Schizophrenia -- Risk factors. Glatt, and Levi Taylor 2. Tsuang, and Sarah I. A Neuropsychological Perspective on Vulnerability to Schizophrenia: Mirsky and Connie C. Kremen and Anne L. Prevention of Schizophrenia and Psychotic Behavior: Hendricks Brown and Stephen V. Faraone, and Ming T. Glatt, and Stephen V.
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Except where otherwise stated, drug dosages and recommendations are for the non-pregnant adult who is not breastfeeding. There are currently recognized precursors of schizophrenia that are apparent during adolescence. A wide variety of early intervention techniques have been developed that draw on the knowledge of these precursors to identify individuals at risk for the illness and to prevent the predisposition toward schizophrenia from developing into the full disorder.
Most of the research that enabled the identification of these precursors and the development of these intervention techniques was performed retrospectively in adults with schizophrenia, with little specific research attention directed toward forms of schizophrenia that manifest during adolescence. In addition, prevention efforts have necessarily lagged behind studies of the risk factors, detection, and early intervention of the disease.
Yet a great deal has already been learned about risk-profiling and early intervention in schizophrenia generally, and those aspects that may be useful in understanding the adolescent forms of the illness are discussed below. Traditionally, prevention efforts have been classified into three levels: This classification scheme is attractive and simple, but it does not distinguish between preventive interventions that have different epidemiological justifications and require different strategies for optimal utilization.
For example, it focuses on intended outcomes rather than on target populations or prevention strategies. The terms universal, selective , and indicated have been adopted as a valuable way to distinguish preventive interventions. All three of these strategies refer to the target population. Universal preventive interventions are applied to whole populations and aim at reducing risk and promoting protective factors. Because obstetric complications have been linked to the subsequent onset of schizophrenia in several studies Zornberg et al.
In contrast to universal prevention strategies, selective and indicated interventions target specific subgroups for intervention. Selective interventions target those who are at elevated risk based on group-level characteristics that are not directly related to etiology. Because schizophrenia is a familial and heritable disorder Gottesman, , a selective prevention program for schizophrenia might focus on asymptomatic children with first-degree affected relatives or, more specifically, on those with particular combinations of schizophrenia-risk-specific gene variants, as they become known.
Finally, an indicated intervention involves targeting individuals who either have signs of the disorder but are currently asymptomatic, or are in an early stage of a progressive disorder. Because there are no universal signs of schizophrenia, indicated interventions for this disorder have a somewhat broad definition. Two lines of research that may lead to indicated interventions for schizophrenia include the study of individuals with prodromal signs of schizophrenia Eaton et al. To develop and refine selective and indicated prevention efforts for schizophrenia, the disorder itself as well as its precursors must be thoroughly understood.
Some of the risk factors for schizophrenia, such as birth complications and a family history of the disorder, are widely recognized. Others are just becoming known or are still being validated. When a wide variety of schizophrenia-specific precursors are available, these features can be used to maximize the efficiency and effectiveness of preventive efforts by narrowly specifying the characteristics of at-risk individuals, allowing only those who would benefit from intervention to be selected to receive it. The schizophrenia syndrome, the delusions, hallucinations, thought disorder, negative features, and cognitive dysfunction, is manifest at some stage during the lives of around 1 in people.
However, important events may be occurring in the period leading up to illness and in the early years of development, the so-called prodromal and premorbid periods. Prodromal and Premorbid Phases of Schizophrenia. In most cases, schizophrenia does not come totally out of the blue; there are important changes that occur before the psychotic syndrome. Fragmentary psychotic symptoms, depression, changes in behavior, attenuated general functioning, and other nonspecific features commonly occur in the weeks, months, and sometimes years before the first psychotic break.
This period before the schizophrenia syndrome is established is known as the prodrome, and it represents a change that can frequently be identified by either the affected individual or his or her family members. The prodrome is a period of considerable interest from a clinical and theoretical point of view because it may be possible to intervene early during this time and so prevent the onset of psychosis or improve its outcome. This exciting prospect of early intervention, considered in Chapter 6 , is technically complex because of the nonspecific nature of some of the symptoms in the prodrome.
Schizophrenia or other psychoses are by no means inevitable in a group of adolescents who show apparently prodromal features. Looking back to adolescents who have developed schizophrenia, the psychological difficulties are, of course, much more difficult. Much research is aiming to understand the biology underlying this period just before and around the onset of schizophrenia when important neuropsychological and structural changes may be occurring Pantelis et al.
There are other differences and abnormalities that occur well before the period of risk shown in Figure 7. They are not only in a psychological domain and show no obvious continuity p. Rather than changes from the preexisting state that herald the illness during a prodrome, these differences are more a long-term part of the person, his or her personality and early development.
These differences are known as premorbid features. The distinction from the prodrome is not always clear, particularly in younger people, but may have theoretical importance because they seem to point toward early vulnerability or predisposing factors, rather than to events that occur as an illness is triggered or precipitated.
The existence of premorbid abnormalities and differences in those who will, years later, develop schizophrenia suggests that parts of the epigenetic puzzle are put in place in very early life. In childhood-onset cases, the distinction may be almost impossible because of the severity and insidious onset of schizophrenia before age 13 Alaghband-Rad et al.
Why look in early life for premorbid differences and causes of schizophrenia? From its first descriptions, schizophrenia has had a longitudinal dimension. When defining the schizophrenia syndrome more clearly, both Kraepelin and Bleuler , noted that many of the people who developed the psychotic syndrome had been different from their peers long before the psychosis began. All ten of my own school comrades who later became schizophrenics were quite different from the other boys. If some of the seeds of schizophrenia are sown in early life, then there ought to be other evidence.
The excess of minor physical abnormalities Green et al. These factors and some of the neuropathological data are probably best explained in terms of developmental processes having gone awry Weinberger, However, these processes are difficult to observe directly. Genetic high-risk studies, where the offspring of people with schizophrenia are followed up, have shown subtle differences in the neurological development of these children at special risk, and in those not known to be so Erlenmeyer-Kimling et al. Genetic studies such as these are discussed in Chapter 5.
This may be partly an artifact of some research designs, as well as an effect of differences in the wiring of male and female brains. Many aspects of development can be seen to be slightly different in children who will later develop schizophrenia. Often these differences are subtle and would not be noticed at the time by parents or professionals.
Here are some examples. Direct evidence of neurodevelopmental differences is available Weinberger, One source is a remarkable piece of opportunistic research by Walker and colleagues , The pre-schizophrenic children were distinguished on both accounts, some with fairly gross but transitory motor differences. These may point to the basal ganglia of the brain as being involved in the underlying mechanism, reminding us that subtle motor disturbances are apparent at the beginning of schizophrenia, before any treatment Gervin et al.
Such developmental differences have now been demonstrated in large, population-based or epidemiological samples. In the British birth cohort, a group of several thousand people born in one week in March have been studied regularly throughout their lives. Their mothers were asked about development when the children were age 2 years, before anyone knew what would happen later on. All the milestones of sitting, standing, walking, and talking were slightly though clearly delayed in those who developed schizophrenia as adults, but there was nothing that would have alarmed parents at the time.
There were other indications that language acquisition was different before onset of schizophrenia. Nurses were more likely to notice a lack of speech by 2 years in the children who developed schizophrenia as adults, and school doctors noted speech delays and problems in them throughout childhood. Developmental differences have been replicated in similar cohort studies in other domains, such as bladder control, fine motor skill, and coordination during late childhood and adolescence Cannon et al. The motor and language delays were replicated and extended in a birth cohort study from Dunedin, New Zealand Cannon et al.
Those who indicated in their mids that they had experienced symptoms suggestive of schizophrenia, mania, and other disorders were compared with those who said that they had never had such phenomena. Developmental differences before the onset of schizophrenia have been observed during the first year of life in the North Finland birth cohort. This comprises about 12, babies due to be born in this geographic area during Rantakallio, Their early development was charted in the first year of life and later linked to information about who had developed schizophrenia through adolescence and into the early 30s Isohanni et al.
The figure for girls was similar. It is clear that not only was there an effect whereby the later a boy learned to toddle, the greater was his chance of developing schizophrenia in later life, but also that this effect seemed to hold true throughout the range of variation in reaching this milestone, all of which might be considered normal.
If one were looking only for very late developers, then one might be more likely to find them within the pre-schizophrenia group than in those who did not develop the illness. However, this approach would completely obscure the widespread nature of this association, the meaning of which is considered later on. There is another finding apparent from Figure 7. For the boys who passed the milestone early, in the 9-month and month categories, the relatively few individuals who developed schizophrenia all did so in their mid-teens to mids; their period of risk seemed fairly short.
For those who were later developers, the period of risk was longer; these groups are still accruing cases of schizophrenia into their early 30s and beyond. It may be that the overall risk period for schizophrenia is shorter where neurodevelopment is more efficient, and longer where it is less efficient.
Studies in this area have also moved on through retrospective research methodologies to cohort designs. Robins undertook a pioneering, historical cohort study in which she followed a group of boys who had been referred to a child guidance clinic in St. Here antisocial behavior was associated with later schizophrenia. Watt and Lubensky ; Watt, traced the school records of people with schizophrenia who came from a geographically defined neighborhood in Massachusetts.
Girls who were to develop schizophrenia were introverted throughout kindergarten into adolescence. This pattern has been identified Done et al.
The two views gave a very similar picture; the shyer someone seemed as a child, the greater the risk. Other studies do, however, remind us of the varied childhood psychiatric conditions that predate schizophrenia Kim et al. The behavioral differences seem to persist toward the prodrome but are independent from it. Four behavioral variables at age 18 were particularly associated with later schizophrenia: Another twist to the story about premorbid behavioral differences comes from the recognition that some of the individual parts of the schizophrenia syndrome, such as hallucinations or delusions, can exist in otherwise well-functioning individuals in the population.
However, they are indeed associated with a greater risk of occurrence of subsequent schizophrenia whether they occur in early adolescence Poulton et al. Thus, there seems to be a consistency over childhood and adolescence, and across several types of study, regarding the presence of premorbid behavioral differences. People who will develop schizophrenia as adolescents and adults are different from their peers in terms of behavior in childhood, just as Bleuler noted a p.
This aspect of psychological function also shows differences in the premorbid period. Aylward, Walker, and Bettes have provided a comprehensive review of intelligence in schizophrenia. They concluded that intellectual function is lower in pre-psychotic individuals than in age-matched controls. Linking the pre-psychotic deficit to outcome, they raised the question as to whether IQ may be an independent factor that can protect otherwise vulnerable individuals, or whether the deficits are part of that vulnerability.
Once again, the birth cohort studies shed light on the question. When the childhood IQ data from the cohort Pidgeon, , are studied in greater detail, it is clear that the lower mean premorbid IQ is not due to a subset of people with very low scores; rather, the whole distribution of those who will develop schizophrenia when they reach adolescence or adulthood is shifted down—the majority or most children seem not to be doing as well as they might have been expected to perform Jones et al.
This is a similar situation to the motor findings in the Finnish cohort. It is not that there is a group of very abnormal individuals driving the findings; the effects are seen across the normal range. There was no evidence of a threshold effect below or above which this relationship did not hold. Very bright individuals can develop schizophrenia, but they are less likely to than those who are less able. Put another way, any individual is more likely to develop schizophrenia than someone who is more able in terms of IQ, although the effect is small.
The range of differences in the developmental histories of people who will develop schizophrenia when they are older suggests that something p. There is evidence for many such early factors, including genetic effects Fish et al. It seems that many events that may lead to early brain development being suboptimal may increase the risk of later schizophrenia. There may be specific causes or combinations of causes, such as gene—environment interactions, that make people vulnerable to developing the schizophrenia syndrome, perhaps after later, necessary events that act as triggers.
These may include normal Weinberger, , or abnormal brain development Feinberg, a , b , ; Pogue-Geile, , as well as traditional precipitants such as psychosocial stressors or drugs see Chapter 6. The behavioral, motor, language, and cognitive differences shown in the premorbid period may be manifestations of vulnerability or predisposition to schizophrenia; they may not be risk modifiers in themselves.
These indicators seem remarkably homogeneous—in retrospect, like a final common pathway. Most or even every person who develops the syndrome may have had a degree of developmental vulnerability, although this will not have been obvious at the time. The early motor findings in the Finnish birth cohort see Fig. The greater the inefficiency, the greater the risk of schizophrenia when that same inefficiency is played out in the formation of complex and integrative systems later in adolescence and adult life see Chapter 5.
There are several candidates to explain this unifying vulnerability. Molecular biology and the investigation of not only the presence but also the functional activity of genes and the proteins for which they code may yield other dimensions of vulnerability. For instance, Tkachev et al. This seems a very good candidate for the homogeneous vulnerability factor posited in this account of premorbid abnormalities before schizophrenia, and may be an endophenotype or hidden manifestation of the disorder.
The deficient gene expression remains to be demonstrated before the onset of schizophrenia and will, itself, have its own prior causes. As mentioned at the beginning of this section, premorbid features of schizophrenia are, in our current understanding, not yet of use in terms of prediction and early intervention.
They occur in multiple domains, but many of the effects we can measure are subtle and leave individuals remaining well within the wide range of normality. Premorbid features tell us a great deal about what we should be looking for in terms of underlying mechanisms and causes of schizophrenia, and when these may operate; they are signposts toward these.
As we learn about the processes that underpin the behavioral, cognitive, and motor differences that we can measure in the premorbid phase of schizophrenia, we may become able to identify those who are vulnerable with enough precision to be able to do something useful for them. Developmental Precursors of Adolescent-Onset Schizophrenia. There are precursors of schizophrenia prior to the first onset of psychosis in many, but not all, adolescents who develop schizophrenia. As will be seen below, the precursors of schizophrenia p. Identifying the developmental precursors of adolescent-onset schizophrenia has important implications both for enhancing our understanding of the underlying neurobiology of schizophrenia, and for the development of preventive interventions for schizophrenia.
Neurobiological factors present in individuals at high risk for developing a schizophrenic disorder, prior to the onset of frank psychotic symptoms, may represent potential etiological factors for schizophrenia. Asarnow, ; Cannon et al. Determining how these neurobiological factors evolve when a schizophrenic disorder develops could provide important clues about how the diathesis for schizophrenia is potentiated into the overt disorder.
A combination of disease-related progressions and maturational changes is hypothesized to exacerbate these dysfunctions when individuals at risk for the disorder convert to having the disorder. Two broad classes of methods have been used to identify developmental precursors of schizophrenia.
The first class of methods is prospective studies of children. A common feature of prospective methods is identifying, then characterizing, a group of children and following them up to determine which children subsequently develop a schizophrenic disorder.
One important prospective method is to study children who are at increased statistical risk of developing a schizophrenic disorder. High-risk studies ascertain individuals with an increased lifetime risk for schizophrenia for inclusion in prospective, longitudinal studies. This is typically accomplished by studying the children of parents with schizophrenia. High-risk studies frequently measure putative etiological factors for schizophrenia prior to the onset of the disorder.
In this way, studies of children at risk for schizophrenia provide a vehicle for testing hypotheses about etiological factors in schizophrenia. Recognition of this problem has led to an interest in complementary strategies for identifying developmental precursors of schizophrenia. Birth cohort studies are prospective studies that can provide information on precursors of schizophrenia that do not have some of the ascertainment biases inherent in high-risk studies.
In contrast to studies of children at risk for schizophrenia, birth cohort studies follow up large, representative samples of entire birth cohorts. Birth cohort studies are designed to provide information about a wide range of medical, psychiatric, and social conditions, so they use very large samples, literally thousands of subjects. For example, the British birth cohort study that provided important data on developmental precursors of schizophrenia studied almost 5, children born in the week of March 9, , then systematically followed them up to determine that 30 children developed schizophrenia, as well as a broad range of other psychiatric and medical outcomes.
A great strength of birth cohort studies is the large, representative sample size. However, a limitation of birth cohort studies is that since they are not typically p. By studying children prior to the onset of the disorder, it becomes possible to identify the precursors or antecedents of the disorder, as opposed to the consequences of the disorder—for example, the initiation of antipsychotic drug treatment. We will review some of the key findings that have emerged from three decades of studies of children at risk for schizophrenia and birth cohort studies.
A second class of methods involves the collection of information on the premorbid development of individuals, usually adults, who have been diagnosed with schizophrenia. Some of the earliest studies of this type relied on retrospective reports from informants who knew the patient as a child. This approach has obvious limitations, among them being the fact that recollections of the past may be subject to bias.
The follow-back method features the ascertainment of individuals with schizophrenia and then, using different types of archival material, characterizing them prior to the onset of psychosis. Since the focus of this section is on adolescent-onset schizophrenia, we will emphasize those few studies that ascertained adolescent-onset schizophrenics. Follow-back studies vary in the type of archival material used to describe the premorbid characteristics of individuals who develop schizophrenia.
There is wide agreement see Watt et al. The major limitation of follow-back studies is that the childhood evaluations were not guided by specific hypotheses about the age-specific manifestations of schizophrenia; as a consequence, the most informative measures may not have been collected. They also have ascertainment biases, the nature of which varies depending on how the sample of schizophrenia patients was identified. Birth cohort and follow-back studies can show associations between childhood characteristics and the development of schizophrenia because in both types of studies individuals with schizophrenia have been identified.
These associations are prospective in birth cohort studies and retrospective in follow-back studies. Because the data used to describe childhood risk factors in birth cohort and follow-back studies were not collected with the intent of testing hypotheses about schizophrenia, the measures may not be sensitive to some of the more subtle manifestations of liability to schizophrenia.
In contrast, the measures included in studies of children at risk for schizophrenia were specifically designed to tap liability to schizophrenia.
Some of the risk factors for schizophrenia, such as birth complications and a family history of the disorder, are widely recognized. Such developmental differences have now been demonstrated in large, population-based or epidemiological samples. Follow-back studies vary in the type of archival material used to describe the premorbid characteristics of individuals who develop schizophrenia. Depending on the risk profile of the intervention, cutting scores on neurocognitive indices could be constructed to either maximize sensitivity or minimize false positives. Studies in this area have also moved on through retrospective research methodologies to cohort designs. The clinical high-risk method is an extension of the Melbourne ultra-high-risk criteria for identifying young people thought to be at high risk of psychosis, also known as New York hillside recognition and prevention NYH-RAP. There was an increased frequency of speech problems up to age 15 in persons who subsequently developed schizophrenia.
On the other hand, most studies of children at risk for schizophrenia, while intended to be longitudinal, were not able to follow up subjects through the age of risk to determine which high-risk subjects developed a schizophrenic disorder. Consequently, while there are extensive cross-sectional comparisons of children at risk for schizophrenia to controls, there is much less information on the long-term predictive validity of childhood risk factors identified in high-risk studies. If the results of follow-back studies of adolescent-onset schizophrenia patients yield converging results to those of children at risk for schizophrenia and birth cohort studies, this would provide reassurance about the generalizability and validity of the results.
There are relatively age-specific manifestations of liability to schizophrenia see J. Asarnow, ; R. Asarnow, ; Erlenmeyer-Kimling et al. For example, one of the interesting findings that emerges from a review of developmental precursors of schizophrenia is that some deficits observed during infancy frequently found in high-risk, birth cohort, and follow-back studies are not found in later stages of development. Another important reason to attend to p.
In Early Clinical Intervention and Prevention in Schizophrenia, leading and internationally recognized researchers review what is known about the liability to . Early Clinical Intervention and Prevention in Schizophrenia: Medicine & Health Science Books @ linawycatuzy.gq
Cited below are comprehensive reviews of the results of high-risk, birth cohort, and follow-back studies. High or variable sensitivity to sensory stimulation. Low communicative competence in mother—child interaction, less social contact with mothers. Inconsistent, variable performance on cognitive tests. More likely to receive a diagnosis of developmental disorder. Passive impairment poor fine motor coordination, Socially balance, sensory perceptual isolated signs, delayed motor development. Poor social adjustment Attentional impairment under ADD overload conditions.
Poor affective control emotional instability, aggressive, disruptive, hyperactive, impulsive. Poor interpersonal relationships, withdrawn Cognitive slippage disturbance. Mixed internalizing-externalizing symptoms, fearful ADD-like syndrome. The format of Table 7. The entries in Table 7. Asarnow , Erlenmeyer-Kimling , , R. Asarnow , and Cornblatt and Obuchowski The entries for birth cohort studies are based on reviews by Jones, Rogers, Murray, and Marmot and Jones and Tarrant The data for entries of follow-back studies of adolescent-onset schizophrenia come from Watkins, Asarnow, and Tanguay , and Walker, Savoie, and Davis Watt and Saiz provided a broad review of follow-back studies of adult-onset schizophrenia.
Two types of risk characteristics are differentiated into separate columns in Table 7. Endophenotypes are putative reflections of the underlying schizophrenic genetic diathesis. Most of the putative endophenotypes employed in high-risk studies are neuromotor or neurocognitive functions e. In contrast, clinical and behavioral features are either non-schizophrenia psychiatric symptoms or behavior problems that, while they may reflect the underlying genetic diathesis, are much more proximal to the overt symptoms of schizophrenia. The reason for making this distinction is that these two different classes of risk characteristics have somewhat different implications as targets for prevention.
The results of high-risk studies have to be considered in the context of a major limitation: Only six studies of children at risk for schizophrenia have obtained diagnostic evaluations in adulthood or late adolescence:. The Copenhagen High-Risk project Cannon et al. The Israeli High-Risk study Ingraham et al. The Jerusalem Infant Development study Hans et al.
The New York High-Risk project studied the largest number of subjects for the longest period of time, and therefore provides the most extensive data on the diagnostic accuracy of childhood and adolescent predictors of schizophrenia-related psychoses. None of these studies focused on the prediction of adolescent-onset schizophrenia. Indeed, there are very few cases of adolescent-onset schizophrenia in the entire high-risk literature. As a consequence, we are making the assumption that the factors that predict adult-onset schizophrenia are germane to the prediction of adolescent-onset schizophrenia.
In these studies neuromotor anomalies were assessed by observation during a pediatric neurological examination or by performance on standardized tests of infant development e. Neurological signs and neuromotor dysfunctions are not specific to infants at risk for schizophrenia and are not rare events in the general pediatric population.
Neurological abnormalities in neonates typically tend to improve.
In contrast, it appears that these abnormalities in children at risk for schizophrenia persist, and may worsen over time. Infants with neurological or neuromotor abnormalities are the high-risk infants most likely to develop schizophrenic disorders in adolescence and early adulthood Fish, ; Marcus et al. Neurological dysregulation in infancy predicts the development of schizophrenia spectrum disorders Fish, Impaired performance on tasks with extensive motor demands during middle childhood also predicts the presence of schizophrenia spectrum disorders during adolescence Hans et al.
Disturbances in early social development are found more frequently in children at risk for schizophrenia than controls. Depending on the study, these disturbances are manifested in difficult temperaments, apathy or withdrawal, being inhibited, less spontaneous and imitative, reduced social contact with mothers, and the absence of fear of strangers.