Introduction 

Psychiatric (mental health) conditions are a spectrum of clinically significant disturbances to individuals’ thinking, emotional regulation, and behaving.¹ These conditions have been shown to have links with Transient Global Amnesia (TGA), a rare, sudden, episodic memory loss. 

There are overlapping symptoms such as emotional distress, confusion, disorientation, and shared potential risk factors of physical, emotional, and psychological stress, as well as anti- anxiety and sedative medications use. These suggest a deeper intersection between mental health and neurological phenomena.

It is crucial to understand the link to offer comprehensive care to affected individuals. The exploration of these intricate dynamics between psychiatric conditions and TGA can not only promote diagnostic accuracy but also facilitate holistic management strategies to address both mental and neurological health. 

What is transient global amnesia (TGA) ? 

Transient Global Amnesia (TGA) is an acute, temporary episode of memory loss that resolves spontaneously ranging from a few to within 24 hours. 

Despite intact consciousness, motor, language, social and executive functioning, TGA is categorized as not being able to recall recent or older memories, and being unable to recognise oneself, family and friends. It is characterised by an abrupt onset of new memory formation difficulties, associated with a sense of distress, confusion, and disorientation towards time and where they are. This increases the need to ask the same questions repetitively for self-assurance. 

However, it is usually harmless. Once memory returns to normal usually within 24 hours, issues are resolved, without residual cognitive impairments or brain dysfunctions. 

Possible causes and risk factors 

The exact cause of TGA is still not known. It is believed to either be temporal lack of sufficient blood flow (known as ischemia), oxygen flow (hypoxia), or seizure activities upon the hippocampus, which is the part of the brain responsible for learning and memory. There is a higher risk for TGA in elderly people, with less cases in those under 40.

Several factors or comorbids are suggested as a trigger of TGA:

• Physical exertion 
• Emotional or psychological stress
• Extreme hot or cold temperatures
• Pain 
• Sexual intercourse 
• Performing the Valsalva maneuver breathing technique 
• Heart disease
• Migraine headaches 
• Underlying vascular issues, such as hyperlipidemia (high cholesterol) or hypoxic-ischemic events 
• History of epilepsy 
• Angiography that involve the larger dose of sedatives or sleep-inducing drugs (e.g., barbiturates)⁽²⁾

It may also be found after substance ingestion such as: 

• Excessive alcohol use 
• Excessive recreational drugs 
• Use of benzodiazepines (for anxiety, insomnia and seizures treatments) 

Differentiation diagnosis 

Despite symptomatic similarities, TGA is distinguished from:

• Stroke for it’s memory loss, but without lasting neurological deficits such as weakness, numbness, and speech disturbances
• Epilepsy by the absence of recurring conscious-altering seizures 
• Dementia by its sudden onset and temporary nature without residual effects, instead of the progressive cognitive decline 

How are psychiatric conditions related to TGA ? 

Given stress and emotional factors are known triggers of TGA, certain psychiatric disorders are more susceptible to TGA episodes due to its impact of stress and memory processing. 

Anxiety and panic disorders 

Anxiety and panic disorders are strongly correlated to TGA occurence. 

Anxiety disorders can alter the amygdala and hippocampus, responsible for emotional processing and memory formation. Fear and irritability can activate hypothalamic-pituitary-adrenal axis (HPA axis) chronically, resulting in hyperarousal of the sympathetic nervous system (SNS) ,causing levels of stress hormones (such as cortisol) to increase. Henceforth, reducing the hippocampal volume and impairing memory signaling.^3,4,5

Panic disorder involves dysregulated neurotransmitter activity, hence hyperactivated amygdala, which is crucial upon fear response generation. The disruptions to the prefrontal cortex (PFC) and hippocampus during panic attacks, especially a severe one, may impair memory functioning.^6,7

In turn, the sense of distress and disorientation induced by an unpredictable TGA episode can further escalate the anxiety-related physical symptoms and fear, creating a vicious bi-directional cycle.⁸

Mood disorders

Mood disorders like depression or bipolar disorder are strongly linked to TGA through shared neurobiological pathways. 

Depression and bipolar disorder (particularly during manic or hypomanic episodes) has been consistently identified as a risk factor of TGA episodes.⁶ Neurotransmitter imbalances, such as serotonin, norepinephrine, and dopamine, pose a higher vulnerability to mood and memory processing. Cognitive disturbances, such as anterograde amnesia, disorientation, difficulties with information processing and recall, are also present during the manic or hypomanic state of bipolar. Heightened arousal, impulsivity, and distractibility associated with mania may also trigger TGA episodes.^9,10

A dysregulated HPA axis plays a role in reducing hippocampal and prefrontal cortex (PFC) volume and neurogenesis (new cell, synaptic formation), while also adversely affecting their activities. Additionally, executive functioning and memory could also be further dampened by increased cortisol levels.^11,12

Stress and trauma-related disorders 

Stress and trauma-related disorders such as dissociative disorderand functional neurological disorder, and post traumatic stress disorder (PTSD), due to their heightened emotional arousal and altered stress response, can all contribute to TGA.

Dissociative disorders 

Dissociative disorders may show difficulties in retrieving and encoding memory due to dissociative amnesia. With less activated PFC, limbic system, and hippocampal and parahippocampal structures, symptoms like continuous anterograde memory loss and confusionsimilar to TGA episodes can be induced.¹³

Functional neurological disorder 

Functional Neurological Disorder is characterized by neurological symptoms without a known organic cause, which exhibit cognitive changes like brain fog, confusion, difficulty focusing, and experiencing dissociative amnesia and depersonalization resembling TGA. 

Post-traumatic stress disorder 

Post-traumatic stress disorder (PTSD), chronic stress, and trauma can induce hippocampal atrophy, overactive amygdala and medial PFC hypo-activity that effects memory functioning, fear responses, and emotional reactivity, leading to TGA episodes.¹⁴ This can cause a wide range of TGA-like symptoms such as short-term memory deficits, impaired episodic memory and difficulty remembering important details.^15,16,17

The dysregulated HPA axis in cortisol release and variations of neurotransmitters like glutamate and apolipopprotein E (ApoE) upon stress and trauma-related disorders (especially PTSD) are also intricately related to TGA.^18,19,20,21

Secondary sleeping disorders 

Secondary sleeping disorders stemming from mental health conditions like anxiety and panic disorders, mood disorders, stress and trauma, can provoke TGA episodes by impairing memory consolidation and cognitive functioning. 

• Anxiety and panic disorders often show up as insomnia, nocturnal panic attack, and sleep anxiety, due to hyperarousal²²
• Depression may exhibit disturbances like insomnia (difficulty falling asleep) or hypersomnia (excessive sleep)²³
• Bipolar disorder usually leads to reduced need of sleep during manic period, whereas insomnia or excessive sleepiness during depressive episodes²⁴
• Dissociative disorders accompany issues like insomnia, nightmares, waking dreams, and sleepwalking
• Conversion disorders exhibit either insomnia or hypersomnia
• PTSD can cause nightmares, night terrors that lead to non-restorative sleep

These resulting sleep deficits can impair hippocampal-dependent memory processing, increasing potential susceptibility to the temporary cognitive disturbances among TGA episodes.²⁵

Diagnosis and management 

When evaluating an individual with a psychiatric disorder, with memory issues presented, differentiating TGA from other similar conditions like dissociative amnesia, fugue states, or mood disorder-associated cognitive disturbances is crucial.²⁶

The diagnostic process still includes a thorough clinical interview, neuropsychological assessment, and neuroimaging tests (i.e., CT scans and MRI). 

Furthermore, key features like transient, sudden obvious anterograde amnesia, absence of clouded consciousness, and the preserved long-term memory, could help differentiate it from dissociative or other psychiatric memory impairments. 

Psychotherapy and stress management 

Given the strong bidirectional relationship upon TGA and various psychiatric conditions, addressing the underlying neurobiological link is crucial.

Psychotherapy

Psychotherapy, such as cognitive-behavioural therapy (CBT) and mindfulness-based interventions, can help individuals with mental health struggles in cultivating adaptive coping strategies for stress management and emotional regulation. 

Stress management techniques 

Stress management techniques including relaxation exercises, biofeedback, and even simple lifestyle modifications, can reduce physiological arousal whilst restoring balance to the stress response system. Therefore, mitigating TGA-associated neurological disturbances. 

Psychoeducation 

Psycho-educating individuals about the connection between mental health conditions and TGA can empower them to recognise warning signs and seek interventions in a timely manner. 

Medicine

The first and foremost intervention should be adjusting or optimising existing medical treatment for the primary condition. For instance, to restore the neurochemical balance and reduce TGA episodic recurrence through mood stabilisers, antidepressants, or anxiolytics (anti-anxiety drugs). 

Nethertheless, some cognitive-enhancing drugs or therapies could aid memory consolidation and retrieval, targeting specific symptoms of TGA. 

How should TGA episodes be recognised and responded to? 

Warning precursors of TGA episodes in psychiatric conditions 

Sudden mood or emotional changes

Prominent upon individuals with bipolar or other mood disorders. Individuals may experience a rapid shift towards a manic or hypomanic state. 

Heightened anxiety and dissociative experience 

The dissociative disorders or PTSD population may display heightened anxiety levels or more frequent dissociative symptoms. 

Cognitive disruptions 

Individuals or their family and friends may notice some subtle changes in cognitive functioning, such as difficulties in memory, concentration, information processing, and executive functions.

Increased physiological arousal 

Due to stress response dysregulations, where hormones like cortisol are elevated, individuals may experience physical symptoms such as increased heart rate or blood pressure. 

Sleep disturbances 

Changes in sleeping patterns such as quality, duration, or sleep-wake cycle can be predictive to a TGA episode due to the neurochemical and hormonal alterations. 

What to do during an episode ? 

• Provide a calm and supportive environment with minimal external stimuli and distractions
• Reassure and support the person emotionally
• Avoid repeatedly asking the individual about their current situation or recent events
• Obtain individuals’ information, such as psychiatric history, current medication, and recent stressful events
• Monitor and document the duration and progression of TGA episodes
• Encourage post-episode rest and recovery

When to seek medical help? 

In cases of TGA episodes, seek immediate medical assistance if the sudden memory loss doesn’t resolve within 24 hours, when there are focal (or widespreading) neurological deficits (indicating stroke), or when there are consciousness altering seizure activities before or during the episode (indicating epilepsy). 

Summary 

Psychiatric conditions can induce transient global amnesia (TGA) episodes through shared neurobiological pathways. Anxiety, panic, stress, and trauma-related disorders can cause heightened emotional arousal, therefore impairing memory consolidation. Mood disorders, where neurotransmitters are dysregulated, may heighten the risk of cognitive disturbances. Sleep disorders, secondary to psychiatric conditions, exacerbate cognitive vulnerabilities and increases TGA susceptibility. While this sophisticated relationship can helpcognitive functioning upon populations with mental health conditions, olistic care and management planning is also promoted to alleviate the risk of TGA episodes, to improve overall emotional and cognitive health upon the population with psychiatric comorbidities.