Introduction

Mania is a condition characterised by abnormally high levels of activity and energy that significantly interfere with daily functioning. Without appropriate treatment, the duration of these episodes can span from a few weeks to several months. Mania can occur in isolation, without subsequent depressive symptoms, but it is most commonly experienced as part of a mental health condition (e.g., schizoaffective disorder). Manic episodes are often associated with bipolar disorder, but mania can also result from conditions such as seasonal affective disorder, postpartum psychosis, and schizoaffective disorder.

Understanding the cause and risk factors associated with the development of mania is essential for an accurate diagnosis and early intervention. This can, in turn, benefit prognosis (disease course) and management of symptoms. For individuals affected by mania, an understanding of the causes and risks of the condition, and help them manage and identify what triggers their manic episodes. Knowledge of mania can also help families and caregivers better understand how to provide support and recognise early symptoms of manic episodes.

Understanding Mania

The DSM-5 defines mania as ‘a period of elevated, expansive (i.e. unrestrained emotional expression) or irritable mood and goal-directed activity that is considered abnormal and persistent’. Episodes typically last for at least one week and are present most of the day (unless there was a need for hospitalization during the first week which qualifies them as manic). The symptoms experienced should not be attributed to the effects of substances, such as medication or recreational drug use/abuse ¹.

For a mania diagnosis, 3 or more of the following symptoms should be present to a significant degree, and a noticeable change from their usual behaviour (4 or more symptoms should be present if the mood is only classed as irritable):¹

• Increased levels of activity or energy.
• Inflated self-esteem and grandiosity.
• Decreased need for sleep (e.g. feels well rested after 3 hours of sleep).
• More talkative than usual or seeming pressured to keep talking.
• Reports of racing thoughts.
• Easily distracted.
• Increase in goal-directed activity.
• Psychomotor agitation (e.g. repetitive movements).
• Unusual involvement in high-risk activities (i.e. shopping sprees, bad business decisions and promiscuity).

Psychotic symptoms such as delusions and hallucinations commonly occur alongside mania. Delusions are false beliefs, for example an individual experiencing grandiose delusions may report having special powers or being very knowledgeable about a certain subject, despite this being untrue. Other forms of delusion include paranoid delusions, when people might believe others are conspiring against them. Most often, these individuals do not realise delusions are happening, but the issue is noticed by others including friends and family.

Causes of Mania

The exact aetiology (cause) of mania remains unclear. However, evidence suggests that it results from the interplay of biological, psychological, and environmental factors.

Biological causes 

Genetic factors

Genetic factors of mania are unclear, however, lots of research has examined bipolar disorder, which is highly associated with mania. Having a relative with first-degree bipolar disorder (bipolar 1) has a lifetime risk of 5-10% for the condition, compared to a lifetime prevalence of 1% in the general population.² This suggests genetic inheritance plays a role in the condition. Twin studies are useful in determining the genetic susceptibility of disorder, for example, if one monozygotic twin (twins with identical genes) has bipolar disorder, the other twin has a 40-70% chance of also having the condition. These statistics suggest that environmental and lifestyle factors also largely contribute to the development of bipolar disorders.² In most cases there is an interaction between multiple genes that individually carry a small increased risk but carrying multiple genes can increase susceptibility. In 2022 the first strong genetic link to bipolar disorder was identified by researchers at MIT and Harvard, the AKAP11 gene ³.

Neurochemical imbalances

The common symptoms associated with mania such as sleep disturbances, appetite changes, and alertness are associated with abnormal brain function. During manic episodes, neurochemical imbalances in the brain can alter behaviour.

For instance, noradrenaline (also known as norepinephrine) plays a key role in the regulation of attention, cognitive functions, stress, and arousal in the brain. A metabolite of noradrenaline, 3-methoxy-4-hydroxyphenylglycol, has been shown to increase during manic episodes. Moreover, noradrenaline has been associated with the switch between depressive to manic episodes that characterise bipolar type 1.⁴ This demonstrates an association between an imbalance in certain neurochemicals and mania symptomatology.

Another neurotransmitter associated with mania is dopamine. Dopamine is well known for its role in reward pathways and motivation. ⁵ In a study where patients with bipolar disorder were given L-DOPA (a molecule involved in the production of dopamine), participants reported hypomanic-like symptoms⁵, results which were also reported in healthy controls after the administration of L-DOPA.⁵

Brain structure and function

Structural brain abnormalities seen in individuals who experience mania are often isolated to one hemisphere of the brain . Moreover, research indicates that compared to healthy controls, those with bipolar disorder exhibit hyperactivity in brain regions such as the amygdala, basal ganglia, and anterior cingulate cortex in the left hemisphere, alongside hypoactivity in the hippocampus and right ventrolateral prefrontal cortex. ^7,8 Many of these regions constitute the limbic system, a network associated with emotional response, which suggests a potential link between emotional dysregulation characteristic of mania and bipolar disorder.⁹

Psychological causes

Although some genetic driving factors of mania have been established, there is evidence to suggest that psychological factors play a role in the onset and outcomes of mania.

Stress and trauma

Significant adverse life events, specifically in early life, have been associated with bipolar disorder. In a sample of 100 individuals with bipolar disorder, approximately half reported experiences of severe childhood trauma.¹⁰ Childhood trauma also increases the likelihood of an earlier onset of the disorder, the occurrence of psychotic symptoms, and the number of lifetime mood episodes.¹¹

Furthermore, significant life events have also been shown to influence the onset of manic episodes. Multiple studies have found that positive life events and goal attainment are more likely to be followed by mania in those with type 1 bipolar disorder.¹²

Environmental and lifestyle factors

Substance abuse

There is a clear association between bipolar disorder and the use of substances such as cannabis, cocaine, opioids, and alcohol.² However, determining the direction of this relationship—whether substance use precedes the onset of bipolar disorder or occurs as a result of it—is challenging. Specifically, cannabis use has been notably associated with bipolar disorder and the onset of psychotic disorders. Research indicates that cannabis users have a threefold increased risk of developing subthreshold manic symptoms, and this drug has been linked to the recurrence of manic symptoms in those with a bipolar diagnosis. ¹³

Sleep patterns

In addition to sleep loss being a core symptom of mania, some research suggests that sleep disturbances can predict and even trigger mania. Even a single night with a significantly reduced amount of sleep can cause mania in individuals with bipolar disorder, a relationship that is more apparent in females¹⁴. Lack of sleep can disrupt the body’s internal clock, or circadian rhythm, which regulates sleep-wake cycles and other essential physiological processes. This disruption can lead to mood instability and trigger mania. Monitoring sleep and ensuring proper sleep hygiene could be considered essential in the management of bipolar and mania.

Medication-induced mania

Medication-induced mania refers to manic episodes that are triggered by the use of certain medications. This can occur in individuals with no prior diagnosis of bipolar disorder, those with a high susceptibility for mood disorders, and individuals who already have a bipolar diagnosis. Medications that are known to induce this effect are¹⁵:

• Levodopa
• Corticosteroids
• Androgenic steroids
• Tricyclic Antidepressants
• Monoamine oxidase antidepressants

The onset of mania due to medication use usually requires a reevaluation of the patient's treatment regimen. This includes a discontinuation or adjustment of the medication, and introducing mood stabilisers or antipsychotics to manage the manic symptoms. Understanding the risk of medication-induced mania is crucial for clinicians to balance the therapeutic benefits with the potential for triggering adverse effects.

Summary

In summary, the causes of mania are complex and not fully understood. Several interacting risk factors can increase the likelihood of developing mania. Key risk factors include a family history of mood disorders, genetic predisposition, lifestyle factors such as substance abuse, and a history of trauma. These factors can collectively contribute to biochemical imbalances and brain dysregulation, leading to the core symptoms of mania. Understanding these risk factors is crucial for early identification, prevention, and effective management of mania.