficits of small to moderate effect size in verbal memory and executive functioning

Question 16

What does the evidence show on the neurocognitive functioning in first episode cases of bipolar disorder and schizophrenia?

Answer 16

• Small effect size in mean difference in IQ between future cases of bipolar disorder and healthy controls
• All-encompassing neurocognitive deficit in first-episode bipolar disorder vs. healthy controls
• Large effect size for future cases of schizophrenia

Question 17

How are cognitive deficits in bipolar disorder associated to the presence of mood symptoms?

Answer 17

The state of complete remission (euthymia) is not associated with better cognitive performance
- except response inhibition

-> cognitive deficits are not dependent on the presence of mood symptoms AND largely unrelated to drug treatment

Question 18

What is euthymia?

Answer 18

A mood of well-being and tranquility

• in bipolar disorder: state neither manic nor depressive but in between

Question 19

What is the evidence on neurocognitive functioning in chronic bipolar disorder?

Answer 19

> Euthymic bipolar patients with average illness duration of 14 years:

• deficits of moderate effect sizes in verbal and working memory (vs. healthy controls)
• deficits of small effect sizes in single task of executive functioning

> Euthymic patients with average illness duration of 15 years

• generalised cognitive impairment of moderate to large effect sizes
• regardless of diagnostic rigour in which euthymia was defined

=> neurocognitive deficits persist in chronic phase of bipolar disorder

Question 20

What is suggested by the diagnostic gradient in effect size seen in results of the mean difference in IQ between future cases and healthy controls in bipolar disorder and schizophrenia?

Answer 20

No matter the time point observed, whatever the bipolar disorder shows in cognitive deficits, it is higher schizophrenia

Question 21

What supports the hypothesis that bipolar disorder is a less severe version of schizophrenia (a “little schizophrenia”)?

Answer 21

> Common genetic influences for schizophrenia and bipolar disorder

> Schizophrenia has a degree of mania or depression

> There are delusions at the height of mania or depression in bipolar disorder

• > epidemiological similarities
• > overlap in symptomatology

> They both have a lifetime prevalence of approx. 1%

Question 22

What is a lifetime prevalence?

Answer 22

Proportion of a population who at some point in life has had a characteristic (e.g. been diagnosed)

Question 23

What are the implications behind the evidence of commonalities between bipolar disorder and schizophrenia?

Answer 23

> Puts into question the Kraepelinian dichotomy

> Supports thinking in terms of dimensions rather than diagnostic categories
- differences between bipolar disorder and schizophrenia are quantitative rather than qualitative

Question 24

Which last view supports the Kraepelinian dichotomy?

Answer 24

Schizophrenia, but not bipolar disorder, is subject to additional genes or early insults which impair neurodevelopment

Question 25

Does recent evidence support the view that schizophrenia, but not bipolar disorder, is subject to additional genes or early insults which impair neurodevelopment?

Answer 25

> Schizophrenia patients have worse resultants then bipolar patients in more than half cognitive tests (moderate to small effect sizes)

-> Cognitive deficits in bipolar disorder are qualitatively similar to those in schizophrenia
BUT less marked than in schizophrenia

> No consistent evidence for progressive deterioration of cognitive function in bipolar disorder or in schizophrenia

> Cognitive deficits present in unaffected first degree relatives of bipolar patients and schizophrenia patients

-> Genes that contribute to risk of cognitive dysfunction for both schizophrenia AND bipolar disorder

=> Similarities and differences in neurocognitive signatures is part of a dimensional model rather than Kraepelinian dichotomy

Question 26

Is there a difference in the genes that contribute to the risk of cognitive dysfunction for both schizophrenia AND bipolar disorder

Answer 26

No, the difference lies in the degree of genes’ influence in both disorders

> Shared genes between the disorder and impaired memory (delayed verbal recall:
- 25% for schizophrenia
vs.
- 7% for bipolar disorder

> Interface between genes that cause the disorder and genes that impair cognitive neurodevelopment:
- more than 3 times larger in schizophrenia than in bipolar disorder