Schizophrenia FAHAD ALOSAIMI MBBS SSCPSYCHOSOMATIC MEDICINE CONSULTANT ASSISTANT

Schizophrenia FAHAD ALOSAIMI MBBS, SSC-PSYCHOSOMATIC MEDICINE CONSULTANT ASSISTANT PROFESSOR KING KHALID UNIVERSITY HOSPITAL KING SAUD UNIVERSITY, RIYADH

Schizophrenia (Background) q. Schizophrenia is a severe, persistent & debilitating brain disease. q. It is not a single disease but a group of disorders with heterogeneous etiologies. q. Symptoms include disturbances in thoughts (delusions), perceptions(hallucinations), mood (or affects), behaviurs and relationships with others. q. People with schizophrenia have lower rates of employment, marriage, and independent living than other people. -

Impression? !

"It is conceivable that the susceptibility of humans to depression or to bipolar disorder may correlate positively specifically with the composition of poetry, " Nash said. He noted that the American poet Robert Lowell was hospitalized at Mc. Lean Hospital near Boston at the same time that Nash was admitted for schizophrenia.

Schizophrenia (Epidemiology) q. Found in all societies and countries with equal prevalence & incidence worldwide. q. A life prevalence of 0. 6 – 1. 9 % q. Annual incidence of 0. 5 – 5. 0 per 10, 000 q. Peak age of onset are: 10 -25 years for ♂ 25 -35 years for ♀. q 10% of schizophrenia patients committed suicide. q. They die 15 years younger than normal population partly because of multiple medical co-morbidities.

Outlines Etiology Clinical features & diagnosis. Differential diagnoses Course & Prognosis Treatment (Pharmacological) Treatment (Psychological )

Case of Mr. June John P is a 25 -year-old male with the diagnosis of schizophrenia. He was a healthy child, but his parents report that he was a bedwetter and seemed slower to develop than his brothers and sisters. A maternal uncle has also been diagnosed with schizophrenia. John had 2 brief hospitalizations in his late teens that were precipitated by anger at his boss, depression, and voices in his head. He has believed that CIA is following him & control his thoughts as well. He found the hospital stays unhelpful. He was treated with haloperidol which gave him dystonic symptoms; he was then treated with olanzapine and gained 10 Kg and developed diabetes mellitus. John smokes marijuana and tobacco frequently to calm himself; he also occaionally use amphetamine.

Cont. Case of Mr. June John's parents support him financially. His brothers & sisters are angry and frightened of him and have nothing to do with him. They are particularly upset by his lack of interest in the outside world. John lives in a boarding home and works in a sheltered workshop with difficulty. John sees a psychiatrist for 15 minutes every 2 months but sometimes misses his appointment. He has a social worker whom he sees often. The psychiatrist would like to switch him to long-acting injectable antipsychotic treatment, but John is afraid of injections and isn't sure that he needs medication. He usually misses his appointments with his primary care physician.

Etiology (Exact etiology is unknown) 1 - Stress-Diathesis Model: q. Integrates biological, psychosocial and environmental factors in the etiology of schizophrenia. q. Symptoms of schizophrenia develop when a person has a specific vulnerability that is acted on by a stressful influence.

2 - Neurobiology a- Dopamine Hypothesis; Too much dopaminergic activity ( whether it is ↑ release of dopamine, ↑ dopamine receptors, hypersensitivity of dopamine receptors to dopamine, or combinations is not known ). b- Other Neurotransmitters; Serotonin, Norepinephrine, GABA, Glutamate & Neuropeptides

c- Neuropathology; Neuropathological and neurochemical abnormalities have been reported in the brain particularly in the limbic system, frontal cortex, basal ganglia and cerebellum. Either in structures or connections.

d- Psychoneuroimmunology; ↓ T-cell interlukeukin-2 & lymphocytes, abnormal cellular and humoral reactivity to neurons and presence of antibrain antibodies. These changes are due to neurotoxic virus ? or endogenous autoimmune disorder ? e- Psychoneuroendocrinology; Abnormal dexamethasone-suppression test ↓ LH/FSH A blunted release of prolactin and growth hormone on stimulation.

3 - Genetic Factors - A wide range of genetic studies strongly suggest a genetic component to the inheritance of schizophrenia that outweights the environmental influence. - These include: family studies, twin studies and chromosomal studies.

Schizophrenia: genes plus stressors Schizophrenia is mostly caused by various possible combinations of many different genes (which are involved in neurodevelopment, neuronal connectivity and synaptogenesis) plus stressors from the environment conspiring to cause abnormal neurodevelopment. There is also abnormal neurotransmission at glutamate synapses, possibly involving hypofunctional NMDA receptors. Stephen M The Genetics Of Schizophrenia Converge, Upon, The NMDA Glutamate Receptor, CNS Spectr. 2007

4 - Psychosocial Factors; q In family dynamics studies: **no well-controlled evidence indicates specific family pattern plays a causative role in the development of schizophrenia. q High Expressed Emotion family : increase risk of relapse.

Weight of different RF: Family history comes first PLOS Medicine

Diagnosis # DSM-IV-TR Diagnostic Criteria for Schizophrenia: A- ≥ two characteristic symptoms of : 1 - Delusions 2 - Hallucinations 3 - Disorganized speech 4 - Disorganized behavior 5 - Negative symptoms

B- Social / Occupation dysfunction C- Duration of at least 6 months D- Schizoaffective & mood disorder exclusion E- Substance / General medical condition exclusion F- Relationship to pervasive developmental disorders

Subtypes of Schizophrenia Paranoid type Disorganized type Catatonic type Undifferentiated type Residual type

Clinical Features q. No clinical sign or symptom is pathognomonic for schizophrenia q. Patient's history & mental status examination are essential for diagnosis. q Premorbid history includes schizoid or schizotypal personalities, few friends & exclusion of social activities. q Prodromal features include obsessive compulsive behaviors

- Picture of schizophrenia includes positive and negative symptoms. - Positive symptoms like: delusions & hallucinations. - Negative symptoms like: affective flattening or blunting, poverty of speech, poor grooming, lack of motivation, and social withdrawal.

Cognitive deficits in schizophrenia

Mental status examination - Appearance & behavior ( variable presentations) - Mood, feelings & affect ( reduced emotional responsiveness, inappropriate emotion) - Perceptual disturbances ( hallucinations, illusions ) - Thought: *Form ( looseness of association, ward salad, neologisms) *stream ( thought blocking, poverty of thought content ) *content ( delusions) *possessions of thoughts ( thought insertion, withdrawal & broadcasting) - Impulsiveness, violence, suicide & homicide - poor cognitive functioning, poor abstraction. - Poor insight and judgment

Differential Diagnosis Nonpsychiatric disorders: Substance-induced disorders Epilepsy ( TLE) CNS diseases Trauma Others Psychiatric disorders: Schizophreniform disorder Brief psychotic disorder Delusional disorder Affective disorders Schizoaffective disorder Personality disorders ( schizoid, schizotypal & borderline personality) Malingering & Factitious disorders

Course & prognosis 25% will be able to lead somewhat normal live. 25% will continue to have episodic exacerbation & inter-episodic moderate residual impairment. 50 % will remain significantly impaired by their illness for their entire live. v. Schizophrenia has better prognosis in developing courtiers because of family relationships, informal economies, segregation of the mentally ill and community cohesion.

Prognosis Good P. F 1. Late age of onset 2. Acute onset 3. Obvious precipitating factors 4. Presence of mood component 5. Good response to Tx 6. Good supportive system (developing 1. 2. 3. 4. 5. 6. 7. 8. Poor P. F Young age of onset Insidious onset Lack of P. F. Multiple relapses Low IQ Poor premorbid personality Negative symptom Positive family history

Treatment What are the indications for hospitalization? Diagnostic purpose Patient & other's safety Initiating or stabilizing medications Establishing an effective association between patient & community supportive systems.

Biological therapies Antipsychotic medications are the mainstay of the treatment of schizophrenia. q Generally, they are safe. q Two major classes: -Dopamine receptor antagonists ( haloperidol, chlorpromazine ) -Serotonin-dopamine receptor antagonists ( Risperidone, clozapine, olanzapine ). q Depot forms of antipsychotics eg. Risperidone Consta is indicated for poorly compliant patients. q - Electroconvulsive therapy (ECT) for catatonic or poorly responding patients to medications. q q Other drugs: -Anticonvulsants -Benzodiazepines -Lithium

Pharmacolog ical Treatment Algorithm Adapted from the Maudsley prescribing Guidelines (Taylor et al, 2005)

Side effects of antipsychotics

Side effects of antipsychotics

Side effects of atypical antipsychotics

Metabolic effects of atypical antipsychotics

Psychosocial therapies Social skills training Family oriented therapies Group therapy Individual psychotherapy Assertive community treatment Vocational therapy

Other Psychotic Disorders due to a general medical condition (e. g Complex partial seizure (e. g. temporal lobe epilepsy, CNS infections, frontal lobe pathology. . ) q. Substance-induced psychotic disorder (e. g. amphetamine, cocaine …) Schizoaffective disorde(Concurrent presence of mood disturbance and schizophrenia features for ≥ 6 m: (there must be delusions or hallucinations, for at least two weeks in the absence of prominent mood symptoms during some phase of the illness).

Other Psychotic Disorders q Schizophreniform disorder (1 -6 m, a deterioration in social or vocational functioning is not required) q Brief psychotic disorder(<1 m) q Delusional disorder(>1 m), only non-bizzare delusion.

Outlines Etiology Clinical features & diagnosis. Differential diagnoses Course & Prognosis Treatment (Pharmacological) Treatment (Psychological )