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• Schizophrenia


  A psychiatric disorder characterized by a constellation of abnormalities in thinking, emotion and behavior
• Although schizophrenia is discussed as if it is a single disease, it probably comprises a group of disorders with heterogeneous etiologies, and it includes patients whose clinical presentations, treatment response, and courses of illness vary
• Signs and symptoms of schizophrenia

  • Changes in perception, emotion, cognition, thinking, and behavior
  • The expression of these manifestations varies across patients and over time
  • The effect of the illness is always severe and is usually long lasting
• The disorder usually begins before age 25 years, persists throughout life, and affects persons of all social classes
• Both patients and their families often suffer from poor care and social ostracism because of widespread ignorance about the disorder
• Schizophrenia is one of the most common of the serious mental disorders, but its essential nature remains to be clarified; thus, it is sometimes referred to as a syndrome, as the group of schizophrenias, or as in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the schizophrenia spectrum
• Clinicians should appreciate that the diagnosis of schizophrenia is based entirely on the psychiatric history and mental status examination. There is no laboratory test for schizophrenia
• Epidemiology


  • Affects approximately 1% of people over their lifetime
  • Men and women are equally affected
  • Men present around 20 years of age
  • Women tend to present around 30 years old
  • It rarely presents before age 15 or after 45
• First degree biological relatives of persons with schizophrenia have a ten times greater risk for developing the disease than the general population
• Persons with schizophrenia have a higher mortality rate from accidents and natural causes than the general population
• The higher rate may be related to the fact that the diagnosis and treatment of medical and surgical conditions in schizophrenia patients can be clinical challenges
• Several studies have shown that up to 80 percent of all schizophrenia patients have significant concurrent medical illnesses and that up to 50 percent of these conditions may be undiagnosed
• Winter birth


  Associated with higher rates of schizophrenia
• Potential theories for higher rates of schizophrenia in winter births include gestational and birth complications, exposure to influenza epidemics, maternal starvation during pregnancy, Rhesus factor incompatibility, and an excess of winter births
• The nature of these factors suggests a neurodevelopmental pathological process in schizophrenia, but the exact pathophysiological mechanism associated with these risk factors is not known
• Dopamine hypothesis


  • Schizophrenia results from too much dopaminergic activity
  • Efficacy and potency of antipsychotic drugs are correlated with their ability to act as dopamine receptor antagonists
  • Drugs that increase dopaminergic activity, like cocaine and amphetamine, are psychotomimetic
• The dopaminergic neurons in the mesocortical and mesolimbic tracts project from their cell bodies in the midbrain to dopaminoceptive neurons in the limbic system and the cerebral cortex
• Excessive dopamine release in patients with schizophrenia has been linked to the severity of positive psychotic symptoms
• Position emission tomography studies of dopamine receptors document an increase in D2 receptors in the caudate nucleus of drug-free patients with schizophrenia
• There have also been reports of increased dopamine concentration in the amygdala, decreased density of the dopamine transporter, and increased numbers of dopamine type 4 receptors in the entorhinal cortex
• Mesolimbic pathway


  • Plays a key and complex role in motivation, emotions, reward, and positive symptoms of schizophrenia
• Bipolar Disorder


  A mood disorder that is characterized by episodes of mania, hypomania, and major depression
• Mesocortical pathway


  • Relevant to the physiology of cognition and executive function (dorsolateral prefrontal cortex)
  • Relevant to the psychology of emotions and affect (ventromedial prefrontal cortex)
  • Hypofunction might be related to cognitive and negative symptoms of schizophrenia
• Types of Bipolar Disorders

  • Bipolar (defined by at least one manic episode and often accompanied by depressed or hypomanic periods)
  • Bipolar II (marked by at least one hypomanic episode, at least one major depressive episode, and the absence of manic episodes)
  • Cyclothymia (alternating periods of hypomania and periods with mild to moderate depressive symptoms over the course of two years)
• Nigrostriatal pathway


  • Contains about 80% of the brain's dopamine
  • Involved in motor planning, dopaminergic neurons stimulate purposeful movement
• Estimated lifetime prevalence of bipolar disorder among adults worldwide is 1-3%
• Tuberoinfundibular pathway


  • Dopaminergic projections influence prolactin release
  • Dopamine is released into the portal circulation connecting the median eminence with the anterior pituitary gland
  • The role of dopamine release is to tonically inhibit prolactin release
• Bipolar Disorder


  • Mean age of onset for bipolar I is 18 years old and bipolar II is 20 years old
  • M:F ratio is 1:1
  • Patients often present in primary care settings
• Other causes of schizophrenia include the downward drift hypothesis and other neurotransmitters like serotonin, histamine, norepinephrine, GABA and glutamate
• 90% of individuals with a history of one manic episode will have another manic episode (particularly susceptible during times of sleep disruption i.e. changing time zones, working a night shift, etc.)
• Glutamate


  An excitatory amino acid neurotransmitter of interest in schizophrenia research because the NMDA glutamate receptor is blocked by phencyclidine (PCP/angel dust) and produces a clinical syndrome similar to schizophrenia
• Bipolar disorder tends to be under diagnosed or misdiagnosed as schizophrenia in ethnic minorities
• Differential diagnosis for medication/substance-induced mania


  • Corticosteroids
  • Sympathomimetics
  • Bronchodilators
  • Levodopa
  • Antidepressants
  • Dopamine agonists
  • Neurological disorders (temporal lobe seizures, multiple sclerosis, viral encephalitis and cerebral tumors)
  • Metabolic (hypothyroidism, Cushing's syndrome)
  • Neoplasms
  • HIV infection
  • Systemic disorders (B12 deficiency, carcinoid syndrome, uremia)
• Psychiatric indications for neuroimaging studies

  • First-episode psychosis
  • Confusion
  • Dementia of unknown cause
  • Prolonged catatonia
  • Movement disorder of unknown etiology
  • Personality changes after age 50
• Mood Disorders


  • Bipolar I (mania, hypomania, euthymia, depression)
  • Cyclothymia (alternating periods of hypomania and mild to moderate depressive symptoms)
  • Bipolar II (hypomania, euthymia, depression)
• The most consistent functional neuroimaging study finding in schizophrenia is hypofrontality
• The exact cause of bipolar disorders is unknown, but may involve biological, psychological, and social factors
• Three phases of schizophrenia

  • Prodromal (decline in functioning that precedes the first psychotic episode)
  • Psychotic (perceptual disturbances, delusions, and disordered thought process/content)
  • Residual (occurs between episodes of psychosis, marked by flat affect, social withdrawal, and odd thinking or behavior)
• How bipolar disorder develops

  1. Genetics (family, twin and adoption studies demonstrate inherited factors are involved, genetic susceptibility is the interaction of many genes rather than a single gene, advancing paternal age can lead to genetic mutations during spermatogenesis)

  2. Psychosocial factors (stressful life events, childhood maltreatment, abuse, sleep deprivation, experimentation of illicit drugs)
• The strongest predictor of treatment outcome in first-episode schizophrenia is the duration of presenting symptoms before treatment