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Running head: BIOLOGICAL BASES OF SCHIZOPHRENIA
Biological Bases of Schizophrenia
Susan B. Anthony
Wichita State University
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BIOLOGICAL BASES OF SCHIZOPHRENIA
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Biological Bases of Schizophrenia
Introduction
Characteristics
Schizophrenia is a disorder characterized by abnormal thoughts and behaviors that fall
into three broad categories of “symptoms”: positive, negative, and cognitive. Positive symptoms
are behavioral excesses including delusions, hallucinations, and disorganized thought and
speech. Negative symptoms are behavioral deficits including flattened or blunted affect, alogia,
avolition, anhedonia, and social withdrawal. Cognitive symptoms are skill deficits including
reduced attention span, lowered processing and reaction time, learning and memory deficits,
difficulty thinking abstractly, and poor problem solving (Carlson, 2013).
Diagnosis
The Diagnostic and Statistical Manual of Mental Disorders (DSM) published by the
American Psychiatric Association (APA) provides diagnostic criteria that an individual must
meet in order to warrant a diagnosis of schizophrenia. Appendices 1 and 2 give both the current
diagnostic criteria for schizophrenia and those proposed for the new edition of the manual
(American Psychiatric Association [APA], 2000; APA, 2012). Mental health professionals (e.g.,
licensed clinical social workers, psychologists, psychiatrists) use psychological assessment,
environmental observations, and family history in tandem with DSM criteria to diagnose
schizophrenia.
Epidemiology
Prevalence and Incidence
The lifetime prevalence of schizophrenia is estimated to be 0.87% (Stilo & Murray,
2010). In a meta-analysis of six epidemiological studies, psychotic disorders (which include
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schizophrenia and disorders with similar symptoms, including schizophreniform disorder,
schizoaffective disorder, delusional disorder, and brief psychotic disorder) were found in 0.9% of
the population over a period of 12 months. However, among those studies, estimates of 12month prevalence ranged from 0.2% to 2.6% (Wittchen & Jacobi, 2005). The yearly incidence
rate of schizophrenia has been estimated to be anywhere from 7.7 cases per 100,000 to 43.0
cases per 100,000, and geographical location has been implicated as one contributor to that
variability (Stilo & Murray, 2010). The age of onset in males tends to be between 20 and 24
years of age, while females tend to develop the disorder later, between their 29th and 32nd year
(Stilo & Murray, 2010). Unfortunately, prognosis for those diagnosed with schizophrenia is
relatively grim. They are 12 times more likely than the general population to die by suicide, and
are also more likely to die from any cause (Kring, Johnson, Davison, & Neale, 2012). In a review
of multiple mortality studies, there were 160% more deaths among schizophrenic patients than
among “normals” within the same time periods (standardized mortality ratio of 2.6; Stilo &
Murray, 2010).
Gender Differences
Mixed results have surfaced regarding gender differences in schizophrenia. As previously
mentioned, males tend to develop the disorder earlier in life. In addition, while cases of “mild
schizophrenia” are distributed relatively evenly among women and men, more severe cases are
disproportionately male (Stilo & Murray). These numbers may need to be taken with a grain of
salt. Longenecker et al. (2010) demonstrated that women may actually be underrepresented in
both epidemiological and non-epidemiological research on schizophrenia. Epidemiological
studies have yielded 1.4 males for every diagnosed female, yet in the non-epidemiological
research critiqued, there were 1.94 male schizophrenia patients for every female studied. This
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underrepresentation may be an alternative explanation for the gender differences reported in
experimental research.
Etiology and Risk Factors
Genetic Contributions
Beyond merely describing schizophrenia and its epidemiology, researchers are searching
for possible causes. Discovering the etiology of this serious condition may help us to prevent or
treat it. Schizophrenia is thought to have a strong genetic component, with heritability estimates
between 66% and 83% (Stilo & Murray, 2010).
Implicated genes. Several studies have found relationships between particular inherited
genetic sequences and later development of schizophrenia. In 2008, Allen and colleagues noted
inconsistencies among the vast number of genetic association studies. The team then created a
database of the findings (“SzGene”), looked for common elements, and distilled out only those
genetic variants with the strongest, most consistent correlations with schizophrenia (according to
the Venice guidelines for cumulative evidence in genetic association studies). They found four
such variants: DRD1 rs4532, DTNBP1 rs1011313, MTHFR rs1801131, and TPH1 rs1800532.
The known functions of these genes are outlined in Appendix 3 (Allen et al., 2008). Also in
2008, Shi, Gerson, & Liu conducted their own meta-analysis of genes previously associated with
schizophrenia and found seven reliable relationships: DAO, DRD4, IL1B, MTHFR, PPP3CC,
SLC6A4, and TP53. When they split the data by race, they found one striking result: GABRB2
rs1816072 was reliably related to schizophrenia in Asians after a stringent alpha correction for
multiple tests.
More recently, the field has turned its attention to a gene known as DISC1 (disrupted-inschizophrenia-1), which has also shown strong associations with schizophrenia. Although the
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exact role of DISC1 in promoting schizophrenia is unknown, research has uncovered connections
to cytoskeletal proteins, neurodevelopmental regulators, neurosignaling regulators, and signal
transduction proteins (Mouaffak et al., 2011). Three variants of DISC1 have correlations with
presentation of schizophrenia: rs3738401, rs6675281, and rs821616 (Mouaffak et al., 2011).
Interestingly, one of these variants—rs3738401—was specifically linked to a type of “ultraresistant” schizophrenia that was in no way alleviated by two rounds of drug treatment.
Animal studies. Animal models have demonstrated the effects of suppressing DISC1 on
neurological development. It appears that DISC1 is necessary for proper developmental
migration and layering of neurons in the hippocampus (Tomita, Kubo, Ishii, & Nakajima, 2011)
and cerebral cortex (Mouaffak et al., 2011). Another study used a rodent model to attempt to
shed some light the exact mechanism of action by which DISC1 might be operating in
schizophrenia. Lipina et al. (2011) found that mutations in the DISC1 sequence appear to result
in excess activation of the protein glycogen synthase kinase-3 (GSK-3). GSK-3 overexpression
has been linked to hyperphosphorylation of the protein tau in Alzheimer’s (causing the hallmark
neurofibrillary tangles of the disease), and has also been implicated in bipolar disorder and
depression (Lipina et al., 2011). Administration of a GSK-3 inhibitor reversed the behavioral
effects of the DISC1 mutation in mice. This evidence points to a defunct DISC1 gene that exerts
its effects on neurodevelopment through the protein GSK-3. It also shows that intervening
downstream at the level of suppressing GSK-3 may be a promising new approach to treatment.
Mutated genes. There is some evidence to suggest that the genetic component of
schizophrenia may be related to parental age through an interesting pathway. In a large Israeli
study, researchers found that children of younger fathers (less than 25 years of age) had only a
.71% chance of developing schizophrenia, while children of older fathers (age 50-54) had a
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2.38% chance of developing the disorder (Stilo & Murray, 2010). This fact, paired with the
knowledge that DNA of individuals with schizophrenia tends to show higher than average copynumber variations (errors in replication that produce variation), has led to the hypothesis that
schizophrenia may be in part caused by increasingly error-riddled DNA of the sperm cells of
older men (Stilo & Murray, 2010). The replication errors that might produce the risk-laden
sequence variants previously described are hypothesized to increase with fathers’ age because of
the high number of times that spermatocytes must replicate (540 times by the age of 35) relative
to their female counterparts (24 times total) (Carlson, 2013).
Epigenetics. As a final note on genetic risk factors for schizophrenia, exciting new
research on schizophrenia has emerged out of the burgeoning field of epigenetics. Melas et al.
(2012) found significantly lower rates of DNA methylation among patients with schizophrenia.
Methylation of DNA sequences is a major contributor to the activation and suppression of
genetic sequences throughout the lifespan, and hypomethylation is generally related to genomic
instability of expression. As further evidence for the link between hypomethylation and
schizophrenia, Melas and colleagues went on to show that treatment with haloperidol (a firstgeneration antipsychotic) boosted patients’ level of methylation closer to normal levels.
Environmental Factors
Prenatal conditions. In addition to genetic risk factors, prenatal factors such as infection
and maternal nutrition are thought to contribute to the development of schizophrenia later in life.
In a large cohort of people born between 1959 and 1967, exposure to influenza during the first
half of gestation increased the risk of schizophrenia by a factor of three. More specifically,
exposure to influenza during the first trimester resulted in seven times the risk of schizophrenia,
while exposure during the second half of pregnancy did not increase the risk (Brown & Derkits,
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2010). Another organism that can increase the risk of schizophrenia given prenatal exposure is
toxoplasma gondii (T. gondii). In findings that have been replicated in the United States and
Denmark, the presence of blood-borne antibodies for this parasite in infant or mother (an
indicator of the parasite’s presence) more than doubled the risk of later onset of schizophrenia
(Brown & Derkits, 2010). Another prenatal factor that may play a role in risk of schizophrenia is
maternal nutrition during pregnancy. Both vitamin D and thiamine deficiencies in mothers, as
well as low maternal weight during pregnancy, have been linked to increased risk of
schizophrenia in offspring (Carlson, 2013).
Perinatal conditions. Both the prenatal environment and perinatal conditions can alter
an individual’s risk for schizophrenia. In another multisite cohort design, perinatal exposure to
herpes simplex virus type 2 (HSV-2) via the mother’s birth canal posed as much as 4.4 times the
risk of later onset of schizophrenia as birth without exposure (Brown & Derkits, 2010). In
addition to pathogen exposure, other events can transpire during the birthing process that
increase the risk of schizophrenia. Delivery complications like bleeding, pre-eclampsia,
asphyxia, uterine atony, and emergency cesarean sections are all significantly associated with
diagnosis of schizophrenia (Stilo & Murray, 2010). Finally, the season in which an infant is born
can also be a contributing risk factor. Individuals born in the late winter and early spring are
more likely to develop schizophrenia. Although the exact cause for this phenomenon is
unknown, a link between season of pregnancy and seasonal surges in infectious disease has been
hypothesized (Stilo & Murray, 2010).
Immune functioning. Li and a team of researchers (2012) have posited another possible
contributor to schizophrenia: the immune hypothesis. They point out that, though the brain is no
doubt the most influential organ in the onset and development of schizophrenia, a profile of 27
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proteins found in the blood throughout the (peripheral) body can reliably predict concurrent
schizophrenia diagnosis (Li et al., 2012). Because many of these proteins are important to
immune functioning, the study concluded that the immune system may be implicated in the
development and maintenance of schizophrenia.
Neurological Correlates
Structural Abnormalities
Schizophrenia is associated with several differences in brain structure, one of which is
enlarged ventricles due to loss of neural tissue (Carlson, 2013). The change in brain volume
appears to occur before the onset of symptoms, and it continues to progress afterward (Piper et
al, 2012). Additionally, though the normal human brain shows some asymmetry (occipital
enlargement in the left hemisphere and frontal enlargement in the right hemisphere; Barrick et
al., 2005), post-mortem studies have revealed that the brains of schizophrenic patients lack that
asymmetry or “torque” (Piper et al., 2012). On a smaller scale, the brain tissues and cells of
individuals with schizophrenia are different than those of healthy controls. Neurons in the cortex
tend to be smaller, and the cortex is underlain by denser white matter composed of glial cells
(Piper et al., 2012).
Neurotransmitter Dysfunction
The role of dopamine. It would be impossible to discuss the biological bases of
schizophrenia without discussing the dopamine hypothesis. The dopamine hypothesis is a longstanding theory of how schizophrenia develops and operates through dysfunction of
dopaminergic neural pathways. As it stands today, the hypothesis can be conceptualized as being
in its third iteration (Howes & Kapur, 2009). The first version of the dopamine hypothesis
focused on excessive presence of dopamine and activity of dopaminergic receptors. This idea
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was borne out of the discovery that dopamine antagonists decreased psychotic symptoms
observed in schizophrenic patients, while dopamine agonists produced symptoms that were
indistinguishable from schizophrenia-related psychosis (Bencherif, Stachowiak, Kucinski, &
Lippiello, 2012). Later, this simplistic view was modified to include excessive dopaminergic
activity in subcortical regions and deficient dopaminergic activity in the prefrontal cortex.
Today, the dopamine hypothesis in its third version takes into account newer findings,
and attempts to synthesize to a common pathway: dopamine dysregulation (Howes & Kapur,
2009). The dopamine hypothesis now recognizes that dopamine dysregulation is caused by
multiple factors, including fronto-temporal dysfunction, genes, stress, and drugs. It focuses on
presynaptic synthesis and release of dopamine (as opposed to postsynaptic receptor
characteristics) as the primary contributor to mismanaged levels of dopaminergic activity. The
modern dopamine hypothesis also makes the more modest claim that dopaminergic processes
produce psychosis—not schizophrenia directly—and that a full schizophrenia diagnosis comes
out of dopamine dysregulation in combination with sociocultural and environmental factors.
Last, today’s dopamine hypothesis links the behaviors of schizophrenia to another
behavioral process commonly associated with dopamine: reward salience. It is hypothesized that
increased presynaptic release of dopamine in the mesolimbic pathway leads to the assignment of
abnormally high salience to stimuli that would otherwise go unnoticed. The high salience
conferred by the mesolimbic pathway is then interpreted as a stimulus having meaning,
importance, or biological relevance. In this way, meaningless stimuli are seen as meaningful,
leading to approach or avoidant behaviors that are inappropriate given the objective
characteristics of the stimuli at hand (Howes & Kapur, 2009).
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The role of glutamate. Although dopamine is perhaps the most well-known
neurotransmitter system indicted in schizophrenia, others are also hypothesized to play a role in
the disorder. For example, glutamate dysfunction has been hypothesized to contribute to the
development of schizophrenia (Egerton and Stone, 2012). The essence of the theory is that stifled
functioning of NMDA (N-methyl-D-aspartate) glutamate receptors leads to understimulation of
GABA (gamma-amino-butyric-acid) inhibitory neurons. This disinhibition results in excessive
release of the excitatory neurotransmitter, glutamate. Because the dopaminergic and
glutamatergic systems are co-modulatory, the increased glutamate works downstream to increase
the amount of dopamine available (Egerton & Stone, 2012).
Functional Differences
Schizophrenia is characterized by a number of functional disturbances, which have been
linked to neural dysfunction through the use of imaging techniques. A recent meta-analysis was
conducted to review neuroimaging studies that investigate functional differences between people
with schizophrenia, their family members, and healthy controls. There was some convergence
found among results derived from functional magnetic resonance imaging (fMRI). On the whole,
schizophrenia patients demonstrated reliably less activity in the bilateral middle frontal area,
right medial frontal lobe, right cingulate, bilateral claustrum, right putamen, left thalamus, right
inferior parietal lobe, and left middle occipital lobe (Goghari, 2011). Meanwhile, the same
patients experienced higher than normal activity in the left superior and inferior frontal lobes, left
precentral, left cingulate, right insula, right superior temporal lobe, right amygdala, left inferior
parietal lobe, and right lingual regions (Goghari, 2011). These data suggest that a simplistic
account of functional differences in schizophrenia that exclusively relies on a hypoactive
prefrontal cortex is no longer sufficient. Schizophrenia appears to be characterized by alterations
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in a number of functional domains. Another compelling result of Goghari’s (2011) review was
the discovery that, for the most part, blood relatives of those diagnosed with schizophrenia show
reliable and distinct functional differences in regions similar to those of their disordered family
member. Together, these findings tell a story that genetic variants provide a predisposition for
dorsolateral prefrontal dysfunction, while other environmental factors may determine the specific
nature of that dysfunction—be it excessive or deficient activity.
Prevention and Treatment
Prevention. With the myriad of factors either theorized or demonstrated to play a role in
the etiology of schizophrenia, it is important to address efforts to manipulate population-wide
risk and protective factors to prevent schizophrenia before it appears. Upon examining the state
of the field, Kirkbride and Jones (2011) determined that there is not enough converging evidence
to support any one coherent prevention strategy that could be employed at a systems level. We
lack an efficient prevention program that we have reasonable cause to expect to be effective.
They emphasize the need for more research that ties together and reconciles the enormous
variety of risk factors and explanatory models of schizophrenia.
Treatment. If prevention is not currently a viable option, mental health professionals are
then left to treat schizophrenia as it arises. Fairly effective pharmacological treatments are
available to ameliorate the positive symptoms of schizophrenia. Both first-generation and
atypical antipsychotic medications are almost ubiquitously used to effectively reduce delusions
and hallucinations.
The problem with these medications has always been their serious and sometimes
permanent adverse effects. For example, both waves of antipsychotics can cause the
development of tardive dyskinesia in patients, which is irreversible brain damage resulting in
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abnormal tics, twitches, and movements of the face, head, and neck (Kring et al., 2012). The
second-generation (or “atypical”) class of antipsychotics were once widely hailed for their ability
to maintain drug benefits while reducing—some have even said eliminating—neurological side
effects like tardive dyskinesia. In 2005, results were published from the CATIE (Clinical
Antipsychotic Trials of Intervention Effectiveness) randomized controlled trial of around 1,500
patients on antipsychotic medications. Half of participants were blindly assigned to use either a
first-generation drug (perphenazine) or one of four atypicals (olanzapine, risperidone,
ziprasidone, or quetiapine). Conclusive results, which have since been replicated by other
researchers (Jones et al., 2006), were that atypicals were not more effective at symptom
management than the first-generation drug, those using atypicals did not have fewer adverse side
effects, and study attrition was almost 75% (Kring et al., 2012). At least two studies demonstrate
that atypical antipsychotics do cause “extrapyramidal” side effects—motor disturbances
characterized by poverty of movement (Miller et al., 2008; Rummel-Kluge et al., 2010).
Moreover, they have additional side effects that weren’t a problem with the first generation of
drugs: significant weight gain, high blood sugar, development of type 2 diabetes, increased risk
for pancreatitis, and high cholesterol (Kring et al., 2012). Needless to say, there is a need for new
pharmacological treatments that reduce debilitating symptoms without causing other serious
diseases and conditions.
An innovative attempt has been made to synthesize some of the different “hypotheses” of
schizophrenia into one coherent explanatory model that may yield a new approach to treatment.
Bencherif et al. (2012) combined hypotheses positing contributions from dopamine, glutamate,
and cholinergic systems. They attempt to reconcile these different theories by stating that
pharmacological activation of alpha7 nicotinic acetylcholinergic receptors would excite
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underactive glutamatergic neurons in the prefrontal cortex. This, in turn, would normalize the
“dopaminergic tone” in both cortical and subcortical regions (Bencherif et al., 2012). Future
research must be conducted to evaluate this new, hypothesized model and associated treatment.
Another recent line of treatment research targets and inhibits the GSK-3 protein which, as
discussed earlier, is overexpressed by certain variants of the DISC1 gene. A new chemical
compound, VP1.15, has shown promising effects on both the positive and cognitive symptoms of
schizophrenia in a rodent analog (Lipina et al., 2013). This drug’s potential ability to address
cognitive deficits such as memory and spatial object recognition makes it a unique and exciting
development unlike any schizophrenia pharmacotherapies that have preceded it.
Conclusion
Schizophrenia is a serious condition that affects a substantial number of people
worldwide. It has been linked to many risk factors and causal agents, yet we do not have a firm
grasp on the precise interaction of biological and environmental mechanisms that operates to put
schizophrenia into play. Genetics, pre- and perinatal conditions, structural abnormalities,
neurochemicals, and functional disturbances will all continue to be important to our
understanding of the disorder. Without a better understanding of the causal milieu, we cannot
effectively act to prevent schizophrenia. Further, our current pharmacological “gold standard”
treatments for the positive symptoms of schizophrenia have major problems that deserve our
immediate attention. We are currently undertaking efforts to find more effective treatments with
less ill effects—those that address more than just positive symptoms.
Future Directions
Promising lines of research are underway and hint at future innovations in the field. We
are beginning to pull together the legion of risk factors for schizophrenia to construct a more
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cohesive narrative about genetic variants and environmental conditions that converge to create
neurodevelopmental problems that ultimately manifest behaviorally as schizophrenia (Stilo &
Murray, 2010). With the SzGene database in place, researchers can continue to pool their
findings and condense them to only the most consistent and useful results. We may come upon
additional striking discoveries like GABRB2, an ethnicity-specific genetic marker for
schizophrenia vulnerability (Shi, Gerson, & Liu, 2008). Research on DISC1 and how to
manipulate its downstream agent, GSK-3, are sure to give us new treatment options (Lipina et
al., 2011; Lipina et al., 2013). Finally, the realization that dopamine dysregulation in psychosis is
the result of presynaptic dysfunction has important implications on how we focus our attention
and efforts in both understanding the mechanisms of the disorder and also attempting to alter
those processes (Howes & Kapur, 2009).
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Appendix 1
Excerpt from the DSM-IV
A.
B.
C.
D.
E.
F.
Schizophrenia
Characteristic symptoms: Two (or more) of the following, each present for a
significant portion of time during a 1-month period (or less if successfully treated):
(1) delusions
(2) hallucinations
(3) disorganized speech (e.g., frequent derailment or incoherence)
(4) grossly disorganized or catatonic behavior
(5) negative symptoms, i.e., affective flattening, alogia, or avolition
Note: Only one Criterion A symptom is required if delusions are bizarre or
hallucinations consist of a voice keeping up a running commentary on the
person’s behavior or thoughts, or two or more voices conversing with each other.
Social/occupational dysfunction: For a significant portion of the time since the
onset of the disturbance, one or more major areas of functioning such as work,
interpersonal relations, or self-care are markedly below the level achieved prior to the
onset (or when the onset is in childhood or adolescence, failure to achieve expected
level of interpersonal, academic, or occupational achievement).
Duration: Continuous signs of the disturbance persist for at least 6 months. This 6month period must include at least 1 month of symptoms (or less if successfully
treated) that meet Criterion A (i.e., active-phase symptoms) and may include periods
of prodromal or residual symptoms. During these prodromal or residual periods, the
signs of the disturbance may be manifested by only negative symptoms or two ro
more symptoms listed in Criteria A present in an attenuated form (e.g., odd beliefs,
unusual perceptual experiences).
Schizoaffective and Mood Disorder exclusion: Schizoaffective Disorder and Mood
Disorder With Psychotic Features have been ruled out because either (1) no Major
Depressive, Manic, or Mixed Episodes have occurred concurrently with the activephase symptoms; or (2) if mood episodes have occurred during active-phase
symptoms, their total duration has been brief relative to the duration of the active and
residual periods.
Substance/general medical condition exclusion: The disturbance is not due to the
direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a
general medical condition.
Relationship to a Pervasive Developmental Disorder: If there is a history of
Autistic Disorder or another Pervasive Developmental Disorder, the additional
diagnosis of Schizophrenia is made only if prominent delusions or hallucinations are
also present for at least a month (or less if successfully treated).
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Appendix 2
Excerpt from the Proposed Revisions to the DSM-V
A.
B.
C.
D.
E.
F.
Schizophrenia
Two (or more) of the following, each present for a significant portion of time during a 1month period (or less if successfully treated) At least one of these should include 1, 2, or
3.
(1) delusions
(2) hallucinations
(3) disorganized speech
(4) grossly abnormal psychomotor behavior, including catatonia
(5) negative symptoms, e.g., diminished emotional expression or avolition
For a significant portion of the time since the onset of the disturbance, one or more major
areas of functioning, such as school, work, interpersonal relations, or self-care, are
markedly below the level achieved prior to the onset (or when the onset is in childhood or
adolescence, failure to achieve expected level of interpersonal, academic, or occupational
achievement).
Continuous signs of the disturbance persist for at least 6 months. This 6-month period
must include at least 1 month of symptoms (or less if successfully treated) that meet
Criterion A (i.e., active-phase symptoms) and may include periods of prodromal or
residual symptoms. During these prodromal or residual periods, the signs of the
disturbance may be manifested by only negative symptoms or by an attenuated form of
two or more symptoms listed in Criterion A (e.g., beliefs perceived as odd, perceptual
experiences described as out of the ordinary).
Schizoaffective Disorder and Depressive or Bipolar Disorder With Psychotic Features
have been ruled out because either (1) no Major Depressive, Manic, or Mixed Episodes
have occurred concurrently with the active-phase symptoms; or (2) if mood episodes
have occurred during active-phase symptoms, their total duration has been less than half
of the total duration of the active periods.
The disturbance is not due to the direct physiological effects of a substance (e.g., an
abused drug, a medication) or a general medical condition.
If there is a history of Autistic Disorder or another Pervasive Developmental Disorder or
other communication disorder of childhood onset, the additional diagnosis of
Schizophrenia is made only if prominent delusions or hallucinations are also present for
at least 1 month (or less if successfully treated).
BIOLOGICAL BASES OF SCHIZOPHRENIA
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Appendix 3
Genes Consistently Associated with Schizophrenia
Gene
DRD1
DTNBP1
MTHFR
TPH1
Known function(s)
Codes for the production of D1 dopamine receptors—the most
common dopamine receptors in the brain. These receptors regulate
neural activity in the prefrontal cortex.
Codes for the production of the protein dysbindin, which is present
in neural tissue.
Codes for 5,10-methylenetetrahydrofolate reductase, which converts
5,10-methylenetetrahydrofolate into 5-methyltetrahydrofolate. This
latter chemical is involved with methylation processes that may alter
the activation of other genes.
Codes for the production of tryptophan hydroxylase 1, which is an
enzyme that breaks down the precursor to serotonin.
BIOLOGICAL BASES OF SCHIZOPHRENIA
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