Major Mental Illnesses

• Thought Disorders• Schizophrenia

• Mood Disorders• Major Depressive Disorder• Bipolar Disorder (Manic-depression)

Characteristics of an Illness

• Affect Individuals• Across Populations• Signs and Symptoms• Course

• Heredity• Diagnosis• Causes• Treatment

Understanding Schizophrenia

Common Symptoms of Schizophrenia

• Positive Symptoms–Disturbances of thinking and perception

• Negative Symptoms–Loss or decrease of normal functions

Positive Symptoms of Schizophrenia

• Disordered thinking– Thoughts “jump” between completely unrelated

topics or may be “blocked”.

• Delusions– Fixed, false beliefs (not based in reality)– Outside of cultural norms

• Hallucinations– False perceptions– Usually auditory

Delusions of Schizophrenia

• Persecution• Control• Grandiose• Reference• Influence• Religious

• Somatic• Mind reading• Thought broadcasting• Thought insertion• Thought withdrawal• Guilt, sin

Hallucinations of Schizophrenia

• Auditory 70%• Voices commenting• Voices conversing• Voices commanding

• Visual 30%• Somatic, tactile 15%• Olfactory 5%

Negative Symptoms of Schizophrenia

• Affect blunted or flat– Lacking emotional expression– “Blank” face, little eye contact, few gestures

• Avolition– Lacking energy, spontaneity, initiative

• Alogia– Diminished amount of speech, or content

• Anhedonia– Lack of interests, or lack of pleasure

Diagnosis: Schizophrenia

How is schizophrenia diagnosed?

Schizophrenia: Diagnosis Across Time

• Kraeplin - Dementia Praecox (1878)• Simple• Paranoid• Hebephrenic• Catatonic

• Bleuler - “Schizophrenia” (1911)• Affect• Associations• Ambivalence• Autism

• Schneider - First Rank Features (1959)

Diagnostic and Statistical Manual of Mental Disorders, fourth

edition (DSM-IV)

DSM-IV Schizophrenia

• Characteristic symptoms for one month• Impairment in functioning• Continuous signs for 6 months• Not do to a “look-alike”

• mood disorder• substance abuse• general medical condition• autism

Types of Schizophrenia• Paranoid type

• Preoccupation with delusions or frequent auditory hallucinations

• Disorganized type• Disorganized speech, disorganized behavior, flat or

inappropriate affect

• Catatonic type• Immobility, peculiar movements, purposeless and excessive

activity

• Undifferentiated type• Residual type

Who Gets Schizophrenia?

• One of every one hundred people• 2.5 million people in the United States

• All ethnicities• Societies throughout the world• Equal among men and women• More prevalent in poorer communities

• “Downward drift”

The Course of Schizophrenia

• Most commonly begins between ages 15-25• Usually begins later in women• One, or multiple episodes• Full or partial recovery between episodes• Positive symptoms lessen with age• Negative symptoms increase with age• Tends to stabilize later in course

What Causes Schizophrenia?

• Unclear• Likely a complex group of brain illnesses

with multiple causes• Heredity• Biochemical theory• Brain anatomy• Brain development

Causes of Schizophrenia

• Heredity

– Genetic component to schizophrenia (runs in families)

– Adoption studies

– Inherit a vulnerability to schizophrenia

Lifetime Risk of Developing Schizophrenia

• General population 1%• Child of one parent with schizophrenia 10-15%• Child of two parents with schizophrenia 30-40%• Sibling with schizophrenia 10%• Fraternal twins 10%• Identical twins 50%

“For every complex problem there is a solution that is neat,

simple and wrong.”

H. L. Menken

“It is better to be wrong than vague, if one is wrong in an

interesting way.”

Bernard Carroll

Stress-Diathesis Model of Schizophrenia

• Genetic Vulnerability (diathesis)• “Second hit”

– Perinatal - pregnancy or birth injury– Viral / Seasonality– Other stresses - puberty, social stresses

• Leads to changes in the brain

Brain Differences in Schizophrenia

• Chemical–Dopamine Hypothesis

• Anatomy / Activity–Many sites

• Developmental–Cell migration

Dopamine Hypothesis of Schizophrenia

• Describes what is wrong in the brain but not how it got that way

• Dopamine system is hyperactive• Too much dopamine• Problem with the dopamine receptors• Clues - amphetamines, Cocaine, L-DOPA

Neuroanatomy of Schizophrenia

• No single change is seen in all people with schizophrenia

• Enlarged ventricles• Underactive frontal lobe

– planning, judgement, abstraction, expressing feelings

• Overactive temporal lobe– preceptions and emotions

Attention / Arousal Modelof Schizophrenia

• Stimulus flooding– Lack of an effective filter– Too much information from the environment– Leads to withdrawal from social contact

• Stimulus overload– Leads to frustration, poor concentration,

nervousness

Examples of Stimulus Overload

• “Everything seems to grip my attention although I am not particularly interested in anything. I am speaking to you just now, but I can hear noises going on next door and in the corridor. I find it difficult to shut these out, and it makes it more difficult for me to concentrate on what I am saying to you.”

• “My concentration is very poor. I jump from one thing to another. If I am talking to someone they only need to cross their legs or scratch their heads and I am distracted and forget what I was saying. I think I could concentrate better with my eyes shut.”

Schizophrenia• IS

– Biological disease of the brain– Disabling and emotionally devastating– Relatively common– Misunderstood and stigmatized– Treatable

• IS NOT– Caused by bad parenting– A personal weakness– Split personality

Understanding Mood Disorders

Major Depression

Bipolar Disorder

Mood Disorders

• Signs and Symptoms• Diagnosis• The Biology • Other Causes• The Course of Illness

Major Depression: Signs and Symptoms

• Emotional• Thought• Somatic (body)• Behavioral

Major Depression: Emotional Symptoms

• Sad, irritable or empty mood• Diurnal variation• Diminished capacity for enjoyment• Diminished interests

Major Depression: Thought (Cognitive) Symptoms

• Difficulty concentrating• Indecisiveness• Memory problems• Depressed content of thought

– Worthlessness– Guilt– Hopelessness– Death and Suicide

Major Depression: Somatic Symptoms (Body Functions)

• Sleep disturbances• Appetite disturbances, weight changes• Fatigue, low energy• Upset stomach, constipation• Physical pain

Major Depression: Behavioral Signs and Symptoms

• Social withdrawal• Increased dependency• Poor frustration tolerance• Suicide attempts• Substance abuse

• Slow motion• Slow speech• Poor eye contact• Tearfulness• Agitation• Poor self-care

Major Depression:Types of Episodes

• Melancholia– No pleasure or “reactivity”– Weight loss– Early morning awakening– Worse in the morning– Excessive Guilt

• Atypical– Mood brightens to positive events– Weight gain– Over-sleeping– Heavy feeling in arms and legs– Interpersonal rejection sensitivity

“Masked Depression”

• May not complain of feeling depressed• Anxious, agitated• Fatigue, insomnia• Chronic pain, unrelieved by pain killers• Confused, disoriented, poor memory• Alcohol or drugs obscure symptoms

Major Depression: DSM-IV• Depressed mood, or loss of interest/

pleasure• Other symptoms (total of 5)

• Increase or decrease in appetite/weight• Insomnia or hypersomnia• Agitation or slowing• Fatigue or loss of energy• Worthlessness or guilt• Poor concentration or indecisiveness• Recurrent thoughts of death or suicide

Major Depression: DSM-IV (continued)

• Two week duration• Impaired functioning in life roles• Rule out “look alikes”

– Secondary depression

Secondary Depression

• Other treatable illnesses cause depression– Examples

• Endocrine problems (thyroid disease, diabetes)• Infections (mononucleosis, influenza)• Anemia• Poor nutrition• Neurologic illnesses (strokes, Parkinson’s disease,

multiple sclerosis• Tumors (lung, pancreas, brain)

Secondary Depression (continued)

• Alcohol• Drugs• Medications

• Examples - steroids, high blood pressure medications, sleeping pills, oral contraceptives

• Toxins

Major Depression: The Causes

• Limbic System• Neurochemical

• Serotonin• Norepinephrine• Others

• Heredity• Identical twins - 40%

• Environmental stresses

Major Depression: The Course

• Can occur at any age– Usual onset similar to schizophrenia, or later– 10% have first episode after age 60

• More common in women (2:1)• Lifetime prevalence 17%• Recurrent in 50-60%

– Later episodes: longer, deeper, more frequent, less of a trigger

• May be seasonal

Major Depression Severity

• Mild to severe• May include psychosis, poor self care, suicide

• Abraham Lincoln describing his own depression:

• “I am now the most miserable man living. If what I feel were equally distributed to the whole human family, there would not be one cheerful face on earth. Whether I shall ever be better, I cannot tell. I awfully forebode I shall not. To remain as I am is impossible. I must die or be better, it appears to me.”

Bipolar Disorder

• Signs and Symptoms of Mania• Diagnosis• Other Causes• The Biology• The Course of Illness

Mania: Signs and Symptoms• Persistently elevated, expansive or irritable

mood lasting at least one week• Associated symptoms

• Inflated self -esteem or grandiosity• Decreased need for sleep• More talkative• Racing thoughts or flight of ideas• Distractibility• Agitation or increase in activities• Excessive involvement in pleasurable activities with

a high risk for painful consequences – Spending sprees, sexual indiscretions, foolish investments

Manic Episode: DSM-IV

• Elevated, expansive, or irritable mood for one week

• Three associated symptoms• Significant impairment in life roles• Not do to a “look-alike”

• Medical condition• Medication• Substance abuse

Hypomania

• Episode similar to mania, but less severe

• No impairment in functioning

• May actually be more productive, creative

• Bipolar II Disorder

Bipolar Disorder: The Course• 1% of general population• Equal in men and women• Age of onset similar to schizophrenia• Episodes can come on very fast (1-7 days)• Later episodes longer, more severe, more frequent• Substance abuse common• Heredity plays a greater role than in depression• Family members also at higher risk for major

depression• High suicide risk

Mood Disorders• ARE

– Biological disease of the brain– Disabling and emotionally devastating for

many– Common– Misunderstood and stigmatized– Treatable

• ARE NOT– The fault of the family– A personal weakness

Characteristics of an Illness

• Affect Individuals• Across Populations• Signs and Symptoms• Course

• Heredity• Diagnosis• Causes

• Treatment

Treatment of Schizophrenia and

Other Psychotic Disorders

Long Acting Antipsychotics

• Haldol Decanoate (Haloperidol)

• Prolixin Decanoate (Fluphenazine)

Clozapine

• Pros–Gold standard for refractory schizophrenia–Effective for positive symptoms–Does not produce EPS or TD–May improve cognition–Effective for mood symptoms

Clozapine

• Cons–Agranulocytosis, blood draws, monitoring–Seizure risk–Other side effects–Titration–Acquisition cost

Risperidone

• Pros–Effective for positive symptoms–Less EPS than with conventional agents–May help cognitive and mood symptoms

• Cons–Dose dependent EPS–Dose dependent prolactin elevation

Olanzapine• Pros

–Effective for positive symptoms–Low EPS and TD liability–FDA indication for mania–May improve cognition

• Cons–Weight gain–Acquisition cost

Quetiapine

• Pros–Effective for positive symptoms–Very low EPS liability–Limited data for mood symptoms, cognition

• Cons–Titration, split dosing, sx break through–Sedation, weight gain

Psychosocial Treatments

• Patient and family psychoeducation• Vocational training• Social Skills training• Clubhouse model• Schizophrenics Anonymous

Update on the Pharmacologic Treatment of Psychosis

Timothy Florence, MD

Clinical Instructor

University of Michigan

Department of Psychiatry

Psychosis

• Defined by impaired reality testing• Characterized by:

– thought content: delusions–perception: hallucinations– thought stream: grossly disorganized–behavior: grossly disorganized

Typical Psychoses

• Schizophrenia• Psychotic mood disorders

– Bipolar disorder– Major depressive disorder with psychotic features

• Substance-induced psychotic disorder• Psychotic disorder due to medical conditions

Mental Health: A Report of the Surgeon General

David Satcher, MD, PhD

www.surgeongeneral.gov/library/mentalhealth/index.html

Surgeon General’s Report:Key Messages

• Mental illnesses are real illnesses and are biologically based

• Effective treatments are available

Surgeon General’s Report:Action Steps

• Overcome STIGMA by disseminating accurate information

• Improve PUBLIC AWARENESS of effective treatments

• Improve access to treatment• Individualize treatment

• Ensure delivery of state-of-the-art treatments

• Reduce financial barriers• Continue to build the science base• Ensure adequate supply of service providers

Characteristics of an Illness

• Affect Individuals• Across Populations• Signs and Symptoms• Course

Diagnostic and Statistical Manual of Mental

Disorders, fourth edition (DSM-IV)

DSM-IV Schizophrenia

• Characteristic symptoms–Delusions–Hallucinations–Disorganized speech–Disorganzied or catatonic behavior–Negative symptoms

Negative Symptoms of Schizophrenia

• Affect blunted or flat– Lacking emotional expression– “Blank” face, little eye contact, few gestures

• Avolition– Lacking energy, spontaneity, initiative

• Alogia– Diminished amount of speech, or content

• Anhedonia– Lack of interests, or lack of pleasure

Negative Symptoms

• Caused by:– Inherent deficit (deficit syndrome)–Positive symptoms–Depression–Medications–Environmental deprivation

DSM-IV Schizophrenia

• Characteristic symptoms for one month• Impairment in functioning• Continuous signs for 6 months• Not do to a “look-alike”

• mood disorder• substance abuse• general medical condition• autism

Positive Symptoms of Schizophrenia

• Disordered thinking– Thoughts “jump” between completely unrelated

topics or may be “blocked”.

• Delusions– Fixed, false beliefs (not based in reality)– Outside of cultural norms

• Hallucinations– False perceptions– Usually auditory

Who Is At Risk For Schizophrenia?

• Prevalence - 1%• All ethnicities• Societies throughout the world• Equal among men and women• More prevalent in poorer communities

• “Social drift”

Who Is At Risk?

• Predisposing factors:– Season– Perinatal

• pregnancy• birth injury

– Nutrition– Heredity

• Precipitating factors:– Environment– Stress– Substance Abuse

The Course of Schizophrenia• Extremely variable• Often chronic• Onset

– Males: 15-25 – Females: 25-35

• Functional decline early• Differential diagnosis of first episode challenging• Recurrent episodes

– More difficult to treat– Longer to remission

Dimensions of Functional Impairment

• Occupational• Social• Instrumental• Self-care• Independent living

Predictors of Functional Status

• Premorbid functioning

• Cognitive symptoms

• Negative symptoms

Severity of Functional Deficits in Schizophrenia

• 10% will work full-time• 33% will work part-time• Less than 10% of males will have a child• Self-care deficits are reflected in high rates

of medical comorbidity

Cognition and Outcome:Reasons for the Correlation

• Cognitive deficits often make learning new skills difficult

• Job success requires the ability to learn and remember the demands of the position

• Deficits in organization make persons unable to perform the job responsibilities

• Deficits in concentration make performance unreliable

Schizophrenia PORT Treatment Recommendations

• Choice of antipsychotic medication should be made based on:– Patient acceptability– Prior individual drug response– Individual side effect profile– Long-term treatment planning

What Is Schizophrenia?

• Heterogeneous• Likely a complex group of brain illnesses

with multiple causes• Genetic predisposition or vulnerability

threshold• Series of consequences resulting from brain

dysfunction• Requires a second “hit”

Lifetime Risk of Developing Schizophrenia

• General population 1%• Child of one parent with schizophrenia 10-15%• Child of two parents with schizophrenia 30-40%• Sibling with schizophrenia 10%• Fraternal twins 10%• Identical twins (adoption studies) 50%

Neuroanatomy of Schizophrenia

• No single change is seen in all people with schizophrenia

• Enlarged ventricles• Underactive frontal lobe

– planning, judgement, abstraction, expressing feelings

• Overactive temporal lobe– preceptions and emotions

Schizophrenia• IS

– Biological disease of the brain– Disabling and emotionally devastating– Relatively common– Misunderstood and stigmatized– Treatable

• IS NOT– Caused by bad parenting– A personal weakness– Split personality

Mania: Signs and Symptoms• Persistently elevated, expansive or irritable

mood lasting at least one week• Associated symptoms

• Inflated self -esteem or grandiosity• Decreased need for sleep• More talkative• Racing thoughts or flight of ideas• Distractibility• Agitation or increase in activities• Excessive involvement in pleasurable activities with

a high risk for painful consequences – Spending sprees, sexual indiscretions, foolish investments

Manic Episode: DSM-IV

• Elevated, expansive, or irritable mood for one week

• Three associated symptoms• Significant impairment in life roles• Not do to a “look-alike”

• Medical condition• Medication• Substance abuse

Bipolar Disorder: The Course• 1% of general population• Equal in men and women• Age of onset similar to schizophrenia• Episodes can come on very fast (1-7 days)• Later episodes longer, more severe, more frequent• Substance abuse common• Heredity plays a greater role than in depression• Family members also at higher risk for major

depression• High suicide risk

The Use of Atypical Antipsychotics for Psychosis

and Mood Stabilization

Timothy Florence, M.D.

Clinical Instructor

Department of Psychiatry

University of Michigan

Theoretical Mood Stabilizing Mechanisms

• Dopamine-Serotonin Interaction– 5-HT inhibits DA release– 5-HT antagonism enhances DA release

• GABA Hypothesis– Inhibitory neurotransmitter system– May mediate Valproate and Carbamazepine

effects

Dopamine-Serotonin Hypothesis

• DA Antagonism– Mesolimbic

• Improves mania– Mesocortical

• Worsens depression– Nigrostriatal

• Worsens depression

• 5-HT Antagonism– Mesolimbic

• Worsens mania– Mesocortical

• Improves depression– Nigrostriatal

• Improves depression

GABA Hypothesis

• No change in GABA receptors with conventional neuroleptics

• GABA receptor down-regulation with chronic Clozapine and Olanzapine treatment

• Mood stabilizing effects may be related to effects on GABA neuro-transmission

Bipolar Disorder Mortality

• At least 25% attempt suicide

• Suicide rate: 11-19%

• Suicidal ideation in mixed mania: 50%

Bipolar Disorder Morbidity

• Recurrent illness for 90% of patients• Fuctional recovery often lags behind

symptomatic recovery• Recurrent episodes may lead to progressive

deterioration• Number of episodes may affect subsequent

treatment response and prognosis• 6th leading cause of disability worldwide

Mood Stabilizing Agents

• FDA Approved–Lithium–Valproate

• Other Anticonvulsants– Carbamazepine– Lamotrigine– Gabapentin– Topiramate

• Benzodiazepines• Conventional Neuroleptics• Atypical Antipsychotics

– Clozapine– Risperidone– Olanzapine

Novel Antipsychotic Agents

• Clozapine• Open - label studies

• Risperidone• One study compared to Haloperidol and Lithium

• Olanzapine• Two double-blind placebo controlled studies

Clozapine for Bipolar Disorder

• Fifteen open trials in treatment-refractory illness suggest antipsychotic and mood stabilizing properties

• Pooled response rate = 70%• May be used in conjunction with other

mood stabilizers • Exception - Carbamazepine

Risperidone in Acute Mania

• Four week, double-blind, randomized study• No placebo control• Comparable and significant reductions in

manic symptoms with Risperidone, Haloperidol, Lithium

Dopamine Rebound Syndrome

• Euphoria / Dysphoria• Hypomania / Mania• Decrease in negative symptoms• Agitation• Psychosis• Dyskinesias• Withdrawal tardive dyskinesia

Cholinergic Rebound Syndrome

• Insomnia• Jitteriness• Restlessness / Anxiety• Somatic distress• Gastrointestinal symptoms

• Sweating• Drooling• Increased urination• Movement disorders• Hypomania / Mania• Delirium