Familial Factors

Research Outcome: ‘To what extent do familial factors contribute to the development of anxiety disorders?’

1.0 Introduction
Anxiety disorders are psychiatric illnesses that result from consistent and excessive anxiety, marked by an individual’s emotional and/or physical anguish. Familial factors can heavily contribute to the development of an individual’s anxiety disorder/s, when their genealogy possesses a history of traumatic experiences such as childhood abuse. Studies of behavioural epigenetics have shown that when ancestors experience trauma, epigenetic changes capable of causing anxiety disorders, are passed on to their descendants. Additionally, research shows that when individuals experience childhood abuse, they acquire a serotonin

deficiency and epigenetic changes also capable of causing anxiety disorder/s. Moreover, when individuals have ancestors with Epilepsy, their chances of developing anxiety disorder/s are increased, as they become predisposed to a Gamma-Amino Butyric Acid (GABA) deficiency that induces anxiety. Thus, when individuals are under the appropriate circumstances, familial factors greatly contribute to the development of anxiety disorders. However, in other cases, the influences of familial factors are not as notable. These include a sedentary lifestyle that promotes excitatory neurotransmitter production, and poor dietary habits consisting of caffeine, L-Tryptophan and Vitamin B6 deficiency, and skipping meals, can lead to anxiety disorder/s development, through causing a serotonin deficiency, stress, hypoglycaemia, and/or hypertensive crisis. Despite the extensive evidence supporting the contribution of familial factors in the development of anxiety disorders, specific traits must exist in an individual’s genealogy, whilst lifestyle and dietary habits are generally self-controlled. Therefore, familial factors contribute to the development of anxiety disorders only to a limited extent.

2.0 Background Knowledge
2.1 What are anxiety disorders?
Anxiety, according to Barlow’s theory, is a “future-oriented mood state” (Barlow, 2004) in which an individual is predisposed to cope with what they perceive as impending negative events. Peter J. Lang’s 1968 three-system model of anxiety assessment categorises anxiety responses as verbal-subjective, overt motor acts, and somato-visceral activity. The underlying anxiety responses listed in Lang’s system are “worry (verbal-subjective), avoidance (overt motor acts), and muscle tension (somato-visceral activity)” (Craske et al., 2011).

Anxiety disorders are the outcome of consistent and excessive anxious behaviours, marked by individual emotional and/or physical disquietude. There are a range of anxiety disorders, each of which focus on different perceived negative events.

3.0 Familial Factors
3.1 Hereditary Anxiety
3.1.1 Behavioural Epigenetics
Familial factors such as trauma oriented behavioural epigenetics can contribute to the development of anxiety disorders to a considerable extent, causing offspring to inherit persistent anxious responses. Epigenetics is “the study of the chemical modification of specific genes or gene-associated proteins” (Fridovich-Keil, 2014-n.d.?), such as the addition or subtraction of methyl groups attached to genes. Methyl groups inform the body of the materials required in synthesising specific proteins, and according to Professor Aharon Razin, they also modulate the action of genes. Geneticists have found that epigenetic changes can be inherited in offspring, “one generation after the next” (Hurley, 2013). This led to the study of behavioural epigenetics, wherein the ways in which

experiences could cause epigenetic changes in an individual’s DNA is investigated. Research suggests that traumatic experiences in ancestors are never diminished, and actually leave “molecular scars adhering to our DNA” (Hurley, 2013), causing offspring to inherit psychological and behavioural predispositions. Experiences of ancestors may affect your epigenome by changing the epigenetic expression of genes in the brain, altering your personality, and hence, instigating anxiety or resilience. An experiment by biochemists Razin and Howard Cedar revealed that attachments of methyl groups to DNA strands could be permanent, and replicated with that DNA strand throughout future generations. They later found that this attachment significantly changed and affected the behaviour of the genes that they attached to, “inhibiting its transcription” (Hurley, 2013), and making it challenging for the genes to produce proteins. Additionally, it was discovered that even in the absence of DNA mutation/s, the attached methyl groups caused lasting, heritable changes in gene function (Hurley, 2013). Moreover, researchers at the Emory University School of Medicine discovered that mice could “pass on learned information about traumatic or stressful experiences” (Gray, 2013). Several studies conducted on mice by researchers and neurobiologists provide evidence for this observation. One study found that mice traumatised in childhood, produced offspring containing heavily methylated DNA, suggesting that physical alterations on their genes due to their predecessors’ trauma could have been inherited. Furthermore, in a study by neurobiologist Isabella Mansuy, it was found that mice pups that were separated from their mothers 14 days after birth, and then nurtured normally after, had epigenetic alterations on their genes related to emotional control and stress response. Mansuy found that these genes were heavily methylated, and that it caused the mice pups to display frequent depressive and anxious behaviours. It was also later discovered that the offspring of these pups had inherited the traumatic experience, possessing heavily methylated DNA, “despite a lack of early trauma” (Knight, 2013). According to Dr Tracy L. Bale, the genetic consequences of early trauma are evident in up to three generations of mice, “even if the subsequent two generations are raised without stress or separation” (Knight, 2013). Dr Bale also inferred that epigenetic changes occur through physical transmission, after finding methylation in mouse sperm. A Science journal article suggests that despite the erasure of epigenetic changes, they can still be inherited generations after. Though the supporting studies mentioned have been conducted on mice, researchers have obtained “retrospective data on humans’ (Knight, 2013) that suggest that the findings may also be true for us. Hence, assuming the same case for humans, when inheriting these anxiety inducing behavioural epigenetic changes, humans will eventually develop anxiety disorders as their anxious responses persist, as marked by the lasting changes on their epigenome. Based on the evidence, familial factors such as inherited behavioural epigenetic changes, can contribute to an individual’s development of anxiety disorder/s, causing them to experience persisting anxious responses, and by definition, develop anxiety disorder/s.

3.1.2 Gamma-Amino Butyric Acid Deficiency
GABA deficiency is a familial factor that can contribute to the development of anxiety disorders to a certain extent, causing anxiety through overstimulation of the brain, but requiring individual’s to be predisposed to disorders such as Epilepsy.

GABA is an inhibitory neurotransmitter in the Central Nervous System (CNS), critical in regulating anxiety and reducing stress. It does this by preventing overstimulation in the brain, and subduing excitatory neurotransmitters, which have the ability to cause anxiety when the brain is overstimulated. Hence, GABA deficiency results in overstimulation in the brain, and consequently, anxiety. Not only that, but those who experience anxiety due to GABA deficiency, often develop anxiety disorder/s. Additionally, as GABA induces relaxation, analgesia, and sleep, “dysfunction of the GABA system is implicated in the pathophysiology of several neuropsychiatric disorders, including anxiety and depression” (Neurotransmitters, Depression and Anxiety, 2008). GABA is synthesised by the amino acid glutamate decarboxylase (glutamine); thus, glutamine deficiency will result in GABA deficiency (Graham, n.d.). Whilst glutamine deficiency can be caused by diets lacking protein, excessive stress, menopause, and diets rich in sugar and starch (GABA Deficiency- Anxiety and Depression, n.d.), it is also commonly a result of Epilepsy (Glutamate decarboxylase deficiency, 2012?). Therefore, Epilepsy inheritance is a familial factor that contributes to an

individual’s development of anxiety disorder/s. Epilepsy has two major causes, the first being due to chemical imbalances in the brain, and the other, brain injuries. That being said, in a majority of Epilepsy cases, a cause is not identified. Whilst chemical imbalances caused by alcohol, cocaine, low blood sugar, low oxygen levels, low blood sodium, and/or low blood calcium can instigate seizures, scientists also believe that there are genetic aspects to Epilepsy (Fisher and Saul, n.d.). Statistics suggest that in every 100 children born to parents with Epilepsy, between 2 and 5 of those will inherit Epilepsy (Epilepsy and inheritance, 2012). Moreover, parents who have idiopathic epilepsy have children who will have a 9% to 12% chance of inheriting that epilepsy; this is the same for identical twins. If one twin has idiopathic epilepsy, the other is likely to have it too (Minassian, 2010). Even if Epilepsy is not directly inherited, individuals are able to inherit a low seizure threshold in their brain, meaning that they are more likely to experience seizures than those with high seizure thresholds. Professionals believe that cases of Epilepsy where a cause is not identified can be attributed to an inherited low seizure threshold (Epilepsy and inheritance, 2012). Additionally, children with mothers or an extensive history of Epilepsy in their genealogy are more susceptible to the disorder, as shown in Figures 1 and 2.

Figure 1: Table showing the risk of a child developing Epilepsy when certain family members have Epilepsy (Epilepsy and inheritance, 2012)

Figure 2: Table showing the risk of a child developing Epilepsy based on the age in which their parent developed Epilepsy (Epilepsy and inheritance, 2012)

According to Minassian, family investigations have shown that certain Epilepsy syndromes are completely determined by genetics, and that some inherited metabolic conditions and chromosomal disorders cause genetic predispositions to Epilepsy. Over 20 inherited single gene disorders have been recognised as a cause for Epilepsy. Some of the most recognised include Tuberous Sclerosis, Down syndrome, and Fragile X Syndrome. Despite that, a specific gene that causes the inheritance of Epilepsy has not yet been discovered, as Epilepsy inheritance is extremely complex (Minassian, 2010). That being said, Epilepsy can also be caused by individual lifestyle choices, such as alcohol withdrawal, toxicity, trauma, nutritional deficiencies, intake of abusive drugs such as ecstasy and cocaine, as well as inhalants (Alcohol and Drugs, n.d.). Thus, GABA deficiency is a genetically predisposed familial factor caused by Epilepsy inheritance, which can contribute to an individual’s development of anxiety disorder/s.