Anxiety disorders are the most frequently occurring problem in adolescent mental

health. According to the American Psychiatric Association (APA, 2022), there are various

temperamental, environmental, genetic and physiological factors that can play the causative

role in the development of anxiety disorders. These factors include social isolation, receptive

language difficulties, life stressors related to the loss of a relative or illness of a relative,

negative affectivity, behavioral inhibition, parental history of shyness, parental divorce,

parental intrusiveness, parental overprotectiveness, parental loss and parental separation,

physical and sexual abuse, negative or traumatic encounters with the feared object or

situation, fear of scrutiny by others, childhood maltreatment and adversity, anxiety

sensitivity, history of fearful spells (related to anxiety), smoking, interpersonal stressors,

being attacked or mugged, harm avoidance (American Psychiatric Association [APA], 2022).

The genetic susceptibility for anxiety disorders varies in each type of anxiety disorder

like in separation anxiety disorder the estimation of heritability is 73% while in specific

phobia, person with first-degree relatives with specific phobia is more likely to develop same

specific phobia and heritability for agoraphobia is 61%. In case of social anxiety disorder,

first-degree relatives have a two to six times greater chance of having social anxiety disorder

and there is an increased risk for panic disorder in case of parents with anxiety, depressive

and bipolar disorder while one-third of the risk of experiencing generalized anxiety disorder

is reported to be genetic along with neuroticism, anxiety and mood disorders (APA, 2022).

According to Narmandakh et al., (2021), adolescent anxiety disorders have

multifactorial causes that fall in specific subgroups like psychosocial and biological causes.

Anxiety disorders have been found to be associated with low socioeconomic status and

parental internalizing problems. It is reported that parents who experience anxiety and

depressive disorders may have limited social resources which reduced their capacity to help

and support their children in coping with stressful social situations that can increase the
chances of experiencing anxiety disorders (Woodruff-Borden et al., 2002; Cabral & Patel,

2020). It has been found that higher socioeconomic status is related to lower risk of anxiety

disorders especially in young girls (Narmandakh et al., 2021).

Beside this, anxiety disorders have been found to be associated with adverse early

experiences (like parental loss, parental divorce, physical and sexual abuse). These adverse

experiences at early age can have long lasting impact and as a result can increase the risk of

anxiety disorders (Oldehinkel & Ormel, 2015). Merikangas (2005) reported that drug use can

also be the potential vulnerability factor for the increased risk of developing anxiety

disorders. There are many studies which reported that there is a three-to-five-fold increased

risk of developing anxiety disorders among the first-degree relatives of those who

experienced anxiety disorders (Merikangas, 2005; Cabral & Patel, 2020).

Studies have also reported causal association between biological (or physiological)

factors and anxiety disorders. One of the most important and potential factors is

dysfunctioning hypothalamic-pituitary-adrenal (HPA) axis. Activation of HPA axis is

associated with the secretion of cortisol by the adrenal cortex. Normally, exposure to stress

activates the HPA axis which secrets the cortisol but a prolonged secretion of cortisol in

response to repeated stressors can up or down regulate the HPA axis and excessive or

insufficient activation of HPA axis have been found to be linked with the development of

anxiety disorder (Herman et al., 2016). Cortisol levels are also found to be associated with the

development of anxiety disorders among children and adolescents both in cross-sectional and

longitudinal studies (Kallen et al., 2008; Adam et al., 2014).

Another biological factor that has been reported in various studies is the irregularities

in the autonomic nervous system (ANS) that consists of sympathetic and parasympathetic

nervous system. Normally, sympathetic nervous system stimulates and parasympathetic

nervous system inhibits the bodily responses to stress. The autonomic nervous system is

particularly involved in controlling the cardiovascular responses. It has been found that low

parasympathetic (Vagal) reactivity and low sympathetic activation play role in the

development of anxiety disorders (Kagan et al., 1987; Porges, 2001). Observational and

experimental studies have reported that higher heart rate and systolic blood pressure is

associated with anxiety disorder among children and adolescents (Kossowsky et al., 2012).

While some studies have found that there is an association between heart rate and

internalizing symptoms and there is no significant association between blood pressure,

cortisol, or BMI and anxiety disorder at adolescent age (Greaves et al., 2010; Narmandakh et

al., 2021). But the results from the study of Narmandakh et al., (2021) indicated that high

heart rate is associated with anxiety disorders in boys but not in girls.

Stressful life events when experienced in early age can have long lasting impact on

certain regions of the brain that change its developmental trajectory and may lead towards the

development of psychiatric disorders including the anxiety disorders (Faravelli, 2012). It has

been reported that motor impairment in childhood due to abnormal functioning in certain

regions of brain was found to be associated with the development of anxiety disorders in late

adolescence (Shaffer et al., 1985).

Normally, the amygdala is involved in translating the perception of threat and is

responsible for initiating a biochemical reaction in response to acute threats. Wang et al.,

(2002) found that abnormal functional connectivity of right amygdala and superior temporal

gyrus was associated with generalized anxiety disorder in adolescents while Liu et al., (2015)

also found that there was abnormal (an increased) amygdala functional connectivity in

adolescents with generalized anxiety disorder. Overall, functional hyperactivity in limbic

regions especially in the right amygdala and inability of higher cortical executive areas to

normalize the limbic response towards the stimuli are found to be the etiological factors of
anxiety disorders (Martin et al., 2009). It has also been found that delayed and

unsynchronized development pattern of fronto-limbic system including higher gray matter

volume in the orbitofrontal cortex is associated with the development of social anxiety

disorder in adolescents (Liu et al., 2021).

Several neurotransmitters have been found to be associated with anxiety disorders. It

has been reported that anxiety disorders develop from a dysfunction in the modulation of the

brain circuits that regulate the emotional response to potentially threatening stimuli (Nuss,

2015). One of the neurotransmitters that has been regarded as central to the regulation of

anxiety disorders is Gamma-Aminobutyric Acid (GABA). GABAergic inhibition (inhibitory

action) is important for maintaining an equilibrium between neuronal excitation and

inhibition. Bowery (2010) reported that neuronal inhibition of GABA is mediated by two

different classes of GABA receptors which are GABA-A (responsible for rapid inhibition)

and GABA-B receptors (responsible for slow and prolonged inhibitory responses).

Abnormalities at GABA-A receptor are found to be associated with anxiety symptoms. It has

been found that there is decreased GABA activity in anxiety disorders that leads towards the

excitability of amygdala (Brehl et al., 2020).

Several studies have found altered concentrations of other important neurotransmitters

like Serotonin (5-HT), Norepinephrine (NE) and Dopamine in anxiety disorders especially in

those regions of brain that are responsible for emotional regulation. Abnormal 5-HT, NE and

dopamine receptors binding was found to be associated with anxiety disorders (Lee et al.,

2021). Reduced levels of serotonin and norepinephrine (which releases in the fight or flight

responses) have also been found to be associated with anxiety disorders (Gosmann et al.,

2021). Higher levels of dopamine due to abnormalities in mesolimbic, mesocortical and

nigrostriatal dopaminergic pathways are found to be associated with higher levels of anxiety.
These abnormalities in the levels of dopamine are especially found in fear related brain

regions (Hjorth et al., 2021).

Some studies have also found that several medical conditions can also play a

causative role in the development of anxiety disorders. Vasa et al., (2002) found that there

was an increase in the anxiety related symptoms after a head injury and this association was

with separation anxiety disorder and specific phobia in particular. It has also been reported

that migraine can lead towards anxiety symptoms in childhood, adolescence and young

adulthood especially in phobia related disorders (Swartz et al., 2000). Respiratory

disturbances like asthma are also reported to be associated with anxiety disorders as a risk

factor especially in panic disorder in terms of past history, comorbidity and family history

(APA, 2022).

According to the cognitive model (Hirsch & Mathews, 2012) and attentional control

theory (Eysenck & Derakshan, 2011), excessive and uncontrollable worry is negatively

associated with executive functions and other cognitive constructs (Zainal & Newman, 2018).

Many researches have reported that anxiety disorders influence many executive functions like

working memory, abstract planning, sustained attention, and mental flexibility. Anxiety

disorders cause clinically significant distress and problems in a person’s routine life which

ultimately impact a person’s mental health. The consequences of these disorders are

disruptive and impairing. People with anxiety disorders often feel difficulty calming

themselves because of excessive worry or fear (Viertio et al., 2021).

The most important cognitive constructs affected by anxiety disorders are cognitive

flexibility and decision making. It has been found that excessive anxiety impacts the ability to

shift flexibly between the strategies in response to any change in the task at hand and also

impacts the ability to maintain the strategy in the presence of distractors. This inability to
inhibit the threatening distractors during a cognitive function hinders the ability of people

with elevated anxiety levels to disengage from threat and return back to the task while some

studies have also reported that people with elevated anxiety take a long time to shift from one

cognitive set to another during the performance of a working memory task (Grant et al.,

2015). The area of brain that is critically involved in controlling behavioral flexibility is

prefrontal cortex (PFC) that is affected by excessive anxiety which leads toward poor

cognitive flexibility and poor decision making (Park & Moghaddam, 2017).

Anxiety disorders are associated with impairments in psychosocial functioning and

decreased quality of life including impairments in occupational, social and interpersonal

functioning. Anxiety disorders are associated with elevated rates of school dropout in

adolescent age particularly due to social anxiety disorder. Panic attacks have been reported to

be associated with higher rates of suicidality and poor quality of life. Beside these elevated

levels of anxiety especially in generalized anxiety disorder, causes physical symptoms like

tiredness and muscle tension which continuously causes significant distress and impairment

in routine life (APA, 2022). It has been reported that adolescents with high levels of anxiety

may appear to be extremely shy, may avoid their usual activities and deny to engage in new

experiences (Morris & D’Souza, 2023).