Core and biological symptoms of depression

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Depression affects emotion, motivation, thinking, the body and social function. Ask what has changed from the person's usual self. Low mood may be described as sadness, emptiness, irritability, emotional numbness or dread. Anhedonia is reduced interest, anticipation or enjoyment and may emerge as stopped music, sport, intimacy or social contact. Reduced energy can appear as exhaustion, slowed initiation or needing exceptional effort for ordinary tasks. Symptoms should be persistent enough and impairing enough to form a syndrome rather than being inferred from one expression of distress.

Biological features require precise description. Ask about sleep onset, maintenance, early waking, hypersomnia and daytime rhythm; appetite, weight and food access; constipation or other physical slowing; libido; menstrual or reproductive change; and observed psychomotor retardation or agitation. Diurnal variation and early-morning waking can support a melancholic pattern but are not diagnostic alone. Fatigue may also reflect anaemia, thyroid disease, sleep apnoea, pain, infection, medicine effects or substance use.

Explore cognition and meaning. Concentration may affect reading, work, driving and medicine use. Guilt can be proportionate regret or a fixed false belief; hopelessness can narrow future thinking and increase suicide risk. Ask about worthlessness, perceived burden, indecision and recurrent thoughts of death. Determine whether nihilistic, persecutory, guilt or poverty beliefs are held with delusional conviction and whether voices accuse, command or reinforce suicide. Psychotic symptoms may not be volunteered because of shame or fear.

Map chronology and context. Establish onset, daily pattern, previous episodes, inter-episode recovery, seasonal or reproductive relationship, life events, trauma, physical illness, medicines and substances. Screen lifetime history for reduced need for sleep, elevated or irritable mood, increased activity, pressured speech, overspending and other hypomanic or manic change. Ask about family history and prior antidepressant activation without treating either as diagnosis. Grief and adversity can precipitate a depressive episode but should not be pathologised solely because distress follows loss.

Assess function and safety at every severity. Eating, hygiene, medicines, parenting, finances, attendance and ability to seek help may deteriorate before the person uses severe language. Ask about self-harm and suicide directly, including intent, plan, means and reasons for living. Identify children and vulnerable adults. Provide communication support and collateral history with consent when baseline or risk is unclear. Summarise a working formulation, competing causes and the immediate plan rather than relying on symptom count alone.

Key points

Core depressive experiences include sustained low mood, reduced interest or pleasure and reduced energy, but the person's language may emphasise emptiness, irritability, numbness or inability to care.
Biological or somatic changes include sleep disturbance, appetite or weight change, psychomotor slowing or agitation, reduced libido, fatigue and sometimes early-morning or diurnal worsening.
Cognitive features include impaired concentration and decision making, guilt, worthlessness, hopelessness, negative expectations and recurrent thoughts of death.
Establish duration, persistence, reactivity, baseline and functional change; a clinically significant episode is more than a bad day and commonly persists for at least two weeks.
Ask directly about self-harm, suicide, neglect, psychosis, mania or hypomania, substances, trauma, pain, pregnancy or postpartum context and risk to dependants.
Observe appearance, speech, psychomotor activity, affect, thought form and content, perception, cognition and insight while distinguishing observation from the patient's report.
Use validated measures to support baseline and monitoring, not as a standalone diagnosis, severity decision or predictor of suicide.
Consider grief, bipolar disorder, anxiety, trauma, substance or medicine effects, endocrine and neurological disease and sleep disorders according to phenotype.
Share the working diagnosis and uncertainty, agree treatment from severity, function and preference, and safety-net early change or emergent suicidal thoughts.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Inherited and developmental vulnerability

Depression reflects polygenic and developmental susceptibility interacting with later experience; family history changes probability but neither establishes a diagnosis nor determines an individual's course.

Illness and treatment contributors

Pain, endocrine or neurological disease, reproductive change, sleep disruption, medicines and substances can precipitate or maintain depressive symptoms through biological and functional pathways.

Psychological and social adversity

Loss, trauma, isolation, discrimination, poverty, unsafe relationships and role disruption can trigger depression, especially when avoidance, hopelessness and reduced access to rewarding activity persist.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Distributed brain-network change
Mood, reward, salience, threat and cognitive-control networks interact in depression; no single region, neurotransmitter concentration or routine scan explains the clinical syndrome.
2
Stress and circadian systems
Prolonged stress, sleep disruption and altered circadian timing can affect arousal, endocrine signalling, cognition and reward, creating feedback with symptoms and daily behaviour.
3
Learning and withdrawal loops
Reduced activity lowers access to mastery and pleasure, while negative predictions and avoidance prevent corrective experience and can perpetuate low mood and hopelessness.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Core affective change

Sustained low mood or markedly reduced interest and pleasure represents a clear change from baseline and is present across much of the day.

Biological disturbance

Sleep, appetite, weight, psychomotor activity, libido or energy changes accompany the mood syndrome and are not better explained by another condition.

Depressive cognition

Hopelessness, worthlessness, excessive guilt, slowed thinking and impaired concentration reinforce withdrawal and may increase suicide risk.

Psychotic depression

Severe depressive symptoms coexist with delusions or hallucinations, often involving guilt, punishment, disease, poverty, nihilism or accusatory voices.

Bipolar clue

A distinct previous period of reduced sleep need and increased activity or mood elevation requires bipolar assessment before routine antidepressant treatment.

Red flags requiring action

Suicidal planning, rehearsal, available means, recent self-harm, severe hopelessness or the belief that others are better off after the person's death requires an immediate scenario-based formulation.
Mood-congruent delusions of guilt, poverty, nihilism or deserved punishment, accusatory voices or command hallucinations indicate psychotic depression until alternatives are assessed.
Marked slowing, mutism, stupor, posturing, negativism, excitement or autonomic disturbance may indicate catatonia and needs urgent medical and psychiatric evaluation.
A previous period of elevated or irritable mood with reduced need for sleep and increased activity may indicate bipolar disorder, changing antidepressant risk and treatment.
Fluctuating attention, altered arousal, focal neurology, fever, new seizure, late abrupt onset or rapid cognitive decline suggests delirium or neurological disease rather than uncomplicated depression.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Collaborative symptom and duration historyFirst step
Why
Establish mood, interest, energy, cognition, biological change, persistence and previous baseline.
Interpretation and limitations
Diagnosis depends on pattern, duration and context. One symptom or questionnaire threshold cannot establish a depressive episode.
02
Functional assessment
Why
Measure effect on self-care, relationships, dependants, work, study, money, healthcare and valued activities.
Interpretation and limitations
Concrete change helps judge severity and support needs; visible grooming during one visit does not prove intact instrumental function.
03
Mental-state and psychosis assessment
Why
Describe affect, psychomotor activity, speech, thought, perception, cognition, insight and psychotic features.
Interpretation and limitations
Separate reported experience from observation and assess cultural context, conviction, behaviour and danger attached to unusual beliefs or voices.
04
Suicide and self-harm formulation
Why
Identify intent, preparation, means, previous acts, dynamic drivers, warning signs and accessible protections.
Interpretation and limitations
Do not use predictive scales or a low-risk label to decide care. Formulate plausible scenarios and specific interventions.
05
Bipolar and organic-cause screen
Why
Identify previous activation, substances, medicines, endocrine, sleep, neurological and reproductive contributors.
Interpretation and limitations
Positive clues prompt targeted examination, tests or specialist assessment; absence of a routine clue does not exclude an atypical cause.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Bipolar depression

Current symptoms may look identical, but prior elevated or irritable activation, reduced sleep need, episodic course and antidepressant activation change diagnosis and management.

Grief and adjustment

Loss-related distress may remain tied to reminders and preserve positive emotion, yet a depressive episode can coexist when pervasive symptoms and impairment extend beyond expected variation.

Medical or substance cause

Thyroid disease, anaemia, sleep apnoea, neurological illness, corticosteroids, alcohol and other exposures can mimic or compound depression and require history-led assessment.

Trauma and anxiety disorders

Avoidance, hyperarousal, intrusive memories, worry and panic can produce insomnia and low mood; chronology and the dominant maintaining processes guide formulation.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Initial assessmentDefine syndrome, function and dangerFirst stepA person reports persistent low mood, reduced motivation, fatigue or loss of interest.

1Establish core, cognitive and biological symptoms, duration, baseline and concrete functional consequences using the person's own language.
2Ask directly about suicide, self-harm, psychosis, catatonia, mania, substances, physical illness and dependants.
3Formulate severity, immediate risk, leading diagnosis and alternatives and arrange urgent or routine care with named follow-up.

02Psychotic or catatonic featuresEscalate and assess physical riskEscalationDelusions, hallucinations, stupor, marked psychomotor change or inability to meet essential needs is present.

1Assess medical stability, hydration, nutrition, medicine effects, delirium and neurological causes and create proportionate observation.
2Clarify content, conviction, commands, behaviour and decision-specific capacity and obtain urgent specialist psychiatric review.
3Use the least restrictive safe setting, protect dependants and communicate the full physical and risk formulation at handover.

03Diagnostic discussionShare a working explanationThe assessment supports a depressive syndrome but cause or subtype may remain uncertain.

1Explain which symptoms and functional changes support depression and what the label does and does not imply.
2Name bipolar, medical, substance, grief or trauma alternatives that require further evidence and arrange targeted work-up.
3Agree treatment and monitoring from current needs and preference and provide clear triggers for earlier reassessment.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Suicide and self-harm

Hopelessness, agitation, intoxication, perceived burden, psychosis and access to means can converge into lethal behaviour, requiring repeated individual formulation.

Functional and social loss

Withdrawal and cognitive impairment can disrupt work, education, parenting, relationships, money and self-care, which may then reinforce shame and depression.

Physical health deterioration

Poor nutrition, inactivity, sleep disruption, substance use, missed treatment and healthcare avoidance can worsen chronic disease and increase preventable morbidity.

Psychosis or catatonia

Severe episodes can develop delusions, hallucinations, stupor or other catatonic signs, increasing medical risk and often requiring urgent specialist treatment.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Track mood, interest, energy, sleep, appetite, psychomotor change, cognition, function and suicide risk rather than relying on total score alone.
Review within the timing required by severity and treatment, earlier after deterioration, self-harm, antidepressant initiation or reduced support.
Ask about emerging activation, reduced need for sleep and impulsive behaviour because a bipolar course may become apparent over time.
Reassess physical and neurological explanations when onset, progression, examination or treatment response remains atypical.
Check dependants, medicine access, nutrition, housing and ability to use the crisis plan at every material change.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Anhedonia has components

A person may still enjoy an activity once engaged but lose anticipation and initiation, so ask separately about wanting, starting and experiencing pleasure.

Mood and affect differ

The person may report persistent low mood while showing brief reactive affect, and that moment should not erase the longitudinal syndrome.

Agitation is depressive too

Pacing, hand wringing and inner unrest can accompany severe depression and may increase immediate distress and suicide capability.

Grief and depression overlap

Loss can produce intense sadness and sleep change, while pervasive worthlessness, sustained anhedonia and suicidal intent may indicate a coexisting depressive episode.

Biology is not a checklist

Somatic symptoms support the phenotype but require interpretation alongside pain, sleep disorders, endocrine disease, medicines and living conditions.

11Common pitfallsFrequent interpretation and management errors.

01
Diagnosing or excluding depression from one PHQ score without clinical assessment.
02
Treating irritability, numbness or somatic language as incompatible with depression.
03
Failing to ask lifetime mania or hypomania before recommending an antidepressant.
04
Missing psychotic guilt or nihilism because hallucinations were the only psychosis question.
05
Assuming grief prevents a depressive disorder or that every grief response is illness.
06
Using visible self-care in clinic as proof that home function and nutrition are safe.
07
Leaving suicide enquiry until the end when hopelessness and burden are already evident.