bdnf, a gene that codes for a protein called brain derived neurotrophic factor that is found in the brain, has also been associated with anxiety and specific patterns of neural activity. and a receptor gene for bdnf called ntrk2 was associated with anxiety in a large genome-wide investigation. the reason that most candidate gene findings have not replicated is that anxiety is a complex trait that is influenced by many genomic variants, each of which has a small effect on its own. increasingly, studies of anxiety are using a hypothesis-free approach to look for parts of the genome that are implicated in anxiety using big enough samples to find associations with variants that have small effects. the largest explorations of the common genetic architecture of anxiety have been facilitated by the uk biobank, the angst consortium and the crc fear, anxiety and anxiety disorders. epigenetics this section is an excerpt from epigenetics of anxiety and stress–related disorders. epigenetics of anxiety and stress–related disorders is the field studying the relationship between epigenetic modifications of genes and anxiety and stress-related disorders, including mental health disorders such as generalized anxiety disorder (gad), post-traumatic stress disorder, obsessive-compulsive disorder (ocd), and more. epigenetic modifications play a role in the development and heritability of these disorders and related symptoms. for example, regulation of the hypothalamus-pituitary-adrenal axis by glucocorticoids plays a major role in stress response and is known to be epigenetically regulated. as of 2015 most work has been done in animal models in laboratories, and little work has been done in humans; the work is not yet applicable to clinical psychiatry. medical conditions many medical conditions can cause anxiety. this includes conditions that affect the ability to breathe, like copd and asthma, and the difficulty in breathing that often occurs near death. conditions that cause abdominal pain or chest pain can cause anxiety and may in some cases be a somatization of anxiety; the same is true for some sexual dysfunctions. conditions that affect the face or the skin can cause social anxiety especially among adolescents, and developmental disabilities often lead to social anxiety for children as well. life-threatening conditions like cancer also cause anxiety. furthermore, certain organic diseases may present with anxiety or symptoms that mimic anxiety. these disorders include certain endocrine diseases (hypo- and hyperthyroidism, hyperprolactinemia), metabolic disorders (diabetes), deficiency states (low levels of vitamin d, b2, b12, folic acid), gastrointestinal diseases (celiac disease, non-celiac gluten sensitivity, inflammatory bowel disease), heart diseases, blood diseases (anemia), cerebral vascular accidents (transient ischemic attack, stroke), and brain degenerative diseases (parkinson's disease, dementia, multiple sclerosis, huntington's disease), among others. substance-induced several drugs can cause or worsen anxiety, whether in intoxication, withdrawal or as side effect. these include alcohol, tobacco, sedatives (including prescription benzodiazepines), opioids (including prescription pain killers and illicit drugs like heroin), stimulants (such as caffeine, cocaine and amphetamines), hallucinogens, and inhalants. while many often report self-medicating anxiety with these substances, improvements in anxiety from drugs are usually short-lived (with worsening of anxiety in the long term, sometimes with acute anxiety as soon as the drug effects wear off) and tend to be exaggerated. acute exposure to toxic levels of benzene may cause euphoria, anxiety, and irritability lasting up to 2 weeks after the exposure. psychological poor coping skills (e.g., rigidity/inflexible problem solving, denial, avoidance, impulsivity, extreme self-expectation, negative thoughts, affective instability, and inability to focus on problems) are associated with anxiety. anxiety is also linked and perpetuated by the person's own pessimistic outcome expectancy and how they cope with feedback negativity. temperament (e.g., neuroticism) and attitudes (e.g. pessimism) have been found to be risk factors for anxiety. cognitive distortions such as overgeneralizing, catastrophizing, mind reading, emotional reasoning, binocular trick, and mental filter can result in anxiety. for example, an overgeneralized belief that something bad "always" happens may lead someone to have excessive fears of even minimally risky situations and to avoid benign social situations due to anticipatory anxiety of embarrassment. in addition, those who have high anxiety can also create future stressful life events. together, these findings suggest that anxious thoughts can lead to anticipatory anxiety as well as stressful events, which in turn cause more anxiety. such unhealthy thoughts can be targets for successful treatment with cognitive therapy. psychodynamic theory posits that anxiety is often the result of opposing unconscious wishes or fears that manifest via maladaptive defense mechanisms (such as suppression, repression, anticipation, regression, somatization, passive aggression, dissociation) that develop to adapt to problems with early objects (e.g., caregivers) and empathic failures in childhood. for example, persistent parental discouragement of anger may result in repression/suppression of angry feelings which manifests as gastrointestinal distress (somatization) when provoked by another while the anger remains unconscious and outside the individual's awareness. such conflicts can be targets for successful treatment with psychodynamic therapy. while psychodynamic therapy tends to explore the underlying roots of anxiety, cognitive behavioral therapy has also been shown to be a successful treatment for anxiety by altering irrational thoughts and unwanted behaviors. evolutionary psychology an evolutionary psychology explanation is that increased anxiety serves the purpose of increased vigilance regarding potential threats in the environment as well as increased tendency to take proactive actions regarding such possible threats. this may cause false positive reactions but an individual with anxiety may also avoid real threats. this may explain why anxious people are less likely to die due to accidents. there is ample empirical evidence that anxiety can have adaptive value. within a school, timid fish are more likely than bold fish to survive a predator. when people are confronted with unpleasant and potentially harmful stimuli such as foul odors or tastes, pet-scans show increased blood flow in the amygdala. in these studies, the participants also reported moderate anxiety. this might indicate that anxiety is a protective mechanism designed to prevent the organism from engaging in potentially harmful behaviors. social social risk factors for anxiety include a history of trauma (e.g., physical, sexual or emotional abuse or assault), bullying, early life experiences and parenting factors (e.g., rejection, lack of warmth, high hostility, harsh discipline, high parental negative affect, anxious childrearing, modelling of dysfunctional and drug-abusing behaviour, discouragement of emotions, poor socialization, poor attachment, and child abuse and neglect), cultural factors (e.g., stoic families/cultures, persecuted minorities including those with disabilities), and socioeconomics (e.g., uneducated, unemployed, impoverished although developed countries have higher rates of anxiety disorders than developing countries). a 2019 comprehensive systematic review of over 50 studies showed that food insecurity in the united states is strongly associated with depression, anxiety, and sleep disorders. food-insecure individuals had an almost 3 fold risk increase of testing positive for anxiety when compared to food-secure individuals. gender socialization contextual factors that are thought to contribute to anxiety include gender socialization and learning experiences. in particular, learning mastery (the degree to which people perceive their lives to be under their own control) and instrumentality, which includes such traits as self-confidence, self-efficacy, independence, and competitiveness fully mediate the relation between gender and anxiety. that is, though gender differences in anxiety exist, with higher levels of anxiety in women compared to men, gender socialization and learning mastery explain these gender differences. treatment the first step in the management of a person with anxiety symptoms involves evaluating the possible presence of an underlying medical cause, the recognition of which is essential in order to decide the correct treatment. anxiety symptoms may mask an organic disease, or appear associated with or as a result of a medical disorder. cognitive behavioral therapy (cbt) is effective for anxiety disorders and is a first line treatment. cbt appears to be equally effective when carried out via the internet. while evidence for mental health apps is promising, it is preliminary. psychopharmacological treatment can be used in parallel to cbt or can be used alone. as a general rule, most anxiety disorders respond well to first-line agents. such drugs, also used as anti-depressants, are the selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors, that work by blocking the reuptake of specific neurotransmitters and resulting in the increase in availability of these neurotransmitters. additionally, benzodiazepines are often prescribed to individuals with anxiety disorder. benzodiazepines produce an anxiolytic response by modulating gaba and increasing its receptor binding. a third common treatment involves a category of drug known as serotonin agonists. this category of drug works by initiating a physiological response at 5-ht1a receptor by increasing the action of serotonin at this receptor. other treatment options include pregabalin, tricyclic antidepressants, and moclobemide, among others. anxiety is considered to be a serious psychiatric illness that has an unknown true pervasiveness due to affected individuals not asking for proper treatment or aid, and due to professionals missing the diagnosis. prevention the above risk factors give natural avenues for prevention. a 2017 review found that psychological or educational interventions have a small yet statistically significant benefit for the prevention of anxiety in varied population types. pathophysiology anxiety disorder appears to be a genetically inherited neurochemical dysfunction that may involve autonomic imbalance; decreased gaba-ergic tone; allelic polymorphism of the catechol-o-methyltransferase (comt) gene; increased adenosine receptor function; increased cortisol. in the central nervous system (cns), the major mediators of the symptoms of anxiety disorders appear to be norepinephrine, serotonin, dopamine, and gamma-aminobutyric acid (gaba). other neurotransmitters and peptides, such as corticotropin-releasing factor, may be involved. peripherally, the autonomic nervous system, especially the sympathetic nervous system, mediates many of the symptoms. increased flow in the right parahippocampal region and reduced serotonin type 1a receptor binding in the anterior and posterior cingulate and raphe of patients are the diagnostic factors for prevalence of anxiety disorder. the amygdala is central to the processing of fear and anxiety, and its function may be disrupted in anxiety disorders. anxiety processing in the basolateral amygdala has been implicated with expansion of dendritic arborization of the amygdaloid neurons. sk2 potassium channels mediate inhibitory influence on action potentials and reduce arborization.