CONTENTS• Introduction• Causes• Symptoms - Positive symptoms - Negative symptoms• Drug treatment• Mechanism of action• Adverse effects• Current trends in the treatment of schizophrenia.
Schizophrenia • Schizophrenia is a complex mental disorder that makes it difficult to- • Tell the differences between real and unreal experiences • Think logically • Have normal emotional responses • Behave normally in social situations
CAUSES• No one knows the exact cause of schizophrenia, but multiple possible factors have been discovered.• It is a complex illness, possibly due to the dysfunction of the mesolimbic or mesocortical dopaminergic neurons.• It has a strong genetic component.
SYMPTOMS• Delusions (strongly held beliefs that are not based on reality)• Hallucinations (Hearing or seeing things that are not there)• Disorganised speech• Disorganised behaviour• Irritable or tense feeling• Lack of emotion
NEGATIVE SYMPTOMS• Affective flattening (person’s range of emotional expression is clearly diminished)• Alogia (A poverty of speech)• Avolition (Inability to initiate and persist in gaol directed activities)
TYPES OF SCHIZOPHRENIA• There are five types of schizophrenia: 1.Paranoid- Person feels extremely suspicious, persecuted. 2.Disorganised- person is often incoherent but may not have delusions. 3.Catatonic- Person is withdrawn, mute, negative and often assumes very unusual postures.
4.Residual- person is no longer delusion orhallucinating, but has no motivation or interest in life. 5.Undifferentiated- does not fit in one of theabove categories because the patient suffers from symptoms of multiple types.
MECHANISM OF ACTION• Dopamine receptor blocking activity in the brain.• Serotonin receptor blocking activity in the brain.
ADVERSE EFFECTS• COMMON SIDE EFFECTS -Lethargy & drowsiness -Anticholinergic effects (dry mouth, blurred vision, constipation & retention of urine) -Postural Hypotension (Dizziness on standing up)
•MOVEMENT DISORDERS -Acute dystonia (muscle spasms) -Parkinsonism (tremors, stiff posture, immobile & expressionless face) -Akathisia (restless fidgeting and pacing)-Tardive dyskinesia (repetitive involuntarymuscle movements, lip-smacking and protrusion of tongue)
CURRENT TRENDS IN THETREATMENT OF SCHIZOPHRENIA • Antipsychotic effects of novel compounds • Partial dopamine agonists • Acetylcholinesterase inhibitors in schizophreni • COX-2 inhibitors as an adjunctive treatment for schizophrenia • Human stem cells in the treatment of schizophrenia
ANTIPSYCHOTIC EFFECTS OF NOVEL COMPOUNDS• The two new receptors which have been implicated in the pathophysiology of schizophrenia are 5HT2 and neurotensin-1 receptors.• Eplivanserine is a 5HT2 receptor antagonist. Antagonism of this receptor appears to regulate dopaminergic activity, and this compound appears to reverse amphetamine induced inhibition of A-10 dopaminergic cells.• SR46349B is a neurotensin-1 receptor antagonist that appears to diminish the spontaneous activity of dopaminergic neurons.• Both these drugs were effective in treating the negative and depressive symptoms as well.
PARTIAL DOPAMINE AGONISTS• The dopaminergic hypothesis of schizophrenia indicates that in this condition there is a both hyperdopaminergic state in the cortical mesolimbic tract (causing positive symptoms) and a hypodopaminergic state in the mesocortical tract (causing negative symptoms).• The full agonist allows full neurotransmitter activity at the synaptic site .• An antagonist, when bound to the receptor allows no receptor activity. In contrast, a partial agonist will allow some neurotransmitter activity when bound to the receptor.• Ariprazole is a dopamine partial agonist that has recently been approved in the United States. It is 10 times more potent than other drugs.
ACETYLCHOLINESTERASE INHIBITORS IN SCHIZOPHRENIA• Neurotransmitters implicated in the pathogenesis of schizophrenia have included dopamine, serotonin, glutamine and acetylcholine.• Cognitive impairment in schizophrenia may at least partially due to diminished acetylcholine activity in the cortex.• Donepezil is an acetylcholinesterase inhibitor that appears to enhance cognitive functioning in patients with schizophrenia.
COX-2 INHIBITORS AS AN ADJUNCTIVE TREATMENT FOR SCHIZOPHRENIA• Recently, increased attention has been paid to the interface between the immune system and the treatment of schizophrenia.• When the mentally ill group was afflicted with an infection, half showed improvements in their psychotic symptoms.• It is believed that there may be an imbalance between the type1 and type2 immune systems in patients with psychosis.• Schizophrenic patients who are treatment-resistant appear to have an increase in interleukin-6 level, which is a part of type1 system.• COX-2 inhibitor Celecoxib is an inhibitor of prostaglandin E2 and IL-6 which was found to restore the imbalance between the type1 and type2 immune systems.
HUMAN STEM CELLS IN THE TREATMENT OF SCHIZOPHRENIA• The National Institutes of Health states that stem cell “have the remarkable potential to develop into many different cells types in the body during early life and growth”.• The stem cells can be coaxed to become brain cells such as neurons. Because they have the DISC1 mutation, they stand to play an important role in the screening of drugs for treatments of major mental illnesses such as schizophrenia.• Inspite of holding the key to an effective treatment, the stem cell research may not work for the disorder as they are still not exactly sure what goes wrong in the schizophrenic brain.
REFERENCES• Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM. Second- generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. Lancet. 2009;373:31-41. Epub 2008 Dec 6. [PubMed]• Psych Central, National Mental Health Association, National Institute for Mental Health, National Alliance for the Mentally Ill, Internet Mental Health.• Kostic D, Manos G, Stock E, et al. Long-term effects of aripiprazole on the negative symptoms of schizophrenia. J Eur Coll Neuropsychopharmacol. 2003;13(supp 4):S328.• Marder SR, McQuade RD, Stock E, et al. Aripiprazole in the treatment of schizophrenia: safety and tolerability in short-term, placebo-controlled trials. Schizophr Res. 2003;61:123-126.