Schizophrenia

• Schizophrenia is a disorder of disorganized thought content and behaviors; false perceptions and beliefs; and a progressive decline in general functioning and ability for self-care.
• It has a 1% lifetime prevalence in the US and that it generally begins between 15 and 35 years of age.
• To make the diagnosis of schizophrenia, a person must have at least 6 months of dysfunctional behavior and at least one of month of active psychotic symptoms.

• Psychotic symptoms are defined as any having at least 2 of the following 5 potential features:

Positive symptoms (which means the presence of a symptom)

• 1. Hallucinations, which are false perceptions. Hallucinations are false perceptions in the absence of an external stimulus: hearing voices without a provoking sound. Compare this to illusions, which are misinterpretations of stimuli: misinterpreting the sound of a door closing as a voice. We represent visual hallucinations, here, but hallucinations can stem from any sensory domain.

• Hallucinations stem from a variety of causes, let's address some of them here:
• Visual. Common causes: Schizophrenia, Delirium, Dementia, Charles Bonnet syndrome (visual impairment produces false visual perceptions (illusion may be a better descriptive term)), Anton's syndrome (denial in setting of stroke/injury to visual cortex), tumors and seizures, migraine aura, illicit drugs (LSD, PCP, etc…), neurodegenerative disorders (eg, Creutzfeldt-Jakob disease).
• Auditory. Prevalent in the same/similar disorders as visual hallucinations but more prevalent in more widespread psychiatric illnesses (mood and psychotic disorders). Like visual hallucinations which stem from visual cortical injury, so too, auditory hallucinations stem from auditory cortical injury, as well.
• Olfactory. Notable causes – temporal lobe epilepsy and temporal lobe tumors.
• Tactile. Notable cause – alcohol withdrawal ("bugs").
• Sleep/Wake transitions. Hypnagogic hallucinations occur upon going to sleep ("agogos" – leading to sleep) whereas hypnopompic hallucinations occur upon awakening from sleep (think "pompous", as you ready yourself for the day). These are notable symptoms of narcolepsy but can occur in the absence of any disorder.
• 2. Delusions, which are false beliefs. For instance, believing that you are a governmental agent despite convincing evidence to the contrary.
• 3. Disorganized speech
• 4. Disorganized behavior

Negative symptoms

• 5. Any negative symptom (which means lacking in a quality). Negative symptoms include apathy (loss of interest), abulia (loss of motivation), flattening of affect, etc…

• Note that negative symptoms can only confer 1 "point", in total, of the 2 required to make a diagnosis of schizophrenia, no matter how many negative symptoms are present.
• Thus, a positive symptom must also be present to make the diagnosis of schizophrenia.
• Also note that negative symptoms confer a worse prognosis, possibly related to the lack of efficacy of dopamine blockade on negative symptoms – see the dopamine hypothesis below.

• It almost certainly involves abnormal dopamine (DA) activity (described further, momentarily), increased norepinephrine (NE) activity, decreased GABA activity (which increases dopamine activity), decreased glutamate (Glu) activity (with hypofunctioning of NMDA receptors), and also abnormal neurodevelopment (abnormal neuronal migration).
• Abnormal dopamine activity can be briefly summed up in the dopamine hypothesis, which states that the positive symptoms of schizophrenia stem from hyperdopaminergic activity from the mesolimbic region (draw a medial portion of the brain and highlight the limbic region) and negative symptoms stem from hypodopaminergic activity from the mesocortical region (draw a lateral portion of the brain and section off the prefrontal cortex).
• The dopamine hypothesis greatly helps our understanding of the neuropharmacology of 1st generation (typical) antipsychotics.

• Also consider that the "stress diathesis" is a common biological explanation for the development of schizophrenia – a patient is born with the potential to develop the illness and a stressor triggers the disease to manifest.

• Although the DSM-5 does not subtype schizophrenia, common phenotypes include paranoid (delusions of grandeur), disorganized (chaotic behavior), and catatonic (rigid/waxy movements).

• Brief psychotic disorder requires at least one positive psychotic symptom (making it a psychotic disorder) and resolves within 1 month (making it "brief").

• Schizophreniform disorder requires at least two schizophrenia symptoms, lasts longer than 1 month (or it would be "brief") but resolves within 6 months (or it would be schizophrenia). It takes the "form" of schizophrenia but is a rapid-onset psychotic disorder without progressive decline in functioning (rather dysfunction is restricted to the time period of the illness). Consider that the majority of schizophreniform patients ultimately do progress to schizophrenia (~ 70%) but they may have a couple of bouts of psychosis before this occurs. Negative symptoms are a negative prognostic indicator.

• Schizoaffective disorder involves both schizophrenia symptoms and also prominent mood disorder symptoms, so neither disorder can be diagnosed exclusively.
• Distinguishing schizoaffective disorder from either schizophrenia with prominent mood symptoms or mood disorder with prominent psychotic symptoms is tricky but as a rule, the psychotic symptoms must occur separate from the mood disorder for at least a two week period of time, making it impossible to exclusively diagnosis the patient with one primary disorder or another.

• The patient has at least one fixed delusion for at least one month in the absence of other psychotic symptoms.
• Delusional types include jealous (aka "Othello syndrome"), persecutory, grandiose (eg, special powers), erotomanic (ie, someone of higher socioeconomic status is in love with the patient), persecutory, or somatic (delusions about the body, itself (health or body shape).
• Note that the popularized shared delusion syndrome is called folie a deux wherein two people, most commonly a mother and daughter, share the same delusion.

• We cannot diagnose a psychiatric illness in the presence of a known toxic or medical cause (eg, illicit drugs). It's easy to mistake mimickers (eg, phencyclidine (PCP) abuse) for schizophrenia if we aren't careful.

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