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Published: 4 June 2021
Last updated: 12 February 2022

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1

Häfner, Heinz, ed. Risk and Protective Factors in Schizophrenia. Heidelberg: Steinkopff, 2002. http://dx.doi.org/10.1007/978-3-642-57516-7.

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2

Vulnerability to psychopathology: Risk across the lifespan. 2nd ed. New York: Guilford Press, 2010.

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3

Risk and protective factors in schizophrenia: Towards a conceptual model of the disease process. Darmstadt, Germnany: Steinkopff, 2002.

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4

McGorry, Patrick D., Alison Yung, and Lisa Phillips. Treating Schizophrenia in the Prodromal Phase. Informa Healthcare, 2004.

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5

Early Clinical Intervention and Prevention in Schizophrenia. Humana Press, 2003.

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6

PhD, Stone William S., Faraone Stephen V, and Tsuang Ming T. 1931-, eds. Early clinical intervention and prevention in schizophrenia. Totowa, N,J: Humana Press, 2004.

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7

Early clinical intervention and prevention in schizophrenia. Totowa, NJ: Humana Press, 2003.

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8

Brar, Jaspreet S. Epidemiology of Schizophrenia. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199331505.003.0003.

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Epidemiology can help us understand who is at risk for developing a disorder, what may happen to them, and perhaps even why people get the disorder to begin with. In this chapter, we will review the incidence and prevalence of schizophrenia and related psychotic disorders, as well as factors affecting such rates. Risk factors for psychosis include socio-demographics (e.g., gender, age, migrant status, class), predisposing factors (e.g., season of birth, perinatal trauma), and precipitating factors (e.g., substance use, psychosocial stress). We will highlight controversial issues such as traumatic life events, prenatal infection, and cannabis use, considering how epidemiological factors can shed light on the pathogenesis of schizophrenia and related illnesses.
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9

A, Miller Gregory, ed. The behavioral high-risk paradigm in psychopathology. New York: Springer, 1995.

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10

Wolfram an der Heiden (Assistant), Franz Resch (Assistant), Johannes Schröder (Assistant), and Heinz Häfner (Editor), eds. Risk and protective factors in schizophrenia: Towards a conceptual model of the disease process. Steinkopff-Verlag Darmstadt, 2003.

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11

E, Rolf Jon, and Garmezy Norman, eds. Risk and protective factors in the development of psychopathology. Cambridge: Cambridge University Press, 1990.

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12

(Editor), Rick E. Ingram, and Joseph M. Price (Editor), eds. Vulnerability to Psychopathology: Risk across the Lifespan. The Guilford Press, 2000.

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13

E, Ingram Rick, and Price Joseph M, eds. Vulnerability to psychopathology risk across the lifespan. 2nd ed. New York: Guilford Press, 2010.

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14

Brunelle, Sarah, Ipsit V. Vahia, and Dilip V. Jeste. Late-onset schizophrenia. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199644957.003.0046.

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Although schizophrenia with onset in middle or late-life is a relatively uncommon, a considerable proportion of patients do experience the first manifestations of the disease after the age of forty. The current nomenclature utilizes terminology based on age at onset: late-onset schizophrenia (LOS) for illness with onset between ages 40 and 60, and very-late-onset schizophrenia-like psychosis (VLOSLP) for onset after age 60. Recent evidence suggests more similarities than differences in epidemiology, etiology or risk factors and clinical presentation between these clinical entities, although a later onset seems to be associated with better premorbid functioning and female gender. Relatively stable cognitive deficits are observed in patients regardless of age at onset and LOS is generally not associated with a dementia, although VLOSLP are more likely to be associated with neurodegenerative processes. Antipsychotic medication is the mainstay of treatment and some psychosocial interventions may prove beneficial, but there is a lack of clinical trials focused on patients with onset in late-life. Response to treatment and outcomes tend to be better than among those with earlier onset, but special consideration should be given to biological and psychosocial factors related to the older age of patients
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15

Wittorf, Andreas. Neuropsychologische Defizite Als Vulnerabilitaetsindikatoren Fuer Schizophrenien: Eine Neuropsychologische Laengsschnittstudie an Schizophrenen Patienten, Gesunden Angehoerigen Ersten Grades und Kontrollen. Lang AG International Academic Publishers, Peter, 2002.

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16

Castle, David J., Peter F. Buckley, and Fiona P. Gaughran. The metabolic syndrome in schizophrenia. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780198811688.003.0003.

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The metabolic syndrome (MS) is a constellation of risk factors including increased waist circumference, high blood pressure, and elevated fasting glucose and triglycerides in conjunction with low levels of high-density lipoprotein. MS is associated with an elevated risk of adverse cardiovascular and other events. The general population rate of MS is increasing, but people with schizophrenia have markedly elevated rates compared to people without a mental illness. Reasons for this excess are complex, but certain antipsychotic agents can exacerbate risk and due care needs to be taken in prescribing such medications, with awareness of longitudinal risk. Treatment needs to be provided following established guidelines, to address aspects of MS should they occur.
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17

Castle, David J., Peter F. Buckley, and Fiona P. Gaughran. Reasons for excess medical morbidity in schizophrenia. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780198811688.003.0002.

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This chapter asks why it is that people with schizophrenia are at such high risk for so many physical health maladies. The answers are complex and multidimensional, encompassing shared aetiological factors, schizophrenia-related factors, personal issues, and system issues. Research into these causes and their associations with each other is advancing and is able to inform appropriate therapeutic interventions. At an individual patient level, it is important for clinicians to appreciate how these factors can interact with each other in increasing risk, so that person-specific factors can be addressed. There is also potential for system-level changes to be informed by these understandings: such changes require an appreciation of the breadth of these issues and of the barriers that act to exacerbate underlying vulnerabilities.
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18

Castle, David J., Peter F. Buckley, and Fiona P. Gaughran. Physical Health and Schizophrenia (Oxford Psychiatry Library). Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780198811688.001.0001.

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The association between mental health and physical health forms the core of this book. While it is recognized that serious mental illnesses such as schizophrenia carry a reduced life expectancy, it is often assumed that suicide is the main cause of this disparity. But in actuality, suicide accounts for no more than a third of the early mortality associated with schizophrenia: the vast majority is due to cardiovascular factors. This book seeks to put this stark fact in context, detailing the extent of cardiovascular risk, sharing information regarding reasons for this excess, and outlining approved approaches for screening for and treatment of such risk factors in people with schizophrenia. As such, this book seeks to inform those caring for people with schizophrenia of these parameters and suggests ways in which they may be addressed, using a holistic model which embraces shared decision-making and which is compatible with the recovery framework. It provides guidance regarding monitoring as well as information about focused interventions that can help ameliorate risk. It also addresses those physical health factors apart from cardiovascular, that add to the burden of ill health amongst people with schizophrenia: pulmonary health, bone health, sexual health, and cancer risk are just some of these. In addition, the book provides patient and carer information material that can be used to try to ensure that all involved have a truly informed role in decision-making about their treatment and that both psychiatric and physical health issues are taken seriously.
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19

Lally, John, and James H. MacCabe. Epidemiology, impact, and predictors of treatment-resistant schizophrenia. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780198828761.003.0004.

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Treatment-resistant schizophrenia (TRS) is a disabling psychotic disorder that affects approximately 30% of those diagnosed with schizophrenia. In a significant proportion (about 70%) of patients with TRS, their illness is treatment-resistant from onset (early or primary treatment resistance), whilst, in the remainder, treatment resistance develops during the course of illness (late or secondary treatment resistance). TRS is associated with reduced quality of life and increased social and economic burden. Multiple sociodemographic, clinical, and biological risk factors have been assessed in relation to TRS, but their interpretation remains limited owing to methodological variation, lack of replicability, and a paucity of longitudinal studies. This chapter will review the epidemiology, societal and economic burden, and risk factors associated with TRS.
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20

Erlich, Matthew D., Thomas E. Smith, Ewald Horwath, and Francine Cournos. Schizophrenia and Other Psychotic Disorders. Oxford University Press, 2014. http://dx.doi.org/10.1093/med/9780199326075.003.0004.

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Patients with schizophrenia experience three categories of symptoms: positive (delusions and hallucinations); negative (blunting of affective expression, loss of volition, and apathy); and disorganized (as reflected by a formal thought disorder). A diagnosis of schizophrenia requires that continuous signs of illness, which may include prodromal and residual symptoms, be present for at least 6 months. Research indicates that schizophrenia is likely a neurodevelopmental illness with clear heritable risk factors. Patients with schizophrenia tend to have an illness onset by young adulthood and a generally debilitating and long-term course, but the degree of disability and functional impairment is widely variable. Other illnesses characterized by prominent psychotic symptoms include schizoaffective disorder and delusional disorder. Treatment for psychotic illnesses includes antipsychotic medication and recovery-oriented psychosocial interventions aimed at “psychiatric rehabilitation” wherein patients can learn or relearn skills necessary to live independently and work competitively.
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21

Ingram, Rick, and Joseph Price. Vulnerability to Psychopathology: Risk across the Lifespan. The Guilford Press, 2002.

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22

Castle, David J., Peter F. Buckley, and Fiona P. Gaughran. Interventions for metabolic problems in people with schizophrenia. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780198811688.003.0008.

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To address the risk factors associated with early death in people with schizophrenia, a comprehensive framework is required. This is required to address individuals, systems, and the community. A number of specific frameworks are available to provide better physical health treatments for people with schizophrenia. The most effective of these embrace elements of self-management and self-efficacy. The engagement of patients, carers, and clinicians requires concerted work and effective communication. Peer workers can play a particular role. Various medications can also be used to address specific aspects of the metabolic syndrome in particular, and care should be taken to try to choose (where feasible) antipsychotic medications with the lowest possible risk of metabolic syndrome.
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23

Prasad, Konasale M. Course, Prognosis, and Outcomes of Schizophrenia and Related Disorders. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199331505.003.0004.

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Course and outcome in schizophrenia and related disorders historically depend on diagnostic conceptualizations, with significant variability even across individuals with the exact same diagnosis. In this chapter, we will review the heterogeneity of course and outcome, providing some context in terms of factors that affect prognosis. Generally speaking, current outcomes are better than previously thought, with three-quarters of individuals having a good prognosis. Although these illnesses cannot be cured, we know that recovery is possible. The best predictors of outcome in schizophrenia are cognitive and negative symptoms (not positive symptoms), along with premorbid functioning, duration of untreated psychosis, and treatment adherence over time. Finally, we will touch on functional outcomes such as risk of violence and suicide, as well as issues around treatment discontinuation.
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24

Sun, Amanda, and Vinod H. Srihari. QTc-Interval Abnormalities and Psychotropic Drug Therapy in Psychiatric Patients. Edited by Ish P. Bhalla, Rajesh R. Tampi, Vinod H. Srihari, and Michael E. Hochman. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190625085.003.0037.

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This chapter provides a summary of a landmark study on schizophrenia and the impact of demographic factors and psychotropic medications on markers of risk for cardiac events. Is QTc prolongation associated with specific psychotropic medications, the dose, or other factors? What is the correlation between other QT or T-wave abnormalities and these factors? Starting with these questions, it describes the basics of the study, including funding, study location, who was studied, how many patients, study design, study intervention, follow-up, endpoints, results, and criticism and limitations. The chapter briefly reviews other relevant studies and information, discusses implications, and concludes with a relevant clinical case.
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25

Brennand, Kristen. Application of Stem Cells to Understanding Psychiatric Disorders. Edited by Dennis S. Charney, Eric J. Nestler, Pamela Sklar, and Joseph D. Buxbaum. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190681425.003.0005.

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While much has been learned through clinical post-mortem and neuroimaging studies of patients and animal models of autism spectrum disorder (ASD), bipolar disorder (BD) and schizophrenia (SZ), these classical approaches have yet to fully elucidate the interaction of complex genetic risk factors on disease predisposition. The derivation of human induced pluripotent stem cells (hiPSCs) from patients with psychiatric disorders permits the study of the full complement of risk variants (known and unknown) that underlie disease predisposition, precisely in the cell types relevant to disease. The following chapter covers work to date regarding the advancements in the use of hiPSCs to model psychiatric disorders.
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26

Castle, David J., Peter F. Buckley, and Fiona P. Gaughran. Smoking and schizophrenia. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780198811688.003.0005.

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Rates of cigarette smoking are extremely high among people with schizophrenia. Reasons include social affiliation factors, negative symptom amelioration, and cognitive enhancement. It is crucial that people with schizophrenia are provided with information about the risks associated with smoking and given the opportunity to engage in smoking cessation programmes. Medications such as nicotine replacement therapy, bupropion, and varenicline can be used effectively and safely, but extra vigilance for neuropsychiatric side effects is required. There is potentially a role for electronic cigarettes in helping people with schizophrenia quit smoking, but more research is required in this regard.
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27

Gelernter, Joel. Complex Trait Genetics and Population Genetics in Psychiatry. Edited by Turhan Canli. Oxford University Press, 2014. http://dx.doi.org/10.1093/oxfordhb/9780199753888.013.016.

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Nearly all behavioral traits, ranging from personality traits such as neuroticism to schizophrenia and autism, are genetically influenced. With only minor exceptions, all are genetically complex—meaning that inheritance is not simply dominant or recessive or sex-linked, but follows more complex patterns indicative of more complex mechanisms. Most risk variants identified to date have only small effects on risk, and, in most cases, many risk variants at many risk loci interact with environmental factors to produce the phenotype. Such complexity has led to great challenges in increasing our knowledge of the inheritance of behavioral traits. Recent methodological advances have provided an improved set of tools that has led to advances in our understanding of the genetic influences on a range of behavioral traits. This chapter examines some of the issues involved that tend to make this a difficult problem and some of the solutions now being employed to approach those problems.
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28

Levinson, Douglas F., and Walter E. Nichols. Genetics of Depression. Edited by Dennis S. Charney, Eric J. Nestler, Pamela Sklar, and Joseph D. Buxbaum. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190681425.003.0024.

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Major depressive disorder (MDD) is a common and heterogeneous complex trait. Twin heritability is 35%–40%, perhaps higher in severe/recurrent cases. Adverse life events (particularly during childhood) increase risk. Current evidence suggests some overlap in genetic factors among MDD, bipolar disorder, and schizophrenia. Large genome-wide association studies (GWAS) are now proving successful. Polygenic effects of common SNPs are substantial. Findings implicate genes with effects on synaptic development and function, including two obesity-associated genes (NEGR1 and OLFM4), but not previous “candidate genes.” It can now be expected that larger GWAS samples will produce additional associations that shed new light on MDD genetics.
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29

Thompson, Alexander, Daniel Williams, Oliver Freudenreich, Andrew Angelino, and Glenn Treisman. Psychotic Disorders and Serious Mental Illness. Edited by Mary Ann Cohen, Jack M. Gorman, Jeffrey M. Jacobson, Paul Volberding, and Scott Letendre. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199392742.003.0019.

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The major public health problem that is HIV/AIDS in persons with a serious mental illness is aptly described a “syndemic.” Having HIV/AIDS puts one at much greater risk for developing a serious mental illness. Conversely, having a serious mental illness, such as schizophrenia, bipolar disorder, major depressive disorder, substance use disorder, is associated with many factors that place one at greater risk for contracting and transmitting HIV. And, in both cases of serious mental illness and HIV/AIDS, each disorder creates many new challenges in the management of the other disorder. This chapter addresses these challenges, which center around being able to participate actively and adhere to medication regimens needed to manage both medical and psychiatric conditions. Fortunately, specialized models of care like comprehensive, integrated clinics and nurse care managers are ways to provide effective, satisfying, and cost-effective care to this most vulnerable population.
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30

Castle, David J., Peter F. Buckley, and Fiona P. Gaughran. Other physical health problems in people with schizophrenia. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780198811688.003.0004.

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While cardiovascular risk remains the most important factor in early death among people with schizophrenia, a host of other physical health maladies are also found in excess in this group of individuals. These include pulmonary problems, poor bone health with associated risk of fractures, sexual health problems, infectious diseases, and poor oral health. Certain cancers are seen in excess in people with schizophrenia, but what is perhaps more of a shameful indictment of our health systems is that if they develop cancer, they are less likely to be effectively treated than people without a mental illness. Intriguingly, there is some evidence of higher pain tolerance among people with schizophrenia, as well as remarkably low rates of degenerative musculoskeletal conditions.
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31

Rothberg, Brian, and Robert E. Feinstein. Suicide. Oxford University Press, 2014. http://dx.doi.org/10.1093/med/9780199326075.003.0012.

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All psychiatric assessments should include screening for recent suicidal ideation and past suicide behavior. The Columbia-Suicide Severity Rating Scale (C-SSRS) provides a reliable objective assessment of suicide risk. A history of past suicide attempts is a risk factor for future suicide, and risk is increased by more serious, more frequent, or more recent attempts. Over 90% of individuals who die by suicide have at least one psychiatric disorder. Patients with schizophrenia, alcohol and other substance use disorders, and borderline and antisocial personality disorders are at increased risk for suicide. Familial transmission of suicide risk appears to occur independent of the familial risk for psychiatric disorders; impulsivity seems to be an inherited trait that makes individuals more vulnerable to suicide. Hospitalization should be considered if suicidal ideation is present in a patient who is psychotic or who has a history of past attempts, particularly if near lethal, and may be the safest option in patients with other contributing medical conditions, limited family or social support, or lack of access to timely outpatient follow-up.
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32

Schaffner, Kenneth F., and Kathryn Tabb. Varieties of social constructionism and the problem of progress in psychiatry. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780198725978.003.0011.

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Chapter 11 discusses how the debates over the relationship between social factors and progress in psychiatry have been muddied by confusion over how the term “social construction” has been, and should be, used. It covers how one option is to move away from the language of social construction, like many in the literature have done since the 1990s. But this move risks obscuring the continued importance of attending to the role of the social in psychiatric progress. This chapter aims to clarify the different positions taken by social constructionists about psychiatric disorders and to advocate for what it calls “inclusionary social constructionism.” Through a comparison between the history of HIV/AIDS and the present state of schizophrenia in research and medical settings, the chapter illustrates and evaluates the space of possible characterizations of social construction by psychiatrists and philosophers of psychiatry.
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33

Chess, Andrew, and Schahram Akbarian. The Human Brain and its Epigenomes. Edited by Dennis S. Charney, Eric J. Nestler, Pamela Sklar, and Joseph D. Buxbaum. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190681425.003.0003.

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Conventional psychopharmacology elicits an insufficient therapeutic response in more than one half of patients diagnosed with schizophrenia, bipolar disorder, depression, anxiety, or related disorders. This underscores the need to further explore the neurobiology and molecular pathology of mental disorders in order to develop novel treatment strategies of higher efficacy. One promising avenue of research is epigenetics.Deeper understanding of genome organization and function in normal and diseased human brain will require comprehensive charting of neuronal and glial epigenomes. This includes DNA cytosine and adenine methylation, hundred(s) of residue-specific post-translational histone modifications and histone variants, transcription factor occupancies, and chromosomal conformations and loopings. Epigenome mappings provide an important avenue to assign function to many risk-associated DNA variants and mutations that do not affect protein-coding sequences. Powerful novel single cell technologies offer the opportunity to understand genome function in context of the vastly complex cellular heterogeneity and neuroanatomical diversity of the human brain.
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34

Lal, Mira, and Roch Cantwell. Preconceptual to postpartum mental health: mental illness and psychosomatic disease. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780198749547.003.0004.

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Chapter 4 examines the advancing field of mental health and psychosomatic disease from preconception to the postpartum period. The reader is reminded of the normal adaptation of different organ systems to pregnancy. This adaptation affects both physical and emotional functioning, and is further modified by the pregnant woman's social circumstances. The transition to the pathological or diseased condition may follow an exaggeration of the physiological alterations or could occur due to health conditions specific to pregnancy. This may result in manifestations due to mind-body interactions that cause psychosomatic disease. Common and unfamiliar psychosomatic clinical conditions associated with childbearing such as anxiety and mood disorders, eating disorders, hyperemesis gravidarum, and substance misuse are discussed, along with the unfamiliar, such as schizophrenia and seizures. Pregnancy-related acute-on-chronic psychosomatic presentations, besides those arising de novo in labour, are illustrated by vignettes representing real-life encounters. Controversies in management are debated to acquaint the less familiar with these clinical challenges, which require patient-centred care. Promoting health during childbearing not only pertains to the health of the mother, but also to the well-being of her infant. This entails concomitant attention to both in order to enhance the physical, mental and social health of the mother-infant dyad. An urgency for improved understanding of biopsychosocial initiating factors is reflected in an UK surveillance report, `Saving Lives Improving Mother's Care: It confirms the continuing fall in fatalities from 'direct' pregnancy-related physical causes, but a rise due to under-recognition of 'indirect' psychiatric causes that represent the psychosomatic interface.
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