Bipolar disorder

Bipolar disorder, also referred to as bipolar affective disorder or manic depressive disorder, is a chronic psychiatric condition characterised by both mania and hypomania as well as depressive episodes.

Let’s discuss what these terms mean:

• Mania - a manic episode may be defined as the following:
• Severity - elevated mood or irritability which are severe enough to:
• Impair social/occupational function.
• Necessitate hospitalisation.
• Include psychotic features (such as hallucinations or delusions).
• Duration - lasting at least 1 week (or any duration if hospitalisation is required).
• Hypomania - a hypomanic episode is defined as the following:
• Severity - elevated mood or irritability which:
• Does not cause significant impairment in function.
• Does not require hospitalisation.
• Does not include psychotic features.
• Duration - lasting at least 4 consecutive days.

• Depression - a depressive episode is defined as the following:
• Severity - depressed mood or loss of interest/pleasure that causes significant distress. Accompanied with at least 4 additional symptoms of
• Insomnia or hypersomnia
• Poor concentration/indecisivenss
• Suicidal ideation
• Fatigue
• Feelings of worthlessness or excessive guilt
• Significant weight loss/gain
• Psychomotor agitation or retardation
• Duration - lasting at least 2 weeks.

So what are psychotic features?

Psychosis is a state of mind in which one sees or hears things that are delusional (things that are clearly not true). Grandiosity (a delusion of grandeur) is when one has an inflated self-importance. Hallucinations are perceptions of things that are not present - such as sounds, voices or objects.

🏘️ Epidemiology

Bipolar disorder is the fourth most prevalent mental health condition globally (after depression, anxiety and schizophrenia).

It usually has onset in teenage years (between 15-19) and rarely presents in early childhood and over the age of 40.

There seems to be no gender or ethnic predisposition.

Pathophysiology

The aetiology and pathophysiology of bipolar disorder is multifactorial and not entirely understood.

Let’s look at the factors involved:

• Genetic factors - there is a 14x increase in risk of developing bipolar disorder if a first-degree relative has the disorder. Genome-wide association studies (GWAS) have identified certain genes as risk factors for developing bipolar disorder:
• ANK3 (Ankyrin 3) - regulates neuronal excitability.
• CACNA1C (Calcium channel gene) - affects synaptic signalling.
• BDNF (Brain-derived neurotrophic factor) - involved in neuroplasticity.
• Dysregulation of neurotransmitters - as neurotransmitters control signalling in the CNS, imbalances may lead to depressive or manic episodes.
• Dopamine - increased in mania and deficient in depression.
• Serotonin - deficient in depression.
• Noradrenaline - increased in mania and deficient in depression.
• Glutamate - increased levels lead to excitotoxicity in mania.
• GABA - deficiencies in GABA lead to reduced inhibition and increased excitability.
• Altered brain function and structure
• Prefrontal cortex - this is the part of the brain that controls executive functions, such as thinking, problem-solving, and decision-making. Changes to the prefrontal cortex leads to impaired emotional regulation.
• Amygdala - this is the part of the brain that processes emotions, especially fear, anxiety, and rage. It also helps with memory, learning, and senses. Hyperactivity of the amygdala leads to instability with mood.
• Hippocampus - the hippocampus is the part of the brain that plays a key role in learning and memory. Reductions in the volume of the hippocampus leads to changes in emotional memory processing.
• Basal ganglia and thalamus - the basal ganglia control motor movement and other cognitive functions while the thalamus is the relay center to the brain. Dysfunction of these two parts of the brain lead to mood changes and psychomotor disturbances.
• Stress precipitants
• Hypothalamic-pituitary-adrenal (HPA) axis dysfunction - shifts in the HPA leads to increased cortisol which contributes to neurotoxicity and mood swings.
• Circadian rhythm abnormalities - alterations to the sleep-wake cycle as a result of altered melatonin secretion leads to mood instability.
• Childhood trauma, abuse or neglect
• Overwhelming stressors in early-life
• Traumatic and life-changing events

⚠️ Risk factors

• Family history of bipolar disorder
• Symptom onset under 20 years of age
• Stressful and traumatic life events
• Adverse-childhood events
• History of depression or anxiety
• Substance misuse
• Toxplasmosis

🔢 Classification

According to the Diagnostic and Statistical Manual of Mental Disorders (DSM) V there are multiple subtypes of bipolar disorder:

1. Bipolar disorder type I - at least one manic episode lasting ≥1 week or requiring hospitalisation, with or without depressive episodes.
2. Bipolar disorder type II - at least on hypomanic episode lasting ≥4 days and one major depressive episode lasting ≥2 weeks without a history of a manic episode.
3. Cyclothymic disorder - chronic fluctuating mood disturbances for ≥2 years (or ≥1 year in children or adolescents) with hypomanic and depressive symptoms (that do not meet full criteria for mania, hypomania or major depression). The symptoms should be present for ≥50% of the time and one should not be asymptomatic for longer than 2 months.
4. Substance/medication-induced bipolar and related disorder - manic, hypomanic, or depressive symptoms caused by substance use (e.g., cocaine, steroids, antidepressants) or withdrawal.
5. Bipolar and related disorder due to another medical condition - mood symptoms caused by medical conditions such as stroke, traumatic brain injury, multiple sclerosis, Cushing’s disease, hyperthyroidism, SLE, HIV/AIDS.

😷 Presentation

A person with bipolar disorder will experience an average of approximately 10 episodes during their lifetime, although there is a large degree of inter-individual variation. Some people may experience chronic, sub-syndromal symptoms, most commonly of depression.

🔍 Investigations

We suspect bipolar disorder if there are symptoms of mania, hypomania, depression, or a mixture of both manic and depressive symptoms.

To confirm diagnosis, referral to the following services is necessary:

• For adults - refer to a specialist mental health service.
• For children and young people:
• Children <14 years of age should be referred to Child and Adolescent Mental Health Services (CAMHS).
• Young people aged 14-18 years may be referred to a specialist early intervention in psychosis service or to a CAMHS team, depending on local service provision.

The urgency of the referral is based on the risk assessment of harm to themselves and/or others (through neglect or through aggression and violence). It is important to take into account their employment, personal relationships, finances, driving, sexual activity and alcohol/drug use. If it is deemed they are a danger to themselves or others then an urgent referral is warranted.

• If the person needs to be admitted to the hospital, every attempt should be made to persuade them to go voluntarily. If the person refuses to go to hospital, compulsory admission may be necessary if the person:
• Requires assessment and/or treatment in a hospital, and
• Needs to be admitted in the interests of their own health or safety, and/or for the protection of other people.
• Compulsory admission may be arranged under sections 2, 3, or 4 of the Mental Health Act.

We can use some tools to assess for depression or mood disorders, such as PHQ-9, mood disorder questionnaire (MDQ), young mania rating scale (YMRS), bipolarity index, etc.

🧰 Management

🚨 Complications

• Suicide and deliberate self-harm
• Consequences of disinhibition and impaired social functioning
• A number of other psychological and physical illnesses:
• Anxiety disorder, alcohol and other substance misuse disorders personality disorders, ADHD
• Cardiovascular disease hypertension
• Type 2 diabetes dyslipidaemia metabolic syndrome, obesity
• Chronic kidney disease
• Respiratory disease