Pathogenesis of schizophrenia: a psychopathological perspective

Owens, David C.; Miller, Patrick; Lawrie, Stephen M.; Johnstone, Eve C.

doi:10.1192/bjp.186.5.386

Cited by 96 publications

(64 citation statements)

References 30 publications

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“…The resulting profound hippocampal dysfunction would in turn prevent an individual from mounting appropriate homeostatic responses to stressors, rendering them more vulnerable to the effects of stress, and increasing their risk for developing schizophrenia. This is also consistent with human epidemiological data showing that, in children at risk for schizophrenia, those that show the greatest response to stressors tend to convert (Johnstone et al, 2002;Owens et al, 2005). If stress during puberty and adolescence is indeed a contributing factor to the transition to psychosis, controlling stress at this vulnerable period may circumvent these pathological changes and prevent the emergence of psychosis later in life (Du and Grace, 2013;Thompson et al, 2004).…”

Section: Discussionsupporting

confidence: 75%

“…It has been suggested that individuals who are at risk for schizophrenia are more susceptible to the effects of stress and that the interaction between a genetic or developmental predisposition and stress in early life could promote symptom onset (Benes, 1997;Tsuang, 2000;Walker et al, 2008). Indeed, in children at risk for schizophrenia, those that show abnormally high responses to stress tend to be those that convert to schizophrenia (Johnstone et al, 2002;Owens et al, 2005). However, the neurobiological substrate for this susceptibility remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Abnormal Stress Responsivity in a Rodent Developmental Disruption Model of Schizophrenia

Zimmerman

Bellaire

Ewing

et al. 2013

Neuropsychopharmacol

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Although numerous studies have implicated stress in the pathophysiology of schizophrenia, less is known about how the effects of stress interact with genetic, developmental, and/or environmental determinants to promote disease progression. In particular, it has been proposed that in humans, stress exposure in adolescence could combine with a predisposition towards increased stress sensitivity, leading to prodromal symptoms and eventually psychosis. However, the neurobiological substrates for this interaction are not fully characterized. Previous work in our lab has demonstrated that rats born to dams administered with the DNA-methylating agent methylazoxymethanol acetate (MAM) at gestational day 17 exhibit as adults behavioral and anatomical abnormalities consistent with those observed in patients with schizophrenia. Here, we examined behavioral and neuroendocrine responses to stress in the MAM model of schizophrenia. MAM-treated male rats were exposed to acute and repeated footshock stress at prepubertal, peripubteral, and adult ages. Ultrasonic vocalizations (USVs), freezing, and corticosterone responses were quantified. We found that juvenile MAM-treated rats emitted significantly more calls, spent more time vocalizing, emitted calls at a higher rate, and showed more freezing in response to acute footshock stress when compared with their saline (SAL) treated counterparts, and that this difference is not present in older animals. In addition, adolescent MAM-treated animals displayed a blunted HPA axis corticosterone response to acute footshock that did not adapt after 10 days of stress exposure. These data demonstrate abnormal stress responsivity in the MAM model of schizophrenia and suggest that these animals are more sensitive to the effects of stress in youth.

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Section: Discussionsupporting

confidence: 75%

Section: Introductionmentioning

confidence: 99%

Abnormal Stress Responsivity in a Rodent Developmental Disruption Model of Schizophrenia

Zimmerman

Bellaire

Ewing

et al. 2013

Neuropsychopharmacol

View full text Add to dashboard Cite

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“…We aimed to assess the impact of interventions on both symptoms and associated outcomes because contemporary approaches include well-being and functional indicators alongside symptomatic recovery (e.g., Remington, Foussias, & Agid, 2010). The experience of psychosis is more than symptoms alone (Birchwood & Trower, 2006) and outcomes associated with psychosis such as emotional distress play an important part in the pathway to psychosis (Hanssen et al, 2003) and relapse (Owens et al, 2005) and should, therefore, be included when assessing the efficacy of interventions. We also coded the nature of the intervention, along with features of the study design, and sample that could influence effect sizes.…”

Section: The Present Reviewmentioning

confidence: 99%

Self-help interventions for psychosis: A meta-analysis

Webb

Rowse

2015

Clinical Psychology Review

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Self-help has been shown to be an effective intervention for a wide range of mental health problems. However, there is less evidence on the efficacy of self-help for psychosis and, to date, there has been no systematic review. A search of bibliographic databases identified 24 relevant studies with a total sample size of N = 1816. Ten studies adopted a repeated measures design and 14 an independent group design (including RCTs and quasiexperimental studies). Self-help interventions had, on average, a small-to-medium-sized effect on overall symptoms (d + = 0.33, 95% CI: 0.17 to 0.48). Sub-analyses revealed that selfhelp interventions had a small-to-medium-sized effect on positive symptoms (d + = 0.42, 95% CI: 0.13 to 0.72), a small-to-medium-sized effect on negative symptoms (d + = 0.37, 95% CI: 0.07 to 0.66), and a small-sized effect on outcomes associated with the symptoms of psychosis such as quality of life (d + = 0.13, 95% CI: 0.02 to 0.24). Moderation analysis identified a number of factors that influenced treatment effects including the complexity of the intervention and amount of contact time. Self-help interventions for psychosis have a lot of potential and recommendations for further research are discussed. Word count: 190Key words: Self-help, psychosis, meta-analysis P r e P u b l i c a t i o n C o p y Self-help interventions for psychosis 3 Self-help interventions for psychosis: A meta-analysis "A massive, systematic, and yet largely silent revolution is occurring in mental health today and is gathering steam for tomorrow" (Norcross, 2000, p. 370) In the quote above, Norcross (2000) refers to the proliferation of self-help approaches for mental health conditions, an approach that has gathered momentum with practitioners, researchers, and policy makers placing an increasing emphasis on self-help for treating mental health problems (Lewis et al., 2003). Self-help interventions are defined as those that are "designed to be conducted predominantly independently of professional contact" (Bower, Richards, & Lovell, 2001, p. 839). Self-help interventions can be administered through a variety of mediums such as face-to-face or group meetings, through computers, mobile, and online platforms. Self-help typically involves working independently through a guide that describes the steps to be taken in order to apply a psychological treatment. A slight variation is guided self-help, which is distinguished "by the support that is given by a professional therapist or coach to the patient when working through the standardized treatment" (Cuijpers, Donker, van Straten, & Andersson, 2010, p. 1934. The support offered can range from assisting the person to work through the self-help program to emotional support and can be provided in a range of ways (e.g., face-to-face, telephone, or email). Most self-help interventions are based on standardized psychological treatments, with the most common interventions being those based on cognitive behavioral therapy (CBT: Cuijpers & Schuurmans, 2007). Self-help inter...

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“…Most people with schizophrenia have symptoms of this illness for more than 18 months before they become overtly psychotic. 36 Studies of the prodrome have reported a strategy to identify those who will go on to have a psychotic break with 86% sensitivity and 91% specificity. 37 Analogous to identifying those at risk for myocardial infarction, one can imagine that early intervention could pre-empt the psychotic break and prevent the long-term disability of this illness.…”

Section: Preventionmentioning

confidence: 99%

Cure therapeutics and strategic prevention: raising the bar for mental health research

2005

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Mental disorders cause more disability than any other class of medical illness in Americans between ages 15 and 44 years. The suicide rate is higher than the annual mortality from homicide, AIDS, and most forms of cancer. In contrast to nearly all communicable and most non-communicable diseases, there is little evidence that the morbidity and mortality from mental disorders have changed in the past several decades. Mental health advocates, including psychiatric researchers, have pointed to stigma as one of the reasons for the lack of progress with mental illnesses relative to other medical illnesses. This review considers how the expectations and goals of the research community have contributed to this relative lack of progress. In contrast to researchers in cancer and heart disease who have sought cures and preventions, biological psychiatrists in both academia and industry have set their sights on incremental and marketable advances, such as drugs with fewer adverse effects. This essay argues for approaches that can lead to cures and strategies for prevention of schizophrenia and mood disorders.

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Pathogenesis of schizophrenia: a psychopathological perspective

Abstract: In genetically predisposed individuals, affective and perceptual disorders are prominent before any behavioural or subjective change that usually characterises the shift to schizophrenic prodrome or active illness.

Cited by 96 publications

References 30 publications

Abnormal Stress Responsivity in a Rodent Developmental Disruption Model of Schizophrenia

Abnormal Stress Responsivity in a Rodent Developmental Disruption Model of Schizophrenia

Self-help interventions for psychosis: A meta-analysis

Cure therapeutics and strategic prevention: raising the bar for mental health research

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