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Schizophrenia

Schizophrenia is a chronic mental health disorder characterized by the presence of psychotic symptoms Psychotic symptoms Brief Psychotic Disorder such as delusions or hallucinations. The signs and symptoms of schizophrenia are traditionally separated into 2 groups: positive (delusions, hallucinations, and disorganized speech or behavior) and negative (flat affect, avolition, anhedonia, poor attention Attention Focusing on certain aspects of current experience to the exclusion of others. It is the act of heeding or taking notice or concentrating. Psychiatric Assessment, and alogia). Schizophrenia is associated with a decline in both cognitive and social functioning that often precedes the development of florid psychosis. The exact etiology of schizophrenia is unknown, although it is thought to be linked to an increase in dopaminergic activity. Treatment includes antipsychotics in conjunction with behavioral therapy.

Last updated: Nov 17, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Epidemiology and Etiology

Definition

Schizophrenia is a chronic serious mental disorder characterized by loss of contact with reality and manifested by two main symptoms: hallucinations and delusions.

  • Should be distinguished from neuroses: less serious mental disorders that cause a sense of distress and deficit in functioning, and are characterized by anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder, depression, or other feelings of distress that are out of proportion to the circumstances of a person’s life
  • Also commonly confused with dissociative identity disorder Dissociative identity disorder Dissociative identity disorder (DID) is a psychiatric condition marked by the presence of ≥ 2 distinct personality identities in a patient, with each personality having their own memories. The patient switches between personalities rapidly, especially under stress. It is associated with a history of childhood trauma or abuse. Dissociative Identity Disorder (DID), previously known as multiple personality disorder (MPD), or commonly called “split personality”

Epidemiology

  • Affects 20 million people worldwide
  • Lifetime prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency of approximately 0.50% in the United States and globally
  • Men and women are equally affected, but with a slight difference in the age of onset
    • Men: average age of onset = 23 years 
    • Women: average age of onset = 26 years

Etiology

  • No single etiological factor is responsible for schizophrenia, a syndrome comprising multiple diseases that present with similar signs and symptoms.
  • The disorder manifests when a person with genetic predisposition is exposed to one of many environmental stressors.
  • Genetic predisposition:
    • Affected first-degree relative = 10% risk
    • Affected monozygotic twin = 48% risk
    • Affected dizygotic twin = 14% risk
    • Offspring with 2 affected parents = 40% risk
  • Environmental stressors are believed to be triggers of schizophrenia rather than true causes of the disorder.
    • Childhood trauma
    • Residence in an urban area
    • Social isolation
    • Frequent cannabis use in early adolescence 
    • Migration
    • Poverty
    • Stress and psychosocial factors 
    • Birth in late winter Winter Pityriasis Rosea or early spring
    • Advanced paternal age at conception

Pathophysiology

Genetic and environmental risk factors appear to act via a common pathway Common pathway Hemostasis of disrupting the function of 1 or more neurotransmitter components.

  • Dopaminergic theory:
    • Almost all drugs with antipsychotic Antipsychotic Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics properties block the dopaminergic D2 receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors.
    • However, antipsychotics are only 70% effective and clozapine Clozapine A tricyclic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2a/2c receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. Second-Generation Antipsychotics, the most effective antipsychotic Antipsychotic Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics for treating schizophrenia, is a weak D2 antagonist.
    • Hyperactivity Hyperactivity Attention Deficit Hyperactivity Disorder of dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS D2 receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors neurotransmission Neurotransmission The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across electrical synapses. Synapses and Neurotransmission in subcortical, and limbic brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification regions contribute to the positive symptoms of schizophrenia.
    • Hypofunctionality of dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS D1 receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors neurotransmission Neurotransmission The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across electrical synapses. Synapses and Neurotransmission in the prefrontal cortex contributes to both negative and cognitive symptoms.
  • Other theories:
    • Hypofunction of the N-methyl-D-aspartate (NMDA) glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors  
    • Dysfunctional gamma-amino-butyric acid ( GABA GABA The most common inhibitory neurotransmitter in the central nervous system. Receptors and Neurotransmitters of the CNS) interneurons
    • Dysfunctional nicotinic acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors
Table: Dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS pathways and their roles in schizophrenia
Dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS pathways Normal function Role in schizophrenia Effects/side effects of antipsychotics
Mesolimbic pathway Role in motivation, emotions, reward Overactivity results in positive symptoms Improvement of positive symptoms
Mesocortical pathway Cognition, executive function, emotions and affect Underactivity results in negative symptoms Worsening of negative symptoms
Nigrostriatal pathway Nigrostriatal pathway Basal Ganglia: Anatomy Control of extrapyramidal system, purposeful motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology planning No direct role in the etiology of schizophrenia Extrapyramidal symptoms Extrapyramidal Symptoms Ataxia-telangiectasia
Tuberoinfundibular pathway Inhibits prolactin Prolactin A lactogenic hormone secreted by the adenohypophysis. It is a polypeptide of approximately 23 kd. Besides its major action on lactation, in some species prolactin exerts effects on reproduction, maternal behavior, fat metabolism, immunomodulation and osmoregulation. Breasts: Anatomy release No direct role in the etiology of schizophrenia Hyperprolactinemia Hyperprolactinemia Hyperprolactinemia is defined as a condition of elevated levels of prolactin (PRL) hormone in the blood. The PRL hormone is secreted by the anterior pituitary gland and is responsible for breast development and lactation. The most common cause is PRL-secreting pituitary adenomas (prolactinomas). Hyperprolactinemia

Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with schizophrenia also have physical abnormalities of the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification tissue, which can be seen in neuroimaging Neuroimaging Non-invasive methods of visualizing the central nervous system, especially the brain, by various imaging modalities. Febrile Infant studies. 

  • Loss of cortical tissue volume, including the limbic system Limbic system The limbic system is a neuronal network that mediates emotion and motivation, while also playing a role in learning and memory. The extended neural network is vital to numerous basic psychological functions and plays an invaluable role in processing and responding to environmental stimuli. Limbic System: Anatomy, prefrontal cortex, thalamus Thalamus The thalamus is a large, ovoid structure in the dorsal part of the diencephalon that is located between the cerebral cortex and midbrain. It consists of several interconnected nuclei of grey matter separated by the laminae of white matter. The thalamus is the main conductor of information that passes between the cerebral cortex and the periphery, spinal cord, or brain stem. Thalamus: Anatomy, hippocampus, and amygdala Amygdala Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the temporal lobe. The amygdala is part of the limbic system. Limbic System: Anatomy
  • Ventricular enlargement (third and lateral)
  • Decreased symmetry
  • Hypoactivity of the frontal Frontal The bone that forms the frontal aspect of the skull. Its flat part forms the forehead, articulating inferiorly with the nasal bone and the cheek bone on each side of the face. Skull: Anatomy lobes and hyperactivity Hyperactivity Attention Deficit Hyperactivity Disorder of the basal ganglia Basal Ganglia Basal ganglia are a group of subcortical nuclear agglomerations involved in movement, and are located deep to the cerebral hemispheres. Basal ganglia include the striatum (caudate nucleus and putamen), globus pallidus, substantia nigra, and subthalamic nucleus. Basal Ganglia: Anatomy

Clinical Presentation

  • Impairment of thoughts and affect, characterized by a distorted perception Perception The process by which the nature and meaning of sensory stimuli are recognized and interpreted. Psychiatric Assessment of reality
  • The impairments are severe enough to affect the patient’s ability to participate in social events or to form relationships. 
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with schizophrenia often lack awareness about their illness ( insight Insight Psychiatric Assessment). 
  • Co-existing substance abuse and dependence is common (“dual diagnosis”).
  • Symptoms can be classified into premorbid, positive, negative, and cognitive (see table below).
Table: Classification of symptoms
Symptom Notes
Premorbid
  • Appear before the onset of the first episode of schizophrenia
  • Include social withdrawal and paranoid thoughts
  • The first psychotic episode can occur without warning (asymptomatic premorbid period).
Positive (psychotic phase)
  • Easy to recognize
  • Delusions:
  • Hallucinations:
    • Perceptual abnormalities in which sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology experiences occur in the absence of external stimuli
    • Can be auditory (most common), visual, somatic, gustatory, and olfactory
  • Illusions: distinguished from hallucinations by the presence of a real external stimuli that is simply misinterpreted by the patient
  • Disorganized speech and/or behavior: can include neologisms, echolalia, flight of ideas, pressured speech, loose associations, among others
Negative (residual phase)
  • Potentially difficult to recognize because of similarities to depression
  • Flat affect (diminished emotional expression)
  • Avolition (lack of initiative)
  • Alogia (poverty of speech)
  • Poor attention Attention Focusing on certain aspects of current experience to the exclusion of others. It is the act of heeding or taking notice or concentrating. Psychiatric Assessment
  • Anhedonia
Cognitive
  • Usually nonspecific; related to the impact on patient’s quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement of life
  • Poor executive functioning, represented by disorganized speech and/or thought that results in impaired communication Communication The exchange or transmission of ideas, attitudes, or beliefs between individuals or groups. Decision-making Capacity and Legal Competence
  • Inattention Inattention Attention Deficit Hyperactivity Disorder
  • Impaired memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment

Mnemonic

To recall the negative symptoms of schizophrenia, remember the 5 As:

Diagnosis

Diagnosis is made by clinical observations based on the type of symptoms presented, their severity and duration, and how the patient’s life is affected by their presence.

  • A total duration of symptoms of at least 6 months, including a period of positive symptoms lasting at least 1 month
  • The presence of a mix of positive and/or negative symptoms, especially delusions, hallucinations, disorganized speech, or grossly disorganized or catatonic behavior
  • The presence of these symptoms must disturb the patient’s daily functioning, including the social, personal, and professional areas of life. 
  • Other conditions must be ruled out to make a definitive diagnosis:
    • Schizoaffective, brief psychotic, and schizoaffective disorders
    • Mood disorders (e.g., major depressive disorder Major depressive disorder Major depressive disorder (MDD), commonly called depression, is a unipolar mood disorder characterized by persistent low mood and loss of interest in association with somatic symptoms for a duration of ≥ 2 weeks. Major depressive disorder has the highest lifetime prevalence among all psychiatric disorders. Major Depressive Disorder, bipolar disorder Bipolar disorder Bipolar disorder is a highly recurrent psychiatric illness characterized by periods of manic/hypomanic features (distractibility, impulsivity, increased activity, decreased sleep, talkativeness, grandiosity, flight of ideas) with or without depressive symptoms. Bipolar Disorder)
    • Substance abuse (requiring urine and blood toxicology tests)

Management and Prognosis

Pharmacological

Antipsychotic Antipsychotic Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics medications form the centerpiece of treatment for schizophrenia, especially the positive symptoms. Only caroprazine has been shown to have significant effects on negative symptoms. The choice of a specific agent is mostly based on the adverse effect profile, required route of administration, and the patient’s previous response to the drug. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who respond usually show the most rapid improvement in the 1st 2 weeks and will often continue to improve during the following weeks. While there is a wide variety of mechanisms of action, most antipsychotics block postsynaptic dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors.

1st-generation antipsychotics ( FGAs FGAs Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics):

  • Older medications (before 1989) 
  • Dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors antagonist 
  • Common side effects: EPS (which may become irreversible), hyperprolactinemia Hyperprolactinemia Hyperprolactinemia is defined as a condition of elevated levels of prolactin (PRL) hormone in the blood. The PRL hormone is secreted by the anterior pituitary gland and is responsible for breast development and lactation. The most common cause is PRL-secreting pituitary adenomas (prolactinomas). Hyperprolactinemia, neuroleptic malignant syndrome Neuroleptic malignant syndrome Neuroleptic malignant syndrome (NMS) is a rare, idiosyncratic, and potentially life-threatening reaction to antipsychotic drugs. Neuroleptic malignant syndrome presents with ≥ 2 of the following cardinal symptoms: fever, altered mental status, muscle rigidity, and autonomic dysfunction. Neuroleptic Malignant Syndrome, QT prolongation, sudden death, and an increased risk of mortality Mortality All deaths reported in a given population. Measures of Health Status in older adult patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders
  • Examples: haloperidol Haloperidol A phenyl-piperidinyl-butyrophenone that is used primarily to treat schizophrenia and other psychoses. It is also used in schizoaffective disorder, delusional disorders, ballism, and tourette syndrome (a drug of choice) and occasionally as adjunctive therapy in intellectual disability and the chorea of huntington disease. It is a potent antiemetic and is used in the treatment of intractable hiccups. First-Generation Antipsychotics, fluphenazine Fluphenazine A phenothiazine used in the treatment of psychoses. Its properties and uses are generally similar to those of chlorpromazine. First-Generation Antipsychotics, chlorpromazine Chlorpromazine The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine’s antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup. First-Generation Antipsychotics

2nd-generation (atypical) antipsychotics ( SGAs SGAs Second-generation antipsychotics (SGA) are also called atypical antipsychotics. Medications in this class include aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, iloperidone, lumateperone, lurasidone, olanzapine, paliperidone, pimavanserin, quetiapine, risperidone, and ziprasidone. Second-Generation Antipsychotics):

  • Newer medications, starting with clozapine Clozapine A tricyclic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2a/2c receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. Second-Generation Antipsychotics (approved in 1989)
  • Associated with a lower risk for EPS compared with FGAs FGAs Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics and therefore the 1st-line drugs to use (although the risk of metabolic syndrome Metabolic syndrome Metabolic syndrome is a cluster of conditions that significantly increases the risk for several secondary diseases, notably cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver. In general, it is agreed that hypertension, insulin resistance/hyperglycemia, and hyperlipidemia, along with central obesity, are components of the metabolic syndrome. Metabolic Syndrome is increased with SGAs SGAs Second-generation antipsychotics (SGA) are also called atypical antipsychotics. Medications in this class include aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, iloperidone, lumateperone, lurasidone, olanzapine, paliperidone, pimavanserin, quetiapine, risperidone, and ziprasidone. Second-Generation Antipsychotics)
  • The decreased risk for EPS is the most important distinction from FGAs FGAs Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics, as the pharmacologic properties, therapeutic effects, and adverse effects are not distinct between the 2 groups.
  • Serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS and dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS antagonists 
  • Common side effects: metabolic syndrome Metabolic syndrome Metabolic syndrome is a cluster of conditions that significantly increases the risk for several secondary diseases, notably cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver. In general, it is agreed that hypertension, insulin resistance/hyperglycemia, and hyperlipidemia, along with central obesity, are components of the metabolic syndrome. Metabolic Syndrome, hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension, sedation, anticholinergic Anticholinergic Anticholinergic drugs block the effect of the neurotransmitter acetylcholine at the muscarinic receptors in the central and peripheral nervous systems. Anticholinergic agents inhibit the parasympathetic nervous system, resulting in effects on the smooth muscle in the respiratory tract, vascular system, urinary tract, GI tract, and pupils of the eyes. Anticholinergic Drugs symptoms, hyperprolactinemia Hyperprolactinemia Hyperprolactinemia is defined as a condition of elevated levels of prolactin (PRL) hormone in the blood. The PRL hormone is secreted by the anterior pituitary gland and is responsible for breast development and lactation. The most common cause is PRL-secreting pituitary adenomas (prolactinomas). Hyperprolactinemia, EPS, cardiac effects, cardiomyopathies Cardiomyopathies A group of diseases in which the dominant feature is the involvement of the cardiac muscle itself. Cardiomyopathies are classified according to their predominant pathophysiological features (dilated cardiomyopathy; hypertrophic cardiomyopathy; restrictive cardiomyopathy) or their etiological/pathological factors (cardiomyopathy, alcoholic; endocardial fibroelastosis). Cardiomyopathy: Overview and Types, cataracts, and sexual dysfunction Sexual dysfunction Physiological disturbances in normal sexual performance in either the male or the female. Sexual Physiology
  • Examples: risperidone Risperidone A selective blocker of dopamine D2 receptors and serotonin 5-HT2 receptors that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of schizophrenia. Second-Generation Antipsychotics, aripiprazole Aripiprazole A piperazine and quinolone derivative that is used primarily as an antipsychotic agent. It is a partial agonist of serotonin receptor, 5-HT1a and dopamine D2 receptors, where it also functions as a postsynaptic antagonist, and an antagonist of serotonin receptor, 5-HT2a. It is used for the treatment of schizophrenia and bipolar disorder, and as an adjunct therapy for the treatment of depression. Second-Generation Antipsychotics, quetiapine Quetiapine A dibenzothiazepine and antipsychotic agent that targets the serotonin 5-HT2 receptor; histamine h1 receptor, adrenergic alpha1 and alpha2 receptors, as well as the dopamine d1 receptor and dopamine D2 receptor. It is used in the treatment of schizophrenia; bipolar disorder and depressive disorder. Second-Generation Antipsychotics, olanzapine Olanzapine A benzodiazepine derivative that binds serotonin receptors; muscarinic receptors; histamine h1 receptors; adrenergic alpha-1 receptors; and dopamine receptors. It is an antipsychotic agent used in the treatment of schizophrenia; bipolar disorder; and major depressive disorder; it may also reduce nausea and vomiting in patients undergoing chemotherapy. Second-Generation Antipsychotics, ziprasidone Ziprasidone Second-Generation Antipsychotics, clozapine Clozapine A tricyclic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2a/2c receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. Second-Generation Antipsychotics
Table: Treatment considerations
Condition Treatment considerations
Acute psychosis
  • Requires immediate attention Attention Focusing on certain aspects of current experience to the exclusion of others. It is the act of heeding or taking notice or concentrating. Psychiatric Assessment
  • Use oral antipsychotic Antipsychotic Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics and benzodiazepine (may require intramuscular due to noncompliance Noncompliance Clinician–Patient Relationship or for more rapid effect).
  • Usually lasts 4–6 weeks
Maintenance phase
  • Obtain laboratory tests: CBC (including differential if clozapine Clozapine A tricyclic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2a/2c receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. Second-Generation Antipsychotics used), electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes, fasting glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance, lipid profile Lipid profile Lipid Disorders, liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, renal and thyroid function tests Thyroid Function Tests Blood tests used to evaluate the functioning of the thyroid gland. Ion Channel Myopathy, and a pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care test in females of fertile age
  • ECG ECG An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG) if history of heart disease or if using drugs that may prolong the QT interval QT interval Electrocardiogram (ECG) ( clozapine Clozapine A tricyclic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2a/2c receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. Second-Generation Antipsychotics, thioridazine Thioridazine A phenothiazine antipsychotic used in the management of psychosis, including schizophrenia. First-Generation Antipsychotics, iloperidone Iloperidone Second-Generation Antipsychotics, ziprasidone Ziprasidone Second-Generation Antipsychotics)
  • Monitor for the 1st few weeks and then regularly for involuntary movement disorders/EPS, since they may become irreversible.
  • Goal is to minimize symptoms, avoid relapses, and promote recovery that allows integration into society.
  • Minimize side effect profile.
  • Recommended maintenance treatment is > 5 years.
  • May use long-acting injectable antipsychotics for non-compliant patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship after checking for tolerability/efficacy with oral agent
Poor responders
  • Roughly 40% of treated patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship will demonstrate positive symptoms that are resistant to treatment.
  • Assess proper dosage Dosage Dosage Calculation and duration of treatment.
  • Do not use 2 antipsychotics at the same time as studies show no benefits.
  • Consider use of clozapine Clozapine A tricyclic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2a/2c receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. Second-Generation Antipsychotics, which can be an effective treatment in persons with schizophrenia that is resistant to treatment with other antipsychotic Antipsychotic Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics drugs; also reduces suicide Suicide Suicide is one of the leading causes of death worldwide. Patients with chronic medical conditions or psychiatric disorders are at increased risk of suicidal ideation, attempt, and/or completion. The patient assessment of suicide risk is very important as it may help to prevent a serious suicide attempt, which may result in death. Suicide risk. However, clozapine Clozapine A tricyclic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2a/2c receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. Second-Generation Antipsychotics is associated with a risk for agranulocytosis Agranulocytosis A decrease in the number of granulocytes; (basophils; eosinophils; and neutrophils). Lincosamides and requires frequent, intense blood monitoring.
Table: Side effects
Side effect Definition/treatment
EPS
  • Movement disorders secondary to drugs that block dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors
  • Movement phenotypes include: dystonia Dystonia Dystonia is a hyperkinetic movement disorder characterized by the involuntary contraction of muscles, resulting in abnormal postures or twisting and repetitive movements. Dystonia can present in various ways as may affect many different skeletal muscle groups. Dystonia (involuntary muscle contractions), akathisia (inner restlessness), parkinsonism Parkinsonism West Nile Virus
  • Treatment options include decreasing dosage Dosage Dosage Calculation, changing to a drug having a lower risk of EPS, or adding an antimuscarinic agent such as benztropine Benztropine A centrally active muscarinic antagonist that has been used in the symptomatic treatment of parkinson disease. Benztropine also inhibits the uptake of dopamine. Anticholinergic Drugs or diphenhydramine Diphenhydramine A histamine h1 antagonist used as an antiemetic, antitussive, for dermatoses and pruritus, for hypersensitivity reactions, as a hypnotic, an antiparkinson, and as an ingredient in common cold preparations. It has some undesired antimuscarinic and sedative effects. Antihistamines; propanolol and benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines are also used, and botulinum toxin Botulinum toxin Toxic proteins produced from the species Clostridium botulinum. The toxins are synthesized as a single peptide chain which is processed into a mature protein consisting of a heavy chain and light chain joined via a disulfide bond. The botulinum toxin light chain is a zinc-dependent protease which is released from the heavy chain upon endocytosis into presynaptic nerve endings. Once inside the cell the botulinum toxin light chain cleaves specific snare proteins which are essential for secretion of acetylcholine by synaptic vesicles. This inhibition of acetylcholine release results in muscular paralysis. Botulism injections are used for focal dystonia Dystonia Dystonia is a hyperkinetic movement disorder characterized by the involuntary contraction of muscles, resulting in abnormal postures or twisting and repetitive movements. Dystonia can present in various ways as may affect many different skeletal muscle groups. Dystonia.
Tardive dyskinesia
  • A subset of EPS
  • Associated with long-term treatment with 1st-generation antipsychotics
  • Movement phenotypes include: torticollis Torticollis A symptom, not a disease, of a twisted neck. In most instances, the head is tipped toward one side and the chin rotated toward the other. The involuntary muscle contractions in the neck region of patients with torticollis can be due to congenital defects, trauma, inflammation, tumors, and neurological or other factors. Cranial Nerve Palsies (involuntary contraction of neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess muscle, causing head tilt), dystonia Dystonia Dystonia is a hyperkinetic movement disorder characterized by the involuntary contraction of muscles, resulting in abnormal postures or twisting and repetitive movements. Dystonia can present in various ways as may affect many different skeletal muscle groups. Dystonia of lips Lips The lips are the soft and movable most external parts of the oral cavity. The blood supply of the lips originates from the external carotid artery, and the innervation is through cranial nerves. Lips and Tongue: Anatomy, tongue Tongue The tongue, on the other hand, is a complex muscular structure that permits tasting and facilitates the process of mastication and communication. The blood supply of the tongue originates from the external carotid artery, and the innervation is through cranial nerves. Lips and Tongue: Anatomy, oromandibular, or pharynx Pharynx The pharynx is a component of the digestive system that lies posterior to the nasal cavity, oral cavity, and larynx. The pharynx can be divided into the oropharynx, nasopharynx, and laryngopharynx. Pharyngeal muscles play an integral role in vital processes such as breathing, swallowing, and speaking. Pharynx: Anatomy
  • Treatment includes drugs (valbenazine and deutetrabenazine) that block vesicular monoamine transporter 2 protein, which then prevents presynaptic dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS release; injection of botulinum toxin Botulinum toxin Toxic proteins produced from the species Clostridium botulinum. The toxins are synthesized as a single peptide chain which is processed into a mature protein consisting of a heavy chain and light chain joined via a disulfide bond. The botulinum toxin light chain is a zinc-dependent protease which is released from the heavy chain upon endocytosis into presynaptic nerve endings. Once inside the cell the botulinum toxin light chain cleaves specific snare proteins which are essential for secretion of acetylcholine by synaptic vesicles. This inhibition of acetylcholine release results in muscular paralysis. Botulism is also used.
Elevated prolactin Prolactin A lactogenic hormone secreted by the adenohypophysis. It is a polypeptide of approximately 23 kd. Besides its major action on lactation, in some species prolactin exerts effects on reproduction, maternal behavior, fat metabolism, immunomodulation and osmoregulation. Breasts: Anatomy
  • Caused by almost all antipsychotics
  • Can result in irregular menses Menses The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle, galactorrhea Galactorrhea Excessive or inappropriate lactation in females or males, and not necessarily related to pregnancy. Galactorrhea can occur either unilaterally or bilaterally, and be profuse or sparse. Its most common cause is hyperprolactinemia. Hyperprolactinemia, and sexual dysfunction Sexual dysfunction Physiological disturbances in normal sexual performance in either the male or the female. Sexual Physiology.
  • Treatment includes dosage Dosage Dosage Calculation reduction/medication changes.
Metabolic
  • Weight gain, hyperlipidemia, hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus, and hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension → increased cardiovascular risk
  • Treatment: Change from high-risk drug (e.g., olanzapine Olanzapine A benzodiazepine derivative that binds serotonin receptors; muscarinic receptors; histamine h1 receptors; adrenergic alpha-1 receptors; and dopamine receptors. It is an antipsychotic agent used in the treatment of schizophrenia; bipolar disorder; and major depressive disorder; it may also reduce nausea and vomiting in patients undergoing chemotherapy. Second-Generation Antipsychotics, quetiapine Quetiapine A dibenzothiazepine and antipsychotic agent that targets the serotonin 5-HT2 receptor; histamine h1 receptor, adrenergic alpha1 and alpha2 receptors, as well as the dopamine d1 receptor and dopamine D2 receptor. It is used in the treatment of schizophrenia; bipolar disorder and depressive disorder. Second-Generation Antipsychotics, risperidone Risperidone A selective blocker of dopamine D2 receptors and serotonin 5-HT2 receptors that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of schizophrenia. Second-Generation Antipsychotics) to an antipsychotic Antipsychotic Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics with lower metabolic risk (e.g., aripiprazole Aripiprazole A piperazine and quinolone derivative that is used primarily as an antipsychotic agent. It is a partial agonist of serotonin receptor, 5-HT1a and dopamine D2 receptors, where it also functions as a postsynaptic antagonist, and an antagonist of serotonin receptor, 5-HT2a. It is used for the treatment of schizophrenia and bipolar disorder, and as an adjunct therapy for the treatment of depression. Second-Generation Antipsychotics or ziprasidone Ziprasidone Second-Generation Antipsychotics) if possible.
  • Monitor and treat each cardiovascular risk factor appropriately.
Neuroleptic malignant syndrome Neuroleptic malignant syndrome Neuroleptic malignant syndrome (NMS) is a rare, idiosyncratic, and potentially life-threatening reaction to antipsychotic drugs. Neuroleptic malignant syndrome presents with ≥ 2 of the following cardinal symptoms: fever, altered mental status, muscle rigidity, and autonomic dysfunction. Neuroleptic Malignant Syndrome
  • Idiosyncratic reaction Idiosyncratic Reaction Neuroleptic Malignant Syndrome to antipsychotics
  • This is a life-threatening emergency.
  • Symptoms include at least 2 of the following cardinal symptoms: fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, altered mental status Altered Mental Status Sepsis in Children, muscle rigidity Muscle rigidity Continuous involuntary sustained muscle contraction which is often a manifestation of basal ganglia diseases. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity. Motor Neuron Lesions, and autonomic dysfunction Autonomic Dysfunction Anterior Cord Syndrome
  • Treatment includes immediate discontinuation of the antipsychotic Antipsychotic Antipsychotics, also called neuroleptics, are used to treat psychotic disorders and alleviate agitation, mania, and aggression. Antipsychotics are notable for their use in treating schizophrenia and bipolar disorder and are divided into 1st-generation antipsychotics (FGAs) and atypical or 2nd-generation antipsychotics. First-Generation Antipsychotics medication and aggressive supportive care.

Nonpharmacological (adjunct)

Nonpharmacological treatments are known to be partially effective in treating the negative and cognitive symptoms of the disorder and increase patient adherence to medications.

  • Hospitalization Hospitalization The confinement of a patient in a hospital. Delirium:
    • May be required to ensure safety of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
    • In certain cases, isolation may be required for a short period of time.
  • Psychosocial therapy:
    • Cognitive-behavioral therapy Cognitive-behavioral therapy Cognitive-behavioral therapy corrects faulty assumptions and tries to replace maladaptive behavior with healthier alternatives. Psychotherapy
    • Compliance Compliance Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. Veins: Histology therapy
    • Individual psychotherapy Psychotherapy Psychotherapy is interpersonal treatment based on the understanding of psychological principles and mechanisms of mental disease. The treatment approach is often individualized, depending on the psychiatric condition(s) or circumstance. Psychotherapy
    • Group therapy Group therapy A form of therapy in which two or more patients participate under the guidance of one or more psychotherapists for the purpose of treating emotional disturbances, social maladjustments, and psychotic states. Psychotherapy
  • Electroconvulsive therapy Electroconvulsive therapy Electrically induced convulsions primarily used in the treatment of severe affective disorders and schizophrenia. Major Depressive Disorder (ECT): mostly treatment-resistant cases for augmentation to pharmacotherapy

Prognostic factors

Table: Positive and negative prognostic factors in schizophrenia
Associated with better outcome Associated with worse outcome
Late onset Early onset
Good social support Poor social support
Positive symptoms Negative symptoms
Negative family history Family History Adult Health Maintenance Positive family history Family History Adult Health Maintenance
Mood symptoms No mood symptoms
Sudden onset Gradual onset
Female gender Gender Gender Dysphoria Male gender Gender Gender Dysphoria
Fewer relapses Many relapses
Good premorbid condition (education, work) Poor premorbid condition (no education, no work)

Differential Diagnosis

The following conditions are differential diagnoses for schizophrenia:

  • Brief psychotic disorder Brief psychotic disorder Brief psychotic disorder is the presence of 1 or more psychotic symptoms lasting more than 1 day and less than 1 month. An episode is often stress-related with a sudden onset, and the patient fully returns to baseline functioning after an episode. Brief Psychotic Disorder: defined as the presence of one or more psychotic symptoms Psychotic symptoms Brief Psychotic Disorder lasting > 1 day and < 1 month. Characterized by a sudden onset, often with a specific trigger Trigger The type of signal that initiates the inspiratory phase by the ventilator Invasive Mechanical Ventilation, and associated with a return to full function. The main distinguishing factor is the duration of symptoms.
  • Schizophreniform disorder: a disorder in which the patient meets the criteria of schizophrenia, with symptoms lasting 1–6 months. The disorder has a much better prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas than schizophrenia. The main distinguishing factor is the duration of symptoms.
  • Schizoaffective disorder Schizoaffective disorder Schizoaffective disorder is a mental disorder that is marked by 2 components: a psychotic component (hallucinations or delusions) and a mood component (mania or depression). Patients must therefore meet the diagnostic criteria for both major mood disorder and schizophrenia. Schizoaffective Disorder: a disorder with features of both affective disorders and schizophrenia. Symptoms of depression or mania Mania A state of elevated excitement with over-activity sometimes accompanied with psychotic symptoms (e.g., psychomotor agitation, inflated self esteem and flight of ideas). It is often associated with mental disorders (e.g., cyclothymic disorder; and bipolar diseases). Bipolar Disorder should be concurrent with features from the criterion of schizophrenia. Schizoaffective disorder Schizoaffective disorder Schizoaffective disorder is a mental disorder that is marked by 2 components: a psychotic component (hallucinations or delusions) and a mood component (mania or depression). Patients must therefore meet the diagnostic criteria for both major mood disorder and schizophrenia. Schizoaffective Disorder excludes patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with separate episodes of schizophrenia and affective disorders. It does, however, require a 2-week period whereby psychotic symptoms Psychotic symptoms Brief Psychotic Disorder exist in the absence of affective symptoms. 
  • Delusional disorder Delusional disorder In delusional disorder, the patient suffers from 1 or more delusions for a duration of 1 month or more, without any other psychotic symptoms or behavioral changes and no decline in functioning abilities. Delusional Disorder: a disorder in which patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship suffer from 1 or more delusions for at least 1 month without any other psychotic symptoms Psychotic symptoms Brief Psychotic Disorder or behavioral changes and no decline in functioning abilities. 
  • Substance-induced psychotic disorder: Alcohol, stimulants Stimulants Stimulants are used by the general public to increase alertness and energy, decrease fatigue, and promote mental focus. Stimulants have medical uses for individuals with ADHD and sleep disorders, and are also used in combination with analgesics in pain management. Stimulants, hallucinogens, and steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors can all prompt psychotic episodes. A detailed history relating to onset, duration, and cessation of symptoms in relation to drug or alcohol use must be taken.
  • Psychotic disorder due to a general medical condition: Organic disorders of the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification (variant Creutzfeldt-Jakob disease Creutzfeldt-Jakob Disease A rare transmissible encephalopathy most prevalent between the ages of 50 and 70 years. Affected individuals may present with sleep disturbances, personality changes, ataxia; aphasia, visual loss, weakness, muscle atrophy, myoclonus, progressive dementia, and death within one year of disease onset. A familial form exhibiting autosomal dominant inheritance and a new variant cjd (potentially associated with bovine spongiform encephalopathy) have been described. Pathological features include prominent cerebellar and cerebral cortical spongiform degeneration and the presence of prions. Transmissible Spongiform Encephalopathies, head injury, encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis, meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis, central nervous system Central nervous system The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. Nervous System: Anatomy, Structure, and Classification tumors), as well as metabolic and endocrine disorders (Cushing’s syndrome, hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism, hypernatremia Hypernatremia Hypernatremia is an elevated serum sodium concentration > 145 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled by the hypothalamus via the thirst mechanism and antidiuretic hormone (ADH) release. Hypernatremia occurs either from a lack of access to water or an excessive intake of sodium. Hypernatremia), can mimic symptoms of schizophrenia.
  • Mood disorders with psychotic features: Psychotic features are mood-congruent and preceded by a clinical picture dominated by symptoms of a mood disorder, including major depressive disorder Major depressive disorder Major depressive disorder (MDD), commonly called depression, is a unipolar mood disorder characterized by persistent low mood and loss of interest in association with somatic symptoms for a duration of ≥ 2 weeks. Major depressive disorder has the highest lifetime prevalence among all psychiatric disorders. Major Depressive Disorder and bipolar disorder Bipolar disorder Bipolar disorder is a highly recurrent psychiatric illness characterized by periods of manic/hypomanic features (distractibility, impulsivity, increased activity, decreased sleep, talkativeness, grandiosity, flight of ideas) with or without depressive symptoms. Bipolar Disorder.
Key differential diagnoses for schizophrenia
Differential diagnosis Duration Negative symptoms Positive symptoms Mood disorder
Schizophrenia > 6 months (with at least 1 month of active phase symptoms) Yes Yes Yes
Brief psychotic disorder Brief psychotic disorder Brief psychotic disorder is the presence of 1 or more psychotic symptoms lasting more than 1 day and less than 1 month. An episode is often stress-related with a sudden onset, and the patient fully returns to baseline functioning after an episode. Brief Psychotic Disorder 1 day to 1 month No Yes Yes
Schizophreniform disorder > 1 month, < 6 months No Yes Yes, rare
Schizoaffective disorder Schizoaffective disorder Schizoaffective disorder is a mental disorder that is marked by 2 components: a psychotic component (hallucinations or delusions) and a mood component (mania or depression). Patients must therefore meet the diagnostic criteria for both major mood disorder and schizophrenia. Schizoaffective Disorder Current mood episodes with active phase of schizophrenia plus at least 2 weeks of lifetime history of delusions or hallucinations without mood symptoms Yes Yes Yes, predominantly

References

  1. Le, T., Bhushan, V. (2020). First Aid for the USMLE Step 1 (30th-anniversary edition). New York: McGraw-Hill Medical.
  2. Semple, D., Smyth, R. (2013). Oxford Handbook of Psychiatry. Oxford: Oxford University Press.
  3. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.).
  4. Fischer BA, Buchanan RS. (Literature review current through July 2020; last updated: June 3, 2020). Schizophrenia in adults: Clinical manifestations, course, assessment, and diagnosis. UpToDate Evidence-Based Medicine. https://www.uptodate.com/contents/schizophrenia-in-adults-clinical-manifestations-course-assessment-and-diagnosis?search=schizophrenia&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1
  5. Stroup TS, Marder S. Pharmacotherapy for schizophrenia: Acute and maintenance phase treatment. (Literature review current through July 2020; last updated: April 21, 2020). UpToDate Evidence-Based Medicine. https://www.uptodate.com/contents/pharmacotherapy-for-schizophrenia-acute-and-maintenance-phase-treatment?search=schizophrenia&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2

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