Stress & Anxiety: Symptoms, Causes, Testing, Treatment

Stress is a normal physiological response of the body to demanding situations. When this response becomes persistent or dysregulated, it may contribute to the development of anxiety that goes beyond everyday worry or fear and can significantly affect quality of life. In reality, chronic stress is not limited to the psychological domain; it has clear biological effects that influence systems such as the endocrine, cardiovascular, and immune systems. Anxiety, although often confused with normal worry, has a distinct neurobiological basis and, in its pathological form, follows specific diagnostic criteria. Early recognition and a comprehensive evaluation of the body, including specialized laboratory testing, can help identify underlying factors that trigger or worsen stress and anxiety, allowing for more targeted interventions. Functional medicine, with its integrative and advanced diagnostic approach, is increasingly recognized as a valuable tool in the holistic management of anxiety. Understanding anxiety across its psychological, biological, and functional dimensions is a key step toward effective management and long-term improvement in overall health and quality of life.

Epidemiological Data

Anxiety is one of the most prevalent mental disorders worldwide, and its overall burden has increased markedly since 2020. According to analyses from the Global Burden of Disease (GBD) 2019/2020, anxiety disorders rank among the leading non-fatal causes of long-term functional impairment, with tens of millions of additional cases attributed to the impact of the COVID-19 pandemic. Meta-analyses conducted in general and specific populations (2021-2023) report a high prevalence of anxiety symptoms among children and adolescents, university students, and healthcare workers, with rates often exceeding 20-30% during the acute phase of the pandemic and remaining elevated in subsequent years. In Europe, longitudinal studies (2021-2022) across multiple countries document persistently increased levels of probable anxiety disorders, with strong determinants including sex (higher prevalence among women), loneliness, financial insecurity, and chronic illness. In Greece, although nationally representative data remain limited, available findings and European comparisons suggest a sustained high prevalence of anxiety following the economic crisis and the COVID-19 pandemic, accompanied by underdiagnosis and reduced access to mental health services. At the same time, contemporary literature strengthens the evidence for a strong association between chronic anxiety and physical conditions such as sleep disorders, irritable bowel syndrome, arterial hypertension, and autoimmune diseases, highlighting the need for comprehensive, interdisciplinary interventions and early detection, particularly in vulnerable populations.

Symptoms and Signs

The symptoms of stress may manifest on three primary levels: physical, psychological and behavioral. Identifying these symptoms, especially when they are persistent and not related to a clear external cause, is the first step toward effective management.

Physical Symptoms

• Tachycardia and palpitations: Patients often report a strong heartbeat or arrhythmias.
• Respiratory discomfort: A feeling of chest heaviness, rapid or shallow breathing, or choking sensation.
• Muscle tension and pain: Often located in the neck, shoulders, or back.
• Gastrointestinal disturbances: Bloating, nausea, and altered bowel habits.
• Dizziness or near-fainting: Especially during panic attacks or episodes of hyperventilation.
• Increased sweating and tremors: Especially in the palms, face and extremities.
   

Psychological Symptoms

• Persistent worry that is not linked to a specific event.
• Irritability or a feeling of imminent “danger”.
• Inability to concentrate or mental “fog”.
• Sleep disturbances, such as insomnia, fragmented sleep or hypersomnia.
• Feelings of hopelessness or pessimism about the future.
   

Behavioral Signs

• Avoidance of situations or social interactions.
• Excessive need for control and perfectionism.
• Dependence on substances such as caffeine, alcohol or tranquilizers.
   

These symptoms can fluctuate in intensity and duration, and are often exacerbated during periods of increased stress or following physical exhaustion.

Underlying Causes of Stress

Stress is not merely the result of psychological stress or challenging circumstances. Numerous organic factors can cause or exacerbate it. The underlying causes often involve imbalances in neurotransmitters, dysfunctions of the endocrine and immune systems, chronic inflammation, and nutritional deficiencies. Functional medicine focuses on identifying these causes through specialized tests and supports therapeutic strategies aimed at restoring the body’s homeostasis. Such causes are:

1. Dysfunction of the Hypothalamic–Pituitary–Adrenal Axis (HPA Axis). The HPA axis regulates the body’s response to stress through the release of cortisol. In situations of chronic stress, this axis becomes hyperstimulated, leading initially to hypercortisolemia and eventually to “adrenal fatigue”. This condition is accompanied by heightened anxiety, fatigue, sleep disturbances, and increased susceptibility to infections.
2. Neurotransmitter Imbalance. Serotonin, dopamine, glutamate, and GABA are critical neurotransmitters that regulate mood and emotional stability. Serotonin deficiency is associated with anxiety disorders, while reduced GABA levels are linked to nervousness and hyperexcitability. The disruption of these neurochemical pathways may be due to genetic, dietary, or inflammatory factors.
3. Gut Dysbiosis and the Gut–Brain Axis. The microbial balance of the gut directly affects neurological function through the production of neurotransmitters and cytokines. Dysbiosis—i.e., an imbalance in the gut microbiota has been associated with increased anxiety, depression, and reduced stress resilience. In addition, inflammation of the intestinal wall can lead to a leaky gut and trigger systemic inflammatory responses.
4. Hormonal Imbalances. Thyroid dysfunctions (especially hyperthyroidism), imbalances in sex hormones (progesterone, estrogen, testosterone), and insulin resistance can induce or intensify anxiety symptoms. Hormonal instability affects energy levels, sleep, and emotional regulation, particularly in women during menopause or in men experiencing andropause.
5. Chronic Inflammation and Oxidative Stress. Chronic inflammation adversely affects brain function, primarily through the elevation of pro-inflammatory cytokines such as IL-6 and TNF-α. Oxidative stress—i.e., the imbalance between free radicals and antioxidant defenses has also been linked to the onset and intensity of anxiety, mainly through neuronal damage and mitochondrial dysfunction.
6. Deficiency in Nutrients. Deficiencies in magnesium, B-complex vitamins (especially B6, B12, and folic acid), zinc, selenium, and omega-3 fatty acids have been documented as contributors to increased vulnerability to anxiety. These nutrients are involved in the synthesis of neurotransmitters and in maintaining nervous system homeostasis.
7. Genetic Predisposition and Polymorphisms. Certain genetic polymorphisms (such as MTHFR or COMT) affect the body’s ability to metabolize folate and serotonin, resulting in reduced stress adaptability and increased risk of anxiety disorders. Knowledge of an individual’s genetic profile may enable a more personalized approach to both prevention and treatment.

Laboratory Testing for Stress Assessment

Investigating anxiety requires a holistic approach that includes both basic biochemical assessments and specialized functional tests. Proper laboratory evaluation can reveal organic causes or underlying imbalances contributing to the onset or worsening of anxiety symptoms.

 Conventional Laboratory Tests:

• ​Thyroid Extended Profile: These tests assess thyroid function. Hyperthyroidism, or even subclinical dysfunctions, can cause pronounced anxiety symptoms.
• Complete Blood Count (CBC): Used to detect anemia or inflammatory conditions that may affect energy levels and mood regulation.
• CRP (C-reactive protein): A marker of chronic inflammation, which can influence the central nervous system and intensify anxiety.
• Fasting Glucose and Insulin: These reveal blood sugar regulation issues. Hypoglycemia or insulin resistance may be linked to anxiety symptoms.
• Vitamin B12 and Folic Acid: Deficiencies negatively affect nervous system function and are associated with irritability, depression, and anxiety.
• Electrolytes (Sodium, Potassium, Magnesium, Calcium): Imbalances affect the conductivity of nerve cells and central nervous system excitability.
   

 Functional Medicine Tests: The following tests are essential tools in functional medicine and are designed to identify dysfunctions that are often undetectable through conventional methods.

• AdrenalScan®: Salivary Cortisol Profile (morning–noon–evening): Assesses the daily secretion rhythm of cortisol, which becomes dysregulated in cases of chronic fatigue and excessive stress. Highly valuable for identifying HPA axis dysfunction.
• MetaBolomiX®: (Urine Metabolic Analysis): Analyzes metabolic intermediates related to gut health, mitochondrial function, neurotransmitter production, and the presence of yeast or bacteria. A powerful tool for detecting dysbiosis and coenzyme deficiencies.
• NeuroScan®: (Urinary Neurotransmitter Panel): Evaluates the balance of serotonin, dopamine, GABA, norepinephrine, and others. Highly recommended for patients with persistent anxiety symptoms without apparent cause.
• Leaky Gut Markers: (Zonulin and FABP2 , LPS , SIBO): Detect the breakdown of intestinal barrier integrity, which is associated with neuroinflammation and elevated anxiety via the gut–brain axis.
• ΩmegaScan®: Fatty Acid Profile (Omega-3/Omega-6 Ratio): Measures the balance between anti-inflammatory and pro-inflammatory fatty acids. Omega-3 deficiency is linked to reduced GABA production and increased inflammation.
• Genetic Analysis: MTHFR , COMT: Assesses polymorphisms that affect the body’s ability to synthesize and degrade neurotransmitters. Particularly useful when pharmacological treatments are ineffective.
   

Additional Tests: Additional testing may be recommended to provide a more comprehensive evaluation when clinically indicated. Brain MRI can be used to identify structural abnormalities that may affect emotional regulation, while carotid artery triplex ultrasound allows visualization of atherosclerotic plaques and measurement of intima–media thickness, offering insight into vascular health. An electroencephalogram (EEG) may be performed to assess potential functional disturbances in brain activity. In parallel, validated psychological screening tools such as the GAD-7 and DASS-21 are commonly used to quantify levels of anxiety and depression and to support clinical assessment and follow-up.

Therapeutic Approaches for Anxiety

Managing anxiety requires a multifaceted approach tailored to each individual’s profile. Treatment selection depends on the severity of symptoms, underlying organic causes, and the presence of comorbidities. In functional medicine, the primary goal is to address the root cause of anxiety rather than merely suppress symptoms. Below is a detailed presentation of both conventional and natural interventions.

Conventional Therapies

The following treatment approaches are mainly used in the management of moderate to severe anxiety, particularly when individuals experience significant impairment in daily functioning or recurrent panic attacks. Anxiolytic medications, such as benzodiazepines (e.g., alprazolam and lorazepam), act rapidly by enhancing the activity of GABA; however, they carry a risk of dependence and tolerance and are therefore recommended primarily for short-term use. Antidepressant medications belonging to the SSRI and SNRI classes, such as sertraline and venlafaxine, increase the availability of serotonin and/or norepinephrine and are considered first-line treatments for the long-term management of generalized anxiety. Beta-blockers, such as propranolol, are mainly used to reduce the physical symptoms of anxiety, including tachycardia and tremor, particularly in situations of social anxiety or performance-related stress. At the same time, Cognitive Behavioral Therapy (CBT) is a well-established, evidence-based approach that focuses on modifying maladaptive thought patterns and gradually exposing individuals to controlled anxiety-provoking situations, demonstrating high effectiveness in long-term management. Counseling and psychotherapy also provide essential support by helping individuals better understand and reframe their experience of anxiety and strengthen stress-coping mechanisms, while all pharmacological treatments should be prescribed exclusively following medical evaluation and under a physician’s prescription.

Natural Therapies

Natural approaches target the organic and neurophysiological parameters that influence anxiety. They are particularly helpful for prevention, reducing underlying causes, and as complementary treatment.

Nutrition: Nutrition is a cornerstone in anxiety management. A diet rich in complex carbohydrates, healthy fats, and adequate protein supports neurotransmitter balance. Key considerations include:

• Avoiding caffeine and alcohol, which intensify nervousness.
• Consuming tryptophan-rich foods (turkey, bananas, nuts) to boost serotonin levels.
• Ensuring adequate intake of B vitamins and magnesium from green vegetables, legumes, and seeds.
• Supporting gut health with probiotic foods (kefir, yogurt, sauerkraut).
   

Lifestyle: Daily habits greatly affect the body’s resilience to stress:

• Consistent sleep: At least 7–8 hours per night, with emphasis on circadian rhythm regulation.
• Exercise: 30 minutes of aerobic activity daily reduces cortisol levels and increases endorphin release.
• Relaxation techniques: Meditation, deep breathing, yoga, or progressive muscle relaxation.
• Nature exposure and screen time reduction, especially before bedtime.
   

Nutritional Supplements and Herbal Therapies: Nutritional supplements and herbal therapies are often used as supportive options in the management of stress and anxiety, particularly in mild to moderate cases or alongside other therapeutic approaches:

• Magnesium may help calm the nervous system and is commonly recommended at 200–400 mg daily, preferably in the evening; mild gastrointestinal discomfort may occur in some individuals.
• Omega-3 fatty acids (EPA/DHA) have anti-inflammatory properties and may contribute to mood regulation, with typical doses ranging from 1–2 g daily, although they should be avoided by individuals with bleeding disorders or those taking anticoagulant therapy.
• Rhodiola rosea, an adaptogenic herb, is used to enhance resistance to stress and is generally taken at doses of 100–400 mg daily, but it is not recommended for individuals with hypertension.
• Ashwagandha (Withania somnifera) may help reduce cortisol levels and support GABA activity; commonly suggested doses are 300–600 mg twice daily, with caution advised in people with thyroid disorders.
• L-theanine, an amino acid, promotes mild relaxation without causing drowsiness and may be particularly helpful in situations of anticipatory anxiety, such as examinations or social events.
• Valerian root is mainly used for short-term sleep disturbances and is typically taken before bedtime; it should not be combined with other central nervous system depressants.
   

It should be noted that nutritional supplements and herbal products are not a substitute for medical treatment. Their use should be individualized and discussed with a healthcare professional, especially in the presence of chronic medical conditions, pregnancy, or concurrent medication use.

Conclusions

Stress and anxiety are multifactorial conditions that affect both mental and physical health. Effective management requires early recognition of symptoms and a comprehensive approach that addresses underlying biological, psychological, and functional factors. Through the use of appropriate diagnostic tools, personalized therapeutic strategies, and healthy lifestyle practices, it is possible to achieve meaningful symptom relief and long-term improvement in overall well-being and quality of life.

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