Schizophrenia is a mental disorder often characterized by abnormal social behavior and failure to recognize what is real. Common symptoms include false beliefs, unclear or confused thinking, auditory hallucinations, reduced social engagement and emotional expression, and lack of motivation. Diagnosis is based on observed behavior and the person's reported experiences.
Genetics and early environment, as well as psychological and social processes, appear to be important contributory factors. Some recreational and prescription drugs appear to cause or worsen symptoms.
Brain angiogenesis inhibitor 3 (ADGRB3/BAI3) belongs to the family of Adhesion G protein-coupled receptors. It is most highly expressed in the brain where it plays a role in synaptic function. Genome-wide association studies have implicated ADGRB3 in disorders such as schizophrenia and epilepsy.
Hsu et al evaluate evidence for genetic association between common RTN4R polymorphisms and schizophrenia in a large family sample of Afrikaner origin and screen the exonic sequence of RTN4R for rare variants in an independent sample from the U.S. They also employ animal model studies to assay a panel of schizophrenia-related behavioral tasks in an Rtn4r-deficient mouse model. They found weak sex-specific evidence for association between common RTN4R polymorphisms and schizophrenia in the Afrikaner patients. In the U.S. sample, they identified two novel non-conservative RTN4R coding variants in two patients with schizophrenia that were absent in 600 control chromosomes. In the complementary mouse model studies, they identified a haploinsufficient effect of Rtn4r on locomotor activity, but normal performance in schizophrenia-related behavioral tasks. We also provide evidence that Rtn4r deficiency can modulate the long-term behavioral effects of transient postnatal N-methyl-D-aspartate (NMDA) receptor hypofunction.
The results do not support a major role of RTN4R in susceptibility to schizophrenia or the cognitive and behavioral deficits observed in individuals with 22q11 microdeletions. However, they suggest that RTN4R may modulate the genetic risk or clinical expression of schizophrenia in a subset of patients and identify additional studies that will be necessary to clarify the role of RTN4R in psychiatric phenotypes. In addition, the results raise interesting issues about evaluating the significance of rare genetic variants in disease and their role in causation 1).
Thomas et al, previously reported NgR1 as receptor for the epilepsy-linked protein LGI1. NgR1 regulates synapse number and synaptic plasticity, whereas LGI1 antagonizes NgR1 signaling and promotes synapse formation. Impairments in synapse formation are common in neurological disease and we hypothesized that an LGI1-NgR1 signaling pathway may contribute to the development of schizophrenia.
Variants in NgR1 and LGI1 may be associated with schizophrenia and variants in NgR1 found in schizophrenic patients have impaired LGI1-NgR1 signaling. Impaired LGI1-NgR1 signaling may contribute to disease progression 2).
The many possible combinations of symptoms have triggered debate about whether the diagnosis represents a single disorder or a number of separate syndromes. Despite the origin of the term, from Greek skhizein, meaning “to split”, and phrēn, meaning “mind”, schizophrenia does not imply a “split personality” or “multiple personality disorder” — a condition with which it is often confused in public perception.
Rather, the term means a “splitting of mental functions”, reflecting the presentation of the illness.
The mainstay of treatment is antipsychotic medication, which primarily suppresses dopamine receptor activity. Counseling, job training and social rehabilitation are also important in treatment. In more serious cases—where there is risk to self or others—involuntary hospitalization may be necessary, although hospital stays are now shorter and less frequent than they once were.
Symptoms begin typically in young adulthood, and about 0.3–0.7% of people are affected during their lifetime.
In 2013 there was estimated to be 23.6 million cases globally.
The disorder is thought to mainly affect the ability to think, but it also usually contributes to chronic problems with behavior and emotion. People with schizophrenia are likely to have additional conditions, including major depression and anxiety disorders; the lifetime occurrence of substance use disorder is almost 50%.
Social problems, such as long-term unemployment, poverty, and homelessness are common. The average life expectancy of people with the disorder is ten to twenty five years less than the average life expectancy.
This is the result of increased physical health problems and a higher suicide rate (about 5%).
In 2013 an estimated 16,000 people died from behavior related-to or caused by schizophrenia.
Aine et al. describe an open-access collection of multimodal neuroimaging data in schizophrenia for release to the community. Data were acquired from approximately 100 patients with schizophrenia and 100 age-matched controls during rest as well as several task activation paradigms targeting a hierarchy of cognitive constructs. Neuroimaging data include structural MRI, functional MRI, diffusion MRI, MR spectroscopic imaging, and magnetoencephalography. For three of the hypothesis-driven projects, task activation paradigms were acquired on subsets of ~200 volunteers which examined a range of sensory and cognitive processes (e.g., auditory sensory gating, auditory/visual multisensory integration, visual transverse patterning). Neuropsychological data were also acquired and genetic material via saliva samples were collected from most of the participants and have been typed for both genome-wide polymorphism data as well as genome-wide methylation data. Some results are also presented from the individual studies as well as from our data-driven multimodal analyses (e.g., multimodal examinations of network structure and network dynamics and multitask fMRI data analysis across projects). All data will be released through the Mind Research Network's collaborative informatics and neuroimaging suite (COINS) 3).
Baquero et al, describe a case of delusional psychosis that was terminated by neurosurgical removal of a large intracranial arachnoid cyst. The patient was suffering his first psychotic episode and had symptoms typical of schizophrenia. The case underscores the importance of considering that an arachnoid cyst can induce psychopathological symptoms, even those of schizophrenia. Indeed, such symptoms may be the cyst's only clinical manifestation. In addition, the case highlights the importance of doing a structural imaging test when confronted with a first episode of psychosis, especially if the episode is relatively late in appearance. Such imaging may lead to a diagnosis that in turn can enable a definitive neurosurgical resolution of the psychosis 4).