Unraveling the Mysteries of Genetic Links to Schizophrenia

By Rose A. Burkholder



The interest in the genetic etiology of psychiatric diseases has grown as more evidence points to the likelihood that they may be genetically predetermined. One of these commonly studied illness is schizophrenia, which is believed to be transmitted through complex, non-Mendelian inheritance patterns. The complex transmission of this disease has complicated research and replication attempts, which still yield inconclusive results after numerous efforts. However, there are currently many theories and research projects that point to a variety of possible genetic factors in this disease. These theories and methods of research will be reviewed and summarized, in order to evaluate the trends and progress of the search to find the genetic causes of schizophrenia.


The recent completion of the Human Genome Project brings promises of unraveling the mysteries of the genetic transmission of many elusive and enigmatic disorders that are thought to have a genetic component or even a primarily genetic basis. Some of the most problematic disorders that have previously and currently stumped geneticists and clinicians alike are not the rare and horribly disfiguring or decidedly fatal diseases that affect miniscule proportions of the population. Rather more common disorders, those concealed within the mind, present one of the biggest and longstanding obstacles to researchers faced with the task of predicting the etiology and prognosis of these diseases.

The psychiatric illness, schizophrenia, exemplifies the problem of determining the genetic basis of disease, having led countless researchers on misleading chases to uncover the definitive genetic component of the disease. Such research efforts have examined a wide variety of possible genetic origins influencing the early neurodevelopment processes that may lead to the disease. Although these examinations have been quite comprehensive, they are anything but conclusive. Studies examining the genetic etiology of schizophrenia often fail to be replicated (Propping & Nothen, 1995) and are often isolated in cases where direct links to molecular genetic factors are found. No single genetic locus has been linked to schizophrenia in more than 30% of family pedigrees that have been reportedly studied (Cannon, Gasperoni, van Erp, & Rosso, 2001). In many other cases, no links or associations between schizophrenia and genetic causes are ever found. This pattern of research bears similarity to a very sophisticated game of hot and cold which accumulates results to finally obtain useful and vital information to determine the genetic causes of schizophrenia. Though this research has been undoubtedly tedious after enduring for nearly three decades, the time spent provides numerous benefits to future researchers and the entire field of human medical genetics. The decades of this research have uncovered and examined many fascinating possibilities of the genetic causes of schizophrenia. These genetic findings continue under exploration today to ultimately determine the inheritance pattern and genetic contributors that cause the disease and affect its symptomatic expression and prognosis.

Schizophrenia is composed of a variety of combinations of psychotic symptoms. Symptoms are categorized and defined according to three qualitative dimensions classified as positive, negative, or disorganized. In order for a patient to be diagnosed accurately as schizophrenic, the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) requires that two or more symptoms of the disorder persist for at least one month. In addition, the DSM-IV definition of schizophrenia requires that a patient display a significant decline in social or occupational function over a continuous period of approximately six months, during which active symptoms may or may not be observed. Positive symptoms are classified as psychotic symptoms by the DSM-IV and refer to distortions of normal functions. Such distortions often manifest themselves in the auditory and visual systems as hallucinations. The belief systems of schizophrenic patients also become distorted by the formation of preposterous and obsessive delusions based on incorrect conclusions derived from the environment (Oltmanns & Emery, 1998).

Negative symptoms observed in schizophrenics reflect a loss of normal functions or behavior. Behavioral traits most often lost in schizophrenics include initiative, social functioning, and emotional affect and response. Negative symptoms are very similar to the third category of symptoms, which are classified as disorganized. The general behavior of many schizophrenics is classified as disorganized when it ceases to conform into either of the other two categories. Behavioral disorganization is most often expressed in the speech patterns of schizophrenics. Signs of disorganized speech include irrelevant remarks or responses to questions, expression of disconnected ideas, and peculiar word usage. This symptom is often referred to as thought disorder, because the assumption has been made that the disorganized speech pattern reflects a disturbance in the cognitive functions that direct verbal communication (Oltmanns & Emery, 1998).

Further classification of schizophrenia differentiates between several known subcategories of the disease. Several different clinical manifestations and levels of disease severity fit into the classification of schizophrenia. Catatonic schizophrenia is a subcategory of schizophrenia in which patients lack sufficient motor skills. This lack of mobility leaves these schizophrenics with a rigid and unusual posture. Another subcategory, termed disorganized schizophrenia, includes patients who are most hindered by disorganized speech and other behaviors that lead to inappropriate social affects or interaction.

Perhaps the most well known subcategory of schizophrenia is the paranoid type. Paranoid schizophrenics most commonly exhibit hallucinations and delusions. Delusions can include content from the outside world or reflect delusions of the inner self, which are referred to as delusions of grandeur. Two less traditional subtypes of schizophrenia also exist to describe patients that do not fit into any of the other three categories. Undifferentiated schizophrenia includes patients who may fit into all of the previously mentioned categories or into none of them, due to a wide and variable amount of symptoms. Residual schizophrenia refers to patients who lack active phase positive symptoms that would qualify them for another category of the disorder. These patients may exhibit some negative symptoms but are generally considered to be in partial remission (Oltmanns & Emery, 1998)

Remission in schizophrenia is usually unlikely, however, the disease can be treated over long periods of time to decrease the most debilitating symptoms and subsequently improve lifestyle quality. Schizophrenia is most often treated with neuroleptic or antipsychotic medications. Though antipsychotic medications are generally useful, they often fail to help nearly a quarter of schizophrenic patients. In other cases, the results of these medications can take several months to have a noticeable and beneficial effect. Treatment with neuroleptics also presents the risk of side effects. Side effects usually hinder motor abilities in patients by inhibiting their control of fine muscular movements. Without the control of muscular movements, patients often exhibit involuntary tremors, spasms, and facial expressions. About 5% of patients experience these types of side effects, which are collectively referred to as tardive dyskinesia (Oltmanns & Emery, Ibid.).

The drug Thorazine, popular for treating schizophrenia for many years, is an example of a neuroleptic that has such problematic side effects. This drug specifically targets the neurotransmitter dopamine’s receptor systems and pathways to decrease possible overactivity in schizophrenics’ mesolimbic system, which plays a role in factors controlling emotions. As a side effect of decreasing dopamine activity at this pathway, a second dopamine pathway affecting motor activity is also decreased (Wong, Buckle, Van Tol, 2000). This decrease makes some simple motor activities for schizophrenics laborious. The ability to walk normally is sometimes severely affected by transforming walking motions into little shuffles. This side effect, commonly referred to as the "Thorazine shuffle", illustrates perfectly the problems that neuroleptic drugs can have on patients.

Schizophrenia occurs in approximately 1% of the population at some point in their life and usually debilitates such patients for the remainder of their life. Though the disorder occurs with less frequency than many other psychiatric diseases, schizophrenia is one of the ten most expensive disorders worldwide and remains the most commonly studied psychiatric illness with a proposed genetic basis (Bayer, Falkai, & Maier, 1999). The extensive genetic studies of schizophrenia have recently but gradually developed into a model applicable to the investigation of genetics in other disorders such as bipolar depression, reaffirming the global importance of efforts to decode the disorder (Oltmanns & Emery, 1998; Vuoristo, Berrettini, Overhauser et al, 2000).

A beginning model examining the genetic patterns of any disorder commonly starts with family, twin, and adoption studies to measure the frequency of the disease in biologically and nonbiologically related populations (Cannon, Huttunen, Lonnqvist et al, 2000; Levinson, Mahtani, Nancarrow et al, 1998). Such studies were the first to establish the notion that the predisposition for schizophrenia is transmitted genetically. Twin and adoption studies were useful in detecting the increased risk for schizophrenia in relatives of patients with the disease. A relative’s risk of developing schizophrenia is directly correlated to the amount of genetic material shared with a schizophrenic relative (Cannon, Huttunen, Lonnqvist et al, 2000). For instance, an individual’s lifetime risk for developing schizophrenia is increased to almost 50% when a parent or identical twin has the disorder, but is only increased to about 15% if a non-twin sibling has the disorder (Cardno & Gottesman, 2000; Tsuang, 2000).

The observations of the increased risk in relatives of schizophrenia patients are very valuable, but they can not provide the most definitive evidence that schizophrenia is a genetically based disease, because relatives generally share the same environmental influences as well. Therefore, the environment could be playing a large role in the increased risk for schizophrenia in the close relatives of schizophrenic patients (Tsuang, Ibid.). To further support the possibility that schizophrenia is genetically transmitted, more sophisticated and scientifically based research is required to directly determine the genetic makeup of schizophrenics and their family members. This research most often involves using molecular genetic techniques to uncover genetic abnormalities present in schizophrenia patients. Once such abnormalities are discovered, further investigations are required to determine if these defects are actually associated with the development of schizophrenia and how these defects are passed along genetically.

Most identifiable and understood genetic diseases are transmitted through predicable patterns of inheritance referred to as Mendelian inheritance. Mendelian inheritance operates through the genetic recombination and transmission of dominant or recessive alleles during reproduction to predispose offspring to an inherited disease. In most known cases of Mendelian inheritance, one known gene contributes to the development of the condition. In this case, the conditions are referred to as single gene disorders. Another subtype of Mendelian inheritance is oligogenic transmission, in which a genetic disease is caused by a few genes. Schizophrenia is not believed to be a single gene disorder that is transmitted according to Mendelian inheritance, though, in some very rare cases, inheritance patterns do seem to follow a Mendelian pattern (DeLisi, Razi, Stewart et al, 2000; Heiden, Willinger, Scharfetter et al 1999; Propping & Nothen, 1995). Genetic studies have also eliminated the possibility that schizophrenia is an oligogenic disease (Levinson, Mahtani, Nancarrow et al, 1998). Rather schizophrenia fits into a category of genetic diseases known as polygenic or multifactorial diseases, which refers to the disease’s multiple gene etiology, or genetic heterogeneity (Cannon, Gasperoni, van Erp, & Rosso, 2001).

Multifactorial diseases are very common yet they remain the least understood of the genetic diseases (Gelehrter, Collins & Ginsburg, 1998). The multiple gene etiology of schizophrenia makes determining the cause of the disease in many different situations difficult. Genetic linkage analysis often fails to detect the responsible loci in genes when a disorder deviates from traditional Mendelian inheritance (Cannon, Gasperoni, van Erp, & Rosso, 2001; Levinson, Mahtani, Nancarrow et al, 1998; Petronis & Kennedy, 1995). It is difficult to detect multiple gene loci that increase disease risk because each parent may carry their own different susceptibility alleles. Multiple combinations can result from these genes in different children and in different pedigrees, which contributes to a lack of consistency in genetic patterns to study.

Studies examining the genetic etiology of schizophrenia with genome scan procedures have uncovered numerous sites in the genome that could contribute to the development of the disease. Genome scans are performed by genotyping and analyzing the linkage of a gene map of chromosomes with evenly spaced genetic markers. These scans have reaffirmed that schizophrenia is a multifactorially transmitted by an undetermined amount of genes (ex. Brzustowicz, Honer, Chow et al, 1997; Freedman, Leonard, Gault et al, 2001; Goodman, 1998; Ishiguro, Okuyama, Toru, & Arinamin, 2000; Levinson, Holmans, Straub et al, 2000; Levinson, Matani, Nancarrow et al, 1998; Philibrit, Sandhu, Hutton et al, 2001; Schwab, Hallmayer, Lerer et al, 1998; Vuoristo, Berrettini, Overhauser et al, 2000) or is affected by "multiple independently inherited dimensions of neural deficit in schizophrenia" (Cannon, Huttunen, Lonnqvist et al, 2000). In one study alone, (Levinson, Holmans, Straub et al, 2000) both chromosome 6q and 10p were found to have associations to schizophrenia, with 6q having a stronger association.

The inheritance pattern of schizophrenia is further complicated by the fact that such genes are likely to interact with one another and exert varying levels of effectivity and phenotypical expression in the disease (Cannon, Huttunen, Lonnqvist et al, 2000; Levinson, Mahtani, Nancarrow et al, 1998; Propping & Nothen, 1995). Variability in phenotypical expression of a disorder is also referred to as penetrance and is often important to genetic studies when it appears to be lacking. When individuals in a genetic pedigree lack penetrance of the disorder that they geneotypically possess, the task of monitoring the inheritance of the disease through the same pedigree proves very difficult. Nonpenetrant carriers of schizophrenia are believed to contribute to the difficulties in unraveling the etiology of schizophrenia. Currently there are no adequate methods of detecting nonpenetrant carriers of schizophrenia, which contributes to the uncertainty of heterogeneity involved in the disease (Cannon, Huttenen, Lonqvist et al, 2000; Cannon, Gasperoni, van Erp, & Rosso, 2001).

Despite this uncertainty, many steps have been made in coming closer to finding the solution to the genetic puzzle of schizophrenia. In addition to chromosomes 6 and 10, another common genomic site that has been studied and linked to schizophrenia in several studies is on chromosome 18p (Schwab, Hallmyer, Lerer et al, 1998; Vuoristo, Berrenttini, Overhauser et al, 2000). In an association and linkage analysis study, a research team led by Schwab (1998) tested eight candidate genes that code for dopamine receptors, dopamine transporters, and G-proteins. G-proteins are large proteins derived from a cell’s cytosol that bind the purine nucleotide guanine and join to transmembrane receptors in order to carry out the transduction of important extracellular signals (Vuoristo, Berrenttini, Overhauser et al, 2000). A certain G-protein known as GNAL was, in a sample of 59 families with a history of the disease, found to be marked by a nucleotide repeat of C and A, which is referred to as a short sequence length polymorphism (SSLP). Polymorphisms generally refer to any common DNA sequence variation involving simple base changes. Polymorphisms are useful to identify inheritable abnormalities within populations and other genetic markers (Gelehrter, Collins, Ginsburg, 1998).

In this population, Schwab (1998) found that the SSLP of GNAL was transmitted in families with a susceptibility to schizophrenia nearly 90% of the time, indicating that this region may be a marker and a possible etiological influence in schizophrenia. In research expanding on and supporting Schwab’s findings, Vuoristo et al (2000) successfully isolated and sequenced the GNAL gene using cDNA library techniques and pinpointed its location to chromosome 18p11, a location on the short arm of the chromosome. In addition, these researchers uncovered GNAL’s relationship to a set of dopamine receptors, which are another molecular component commonly investigated in genetic studies of schizophrenia because of the role they may play in contributing to the overactivity and production of dopamine.

Several studies have directly examined dopamine receptors for their role in schizophrenia (Amin, Silverman, Siever, et al, 1999; Coon, Byerley, Hoff et al, 1993; Jonsson, Nothen, Neidt et al, 1999; Wong, Buckle, Van Tol, 2000). Jonsson et al (1999) focused their research on a promoter polymorphism involving an insertion and deletion of nucleotides in the dopamine 2 receptor. A polymorphism present at the promoter region in a gene could adversely affect the ability of the transcription process and expression of the gene. Results suggest that this may have been the case, because the polymorphism was related to schizophrenia.

Another recent study by Wong et al (2000) also examined the trend in research examining polymorphisms in dopamine receptors for a possible linkage to schizophrenia and also the pharmacogenetic response to antipsychotic drug treatment. Dopamine receptors 1through 5 have been the most commonly studied for association to schizophrenia in previous research attempts. Several polymorphisms have been reported on all of these dopamine receptors. However, results fail to conclude whether these DNA variations actually contribute to the development of schizophrenia and the pharmacogenetic response to antipsychotic drug treatment. These authors (Wong, Ibid.) suggest that dopamine receptors may only be one component in the "array of neurotransmitter receptor systems that influence behavior in concert with genes that control neurodevelopment, connectivity, neuronal signaling, and synaptic plasticity." Therefore, with so many influences, it may be too difficult to effectively and conclusively determine the effect of a single receptor gene or a single receptor gene’s polymorphism on the development of schizophrenia and response to drug treatment.

A recent study by Austin, Buckland, Cardno et al (2000) analyzed a specific receptor related to dopamine neurotransmitter system. High affinity neurotensin receptor genes (NTSR1) are localized within dopaminergic neurons and aid in the modulation of dopamine neurotransmission. These researchers suggested that altered neurotensin functioning could contribute to the etiology of schizophrenia. Measures of the cerebral spinal fluid of schizophrenics revealed that neurotensin activities are low and the number of receptors are reduced. Austin et al (Ibid.) searched to find DNA sequence variations that could explain the abnormal expression of NTSR1 in schizophrenics. Although half of their sample size showed mutations, none resulted in amino acid changes. Since significant alteration of this gene was lacking, no direct association between NTSR1 and schizophrenia could be inferred.

In addition to dopamine receptors, acetylcholine receptors have also been studied in relation to schizophrenia, suggesting that this neurotransmitter also influences the disorder (Freedman, Coon, Myles-Worsley et al, 1997; Freedman, Leonard, Gault et al 2001). A nicotinic acetylcholine receptor type on chromosome 15q13-14 was found to show involvement in the genetic transmission of schizophrenia in parent-child triads in both studies by Freedman et al (Ibid.). A fairly simple restriction fragment length polymorphism (RFLP) served as a way to identify this altered gene. A RFLP is similar to other polymorphisms because it does alter the nucleotide sequence, however these variations are significant in the way they are detected. Because of an alteration in nucleotide sequence, a gene containing a RFLP can not be fragmented normally by restriction enzymes. The RFLP alters the site where an enzyme would normally splice, making it unrecognizable to the enzyme. When a RFLP becomes unrecognizable to a restriction enzyme, it becomes easily recognizable to researchers, who can compare the sequence to normal samples that lack the polymorphism. In these studies, the commonly used restriction enzyme Bam1 detected the RFLP.

This RFLP on the nicotinic receptor is believed to play a role in the auditory deficits of schizophrenics as well as the general genetic transmission. Schizophrenics often show decreased brain activity to auditory stimuli in experimental settings. This deficit is often used as a genetic marker when identifying the disorder and predicting its likelihood of formation in psychiatrically normal patients who show the abnormality. An auditory abnormality such as this one is of particular interest when studying schizophrenia because such a sensory component could underlie patients’ more apparent and drastic symptoms of hallucinations and delusions (Freedman, Coon, Myles-Worsley, et al, 1997). Though this auditory abnormality seems very relevant to the identification of schizophrenia, some researchers have shown concern that a marker such as this one may not be accurate in diagnosing the disorder. Faraone, Kremen, Lyons et al, (1995) found that several phenotypes used to identify schizophrenia may not be useful in diagnosis because of high false positive rates leading to loss in statistical power. Other diagnostic phenotypes considered to be problematic are eye tracking dysfunction (Arolt, Lencer, Purmann et al, 1999) and attentional impairment.

In addition to neurotransmitter receptor chromosomes, sex chromosomes have been examined for a possible role in schizophrenia. A very recent study examining other polymorphisms’ role in schizophrenia targeted the HOPA (human opposite paired) gene located on the X chromosome at the q arm and loci 13 (Philibert, Sandhu, Hutton et al, 2001). The HOPA gene is involved in the coding process for a nuclear receptor co-activator of thyroxine, which is important to the formation of thyroid hormone. Philibert et al (2001) found that two polymorphisms on the exonic, or genetically expressed, region in the HOPA gene were associated with an increase in frequency of schizophrenia in a substantially sized cohort compared to a sample of newborn controls. One polymorphism was identified as having a nucleotide expansion repeat while the other was characterized by a deletion. In addition to being associated with schizophrenia, these polymorphisms were related to the incidence of hypothyroidism in the same sample. A genetic defect that shows an association to two or more different phenotypes is referred to as being pleiotrophic (Gelehrter, Collins, & Ginsburg, 1998). The incidence of plietrophy also complicates the procedures of uncovering its genetic cause.

Other studies examining polymorphisms in association to schizophrenia have not been as successful in finding results indicative of a possible association to schizophrenia. Bennett, Hoff, Rosenthal et al (2000) studied polymorphisms located on the gene for an amino acid transporter ASCT 1. Although several of these polymorphisms actually resulted in the changing of the proteins in some schizophrenics, these changes were not found to be significant enough to cause the disease. Ohara, Ikeuchi, Suzuki et al (2000) looked at a specific trinucleotide expansion repeat of the sequence CAG and found no significant indication that this DNA variation played a role in the development of schizophrenia. Their research attempted to replicate previous findings that this trinucleotide repeat did appear to influence the pattern of inheritance of schizophrenia in Chinese and Japanese populations (Ohara, Xu, Mori et al, 1997). The inability to replicate previous findings accurately illustrates a common problem that often occurs in genetic studies of schizophrenia.

Ohara, Ikeuchi, Suzuki et al (2000) also discussed the importance of two other factors in schizophrenia research in their aim to replicate previous findings. The phenomena of both anticipation and imprinting have been commonly studied in reference to schizophrenia in previous years, because they may serve as important contributing mechanisms that may help explain the complex pattern of inheritance in the condition (Heiden, Willinger, Scharfetter et al, 1999; Husted, Scutt, & Bassett, 1998;Ohara, Xu, Mori et al, 1997). Anticipation refers to an inheritance pattern within a certain pedigree that is signified by a decreased age of onset that occurs with or without an increase in severity of the disease in successive generations. Anticipation is believed to be caused by the tendency of DNA trinucleotide repeat variations to increase in size in successive generations. Such an increase in variation will in turn increase the severity of the disease and decrease the duration of time for the disease to manifest itself. The age of onset is defined as the age at which the criterion for diagnosis for schizophrenia is met according to the DSM-IV. Often the age at which hospitalization occurs is taken into account as well. Early onset schizophrenia is usually considered to appear in the early twenties, while late onset schizophrenia doesn’t appear until age 40 to 45 years.

Imprinting is characterized by a variation in expression of genes and phenotypical results depending on whether the genes originated from the mother or father. In both studies, Ohara et al (1997; 2000) support that there is anticipation and imprinting occurring in the genetic transmission pattern of schizophrenia. Ohara et al (1997) found that the incidence of anticipation was shown by a significantly lower age of onset without an increase in severity. Imprinting was inferred from negative symptom and clinical scores that were much higher in schizophrenics with a pattern of paternal transmission in comparison to patients with patterns of maternal transmission. In a more comprehensive and conjoined study on imprinting and anticipation, Husted, Scutt, and Bassett (1998) found that patterns of paternal transmission were likely to be associated to anticipation. The age of onset of patients with paternally acquired schizophrenia was significantly lower than the age of onsets in patient with maternally transmitted schizophrenia. However the authors (Husted, Scott, & Bassett, Ibid.) point out that more conclusive studies are required to determine if anticipation and imprinting really play large influences in the expression of the disease.

In a recent study, the age of onset of schizophrenics was associated to differences in the allelic distribution occurring with different ages of onset (Krebs, Guillin, Bourdel et al, 2000). In addition to this finding, the researchers also found that the allele distribution was significantly different in schizophrenic populations that either responded to neuroleptic treatment or did not. This result reintroduced the possibility that pharmacogenetics are likely to play a role in the prognosis of schizophrenia despite other researchers (Wong et al, 2000; DeLisi, Razi, Stewart et al, 2000) failure to find such results. The genetic factor that was determined to play a role in the genetic variability in schizophrenics with different onset and therapeutic response was a dinucleotide repeat polymorphism on Brain Derived Neurotrophic Factor (BDNF). The length of this polymorphism was found to be larger in patients with late onset ages and detectable responses to neuroleptics in comparison to early onset patients and those failing to respond to the appropriate pharmacological treatment. This study also found that "the BDNF gene variants could influence the phenotypic expression of schizophrenia in relation to predisposition to substance abuse". Such a relationship indicates that polymorphisms not only may play a role in schizophrenia’s etiology, imprinting and anticipation patterns, and response to pharmacological treatments, but also behavioral symptoms related to the disorder.

Violence is another behavioral symptom of schizophrenia that has been studied for an association to possible polymorphic forms of schizophrenia. Lachman, Nolan, Mohr et al (1998) found that low activity of a genetically controlled enzyme inactivating catecholamines was related to the violent behavior observed in patients with schizophrenia and schizoaffective disorder. The decreased activity of this catechol O-methyltransferase (COMT) was attributed to a small polymorphism. A more recent study aimed to identify the role of polymorphisms in serotonin pathways in the violent behavior of schizophrenics (Nolan, Volavka, Lachman, & Saito, 2000). Serotonin pathways have been previously indicated in the contribution to impulsive and aggressive behavior in normal populations and were therefore of interest to diseased populations, in which violent behavior often manifests itself. Several polymorphisms, in two separate genes, related to the activity and metabolism of serotonin, were isolated to identify possible associations to violent behavior in schizophrenics. Despite previous findings that these polymorphisms relate to behavior in alcoholics and antisocial personalities, there was no significant association to schizophrenia. However these negative results are not likely to deter further studies examining the role of genes and behavior in individuals with this highly behaviorally orientated disease.

The genetic origin of schizophrenia has not only been studied directly and in a traditional manner, but also indirectly in research projects examining possible genetic subtypes of the disorder. Basset and Chow (1999) examined a deletion on chromosome 22q11 and suggested the possibility that this abnormality is a subtype of schizophrenia. This deletion is classified independently as a syndrome, signifying that it is detectable by a particular set of symptoms. The symptoms of 22q11 Deletion Syndrome include congenital defects, learning disabilities, and excessively nasal speech production. Behavioral symptoms observed in people with this deletion closely resemble the behavior of schizophrenics, indicating that it may be related to the disease.

The 22q11 deletion is relatively common with an occurrence of 1 in 4000. Though the deletion is most likely to occur spontaneously, it is estimated that about 10% of the deletions are transmitted from parents to their children. In schizophrenics, it is estimated that the deletion is 80 times more prevalent than in the general population. Evidence seems to indicate that the two disorders are related, however, other psychiatric disorders also appear to be related to the 22q11 deletion indicating pleiotrophy. Other disorders found to be linked to the 22q11 deletion include schizoaffective disorder, major depression, and bipolar disease. Though the relationship between 22q11 Deletion Syndrome and schizophrenia is not conclusively defined, it is worthwhile to further explore. The identification of more subtypes or homogeneous forms of schizophrenia such as 22q11 Deletion Syndrome can be useful to reduce the ambiguities in what is currently known about the transmission of the disease.

Though current research has significantly improved and increased the quality and quantity of what is known about the genetic transmission pattern of schizophrenia, many questions still remain unanswered and controversial. Researchers often fail to agree on the significance of findings or fail to replicate potentially significant findings. Such inconsistencies are undoubtedly frustrating to scientists who have dedicated much of their professional lives to finding the solution to such a complex genetic problem. These inconsistencies are also likely to disturb many families affected by schizophrenia. People in this predicament have likely spent considerable portions of their personal lives seeking vital information concerning the likelihood of this terrible disease reappearing in their family. Currently, predicting such a likelihood is anything but foolproof, however, with continuing and diligent research more accurate predictions can be made and more definitive and global genetic causes of schizophrenia can be uncovered.




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