Major Psych Illnesses

Schizophrenia

Psychotic Disorders

Psychosis = a mental disorder causing an inability to distinguish between reality and imagination, characterised by delusions and hallucinations.

i. Schizophrenia

Brief psychotic episode Schizophreniform disorder

ii. Schizoaffective disorder

iii. Delusional disorder

iv. Post-partum psychosis

v. Psychotic disorder NOS (Atypical psychosis)

i. Schizophrenia

Definition:

A psychotic disorder or unknown aetiology and variable presentation, characterised by positive and negative (deficit) sxs. Although not a cognitive disorder, the condition often causes cognitive impairments. Epidemiology: 1% of population (no gender difference) Most common in people aged 15-35yrs; Rare in people aged 40yrs

Average onset younger for men than women (18-25yrs vs. 25-35yrs)Causative or Contributory Factors

Genetics & Family Hx: Adoptive MZ studies show ~50% concordance rate vs. 12% in DZ twins Greater genetic loading = Greater risk (40% in child of two parents with schizophrenia, 12% in child with one schizophrenic parent) 8% in non-twin sibling of patient with schizophrenia

10% of a patients 1st degree relatives are likely to be schizophrenia sufferersBirth Cxs: Schizophrenia is specifically associated with birth trauma and foetal hypoxia, but contribution is small (~5%)Infection & Birth Season: children born in winter have a higher risk of schizophrenia (5%). A viral cause is the suspected link.Psychosocial Stress: first episode (precipitant) or relapse is commonly correlated with stressful life events eg. Marriage breakdownLow socioeconomic Class: This class has a disproportionate number of patients. Whether this is a cause or effective of the illness is uncertain.

NeurobiologyDopamine hypothesisHyperactivity of the dopaminergic system (dopamine release, number / hypersensitivity of receptors) is supported by: Efficacy of dopamine D2 receptor antagonists (typical antipsychotics) in Rx Drugs that (dopaminergic activity induce psychosis eg. Amphetamines

Serotonin (5-Hydroxytriptamine)

Increasing research into the role of 5-HT given efficacy of dopamine-serotonin antagonists (SDAs atypical antipsychotics) in Rx. Further, Lysergic acid diethylamide (LSD) affects 5-HT levels and causes hallucinations.Neuropathology

Limbic SystemSystem including many cortical and sub-cortical structures, its role is controlling emotion, motivation, and emotion associated with memory.Decreased size in patients with schizophrenia shown by MRI

Ventricles & Cortex

MRI and CT have consistently shown increased lateral, third and cerebral ventricular size and reduced cortical volume. However, ventricular size are usually still within normal limits.DSM IV-TR Diagnostic Criteria

A. 2 Characteristic (cardinal) Sxs:1. Delusions

Paranoid or persecutory delusions

Delusions of grandeur

Delusions of reference eg. TV talking about them Somatic delusions eg. of terrible illness

2. Hallucinations

3. Disorganised speech / thought (eg. frequent derailment or incoherence) aka word salad4. Grossly disorganised or catatonic behaviour Variously characterized by stupor/inactivity, mania, odd posturing for an extended time, catatonia, rigidity or extreme (waxy)flexibility of the limbs5. Negative Sxs: Flat or blunt affect

Marked apathy & Lack of motivation Poverty of speech & speech content Blocking of thought Poor grooming

Social withdrawal

B. Social / Occupational Dysfunction for a significant portion of time since the onset of sxs

C. Duration: Continuous signs / sxs persist for 6 months

D. Schizoaffective and Mood disorders excluded

E. Substance / General medical conditions excluded

Clinical Features

No single feature is pathognomonic for schizophrenia.

Pre-morbid sxs may include having few friends at school / college, being socially withdrawn, acute onset of OCD. Often their pre-morbid personalities are quiet, passive and introverted.Sub-types: 4 Major DSM Types1. Paranoid: Characterised by the presence of delusions & auditory hallucinations, typically persecutory Does not have any other positive sxs (incoherence, loosening of associations, flat or inappropriate affect, catatonic behaviour, etc) Sub-type with later onset and the best Px2. Disorganised (hebephrenic): Characterised by marked regression to primitive, uninhibited and disorganised behaviour. Marked positive & negative sxs; Inappropriate bursts of laughter and cognitive & attention deficits

Subtype is usually early onset and a/w poor Px.3. Catatonic: Classic feature is marked disturbance in motor function eg. Stupor, rigidity, excitement, posturing Marked negative sxs. Also a/w poor Px.4. Undifferentiated: Marked positive sxs but does not meet the criteria for any other typeSub-types: Type I vs. Type IIThis system of classification is not accepted by the DSM, but clinically has been significant with respect to research. It is based on whether the patient demonstrates positive or negative sxs. Type I patients have mostly positive (or productive) sxs, including delusions and hallucinations, acute onset, normal brain structures on CT, and relatively good response to Rx, good Px. Type II patients have mostly negative sxs, chronic onset, structural brain abnormalities on CT, poor responses to Rx and poor Px.MSE

General Appearance & Behaviour:Appearance may range from dishevelled to obsessively groomed

Behaviour may be unprovoked agitation and violence to catatonic

Speech may be talkative or silentMood & Affect: Affect may be flat, blunted, inappropriate, labile.Thought:Stream can be slow, normal or manicForm Formal thought disorder ie. derailment, tangentiality, blocking, circumstantiality, loosening of associations commonly seen (also in mania), Content delusions characteristicPerception: Auditory and visual hallucinations are common, but in the other modalities it is unusual. Illusions may also occur in any phase of the illness.Consciousness & Cognition: Consciousness may be depressed (in stupor) but usually normal. Orientation and memory are usually normal. Attention / Cognition can be affected. Classically, insight into their illness is poor, correlated with lack of compliance. Judgement is poor with psychosis. Rapport: often difficult to build rapport with patients, as agitation can occur without provocation. DDxi. Psychotic disorder due to a general medical condition

Hyper- / Hypothyroidism Cushings disease or syndrome

Chest infection

Vitamin B12 or folate deficiency

Meningitis

Space-occupying lesions (may cause visual hallucinations)( Must always pursue an undiagnosed non-psychiatric medical condition in patients exhibiting unusual or rare sxs or any variation in consciousness

ii. Medications / Substance Abuse

Medications (levodopa, antipsychotics, steroids, tranquilizers)

ETOH withdrawal, Lysergic acid diethylamide (LSD) usage, etc.iii. Other psychotic disorders

Brief psychotic disorder = schizophrenic sxs lasting between 1 day and 1 month

Schizophreniform disorder = schizophrenic sxs lasting between 1 and 6 months

Schizoaffective disorder = bipolar or depressive syndrome develops concurrently with the major schizophrenic sxs but where psychotic sxs persist despite remission of mood disorder sxs. Delusional disorder = non-bizarre delusions present for 1 month w/o other schizophrenic sxs

iv. Mood Disorders with Psychotic sxs

MDD: delusions typically consistent with depressed mood (ie. mood congruent delusions) such as guilt, worthlessness, etc.

Bipolar disorder: commonly delusions (grandiose) & manic behaviour during episodes of mania though hallucinations are rare MDD and antipsychotics can also cause negative symptoms

v. Seizure disorders

Mood disorders can be a feature of epilepsy post-seizurevi. Malingering / Factitious disordersNatural Hx

Classic course of schizophrenia is exacerbations and remissions. A further deterioration of baseline functioning occurs after each relapse of psychosis. This failure to return to baseline functioning is the key distinction between schizophrenia and the mood disorders. A minority will only have one schizophrenic episode.Prognosis

Rule of thirds: One third have somewhat normal lives, One third have continual sxs but can function within society, One third are markedly impaired and require frequent hospitalisations.4 ~50% can be described as having a poor outcome, with repeated hospitalisation, exacerbation of sxs, episodes of major mood disorders and suicide attempts.2Factors associated with a good prognosis include:

Late and / or acute onset

Obvious precipitating factors

Good premorbid social, sexual and work hxs

Mood disorder sxs (especially depressive disorders)

Positive sxs

Good support systems

Cxs

Suicide: ~50% of patients will attempt suicide, and 10-15% die by suicide.

Depression: Lifetime risk of MDD is 50% and it contributes to risk of relapse (despite sxs of mood disorders being a good prognostic factor) Drug & ETOH abuse: 30-50% ETOH, 15-25% cannabis, 5-10% cocaine.

STDs: Patients are statistically more likely to practice more sexually risky behaviours (10 times increased risk of HIV) Increased all-cause morbidity: ~double the requirement of physical healthcare Increased all-cause mortality: (3-fold relative to normal population

Pharmacological Therapy

Dopamine receptor antagonists

[Typical antipsychotics]Chlorpromazine, Pericyazine, Thioridazine // Haloperidol, Fluphenazine, Flupenthixol Used as 2nd line Rx

Effective for Rx of the positive sxs & for sedation (eg. if agitated) Often cause significant SEs: Akathisia (restlessness), EP Sxs (rigidity, tremor), Acute dystonia, Tardive dyskinesia, Neuroleptic malignant syndrome SEs (first 3): Marked sedation (often exploited), Anticholinergic SEs (especially Thioridazine), Sun sensitivity & sunburn (Chlorpromazine). Depots: Haloperidol, Fluphenazine, FlupenthixolSerotonin-Dopamine Antagonists (SDAs) [Atypical antipsychotics]

Risperidone (Risperidal), Olanzapine (Zyprexa), Quetiapine (Seroquel), Aripiprazole (Abilify), Clozapine (Clozaril) Used as 1st line Rx for schizophrenia & psychosis Antagonises different dopamine receptors as well as 5-HT receptors

Much more effective for ve sxs and at least as effective for +ve sxs

Minimal or no extrapyramidal sxs (except risperidone) due to looser bonding at D2-receptor sites Depots: Risperidal constaTypical AgentsRisperidoneOlanzapineQuetiapineClozapine

CNS:

Extrapyramidal Sxs (EPS)+++0 to ++0 to +00

Tardive dyskinesia++++000

Sedation+ to +++++++++++

Seizures0 to +0+0+++

Other:

Neuroleptic malignant Syn.+++?+

Weight gain0 to ++++++++++

Orthostatic Hypotension+ to +++++0++

Anticholinergic SEs0 to +++0+0+++

(Prolactin++++ to ++000

(Liver transaminases0 to ++0 to ++++ (2%)0 to +0 to +

Agranulocytosis0000+++ (1%)

(Kaplan & Sadock, 2001)Mx

1. Safety AssessmentRisk of patient to themselves (risk of repeated attempts + risk of successful suicide) & to others must be assessed (Low, Medium, High)2. Ix of causes & Dx (eg. Screen for medical causes of psychosis)3. Immediate Rx

Antipsychotics (except clozapine) are remarkably safe and can be given in ER situations w/o conducting physical or lab examinations.4. Long-term Rx

Pharmaceutical: SDAs (atypical) should be mainstay; long-term use of DAs (typical) is highly questionable due to risk of tardive dyskinesia

> 1 antipsychotic at a time is rarely (if ever) indicated

Minimum length of antipsychotic trial is 4-6 weeks

Use lowest effective dose but monitor plasma levels [Clozapine requires monthly FBEs to monitor agranulocytosis]

Combination with other drugs (eg. lithium, carbamazepine, BZDs) may be indicated for resistant or complicated cases Rx Extrapyramidal sxs and Acute dystonia with anticholinergics (eg. benzhexol, benztropine)

Electroconvulsant Therapy (ECT) Efficacy

2. Sadock & Sadock (2004), Concise Textbook of Clinical Psychiatry, pp. 134-1533. FIRSTConsult, Schizophrenia, < http://www.firstconsult.com >

4. Kaplan & Sadock (2001), Pocket handbook of clinical psychiatry, 3rd edn, Lippincott Williams & Wilkins.

5. Katona C & Robertson M (2005), Psychiatry at a glance, 3rd edn, Blackwell publishing, Australia.6. MIMS online, 2003 < http://mims.hcn.net.au >

SchizophreniaDepressionBipolar (Manic)

Disorder typePsychotic, +ve & -ve sxsMood disorderMood disorder

Epidemiology1% population; = 20% popn; : = 1:2~1% population; =

AetiologyGenetics (( with FamHx;

MZ:DZ = 50%:10%)

Dopamine (& 5-HT) hypothesis

Psychosocial stress

(Ventricle size, (Cortical volume, and (Amygdala & hippocampus size(5-HT, (NA, (DA

Psychosocial: loss of parent or spouse, unemployment, birth.

Genetics: Less important than for Bipolar I; MZ>DZ concordance but still less than Bipolar.

Medical: eg. Thyroid5-HT, NA & DA levels

Psychosocial stressors

Genetics: 25% with one parent, 50-75% with two, MZ:DZ ( 60:20.

Medical: eg. Cushings

MSE

Appearance, Behaviour & SpeechBehaviour: Variable (eg. Agitated, withdrawn, postured, catatonic)

Speech: Normal to incoherentA: (-motor retardation agitation, poor eye contact, tearful, poor grooming.

S: Slowed, soft, monotone, long pauses, non-spontaneous, monosyllabic.A: (-motor agitation, bizarre or colourful clothing, excess makeup

B: Hyper-excited, intrusive, threatening, entertaining

S: Pressured, loud, dramatic, incoherent

Mood & AffectA: Flat, blunted, labile, inappropriateM: Depressed, irritable, frustrated, sad

A: Constricted or labileM: Euphoric, expansive, irritable, flirtatious.

A: Labile & swinging

PerceptionHallucinations, most commonly AuditoryHallucinations rareHallucinations less common

Thought

StreamNormalSlowedFast (racing thoughts)

FormDerailment, tangentiality, circumstantiality, loosening of associations10% have sxs of Thought disorder (blocking, poverty of ideas)Flight of ideas (severe can be incoherent), tangentiality, circumstantiality, neologisms, clang-assoc.

ContentDelusions, ideas of reference, passivity, poverty, Suicidal ideation (60%)

Negativity is customary, obsessive rumination, worthlessness, guilt.

Delusions possible.Grandiosity, (Self-esteem, mood congruent delusions, hallucinations rarer.

Cognition

ConsciousnessNormal

(Unless catatonic)DecreasedIncreased (excitable)

Attention & ConcentrationNormalDistractible,

Difficulty concentratingEasily distracted

Executive functionFrontal lobe can be affected, causing cognitive deficits. Impaired abstract thoughtNormal

Orientation & MemoryNormalOrientated, Poor memory,Normal

Judgement & InsightImpairedImpaired judgement

Insight: Sxs often over-emphasisedExtremely impaired judgement and insight is the hallmark of mania

Mood DisordersPsychopathological conditions in which a persuasive disturbance of mood is the primary feature, usually with a return to normal functioning in b/w episodes.Aetiology of Mood Disorders:

Some clinicians believe stress is the primary cause of depression, whilst others believe its role is limited. Aetiology is really a mix of genetic and environmental factors, but depressive illnesses involve both mind and body, which are themselves indivisible.

Genetic:

Genetic factors are much more significant in Bipolar I disorder than MDD, but no specific gene has yet been identified.

Family Studies:

1st degree relatives of Bipolar I disorder have 8-18 times risk of Bipolar I and 2-10 times risk of MDD

If one parent has a Bipolar I, child has 25% chance of a mood disorder; if both have Bipolar I, child has 50-75% chance.

1st degree relatives of someone with MDD have a 10% chance

Adoption Studies:

Biological children of affected parents remain at (risk even if reared in non-affected adoptive families.

Twin Studies:

Concordance rate for MDD in monozygotic twins is ~50%

Concordance rate for bipolar I in monozygotic twins is between 33-90%

Neurobiology:

Serotonin (5-HT)

Efficacy of Selective Serotonin Re-uptake Inhibitors (SSRIs)

Depletion of serotonin may precipitate depression

Noradrenaline (NA)

Down regulation of -Adrenergic receptors is associated with depression

Efficacy of clinical anti-depressants which also block NA-receptors eg. Tricyclic anti-depressants, Setraline (SSRI)

Dopamine (DA)

Drugs that reduce DA and diseases that reduce DA concentrations (eg. Parkinsons) are associated with depressive Sxs. In contrast, drugs that (DA concentrations (eg. amphetamines) reduce the sxs of depression.

Data suggests that (dopamine activity is associated with depression and (activity with mania.

Medical / Hormonal factors:

Cortisol (Cushings Syn. / disease)

Correlation with (cortisol and depression has been one of the oldest observations in psychiatry; ~50% of depressed patients have (cortisol levels

New data suggests that a +ve Dexamethasone-Suppression Test (DST) (ie. non-suppression of cortisol) may correlate with relapse rates, but +ve results also occur in other psychiatric illnesses

Thyroid

Thyroid disorders found in 5-10% of depressed patients

Physical Illness & Medications

The major cause of depression in later life

HIV, Multiple sclerosis and cancer carry an especially increased risk

L-Dopa & Interferon are medications known to precipitate depression

Psychosocial Factors:

Life Events & Environment

Stressful life events more often precede the first (rather than subsequent) episodes of mood disorders

The life event most often a/w depression is losing a parent < Age 11

Environmental stressor most often a/w depression is loss of a spouse Unemployed have 3 times risk of depression compared to employed Childbirth: 45% of women who develop bipolar have their first episode in the post-partum periodCxs

Suicide and self-harm 10-15% of depressed pts will commit suicide; 66% will have suicidal ideation

(Risk of CVS event

Major Depressive Disorder (MDD)

Synonyms: Unipolar depression, Clinical depression, Major depression.Epidemiology: Lifetime prevalence is 10-25% women; 5-12% men (: = 2:1) Mean age of onset ~40yrs (50% cases between 20-50yrs); Cases