Investigations for Mentally Ill Patients

Introduction

The assessment and management of mentally ill patients often requires a comprehensive approach that includes various diagnostic investigations. These investigations help clinicians to rule out organic causes of psychiatric symptoms, monitor medication effects and side effects, and understand the neurobiological basis of mental disorders.

The brain and body do not exist in isolation – mental health affects physical health and vice versa. Having a complete picture of both neurological and systemic function is essential for providing optimal care for patients with psychiatric disorders.

Why Investigations Matter in Psychiatry

Despite the historical separation between psychiatry and other medical specialties, modern psychiatric practice recognizes that:

Many physical conditions can manifest with psychiatric symptoms
Psychiatric medications can affect multiple body systems requiring monitoring
Mental disorders have neurobiological correlates that can be observed through brain imaging
Comorbid medical conditions are common in psychiatric populations

This guide focuses on four key investigative modalities:

Blood Chemistry Tests

Laboratory tests that analyze various components in blood to assess general health, identify medical conditions that may mimic psychiatric disorders, and monitor medication effects.

Electroencephalography (EEG)

A non-invasive method that records electrical activity of the brain to detect abnormalities in brain function, which can be relevant in various psychiatric conditions.

Computed Tomography (CT)

An imaging technique that uses X-rays to produce detailed images of the brain, helping to rule out structural abnormalities that might contribute to psychiatric symptoms.

Magnetic Resonance Imaging (MRI)

An advanced imaging modality that provides detailed structural and functional information about the brain without using radiation.

Blood Chemistry Tests

Blood tests are essential components of the psychiatric evaluation, helping clinicians to rule out medical causes of psychiatric symptoms, establish baseline health parameters before starting medications, and monitor for medication effects and side effects.

Basic Blood Tests in Psychiatric Assessment

Test Category	Specific Tests	Clinical Relevance
Complete Blood Count (CBC)	Hemoglobin, WBC, RBC, platelets, hematocrit	Anemia (can cause fatigue, depression), infection, inflammation
Basic Metabolic Panel	Sodium, potassium, chloride, BUN, creatinine, glucose	Electrolyte imbalances, kidney function, diabetes (can all affect mental status)
Comprehensive Metabolic Panel	Basic panel plus liver enzymes (AST, ALT, ALP)	Adds liver function assessment (important for medication metabolism)
Thyroid Function Tests	TSH, Free T4, Free T3	Hypothyroidism (depression, cognitive slowing), hyperthyroidism (anxiety, insomnia)
Lipid Panel	Total cholesterol, LDL, HDL, triglycerides	Monitoring for metabolic effects of second-generation antipsychotics
Hemoglobin A1c	Glycated hemoglobin	Screening for diabetes/prediabetes, especially with atypical antipsychotics

MNEMONIC: “BASIC MED” Blood Tests

B – Blood count (CBC)

A – A1c (Hemoglobin A1c)

S – Sodium & other electrolytes

I – Iron studies (if anemia suspected)

C – Creatinine (kidney function)

M – Metabolic panels

E – Enzymes (liver)

D – Drug levels (when applicable)

Specialized Blood Tests

Medication Monitoring

Lithium levels: Therapeutic range 0.6-1.2 mEq/L; requires regular monitoring due to narrow therapeutic window
Valproic acid levels: For mood stabilization; therapeutic range 50-100 µg/mL
Carbamazepine levels: For mood stabilization; therapeutic range 4-12 µg/mL
Clozapine levels: Can guide dosing of this atypical antipsychotic, especially in partial responders

Substance Use Screening

Urine drug screen: Detects common substances of abuse
Blood alcohol level: Quantifies alcohol consumption
Liver function tests: May indicate alcohol-related liver damage

Emerging Biomarkers

C-reactive protein (CRP): Marker of inflammation, may predict antidepressant response
Genetic testing: Pharmacogenomics to guide medication selection based on metabolism
MindX Blood Tests: RNA sequencing to assess, predict, or manage mood disorders

Additional Tests Based on Presentation

Vitamin B12 & Folate: Deficiencies associated with depression, psychosis
Vitamin D: Low levels linked to depression, especially seasonal
Prolactin: May be elevated by antipsychotic medications
Cortisol: Abnormal in some patients with major depression

Clinical Pearl: When to Order Specialized Tests

Specialized tests should be ordered based on clinical suspicion and history, not as a routine battery. Consider them when:

Standard treatments are not effective
Presentation is atypical or suggests medical etiology
Monitoring specific medication effects or side effects
Evaluating potential medication interactions

Interpretation & Clinical Significance

Interpreting blood test results requires context and clinical correlation. Abnormalities may represent:

Medical Causes of Psychiatric Symptoms

Thyroid disorders: Hypothyroidism mimicking depression; hyperthyroidism resembling anxiety
Anemia: Fatigue, cognitive symptoms, depression
Electrolyte imbalances: Confusion, altered mental status, mood changes
B12 deficiency: Depression, psychosis, cognitive impairment
Hepatic or renal impairment: Encephalopathy, cognitive changes

Medication Effects and Side Effects

Metabolic changes: Elevated glucose, lipids with second-generation antipsychotics
Hematologic effects: Leukopenia with clozapine, agranulocytosis (rare)
Hepatic effects: Elevated liver enzymes with valproic acid, carbamazepine
Renal effects: Lithium-induced nephropathy with long-term use
Endocrine effects: Hypothyroidism with lithium; hyperprolactinemia with some antipsychotics

Blood tests for mental health assessment flowchart

Figure 1: Blood tests for mental health assessment

MNEMONIC: “THINK MED” Causes of Psychiatric Symptoms

T – Thyroid disorders (hypo/hyperthyroidism)

H – Hematologic issues (anemia, B12 deficiency)

I – Infection (systemic, encephalitis)

N – Nutritional deficiencies (B vitamins, folate)

K – Kidney function abnormalities

M – Metabolic disturbances (glucose, electrolytes)

E – Endocrine disorders (adrenal, pituitary)

D – Drugs/toxins (prescription, illicit, alcohol)

Electroencephalography (EEG)

Electroencephalography (EEG) is a non-invasive technique that records the electrical activity of the brain through electrodes placed on the scalp. While primarily used in neurology for diagnosing epilepsy, EEG has important applications in psychiatry for examining brain function in various mental disorders.

Basics & Electrode Placement

EEG measures electrical potentials generated by neurons within the cerebral cortex, with signals primarily originating from pyramidal cells. The standard electrode placement follows the International 10-20 System, which ensures consistent electrode positioning across patients.

EEG electrode placement using the 10-20 System

Figure 2: International 10-20 System for EEG electrode placement

Key Components of EEG Recording

Electrodes: Typically 21 recording electrodes plus ground and reference
Montages: Specific arrangements of electrode pairs for viewing the data
Filters: Remove unwanted signals and artifacts
Time base: Usually 30mm/second
Sensitivity: Typically 7μV/mm

Types of EEG Recording

Routine EEG: 20-40 minutes, includes resting state, hyperventilation, photic stimulation
Sleep-deprived EEG: Performed after sleep deprivation to increase sensitivity
Ambulatory EEG: 24-72 hour monitoring
Video EEG: Synchronized video and EEG recording
Quantitative EEG (QEEG): Computerized analysis of EEG data

Clinical Pearl: EEG Indications in Psychiatry

EEG is indicated in patients with:

New-onset psychosis to rule out seizure disorders
Rapid changes in mood or behavior that might suggest organic etiology
Fluctuating or progressive cognitive impairment
Suspected delirium or encephalopathy
Treatment-resistant depression or psychosis
First-episode catatonia

Brain Wave Patterns

EEG activity is classified by frequency bands, each associated with different states of consciousness and brain activity.

Figure 3: Types of brain waves and their frequency ranges

Wave Type	Frequency	Normal Occurrence	Psychiatric Significance
Delta (δ)	0.5 – 4 Hz	Deep sleep, infants, serious brain diseases	Increased in delirium, encephalopathy, and some medications
Theta (θ)	4 – 7 Hz	Drowsiness, childhood, meditation	Excess may indicate encephalopathy, medication effects, or cognitive disorders
Alpha (α)	8 – 12 Hz	Relaxed wakefulness, eyes closed	Asymmetry linked to depression; decreased in anxiety, stress
Beta (β)	13 – 30 Hz	Alert, active concentration	Increased in anxiety disorders, stimulant use; enhanced by benzodiazepines
Gamma (γ)	>30 Hz	Higher cognitive processing, perception	Abnormalities in schizophrenia, cognitive disorders

MNEMONIC: “BATD” – Brain Wave Sequence

From fastest to slowest frequency:

B – Beta (13-30 Hz): Busy, active mind

A – Alpha (8-12 Hz): Awakened relaxation

T – Theta (4-7 Hz): Tired, drowsy state

D – Delta (0.5-4 Hz): Deep sleep

EEG Findings in Psychiatric Disorders

Depression

Alpha asymmetry: increased right vs. left frontal alpha power
Reduced slow-wave (delta) activity during sleep
EEG changes may predict antidepressant response

Schizophrenia

Reduced alpha activity
Abnormal gamma oscillations during cognitive tasks
Reduced sleep spindles
Non-specific slowing in some patients

Bipolar Disorder

Increased beta activity during manic episodes
EEG may predict response to lithium vs. valproate
Some patients show epileptiform activity that may respond to anticonvulsants

Anxiety Disorders

Increased beta activity, especially frontally
Decreased alpha activity
Hypercoherence between frontal regions in some cases

Limitations of EEG in Psychiatry

No specific diagnostic patterns for most psychiatric disorders
Findings are often non-specific or inconsistent
Limited spatial resolution compared to neuroimaging techniques
Interpretation requires specialized training
Results must be interpreted in clinical context

Clinical Pearl: Epileptiform Activity in Psychiatric Patients

Subclinical epileptiform activity may be present in 10-30% of patients with certain psychiatric disorders, particularly those with:

Treatment-resistant psychosis
Episodic behavioral disturbances
Atypical presentation of mood disorders
History of head injury or other neurological insult

In these cases, a trial of anticonvulsant medication may be beneficial, even without a clinical diagnosis of epilepsy.

Computed Tomography (CT)

Computed Tomography (CT) is an imaging technique that uses X-rays to create cross-sectional images of the brain. In psychiatry, CT scans are primarily used to rule out structural abnormalities that might contribute to or mimic psychiatric symptoms.

Principles & Techniques

CT imaging works by rotating an X-ray source around the patient’s head, with detectors measuring the X-ray attenuation through different tissues. A computer reconstructs these measurements into cross-sectional images.

Key Features of CT Scanning

Quick scan time: Typically 5-10 minutes
Good bone imaging: Superior to MRI for bony structures
Readily available: More accessible than MRI in many settings
Minimal contraindications: Safe with most implants
Cost-effective: Less expensive than MRI

Limitations of CT

Radiation exposure: Uses ionizing radiation
Limited soft tissue contrast: Less detailed than MRI
Posterior fossa artifacts: Difficulty visualizing brainstem, cerebellum
No functional information: Shows structure only
Limited sensitivity: May miss subtle abnormalities

Normal CT scan of the brain with labeled anatomy

Figure 4: Normal brain CT scan (axial view) with anatomical structures labeled

CT Brain Anatomy – Key Structures

When interpreting a CT brain scan, these key structures should be evaluated:

Ventricles: Size, symmetry, presence of blood
Gray-white matter differentiation: Should be clear
Midline structures: Any shift indicates mass effect
Basal cisterns: Should be open and visible
Sulci & gyri: Pattern and symmetry
Skull: Integrity, thickness, abnormalities

CT Applications in Psychiatry

While CT scans cannot diagnose primary psychiatric disorders, they play an important role in the evaluation of patients with psychiatric symptoms.

Indications for CT in Psychiatric Patients

First episode psychosis: Rule out organic causes
Late-onset psychiatric symptoms: After age 40
Atypical presentation: Not fitting standard diagnostic patterns
Neurological signs: Focal deficits, abnormal reflexes
History of head trauma: Evaluating structural damage
Rapid cognitive decline: Rule out space-occupying lesions
Treatment resistance: When symptoms don’t respond to standard treatment

CT Finding	Potential Psychiatric Manifestation	Clinical Significance
Brain tumor	Personality changes, psychosis, depression, anxiety	Location-dependent; frontal tumors often present with psychiatric symptoms
Subdural hematoma	Fluctuating consciousness, cognitive impairment, personality changes	May be chronic and subtle, especially in elderly; often history of falls
Hydrocephalus	Cognitive slowing, apathy, incontinence, gait disturbance	Normal pressure hydrocephalus can mimic dementia or depression
Cerebral atrophy	Cognitive impairment, behavioral changes	May be seen in dementia, chronic schizophrenia, alcoholism
Silent infarcts	Late-life depression, cognitive impairment	Vascular depression hypothesis; may predict treatment resistance
Calcifications	Varies by location	Basal ganglia calcifications may cause neuropsychiatric symptoms

MNEMONIC: “HEAD CT” – When to Order a CT Scan

H – History of trauma or falls

E – Elderly onset of psychiatric symptoms

A – Atypical presentation of mental illness

D – Deficit, neurological (focal signs)

C – Cognitive changes, rapid or unexplained

T – Treatment resistance to psychiatric medications

Clinical Pearl: CT vs. MRI in Emergency Settings

CT is preferred over MRI in emergency settings for psychiatric patients when:

Acute altered mental status needs rapid evaluation
History of trauma or suspicion of acute bleeding
Patient is agitated and cannot remain still for MRI
MRI contraindications are unknown or present
Immediate availability is required

Magnetic Resonance Imaging (MRI)

Magnetic Resonance Imaging (MRI) uses strong magnetic fields and radio waves to generate detailed images of the brain. It provides superior soft tissue contrast compared to CT, making it the preferred modality for detailed neuroanatomical evaluation in psychiatric patients when time permits.

Principles & Techniques

MRI works by aligning hydrogen atoms in the body with a strong magnetic field, then disturbing this alignment with radio frequency pulses. As the atoms return to alignment, they emit signals that are detected and processed into images.

Basic MRI Sequences

T1-weighted: Good for anatomical detail; CSF appears dark
T2-weighted: Highlights pathology; CSF appears bright
FLAIR: Fluid-attenuated inversion recovery; suppresses CSF signal
DWI: Diffusion-weighted imaging; sensitive for acute stroke
SWI: Susceptibility-weighted imaging; detects blood products, calcifications

Advanced MRI Techniques

fMRI: Functional MRI; measures blood flow changes during tasks
DTI: Diffusion tensor imaging; shows white matter tracts
MRS: Magnetic resonance spectroscopy; measures brain metabolites
Perfusion MRI: Measures cerebral blood flow
Volumetric MRI: Quantifies regional brain volumes

Figure 5: Normal brain MRI (axial view) with key structures labeled

Advantages of MRI over CT

Superior soft tissue contrast
No ionizing radiation exposure
Multiplanar imaging (axial, coronal, sagittal) without repositioning
Better visualization of posterior fossa structures
Ability to detect subtle abnormalities
Advanced functional and metabolic imaging capabilities

Limitations and Contraindications

Absolute contraindications: Certain implanted devices (pacemakers, cochlear implants), ferromagnetic foreign bodies, claustrophobia (severe)
Relative contraindications: Pregnancy (first trimester), tattoos with metallic ink, claustrophobia (mild to moderate)
Practical limitations: Longer scan time, higher cost, reduced availability, requires patient compliance

MRI Applications in Psychiatry

MRI has revolutionized our understanding of the neurobiological basis of psychiatric disorders by revealing structural and functional brain changes associated with various conditions.

Psychiatric Disorder	Common MRI Findings	Clinical Significance
Schizophrenia	Ventricular enlargement, reduced gray matter in prefrontal and temporal regions, thalamic abnormalities	Supports neurodevelopmental hypothesis; findings correlate with symptom severity and cognitive impairment
Major Depression	Reduced volume in hippocampus, amygdala, anterior cingulate cortex; white matter hyperintensities in late-life depression	Hippocampal volume may predict treatment response; white matter changes associated with vascular depression
Bipolar Disorder	Reduced volume in prefrontal regions, enlarged amygdala, white matter abnormalities	Some findings overlap with schizophrenia; white matter changes suggest connectivity issues
PTSD	Reduced hippocampal volume, hyperactive amygdala on fMRI, reduced anterior cingulate activation	Supports stress-related neurotoxicity model; may predict treatment outcomes
OCD	Alterations in cortico-striatal-thalamo-cortical circuits; caudate nucleus abnormalities	Suggests circuit-based pathophysiology; may help target interventions
Dementia	Hippocampal atrophy (Alzheimer’s), frontal/temporal atrophy (FTD), subcortical infarcts (vascular)	Aids differential diagnosis; can distinguish neurodegenerative from psychiatric causes

Research Applications of Advanced MRI in Psychiatry

Functional MRI (fMRI): Maps brain activity during cognitive tasks or at rest; identifies dysfunctional neural circuits
Diffusion Tensor Imaging (DTI): Evaluates white matter tract integrity; reveals connectivity issues
MR Spectroscopy: Measures brain metabolites like N-acetylaspartate (neuronal marker), choline (cell membrane turnover), and glutamate (excitatory neurotransmitter)
Volumetric Analysis: Quantifies regional brain volumes; can track progression over time

Clinical Pearl: When to Order MRI vs. CT in Psychiatry

Consider MRI over CT when:

Detailed evaluation of brain structure is needed
Suspected abnormalities involve areas poorly visualized on CT (posterior fossa, temporal lobes)
Following up on indeterminate CT findings
Evaluating neurodegenerative conditions
Patient can tolerate longer scan time and has no contraindications
Radiation exposure is a concern (younger patients, need for repeated imaging)

MNEMONIC: “IMAGES” – Benefits of MRI in Psychiatry

I – Improved soft tissue contrast

M – Multiple planes available

A – Advanced functional assessment (fMRI)

G – Gray matter analysis optimized

E – Excellent posterior fossa visualization

S – Safe (no radiation)

Comparison of Imaging Modalities

Selecting the appropriate imaging modality depends on the clinical context, availability, patient factors, and the specific information needed.

Feature	CT	MRI	EEG
Primary Function	Structural imaging	Structural & functional imaging	Functional assessment of brain electrical activity
Time Required	5-10 minutes	30-60 minutes	20-40 minutes (routine)
Cost	Moderate	High	Low to moderate
Radiation	Yes (ionizing)	No	No
Availability	Widely available	Less widely available	Moderately available
Contraindications	Few; pregnancy (relative)	Many; metallic implants, claustrophobia	Very few; skin conditions at electrode sites
Best For	Acute evaluation, trauma, hemorrhage, bone abnormalities	Detailed structural analysis, subtle abnormalities, white matter pathology	Seizure activity, encephalopathy, medication effects on brain function
Temporal Resolution	Low	Low (standard); moderate (functional)	Excellent (milliseconds)
Spatial Resolution	Moderate	High	Low

Best Uses of CT in Psychiatry

Emergency evaluation
Screening for organic causes
Patients who cannot tolerate MRI
Acute altered mental status
Following head trauma

Best Uses of MRI in Psychiatry

Detailed evaluation after screening CT
Suspected neurodegenerative disorders
Subtle abnormalities or lesions
Research protocols
Following disease progression

Best Uses of EEG in Psychiatry

Suspected seizure disorder
Encephalopathy evaluation
Unexplained altered consciousness
Monitoring medication effects
Evaluating sleep disorders

Clinical Approach to Investigations

A systematic approach to selecting and interpreting investigations is essential for cost-effective and clinically meaningful diagnostic workup of mentally ill patients.

Step 1: Basic Screening

Initial evaluation for all new psychiatric patients:

Complete history and physical examination
Basic blood chemistry (CBC, electrolytes, glucose)
Liver and renal function tests
Thyroid function tests
Urine toxicology screen when indicated
Consider vitamin B12, folate

Step 2: Risk Stratification

Based on clinical presentation, determine if additional testing is warranted:

Age of onset (late onset suggests organic cause)
Atypical features
Neurological signs or symptoms
Treatment resistance
History of trauma, substance use
Rapid cognitive decline

Step 3: Targeted Investigations

Select additional tests based on clinical suspicion:

CT brain (acute presentations, emergency settings)
MRI brain (detailed evaluation, follow-up)
EEG (suspected seizures, encephalopathy, fluctuating course)
Specialized blood tests (medication levels, autoimmune markers)
Lumbar puncture (when CNS infection/inflammation suspected)

Step 4: Interpretation & Integration

Correlate findings with clinical presentation:

Consider normal variants vs. pathological findings
Assess clinical significance of abnormalities
Determine need for further investigation or specialist referral
Integrate findings into diagnostic formulation
Develop treatment plan based on comprehensive assessment

Clinical Pearl: Red Flags That Warrant Imaging

Consider brain imaging when these features are present:

New-onset headache with psychiatric symptoms
Late onset (>40 years) of first psychiatric symptoms
Neurological abnormalities on examination
Rapid unexplained cognitive decline
History of significant head trauma
New-onset seizures
Symptoms that fluctuate with level of consciousness
Treatment resistance to appropriate psychiatric interventions

MNEMONIC: “TEST WISE” – Approach to Investigation Selection

T – Targeted tests based on clinical suspicion

E – Evidence-based selection (not shotgun approach)

S – Stepwise progression from basic to advanced tests

T – Timing considered (emergency vs. elective)

W – Weigh risks and benefits

I – Interpret in clinical context

S – Specialists consulted when needed

E – Economical use of resources

Summary