Schizophrenia

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Auditory hallucinations are now the most common manifestation of schizophrenia: although rates vary between cultures and regions. 

 

Auditory hallucinations are most commonly intelligible voices. 

Affects approximately 1% of the population.

Among the top 10 global causes of disability.

Approximately 2.5 million people living with schizophrenia in US.

Increased rate in monozygotic twins suggests a genetic relationship.

The environment, obstetrical complications, early life adversity, early childhood residence in urban areas, all interact with genetic risks interact with the likeliness of schizophrenia.

The Disrupted in Schizophrenia 1 (DISC1) gene is associated with risk for, and cause of, schizophrenia-spectrum disorders and other mental illnesses and is associated with social anhedonia within the general population.

Some patients have hyperactivity of dopaminergic, serotonergic and noradrenergic systems.

May be associated with abnormalities in the frontal lobes.

Schizophrenic patients have lower gray-matter volumes on MRI imaging than matched controls and fewer dendrites and dendritic spines on postmortem examination.

The rate of grey-matter loss is associated with elevated levels of immune markers, such as tumor necrosis factor alpha, that participate in activation of brain microglia suggesting that cytokine-mediated activation of microglia may play a role in schizophrenia.

It is suggested that dopamine plays a role in reward-based learning and is associated with the initiation of behaviors that predict subsequent reward.

Increase dopamine synthesis has been observed in schizophrenia.

There is a wide variation in patient’s ability to function in their daily activities from severely disabled to functional at a high-level.

Onset in males 15-25 years and in females later onset, 25-35 years.

On average, males with schizophrenia are diagnosed at a younger age, have more severe symptoms, worse treatment prognosis, and a decrease in overall quality of life compared to females with the disorder.

Typically,indications appear in the late teens and early 20s, but some children have social awkwardness, physical clumsiness, and low intelligence quotient than their siblings at similar age and then have schizophrenia years later.

Incidence of late onset and very late onset schizophrenia is 12.6 and 17-24 cases per hundred thousand population per year, respectively.

Frequently there is a period of months or years prior to diagnosis characterized by changes in behavior in decline in function, this is noted to be the period of psychosis prodrome.Heated

Cases of schizophrenia diagnosed after age 65 tend to be predominately among women, have better occupational and marital histories and have more paranoid delusions and hallucinations and less disorganization and negative symptoms.

The estimated heritability of schizophrenia is 70% to 90%.

Can be associated with enlargement of the lateral and third ventricles of the brain.

Intrauterine and childhood undernutrition are associated with an increased lifetime risk.

Patients with schizophrenia are more than twice as likely to die from breast, colorectal, lung and oral cancers due to differences in reception of stage appropriate treatment.

Women with schizophrenia have same breast cancer incidence as women without mental illness, but they experience 2-3 times greater breast cancer mortality.

Associated with 22q11 deletion syndrome, ranging from 0.5 to 2% and averaging about 1%, compared with the overall estimated 0.025% risk of the 22q11.2 deletion syndrome in the general population.

75-85% of patients with schizophrenia smoke cigarettes compared to 23% of the general U.S. population.

Smokers with schizophrenia acquire more nicotine per cigarette than do control smokers and have a 130% higher age-adjusted death rate due to pulmonary disease than the general population.

Patients with schizophrenia die 15-25 years earlier than the general population.

Lifetime risk of schizophrenia among people convicted of homicide is 5%.

The greater the intensity of antipsychotic treatment the greater the reduction in generalized and specific brain tissue dopamine D2 receptors.

Antipsychotic drug treatment of schizophrenia include:  prophylaxis in those at high risk of developing psychosis, treatment of first episode psychosis, maintenance therapy, maintenance therapy, and treatment of recurrent episodes of acute psychosis.

Inflammation coming from an infectious source or from an autoimmune disease is a risk factor for schizophrenia, not only during development but also later in life.

In schizophrenia the risk is increased in a dose-dependent manner, associated with the number of infections individuals experience.

Reemergence of psychosis can be associated with delusions, hallucinations, and disorganization.

The risk of relapse is increased by poor adherence of medical programs, substance-abuse, and social stress.

Non-adherence rates with antipsychotic medications are estimated at 40%.

Antipsychotics approved for schizophrenia work primarily by antagonizing D 2 dopamine receptors.

 

Muscarinic system is also involved in the pathophysiology of schizophrenia.

Long acting injectable antipsychotic medications reduce nonadherence and relapse in patients diagnosed with a schizophrenia spectrum disorder.

Diagnosis includes the presence of two of the following five items, each present for a significant portion of time during one month period, with her at least one of them being items one, two, or three: delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior, and negative symptoms with decreased motivation and diminished expressiveness.

For diagnosis there should be clinical evidence of disturbed functioning in work, self-care, or interpersonal relationships.

Schizoaffective disorders, depression or bipolar disorders and disturbances attributed to substance-abuse should be ruled out.

Antipsychotic drugs are affected for reducing psychotic symptoms in acute episodes of schizophrenia.

Antipsychotic drugs are most often administered orally but can be administered short-term intramuscularly for patients who cannot receive oral medications.

Antipsychotic medications are effective when CNS levels are approximately 70% of D2 receptors.

Commonly prescribed antipsychotic medications include:

Haloperidol

Perphenazine

Clozapine

Risperidone

Olanzapine

Quetiapone

Ziprasidone

Aprpiprazole

Paliperidone

Iloperidone

Asenapine

Lurasidone

Catiprazine

Brexpiprazole.

At least 30% of patients show some improvement, but will have persistent psychotic or residual symptoms that effect their a functioning and quality.

The theory that psychosis is related to excessive dopamine activity is challenged by the fact that there is a lag of 2-4 weeks between the peak blockade of D2 receptors by medications and clinical response, which suggests the antipsychotic efficacy of drugs depend on other neurochemical mechanisms rather than decreased dopamine transmission.

Postmortem examination suggest your alterations in the micro structure and functioning of micro circuits in schizophrenia.

The most effective anti-psychotic medication for patients with poor or partial response is clozapine.

Between 10 and 30% of patients will have limited benefit from antipsychotic medications.

Treatment resistant to disease refers to a patient who is had no period of satisfactory emotional and behavioral adjustment in the previous five years, if the patient has had prior non-response to at least two antipsychotic drugs or two different chemical classes, and displays moderate to severe psychopathology, especially positive symptoms such as conceptual disorganization, suspiciousness, delusions, or hallucinations.

Continued administration of antipsychotic medications after recovery from a psychotic episode is effective in reducing the risk of relapse of psychosis: approximately 64% of patients have a relapse during the first year while receiving a placebo, as compared to 27% who have a relapse while receiving an antipsychotic medication.

It is current practice to continue antipsychotic medications indefinitely.

When concern about non-adherence exists long-term injectable antipsychotic medications are available: haloperidol, paliperidone.

Metabolic side effects of antipsychotic drugs includes: weight gain, elevation in lipid levels, and insulin resistance, all of which increase cardiovascular disease risks.

Antipsychotic medications can elevate prolactin levels and may be associated with galactorrhea and menstrual disturbances in women and sexual dysfunction and gynecomastia in men.

Past or current use of cannabis is common in patients with schizophrenia, particularly among young individuals with the first episode.

Cannabis has the potential for worsening psychotic symptoms and increasing apathy.

There is evidence that the use of cannabis is associated with an earlier on set of schizophrenia.

The use of marijuana or synthetic cannabinoids has the potential to worsen the course of illness and provoke violence and suicidality in schizophrenia.

Nonpharmacologic interventions such as social skill training, community treatment, cognitive behavior therapy, family based services are effective for improving outcomes in patients with schizophrenia.

On average, males with schizophrenia are diagnosed at a younger age, have more severe symptoms, worse treatment prognosis, and a decrease in overall quality of life compared to females with the disorder.

Antipsychotic medications have significant side effects including: restlessness, stiffness, or sedation and should be monitored.

Antipsychotic medications effectiveness is related to their antagonistic activity of dopamine receptors in the mesolimbic dopamine tract, but they may have activity in reducing dopamine activity in the nigrostriatal pathway leading to extraparametal side effects.

Akathisia is the most common extrapyradimal side effects characterized by restless movements, usually restless leg movements, as well as the subjective unpleasant experience of restlessness.

Drug induced parkinsonism can also occur.

Mild Extrayramidal syndromes include decreased arm swing while walking.

Drug induced dystonias are characterized by involuntary muscle contractions usually in the neck, jaw, or arms.

Acute extrapyramidal side effects are managed by reducing medication dose, changing medications or adding anticholinergic medications.

Tardive dyskinesia may occur after months or years of treatment within antipsychotic medication.

Approximately 1/4 of patients who have a response to antipsychotic drugs will have a relapse while receiving medication and then approximately 3/4 of patients who have an initial response but who become non-adherent will have a relapse suggesting that an antipsychotic drugs are palliative rather than curative of the underlying vulnerability to psychotic symptoms.

Higher brain glutamate levels appear to be a biomarker of illness severity in patients with schizophrenia, according to a participant-level mega-analysis of proton magnetic resonance spectroscopy data that probed associations between altered glutamatergic function and various clinical and demographic factors in patients.

 

Higher glutamate levels may be associated with greater illness severity.

 

Glutamate levels may be reduced through effective antipsychotic treatment.

 

There is a correlation between higher glutamate levels in the medial frontal cortex and medial temporal lobe and more severe symptoms in patients with schizophrenia.

 

Glutamatergic measures as a potential biomarker of illness severity.