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Markus Heinimaa

Other affiliations: Åbo Akademi University
Bio: Markus Heinimaa is an academic researcher from University of Turku. The author has contributed to research in topics: Psychosis & Schizophrenia. The author has an hindex of 22, co-authored 62 publications receiving 2243 citations. Previous affiliations of Markus Heinimaa include Åbo Akademi University.


Papers
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Journal ArticleDOI
TL;DR: A differential predictive clinical model of transition to first-episode psychosis is developed that identified an increased risk of psychosis with appropriate prognostic accuracy in a sample of help-seeking patients.
Abstract: Context Indicated prevention is currently regarded as the most promising strategy to attenuate, delay, or even avert psychosis. Existing criteria need improvement in terms of specificity and individual risk assessment to allow for better targeted and earlier interventions. Objective To develop a differential predictive clinical model of transition to first-episode psychosis. Design Prospective multicenter, naturalistic field study with a total follow-up time of 18 months. Setting Six early-detection outpatient centers in Germany, Finland, the Netherlands, and England. Participants Two hundred forty-five help-seeking patients in a putatively prodromal state of psychosis according to either ultra-high-risk (UHR) criteria or the basic symptom–based criterion cognitive disturbances (COGDIS). Main Outcome Measure Incidence of transition to psychosis. Results At 18-month follow-up, the incidence rate for transition to psychosis was 19%. Combining UHR and COGDIS yielded the best sensitivity. A prediction model was developed and included positive symptoms, bizarre thinking, sleep disturbances, a schizotypal disorder, level of functioning in the past year, and years of education. With a positive likelihood ratio of 19.9, an area under the curve of 80.8%, and a positive predictive value of 83.3%, diagnostic accuracy was excellent. A 4-level prognostic index further classifying the general risk of the whole sample predicted instantaneous incidence rates of up to 85% and allowed for an estimation of time to transition. Conclusions The prediction model identified an increased risk of psychosis with appropriate prognostic accuracy in our sample. A 2-step risk assessment is proposed, with UHR and cognitive disturbance criteria serving as first-step criteria for general risk and the prognostic index as a second-step tool for further risk classification of each patient. This strategy will allow clinicians to target preventive measures and will support efforts to unveil the biological and environmental mechanisms underlying progression to psychosis.

623 citations

Journal ArticleDOI
TL;DR: These results suggest that the changes of striatal presynaptic dopamine synthesis seen previously in neuroleptic-naive schizophrenic patients is also present in FDRs of patients with schizophrenia, which has implications for the early detection of psychosis as well as for pharmacological interventions in individuals at risk for psychosis.

117 citations

Journal ArticleDOI
TL;DR: This communication will describe representative samplings of how treatment-seeking prodrome of psychosis patients are currently recruited and treated in prodromal clinics worldwide.
Abstract: The prodrome of psychosis has become a target for early identification and for treatments that address both symptoms and risk for future psychosis. Interest and activity in this realm is now worldwide. Clinical trials with rigorous methodology have only just begun, making treatment guidelines premature. Despite the sparse evidence base, treatments are currently applied to patients in the new prodromal clinics, usually treatments developed for established psychosis and modified for the prodromal phase. This communication will describe representative samplings of how treatment-seeking prodromal patients are currently recruited and treated in prodromal clinics worldwide. Recruitment includes how prodromal patients are sought, initially evaluated, apprised of their high-risk status, and informed of the risks and benefits of prodromal treatments and how their mental state is monitored over time. The treatment modalities offered (and described) include engagement, supportive therapy, case management, stress management, cognitive behavioral treatment, family-based treatment, antipsychotic pharmacotherapy, and non-antipsychotic pharmacotherapy. References for details are noted.

116 citations

Journal ArticleDOI
TL;DR: The PROD‐screen is described, an instrument for screening prodromal symptoms indicating risk for psychotic conversion in the near future and consists of 29 questions assessing performance and symptoms.
Abstract: The aim of this study was to describe the PROD-screen, an instrument for screening prodromal symptoms indicating risk for psychotic conversion in the near future. PROD-screen consists of 29 questions assessing performance and symptoms. Clinical construct validity was tested by comparing scores from the unselected general population (GP, n = 64) with those of general psychiatric patients from a community mental health centre (CMHC, n = 107). The concordant validity of PROD-screen for prodromal symptoms of psychosis was assessed in a large epidemiologically mixed sample of research subjects (n = 132) by comparing PROD-screen scores with the prodromal diagnosis made by Structured Interview for Prodromal Symptoms as a gold standard. Using the cut-off point of 2/12 specific symptoms, PROD-screen gave correct classification of prodromal status in 77% of cases, distinguishing prodromal from non-prodromal subjects with reasonable sensitivity (80%) and specificity (75%) in the epidemiologically mixed sample. According to subsample analysis PROD-screen functions well with first-degree relatives of schizophrenic patients and probably also with general population samples, but not with psychiatric outpatients. In conclusion, PROD-screen is a useful tool for screening prodromal symptoms of psychosis and selecting subjects for more extensive research interviews.

113 citations

Journal ArticleDOI
TL;DR: Certain domains of social disability might contribute to the prediction of psychosis in a sample clinically at high risk.
Abstract: Background Decline in social functioning occurs in individuals who later develop psychosis. Aims To investigate whether baseline differences in disability are present in those who do and those who do not make a transition to psychosis in a group clinically at high risk and whether disability is a risk factor for transition. Method Prospective multicentre, naturalistic field study with an 18-month follow-up period on 245 help-seeking individuals clinically at high risk. Disability was assessed with the Disability Assessment Schedule of the World Health Organization (WHODAS–II). Results At baseline, the transition group displayed significantly greater difficulties in making new friends (z = –3.40, P = 0.001), maintaining a friendship (z =–3.00, P = 0.003), dealing with people they do not know (z =–2.28, P = 0.023) and joining community activities (z =–2.0, P = 0.05) compared with the non-transition group. In Cox regression, difficulties in getting along with people significantly contributed to the prediction of transition to psychosis in our sample (β = 0.569, s.e. = 0.184, Wald = 9.548, P = 0.002, hazard ratio (HR) = 1.767, 95% CI 1.238–2.550). Conclusions Certain domains of social disability might contribute to the prediction of psychosis in a sample clinically at high risk.

110 citations


Cited by
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Journal ArticleDOI
TL;DR: The dopamine hypothesis of schizophrenia-version III is synthesized into a comprehensive framework that links risk factors, including pregnancy and obstetric complications, stress and trauma, drug use, and genes, to increased presynaptic striatal dopaminergic function.
Abstract: The dopamine hypothesis of schizophrenia has been one of the most enduring ideas in psychiatry. Initially, the emphasis was on a role of hyperdopaminergia in the etiology of schizophrenia (version I), but it was subsequently reconceptualized to specify subcortical hyperdopaminergia with prefrontal hypodopaminergia (version II). However, these hypotheses focused too narrowly on dopamine itself, conflated psychosis and schizophrenia, and predated advances in the genetics, molecular biology, and imaging research in schizophrenia. Since version II, there have been over 6700 articles about dopamine and schizophrenia. We selectively review these data to provide an overview of the 5 critical streams of new evidence: neurochemical imaging studies, genetic evidence, findings on environmental risk factors, research into the extended phenotype, and animal studies. We synthesize this evidence into a new dopamine hypothesis of schizophrenia-version III: the final common pathway. This hypothesis seeks to be comprehensive in providing a framework that links risk factors, including pregnancy and obstetric complications, stress and trauma, drug use, and genes, to increased presynaptic striatal dopaminergic function. It explains how a complex array of pathological, positron emission tomography, magnetic resonance imaging, and other findings, such as frontotemporal structural and functional abnormalities and cognitive impairments, may converge neurochemically to cause psychosis through aberrant salience and lead to a diagnosis of schizophrenia. The hypothesis has one major implication for treatment approaches. Current treatments are acting downstream of the critical neurotransmitter abnormality. Future drug development and research into etiopathogenesis should focus on identifying and manipulating the upstream factors that converge on the dopaminergic funnel point.

2,311 citations

Book
01 Aug 2009
TL;DR: Mental, emotional, and behavioral (MEB) disorders—which include depression, conduct disorder, and substance abuse—affect large numbers of young people.
Abstract: This report builds on a highly valued predecessor, the 1994 Institute of Medicine (IOM) report entitled Reducing Risks for Mental Disorders: Frontiers for Preventive Intervention Research. That report provided the basis for understanding prevention science, elucidating its then-existing research base, and contemplating where it should go in the future. This report documents that an increasing number of mental, emotional, and behavioral problems in young people are in fact preventable. The proverbial ounce of prevention will indeed be worth a pound of cure: effectively applying the evidence-based prevention interventions at hand could potentially save billions of dollars in associated costs by avoiding or tempering these disorders in many individuals. Furthermore, devoting significantly greater resources to research on even more effective prevention and promotion efforts, and then reliably implementing the findings of such research, could substantially diminish the human and economic toll.

1,744 citations

Journal ArticleDOI
TL;DR: The relatively new field of HR research in psychosis has the potential to shed light on the development of major psychotic disorders and to alter their course and provides a rationale for service provision to those in need of help who could not previously access it.
Abstract: Context During the past 2 decades, a major transition in the clinical characterization of psychotic disorders has occurred. The construct of a clinical high-risk (HR) state for psychosis has evolved to capture the prepsychotic phase, describing people presenting with potentially prodromal symptoms. The importance of this HR state has been increasingly recognized to such an extent that a new syndrome is being considered as a diagnostic category in the DSM-5. Objective To reframe the HR state in a comprehensive state-of-the-art review on the progress that has been made while also recognizing the challenges that remain. Data Sources Available HR research of the past 20 years from PubMed, books, meetings, abstracts, and international conferences. Study Selection and Data Extraction Critical review of HR studies addressing historical development, inclusion criteria, epidemiologic research, transition criteria, outcomes, clinical and functional characteristics, neurocognition, neuroimaging, predictors of psychosis development, treatment trials, socioeconomic aspects, nosography, and future challenges in the field. Data Synthesis Relevant articles retrieved in the literature search were discussed by a large group of leading worldwide experts in the field. The core results are presented after consensus and are summarized in illustrative tables and figures. Conclusions The relatively new field of HR research in psychosis is exciting. It has the potential to shed light on the development of major psychotic disorders and to alter their course. It also provides a rationale for service provision to those in need of help who could not previously access it and the possibility of changing trajectories for those with vulnerability to psychotic illnesses.

1,213 citations

Journal ArticleDOI
TL;DR: The state of clinical high risk is associated with a very high risk of developing psychosis within the first 3 years of clinical presentation, and the risk progressively increases across this period.
Abstract: Context A substantial proportion of people at clinical high risk of psychosis will develop a psychotic disorder over time. However, the risk of transition to psychosis varies between centers, and some recent work suggests that the risk of transition may be declining. Objective To quantitatively examine the literature to date reporting the transition risk to psychosis in subjects at clinical high risk. Data Sources The electronic databases were searched until January 2011. All studies reporting transition risks in patients at clinical high risk were retrieved. Study Selection Twenty-seven studies met the inclusion criteria, comprising a total of 2502 patients. Data Extraction Transition risks, as well as demographic, clinical, and methodologic variables, were extracted from each publication or obtained directly from its authors. Data Synthesis There was a consistent transition risk, independent of the psychometric instruments used, of 18% after 6 months of follow-up, 22% after 1 year, 29% after 2 years, and 36% after 3 years. Significant moderators accounting for heterogeneity across studies and influencing the transition risks were the age of participants, publication year, treatments received, and diagnostic criteria used. There was no publication bias, and a sensitivity analysis confirmed the robustness of the core findings. Conclusions The state of clinical high risk is associated with a very high risk of developing psychosis within the first 3 years of clinical presentation, and the risk progressively increases across this period. The transition risk varies with the age of the patient, the nature of the treatment provided, and the way the syndrome and transition to psychosis are defined.

1,159 citations

Journal ArticleDOI
TL;DR: It is suggested that inhibition of anandamide deactivation may contribute to the antipsychotic effects of cannabidiol potentially representing a completely new mechanism in the treatment of schizophrenia.
Abstract: Cannabidiol is a component of marijuana that does not activate cannabinoid receptors, but moderately inhibits the degradation of the endocannabinoid anandamide. We previously reported that an elevation of anandamide levels in cerebrospinal fluid inversely correlated to psychotic symptoms. Furthermore, enhanced anandamide signaling let to a lower transition rate from initial prodromal states into frank psychosis as well as postponed transition. In our translational approach, we performed a double-blind, randomized clinical trial of cannabidiol vs amisulpride, a potent antipsychotic, in acute schizophrenia to evaluate the clinical relevance of our initial findings. Either treatment was safe and led to significant clinical improvement, but cannabidiol displayed a markedly superior sideeffect profile. Moreover, cannabidiol treatment was accompanied by a significant increase in serum anandamide levels, which was significantly associated with clinical improvement. The results suggest that inhibition of anandamide deactivation may contribute to the antipsychotic effects of cannabidiol potentially representing a completely new mechanism in the treatment of schizophrenia. Translational Psychiatry (2012) 2, e94; doi:10.1038/tp.2012.15; published online 20 March 2012

812 citations