L4: Bipolar disorders

What are mood disorders? - definition

mental health conditions in which the principle feature is prolonged, intense, pervasive affective disturbance

What are mood disorders? - 2 types

unipolar = includes only depressive episodes

bipolar = both manic and hypomanic and depressive episodes

Are depressive and manic episodes 2 ends of the same spectrum?

• individually conceptualised as dichotomous ‘highs’ and ‘lows’ BUT

• one can cycle rapidly between depressive and manic symptoms within the same episode (mixed episode)

• Symptoms are Not the ‘opposite’ of each other

Bipolar I disorder: DSM5 diagnostic criteria

A - criteria have been met for at least one manic episode

B - presentation is not better explain by Schizophrenia- spectrum disorder

Bipolar II disorder: DSM5 diagnostic criteria

A - criteria have been met for at least 1 hypomanic episode, and at least one major depressive episode

B - there has never been a manic episode

C - presentation is not better explained by Schizophrenia disorder

D - symptoms of depression/unpredictability caused by mood alternation causes clinically significant distress/impairment in functioning

Key diagnostic differences between Bipolar I and II - bipolar one the person typically experiences:

• full blown mania, with very marked functional impairment

• Depressive symptoms which may - or may not - meet the threshold for MDD

Key diagnostic differences between Bipolar I and II - bipolar II the person typically experiences:

• hypomania but symptoms are below the threshold for full blown mania, which less marked functional impairment

• Depressive symptoms which meet criteria for major depression

What other bipolar - type disorder exists ? - Cyclothymic disorder

• cyclical mood changes less severe than seen in bipolar disorders

• numerous periods of depressive then hypomanic symptoms for less than 2 years

• No period of mood stability lasting longer than 2 months

• Has never met the criteria for a full mania, hypomanic or depressive episode

• Cause sig functional impairment

Image on the patterns of mood variation of the manic-depressive spectrum

Are depressive symptoms qualitatively or quantitively similar in MDD and bipolar II - in bipolar II depressive episodes are more

• servere, and frequent, cause more role impairment

• shorter

• more frequently have psychotic features and psychomotor difficulties, substance use and mood lability as associated factors

Are depressive symptoms qualitatively or quantitively similar in MDD and bipolar II - in MDD depressive episodes are more

• are accompanied by higher levels of anxiety, agitation, insomnia, physical symptoms and weight loss

lifetime and 12 month prevalence of bipolar disorders

male - 0.8% for BP1, 0.9% for BP11 and 2.6% for sub threshold BP

Female - 1.1% for bp1, 1.3% for bp2 and 2.1% for sub threshold BPD

• broadly equivalent for men and women

Global prevalence of bipolar disorders

• Africa - 0.1-1.83%

• Europe - 0.6-6.2%

• Worldwide - 1% for b1 , and 1.5% for bipolar 2

Epidemiology of bipolar disorder

• prevalence does not appear to vary with ethnicity

• Evidence mixed on whether type 1 or 2 has greater prevalence: indication that 2 is more common

• 40% of people with MDD experience subclinical hypomanic symptoms, suggesting more heterogeneity in the MDD category than initially thought

• if a person is untreated, episodes of bipolar -related mania can last 3-6 months

• episodes of depression last 6-12 months

Age of onset - trimodal

• onset has 3 peaks (trimodal), some argue that there is a peak In each life phase

Prodromal symptoms of bipolar disorder - Faedda et al (2015) - method

reviewed 25 papers with prospective and retrospective designs to look at what ‘comes before’ bipolar diagnosis’s

Prodromal symptoms of bipolar disorder - Faedda et al (2015) - Prodormal features were

• mood lability

• subliminal hypomania/deppresion

• Other specified bipolar related disorders

• Major depression, especially with hypomanic or psychotic symptoms

Prodromal symptoms of bipolar disorder - another review noted that

specific prodromal neurocognitive impairments in verbal memory, attention and executive functions but no decrement to general intelligence

Clinical course of bipolar disorder - Gignac et al (2015) - reviewed outcomes of 1st mania

syndromal recovery rates were 77% at 6 months and 84% at 1 year

• recurrence was 26% with 6 months, 41% by 1 year and 60% by 4 years

• younger age at first episode was associated with risk of recurrence after 1 year

Clinical course of bipolar - b2 - Vieta and Suppess (2008)

• greater number of total mood episodes than B1

• Shorter duration of mood episodes

• More persistent depression

• Less chance of psychosis or hospitalisation

• Low rates of cross over to bipolar 1

clinical course of bipolar - Judd et al - followed cohort of people w B1 across 13 years

• patients has symptoms for 48% of weeks

• Depressive symtoms (32%) were common than manic/hypomanic symptoms (9%) or cycling/mixed symptoms (6%)

• Minor depressive, and hypomanic symtoms combined were more frequent than major depressive and manic symptoms (30% vs 11)(

clinical course of bipolar - Judd et al - followed cohort of people w B1 across 13 years - conclusions

the longitudinal weekly symptomatic course of bipolar 1 disorder appear chronic. More time is spent depressed than manic, and subsyndromal symptoms predominate

Clinical course for bipolar II disorder - Judd et al, longitudinal study across 13 years

• p’s had symptoms for 54% of weeks

• Depressive symptoms (50%) were more common than manic/hypomanic symptoms (1%) or cycling/mixed symptoms (2%)

• Minor depressive, and hypomanic symptoms combined were 3x more frequent than major depressive and manic symptoms (40% vs 13%)

Clinical course for bipolar II disorder - Judd et al, longitudinal study across 13 years - conclusion

the longitudinal weekly symptomatic course of B2 disorder is chronic and overwhelmingly dominated by depressive symptoms. As w bipolar I subsyndromal symptoms predominate

The brain in bipolar disorder - what is default mode network

• default mode network: brain activity when a person is restfully awake

• includes contemplation, remembering, thinking of others and planning for the future…. internal narrative

The brain in bipolar disorder - how is the Default Mode network involved

• DMN activity inversely correlated with other networks such as attention and memory performance

• DMN activity is different in bipolar disorder compared to controls : patterns of hypo and hyper connectivity

• Pattern of interaction between network may themselves differ in bipolar…. need more research

The brain and b bipolar disorder: distinguishing between unipolar and bipolar depression - key structural differences:

• Lower volume in anterior cingulate cortex for U

• Lower volume in hippocampus and amygdala in B

• Lower white matter integrity in B

The brain and b bipolar disorder: distinguishing between unipolar and bipolar depression - key functional differences: emotional stimuli

• more activation in the amygdala in unipolar towards neg emotional stumili

• Less activation in the amygdala in unipolar towards positive emotional stimuli

The brain and b bipolar disorder: distinguishing between unipolar and bipolar depression - key functional differences: DM network

• failure to activate the default mode during cognitive tasks greater for bipolar

• Stronger functional connectivity in bipolar for the default mode network

• Stronger functional connectivity in bipolar in prefrontal cortex, anterior Cingular cortex, parietal and temporal regions and thalamus

Cogntion and bipolar disorder

impairments in attention, verbal learning and memory and executive functions

• some experience cognitive decline across the course but others resume usual levels

Genetics and bipolar disorder

• MZ concordance rate of 40-70%

• First degree relatives have 5-10% risk - 7 x higher than general population

• relatives more likely to develop unipolar depression than bipolar, suggest genetic risk transcends mood disorders

• Also shared genetic risk between diagnoses of bipolar and depression

risk is polygenic =

multiple single nucleotide polymophisms, which are highly prevalent in the general population and confer a small increased risk induvidually

Polygenic risk scores

Genetic variants (SNPs) affecting 100s loci are found more frequently in groups of people with a given condition

• enables a statistical estimate of how a person’s variants affect their risk of developing it.

A polygenic risk score:

“ An individuals relative risk of a specific condition based on the collective influence of many genetic variants compared to someone without the variants (a control) “

Socioenvrionmental risk factors of bipolar disorder

• childhood trauma and abuse (especially emotional)

• childhood adversity and neglect

• childbirth

• substance misuse (especially opioids)

• canabis and cocaine use (predict onset of mania)

• some other medical conditions e.g. asthma,IBS(suggest shared autoimmune pathway)

bipolar and the immune system - fries et al (2019)

consider how evidence of epigenetic in bipolar disorder can be squared with its high heritability

• suggest that findings of consistent immune-related epigenetic alterations in people with bipolar may demonstrate how immune dysfunction is transmitted across generations

Diathesis stress for bipolar

Treatment for bipolar disorder - different mood stabilisers used for

different mood phases of bipolar disorder. lithium is used in both phases

Treatment for bipolar disorder - treatment timings

pharmacological and psychological treatment in early illness is more effective than later stages in terms of response, relapse rate, time to recurrence, symptomatic relief, remission, psychosocial functioning and employment

The role of lithium in mood stabilisation

• lithium carbonate is used to help with both hypomanic and manic and depressed phases as a long term treatment

• unknown how it woks, we do know it reduced norepinephrine levels, increases serotonin synthesis and has some anti-inflammatory actions

• Possible routes include changes to levels and properties of glutamate, GABA, dopamine and neurotrophic factors

Treating depressive episodes in bipolar disorder - SSRI’s should not be

prescribed on their own as they can worsen mania and hypomania, should be combined with olanzapne or another antipsychotic

Treating depressive episodes in bipolar disorder - SSRI’s should not be - however

balance of risk and benefit may shift for people with B2, who how no evidence of hypomania with low dose antidepressants: in this case, an SSRI on its own may be merited

Distinguishing MDD from Bipolar at first presentation with depressive symptoms - markers of bipolar can include

• easier age at onset of illness

• hyperhagia, hyperwsommnia, and psychosis

• higher frequency of affective episodes

• Comorbid substance use disorders, anxiety disorders, binge eating disorders and migranes

• Family history of psychopathy

Distinguishing MDD from Bipolar at first presentation with depressive symptoms - markers of bipolar can include - if decide to administer antidepressants need to be careful of

• insufficient response

• amplification of anxiety, dysphoria and mood instability

Psychological treatment for bipolar disorder - normally trialed as adjunctive therapies (alongside meds)

a systematic review of 39 trails found that, in comparison to medication alone, psychological treatments reduce episodic recurrence. some therapies also stabilise depressive symptoms

sychological treatment for bipolar disorder - commonly used approaches

• CBT

• Psychoeducation

• Family therapy

Similarities of bipolar and Schizophrenia

• share polygenetic risk

• Show cogntive, neurological and functional progression without effective treatment

• Feature similar symptoms

• Show prodromal symptoms, before initial onset and also before relapse