Background
Schizophrenia is a severe, persistent, debilitating, and poorly understood psychiatric disorder that probably consists of several separate illnesses. The hallmark symptoms of schizophrenia are psychotic symptoms, such as auditory hallucinations (voices) and delusions (fixed false beliefs). Impaired cognition or a disturbance in information processing is a less vivid symptom that is highly disruptive. People with schizophrenia have lower rates of employment, marriage, and independent living compared with other people.
For more information, see Medscape's Schizophrenia Resource Center.
Case study
John P is a 25-year-old male with the diagnosis of schizophrenia. He was a healthy child, but his parents report that he was a bedwetter and seemed slower to develop than his brothers and sisters. A maternal uncle has also been diagnosed with schizophrenia.
John had 2 brief hospitalizations in his late teens that were precipitated by anger at his boss, depression, and voices in his head. He found the hospital stays unhelpful. He was treated with haloperidol, which gave him muscle cramps; he was then treated with olanzapine and gained 20 pounds and developed diabetes mellitus.
John smokes marijuana and tobacco frequently to calm himself; he also drinks vodka.
John's parents support him financially. His brothers are sisters are angry and frightened of him and have nothing to do with him. They are particularly upset by his lack of interest in the outside world. John lives in a boarding home and works in a sheltered workshop with difficulty.
John sees a psychiatrist for 15 minutes every 2 months but sometimes misses his appointment. He has a social worker whom he sees often. The psychiatrist would like to switch him to long-acting injectable antipsychotic treatment, but John is afraid of injections and isn't sure that he needs medication. He has no primary care physician.
Pathophysiology
Neuroimaging studies have demonstrated anatomical abnormalities, such as enlargement of the ventricles and decreased brain volume in medial temporal areas.[1] These findings are of greater research interest than clinical use.
The hippocampus is a small, cortical, supposedly seahorse-shaped part of the brain, curled within the medial border of the temporal lobe. The hippocampus is functionally part of the limbic system, where emotions are processed. The hippocampus is where we form declarative or episodic memories (memories of facts or events). The hippocampus is affected in Alzheimer disease, the preeminent disease of memory problems.
The hippocampus is also one of the many parts of the brain affected in schizophrenia. Disturbances in declarative memory are common in schizophrenia, although not as marked as in Alzheimer disease. Changes in the hippocampus, such as volume loss, change in perfusion, and change in contour, observed in brains from patients with schizophrenia (including nonmedicated patients) and relatives may be related to the cognitive problems of schizophrenia.[2]
Mattai et al studied a group of children with schizophrenia and their healthy siblings and controls.[3] The average age at the beginning of the study was 12 years. The hippocampal volume of the ill children was less than that of their siblings and controls and steadily decreased over 12 years of follow up, although not at an increasing rate. The children with schizophrenia were administered antipsychotic medications. The authors concluded that the hippocampal volume deficit was more likely due to the illness itself rather than the use of antipsychotic medication.
Interest has also focused on the various connections within the brain rather than localization in one part of the brain. Indeed, neuropsychological studies show impaired information processing in schizophrenia, and MRI studies show anatomic abnormalities in a network of neocortical and limbic regions and interconnecting white matter tracts.[4] A meta-analysis of studies using diffusion tensor imaging to examine white matter found that 2 networks of white matter tracts are reduced in schizophrenia.[5]
Other studies reveal less specific changes. In the Edinburgh High-Risk Study, researchers examined brain images of people at high genetic risk for schizophrenia. Seventeen of 146 people had reductions in whole brain volume and left and right prefrontal and temporal lobes. The changes in prefrontal lobes were associated with increasing psychotic symptoms.[6]
In a meta-analysis of 27 longitudinal structural MRI studies of patients with schizophrenia compared with controls, the authors found that schizophrenia was associated with loss of whole brain volume in both gray and white matter and an increase in ventricular volume over time.[7]
The first clearly effective antipsychotic drugs, chlorpromazine and reserpine, were structurally different from each other, but they shared antidopaminergic properties. Drugs that diminish the firing rates of mesolimbic dopamine D2 neurons are antipsychotic, and drugs that stimulate these neurons (eg, amphetamines) exacerbate psychotic symptoms. Therefore, abnormalities of the dopaminergic system are thought to exist in schizophrenia; however, little direct evidence supports this. This theory has recently undergone considerable refinement.
Hypodopaminergic activity in the mesocortical system, leading to negative symptoms, and hyperdopaminergic activity in the mesolimbic system, leading to positive symptoms, may coexist. (Negative and positive symptoms are defined below.) Moreover, the newer antipsychotic drugs block both dopamine D2 and 5-hydroxytryptamine (5-HT) receptors.
Clozapine, perhaps the most effective antipsychotic agent, is a particularly weak dopamine D2 antagonist. Undoubtedly, other neurotransmitter systems, such as norepinephrine, serotonin, and gamma-aminobutyric acid (GABA), are involved. Some research focuses on the N -methyl-D-aspartate (NMDA) subclass of glutamate receptors because NMDA antagonists, such as phencyclidine hydrochloride and ketamine, can lead to psychotic symptoms in healthy subjects.[8]
Epidemiology
Frequency
International
The prevalence of schizophrenia is approximately 1% worldwide.
Mortality/Morbidity
People with schizophrenia have a 10% lifetime risk of suicide. Mortality is also increased because of medical illnesses, due to a combination of unhealthy lifestyles, side effects of medication, and decreased health care.
Race
No known racial differences exist in the prevalence of schizophrenia. Some research indicates that schizophrenia is diagnosed more frequently in black people than in white people. This finding has been attributed to cultural bias of practitioners.
Sex
The prevalence of schizophrenia is about the same in men and women. The onset of schizophrenia is later and the symptomatology is less severe in women than in men. This may be because of the antidopaminergic influence of estrogen.
Age
The onset of schizophrenia usually occurs in adolescence, and symptoms remit somewhat in older patients. Most of the deterioration that occurs in patients with schizophrenia occurs in the first 5-10 years of the illness and is usually followed by decades of relative stability, although a return to baseline is unusual. Positive symptoms are more likely to remit than cognitive and negative symptoms.
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