Known Causes of Depression, Anxiety, and Psychotic Disorders
Depression, anxiety, and psychotic disorders arise from multifactorial etiologies including genetic predisposition (30-50% heritability for anxiety), environmental stressors, nutritional deficiencies, substance use, and underlying medical conditions, with treatment requiring identification of primary versus secondary causes before initiating appropriate pharmacologic and psychotherapeutic interventions.
Etiologic Factors for Depression and Anxiety
Genetic and Biological Factors
- Genetic heritability accounts for 30-50% of anxiety disorder risk, with studies demonstrating familial clustering patterns 1
- Congenital genetic mutations and epigenetic events contribute significantly to depression vulnerability 2
- Neurotransmitter dysregulation and neurobiological pathway alterations underlie mood and anxiety symptomatology 1
Environmental and Psychosocial Triggers
- Social or environmental factors including isolation, anger, interpersonal stress, and family discord precipitate depressive and anxiety symptoms 1
- Childhood experiences, including physical or sexual abuse, significantly increase risk for developing mood and anxiety disorders 1
- Birth patterns, feeding patterns, dietary patterns, education levels, and economic status influence depression development 2
- Concerns about appearance, earlier sexualization, changing media culture, and poor self-esteem serve as important triggers, particularly in women 1
Cognitive Factors
- Cognitive distortions accompanying depression, particularly hopelessness, contribute to symptom persistence and treatment dropout 1
- Inappropriate coping styles such as impulsivity or catastrophizing worsen outcomes 1
Causes of Psychotic Disorders
Primary Psychotic Disorders
- Primary psychosis stems from underlying psychiatric disorders including schizophrenia, bipolar disorder, schizoaffective disorder, or depression with psychotic features 1
- These conditions involve intrinsic neurobiological dysfunction rather than external precipitants 3
Secondary Psychotic Disorders
- Secondary psychosis results directly from drug/alcohol use, withdrawal, or underlying medical causes 1
- Medical conditions presenting with psychotic symptoms include:
- Endocrine disorders (thyroid dysfunction) 1
- Autoimmune diseases 1
- Neoplasms and paraneoplastic processes 1
- Neurologic disorders 1
- Infections (urinary tract infections, pneumonia, CNS infections) 1
- Genetic or metabolic disorders 1
- Nutritional deficiencies (folate, B12, thiamine, omega-3 fatty acids) 4
- Drug-related intoxication, withdrawal, side effects, and toxicity 1
Specific Nutritional Deficiency Mechanisms
- Folate deficiency causes neuropsychiatric manifestations including depression, irritability, insomnia, cognitive impairment, and psychosis 4
- Thiamine deficiency leads to Wernicke's encephalopathy and Korsakoff psychosis, particularly in alcohol use disorders 4
- Omega-3 fatty acid deficiency may contribute to depression with psychotic features 4
Age-Related Considerations
- Prevalence of psychotic disorders due to general medical conditions is higher in those 65 years or older 1
Comorbidity Patterns
Depression-Anxiety Overlap
- The estimated prevalence of anxiety disorders in patients with major depressive disorders is 56% 1
- Anxiety disorders frequently co-occur with depressive disorders, substance use, and posttraumatic stress disorder 1
- Up to 40% of people with psychosis have clinical levels of depression, and anxiety symptoms occur in 60% of patients with chronic psychotic disorder 5
Psychosis-Mood Disorder Relationships
- Psychiatric diagnoses commonly associated with suicidal behavior include depression, mania or hypomania, mixed states or rapid cycling, and substance abuse 1
- Psychotic depression represents an independent trait that may accompany mood disorders of varying severity, not simply a continuum of depression severity 6
Treatment Approaches Based on Etiology
For Secondary Psychotic Disorders
- Treatment of the underlying nutritional deficiency or medical cause should be the primary approach rather than antipsychotic medications 4
- After treating secondary causes, control psychotic symptoms as needed 1
- Folate levels should be rechecked within 3 months after supplementation to verify normalization 4
For Primary Psychotic Disorders
- Pharmacologic management with antipsychotic medications combined with psychological therapy and psychosocial interventions 1, 3
- For psychotic depression specifically, acute treatment involves combination of an antidepressant and an antipsychotic drug or electroconvulsive therapy 6
For Anxiety Disorders
- Cognitive behavioral therapy (CBT) and other forms of psychotherapy are initial treatments for most patients 1
- Medications are usually secondary, most commonly SSRIs and SNRIs 1
- Psychotherapy with or without anxiolytics or antidepressants is recommended after eliminating medical causes 1
For Depression
- Antidepressants (SSRIs) and anti-anxiety drugs are beneficial in treating depression and anxiety in adult patients 1
- Cognitive behavioral interventions effectively improve depression and anxiety symptoms in patients with psychosis spectrum disorders 7
Critical Clinical Pitfalls
Diagnostic Errors
- Delirium diagnosis can be missed by inadequate screening, yet mortality may be twice as high if diagnosis is missed 1, 3
- When evaluating psychotic symptoms, clinicians must consider secondary causes including nutritional deficiencies before diagnosing primary psychotic disorders 4, 3
- Unlike delirium, awareness and level of consciousness in psychotic patients are typically intact 1, 3
Treatment Hazards
- Treating folate deficiency without checking B12 status can be dangerous, as folate supplementation may improve blood parameters while worsening neurological manifestations of B12 deficiency 4
- Anxiety symptoms at baseline and anxiety disorder diagnoses differentially impact depression treatment outcomes, with panic disorder associated with worse clinical outcomes regardless of treatment 8