Presynaptic Striatal Dopamine Dysfunction in People at Ultra-high Risk for Psychosis: Findings in a Second Cohort

Egerton, Alice; Chaddock, Christopher; Winton-Brown, Toby; Bloomfield, Michael; Bhattacharyya, Sagnik; Allen, Paul; McGuire, Philip; Howes, Oliver

doi:10.1016/j.biopsych.2012.11.017

Cited by 210 publications

(167 citation statements)

References 52 publications

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“…, elevated dopaminergic activity in the striatum 19 and midbrain 15 , and abnormalities in levels of glutamate 20 and GABA 21 . In general, these abnormalities are qualitatively similar but less severe than those seen in patients with psychotic disorders 5 .…”

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confidence: 99%

Using neuroimaging to help predict the onset of psychosis

et al. 2017

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The aim of this review is to assess the potential for neuroimaging measures to facilitate prediction of the onset of psychosis. Research in this field has mainly involved people at 'ultra-high risk' (UHR) of psychosis, who have a very high risk of developing a psychotic disorder within a few years of presentation to mental health services.The review details the key findings and developments in this area to date, and examines the methodological and logistical challenges associated with making A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT2 predictions in an individual subject in a clinical setting. Key wordsPsychosis prediction; Ultra High-Risk of psychosis; machine learning; Support Vector Machines; multimodal neuroimaging; multicentre neuroimaging studies; graph analysis Psychosis prediction and the ultra high-risk statePsychosis describes a syndrome that includes symptoms such as hallucinations, delusions, disorganised thought, and catatonia Criteria for UHR status include attenuated psychotic symptoms and / or a brief limited intermittent psychotic episode and / or a genetically determined vulnerability, alongside deterioration in social and occupational functioning 7 8 . UHR status comes A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT3 with the caveat that those who meet UHR status are selectively those who have come into contact with clinical services. This review uses the term UHR throughout.The UHR population is strikingly heterogeneous in terms of clinical outcomes.Follow-up studies 9 10 suggest that 7 years after clinical presentation, approximately a third of UHR subjects will have developed a psychotic disorder, with most transitions occurring in the first 2 years 11. Most of those who do not develop a psychotic disorder will have persistent attenuated symptoms and / or have developed another mental health disorder, whilst 14% will have recovered (see figure 1).Clinical intervention in the UHR group may reduce the likelihood of the onset of a psychotic disorder 12. However, as most UHR subjects do not develop a psychotic disorder, providing preventative treatment to all of those at risk is clinically inefficient. Identifying biomarkers that could be used to stratify the UHR group according to clinical outcome would enable the selective delivery of preventative interventions to the subgroup that would benefit the most.It is difficult to predict clinical outcomes in an UHR subject on the basis of their clinical features at presentation. Although the clinical assessment at presentation has good diagnostic validity for ruling out a future psychotic disorder (meta analytical sensitivity of UHR assessment = 0.96) 13, it has only a modest ability to rule in a future psychotic disorder (meta-analytical specificity of UHR assessment = 0.47) 13.There is thus a need to find other forms of assessment that can improve the specificity of psychosis prediction. Fusar-Poli et al. (2015) 14 and based on data by Lin et al. (2011) 10 . A C C E P T E D M A N U S C R I P T ACCEPTED MANU...

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Using neuroimaging to help predict the onset of psychosis

et al. 2017

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“…De forma comparativa, hay evidencia sólida de alteraciones en población UHR a varios niveles, entre los que resaltan estudios con tomografía por emisión de positrones, que demostraron un aumento en la síntesis estriatal de dopamina en pacientes con APS comparados a controles (65,66). Otros hallazgos dan fe de cambios estructurales, como volúmenes de materia gris disminuidos a distintos niveles e hiperperfusión en reposo en hipocampo, mesencéfalo y ganglios basales (67-69).…”

Section: Rev Neuropsiquiatr 80 (1) 2017unclassified

Estados clínicos de alto riesgo para esquizofrenia y otras formas de psicosis: una breve revisión.

2017

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RESUMENLa esquizofrenia y cuadros psicóticos relacionados son trastornos complejos que generalmente emergen en el período de transición de la adolescencia hacia la adultez, por lo que sus consecuencias pueden ser deletéreas y producir un alto número de años de vida perdidos por discapacidad. Un importante factor pronóstico es el tiempo transcurrido entre el inicio de la enfermedad y el inicio del tratamiento farmacológico, por lo que la detección temprana de la enfermedad es factor imprescindible. En esta revisión se examinan aspectos históricos, neurobiológicos y concepciones acerca de los estadios clínicos de alto riesgo para el desarrollo de esquizofrenia. En el ámbito de predicción clínica se presentan el modelo de los "síntomas básicos" de Huber y Gross, y el modelo de "criterios de riesgo ultra alto para esquizofrenia" de Mc Gorry y colaboradores. Se revisan los debates y resultados de abordajes tanto farmacológicos como psicoterapéuticos y se subraya claramente la necesidad de utilizar protocolos de detección de las fases preclínicas de esquizofrenia y otras psicosis en nuestro país.PALABRAS CLAVE: Esquizofrenia, espectro esquizofrénico, trastornos psicóticos, diagnóstico precoz. SUMMARYSchizophrenia and related psychotic conditions are complex disorders that generally emerge during the transition from adolescence to adulthood, so that their consequences may be deleterious and produce a high number of years of life lost due to disability. An important prognostic factor is the time elapsed between the onset of the disease and the beginning of pharmacological treatment, reason for which the early detection of the disease is an essential factor. This review examines historical aspects, neurobiological findings and conceptions about the high risk clinical stages for the development of schizophrenia. . In the field of clinical prediction, Huber and Gross' "basic symptoms" model, and Mc Gorry et al's "ultrahigh risk criteria for schizophrenia" model are presented. Debates about and results of both pharmacological and psychotherapeutic approaches are examined and the need to utilize detection protocols of the preclinical phases of schizophrenia and other psychoses in our country is strongly emphasized.

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“…The HV group was recruited from the same geographic area and had no personal of psychiatric symptoms, or psychotropic medication. Both the CHR and HV groups included subjects who had participated in previous dopamine imaging studies 19,21 where information on immigration status was available. Exclusion criteria for all participants included pregnancy or other contra-indications to PET imaging.…”

Section: Uk Study: Striatal Dopamine Synthesis Capacitymentioning

confidence: 99%

“…The absence of illicit substance use other than cannabis was confirmed by urine drugs screen at the time of PET imaging. 19 or a CTI/Siemens ECAT HR++ 966 tomograph (10 HV; 24 CHR) 21 (Siemens Molecular Imaging). All participants were asked to fast for 12 h before imaging and received carbidopa (150 mg) and entacapone (400 mg) orally 1 h before imaging to ]-DOPA injection with four 60-s frames, three 120-s frames, three 180-s frames, and fifteen 300-s frames).…”

Section: Uk Study: Striatal Dopamine Synthesis Capacitymentioning

confidence: 99%

“…[19][20][21][22][23] Here, we tested this hypothesis directly using positron emission tomography (PET) in vivo in immigrants and their children with, or at risk for, schizophrenia. To further validate our finding we report two complementary PET DA neuroimaging approaches to study two immigrant populations, one in Canada and one in the United Kingdom.…”

Section: Introductionmentioning

confidence: 99%

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Elevated striatal dopamine function in immigrants and their children: a risk mechanism for psychosis

Mizrahi¹

2016

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Migration is a major risk factor for schizophrenia but the neurochemical processes involved are unknown. One candidate mechanism is through elevations in striatal dopamine synthesis and release. The objective of this research was to determine whether striatal dopamine function is elevated in immigrants compared to nonimmigrants and the relationship with psychosis. Two complementary case-control studies of in vivo dopamine function (stress-induced dopamine release and dopamine synthesis capacity) in immigrants compared to nonimmigrants were performed in Canada and the United Kingdom. The Canadian dopamine release study included 25 immigrant and 31 nonmigrant Canadians. These groups included 23 clinical high risk (CHR) subjects, 9 antipsychotic naïve patients with schizophrenia, and 24 healthy volunteers. The UK dopamine synthesis study included 32 immigrants and 44 nonimmigrant British. These groups included 50 CHR subjects and 26 healthy volunteers. Both striatal stress-induced dopamine release and dopamine synthesis capacity were significantly elevated in immigrants compared to nonimmigrants, independent of clinical status. These data provide the first evidence that the effect of migration on the risk of developing psychosis may be mediated by an elevation in brain dopamine function.

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Presynaptic Striatal Dopamine Dysfunction in People at Ultra-high Risk for Psychosis: Findings in a Second Cohort

Cited by 210 publications

References 52 publications

Using neuroimaging to help predict the onset of psychosis

Using neuroimaging to help predict the onset of psychosis

Estados clínicos de alto riesgo para esquizofrenia y otras formas de psicosis: una breve revisión.

Elevated striatal dopamine function in immigrants and their children: a risk mechanism for psychosis

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