Browsing by Subject "Schizophrenia"

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  • Hannon, Eilis; Dempster, Emma; Viana, Joana; Burrage, Joe; Smith, Adam R.; Macdonald, Ruby; St Clair, David; Mustard, Colette; Breen, Gerome; Therman, Sebastian; Kaprio, Jaakko; Toulopoulou, Timothea; Pol, Hilleke E. Hulshoff; Bohlken, Marc M.; Kahn, Rene S.; Nenadic, Igor; Hultman, Christina M.; Murray, Robin M.; Collier, David A.; Bass, Nick; Gurling, Hugh; McQuillin, Andrew; Schalkwyk, Leonard; Mill, Jonathan (2016)
    Background: Schizophrenia is a highly heritable, neuropsychiatric disorder characterized by episodic psychosis and altered cognitive function. Despite success in identifying genetic variants associated with schizophrenia, there remains uncertainty about the causal genes involved in disease pathogenesis and how their function is regulated. Results: We performed a multi-stage epigenome-wide association study, quantifying genome-wide patterns of DNA methylation in a total of 1714 individuals from three independent sample cohorts. We have identified multiple differentially methylated positions and regions consistently associated with schizophrenia across the three cohorts; these effects are independent of important confounders such as smoking. We also show that epigenetic variation at multiple loci across the genome contributes to the polygenic nature of schizophrenia. Finally, we show how DNA methylation quantitative trait loci in combination with Bayesian co-localization analyses can be used to annotate extended genomic regions nominated by studies of schizophrenia, and to identify potential regulatory variation causally involved in disease. Conclusions: This study represents the first systematic integrated analysis of genetic and epigenetic variation in schizophrenia, introducing a methodological approach that can be used to inform epigenome-wide association study analyses of other complex traits and diseases. We demonstrate the utility of using a polygenic risk score to identify molecular variation associated with etiological variation, and of using DNA methylation quantitative trait loci to refine the functional and regulatory variation associated with schizophrenia risk variants. Finally, we present strong evidence for the co-localization of genetic associations for schizophrenia and differential DNA methylation.
  • Wegelius, Asko; Pankakoski, Maiju; Tomppo, Liisa; Lehto, Ulriika; Lonnqvist, Jouko; Suvisaari, Jaana; Paunio, Tiina; Hennah, William (2015)
    Pre- and perinatal environmental factors have been shown to increase schizophrenia risk particularly when combined with genetic liability. The investigation of specific gene environment interactions in the etiology of psychiatric disorders has gained momentum. We used multivariate GEE regression modeling to investigate the interaction between genes of the DISCI pathway and birth weight, in relation to schizophrenia susceptibility in a Finnish schizophrenia family cohort. The study sample consisted of 457 subjects with both genotype and birth weight information. Gender and place of birth were adjusted for in the models. We found a significant interaction between birth weight and two NDE1 markers in relation to increased schizophrenia risk: a four SNP haplotype spanning NDE1 (b = 1.26, SE= 0.5, p = 0.012) and one of its constituent SNPs rs4781678 (b = 1.33, SE = 0.51, p = 0.010). Specifically, high birth weight (> 4000 g) was associated with increased schizophrenia risk among subjects homozygous for the previously identified risk alleles. The study was based on a family study sample with high genetic loading for schizophrenia and thus our findings cannot directly be generalized as representing the general population. Our results suggest that the functions mediated by NDE1 during the early stages of neurodevelopment are susceptible to the additional disruptive effects of pre- and perinatal environmental factors associated with high birth weight, augmenting schizophrenia susceptibility. (C) 2015 The Authors. Published by Elsevier Ireland Ltd.
  • Schwarz, Emanuel; Maukonen, Johanna; Hyytiäinen, Tiina; Kieseppä, Tuula; Oresic, Matej; Sabunciyan, Sarven; Mantere, Outi; Saarela, Maria; Yolken, Robert; Suvisaari, Jaana (2018)
    The effects of gut microbiota on the central nervous system, along its possible role in mental disorders, have received increasing attention. Here we investigated differences in fecal microbiota between 28 patients with first-episode psychosis (FEP) and 16 healthy matched controls and explored whether such differences were associated with response after up to 12 months of treatment. Numbers of Lactobacillus group bacteria were elevated in FEP-patients and significantly correlated with severity along different symptom domains. A subgroup of FEP patients with the strongest microbiota differences also showed poorer response after up to 12 months of treatment. The present findings support the involvement of microbiota alterations in psychotic illness and may provide the basis for exploring the benefit of their modulation on treatment response and remission. (C) 2017 Elsevier B.V. All rights reserved.
  • Huhtaniska, Sanna; Korkala, Iikka; Heikka, Tuomas; Björnholm, Lassi; Lehtiniemi, Heli; Hulkko, Anja P.; Moilanen, Jani; Tohka, Jussi; Manjon, Jose; Coupe, Pierrick; Kiviniemi, Vesa; Isohanni, Matti; Koponen, Hannu; Murray, Graham K.; Miettunen, Jouko; Jääskeläinen, Erika (2018)
    The aim of this paper was to investigate differences in brain structure volumes between schizophrenia and affective psychoses, and whether cumulative lifetime antipsychotic or benzodiazepine doses relate to brain morphology in these groups. We conducted two systematic reviews on the topic and investigated 44 schizophrenia cases and 19 with affective psychoses from the Northern Finland Birth Cohort 1966. The association between lifetime antipsychotic and benzodiazepine dose and brain MRI scans at the age of 43 was investigated using linear regression. Intracranial volume, sex, illness severity, and antipsychotic/benzodiazepine doses were used as covariates. There were no differences between the groups in brain structure volumes. In schizophrenia, after adjusting for benzodiazepine dose and symptoms, a negative association between lifetime antipsychotic dose and the nucleus accumbens volume remained. In affective psychoses, higher lifetime benzodiazepine dose associated with larger volumes of total gray matter and hippocampal volume after controlling for antipsychotic use and symptoms. It seems that in addition to antipsychotics, the severity of symptoms and benzodiazepine dose are also associated with brain structure volumes. These results suggest, that benzodiazepine effects should also be investigated also independently and not only as a confounder.
  • Karpov, B.; Joffe, G.; Aaltonen, K.; Suvisaari, J.; Baryshnikov, I.; Naatanen, P.; Koivisto, M.; Melartin, T.; Oksanen, J.; Suominen, K.; Heikkinen, M.; Paunio, T.; Isometsa, E. (2016)
    Background: Comorbid anxiety symptoms and disorders are present in many psychiatric disorders, but methodological variations render comparisons of their frequency and intensity difficult. Furthermore, whether risk factors for comorbid anxiety symptoms are similar in patients with mood disorders and schizophrenia spectrum disorders remains unclear. Methods: The Overall Anxiety Severity and Impairment Scale (OASIS) was used to measure anxiety symptoms in psychiatric care patients with schizophrenia or schizoaffective disorder (SSA, n = 113), bipolar disorder (BD, n = 99), or depressive disorder (DD, n = 188) in the Helsinki University Psychiatric Consortium Study. Bivariate correlations and multivariate linear regression models were used to examine associations of depressive symptoms, neuroticism, early psychological trauma and distress, self-efficacy, symptoms of borderline personality disorder, and attachment style with anxiety symptoms in the three diagnostic groups. Results: Frequent or constant anxiety was reported by 40.2% of SSA, 51.5% of BD, and 55.6% of DD patients; it was described as severe or extreme by 43.8%, 41.4%, and 41.2% of these patients, respectively. SSA patients were significantly less anxious (P = 0.010) and less often avoided anxiety-provoking situations (P = 0.009) than the other patients. In regression analyses, OASIS was associated with high neuroticism, symptoms of depression and borderline personality disorder and low self-efficacy in all patients, and with early trauma in patients with mood disorders. Conclusions: Comorbid anxiety symptoms are ubiquitous among psychiatric patients with mood or schizophrenia spectrum disorders, and in almost half of them, reportedly severe. Anxiety symptoms appear to be strongly related to both concurrent depressive symptoms and personality characteristics, regardless of principal diagnosis. (C) 2016 Elsevier Masson SAS. All rights reserved.
  • Kivimies, Kristiina; Repo-Tiihonen, Eila; Kautiainen, Hannu; Tiihonen, Jari (2018)
    BackgroundSubstance use disorders are associated with poorer clinical outcomes in patients with schizophrenia. There is no specific treatment for amphetamine or cannabis use disorder, but methadone and buprenorphine are used as replacement therapy in the treatment of opioid dependence. Our aim was to study whether patients with schizophrenia have received opioid replacement therapy for their opioid use disorder.MethodsThe study sample consisted of 148 individuals diagnosed with schizophrenia who were in involuntary psychiatric treatment as forensic patients in Finland in 2012. The proportion of the study sample with comorbid opioid use disorder having received opioid replacement therapy prior to their forensic psychiatric treatment was compared to the available information of opioid dependent patients in general. The data were collected from forensic examination statements, patient files and other medical registers retrospectively.ResultsOf the study sample, 15.6% (23/148) had a history of opioid use disorder, of whom 8.7% (2/23) had received opioid replacement treatment (95% confidence interval (Cl): 1.1-28.0), even though opioid use disorder had been diagnosed in the treatment system. According the available information the corresponding proportion among patients with opioid use disorder and using substance use disorder services was 30.4% (565/1860, 95% Cl: 28.3-32.5). The fraction of patients receiving opioid replacement therapy was significantly lower among patients with schizophrenia (p=0.022).ConclusionsOpioid replacement therapy was seldom used among schizophrenia patients who were later ordered to involuntary forensic psychiatric treatment. More attention should be paid to the possible use of opioids when planning treatment for patients with schizophrenia.Trial registrationOur study is not a randomized controlled trial (but a register-based study); thus the trial registration is not applicable.
  • Kivimies, Kristiina; Repo-Tiihonen, Eila; Kautiainen, Hannu; Tiihonen, Jari (BioMed Central, 2018)
    Abstract Background Substance use disorders are associated with poorer clinical outcomes in patients with schizophrenia. There is no specific treatment for amphetamine or cannabis use disorder, but methadone and buprenorphine are used as replacement therapy in the treatment of opioid dependence. Our aim was to study whether patients with schizophrenia have received opioid replacement therapy for their opioid use disorder. Methods The study sample consisted of 148 individuals diagnosed with schizophrenia who were in involuntary psychiatric treatment as forensic patients in Finland in 2012. The proportion of the study sample with comorbid opioid use disorder having received opioid replacement therapy prior to their forensic psychiatric treatment was compared to the available information of opioid dependent patients in general. The data were collected from forensic examination statements, patient files and other medical registers retrospectively. Results Of the study sample, 15.6% (23/148) had a history of opioid use disorder, of whom 8.7% (2/23) had received opioid replacement treatment (95% confidence interval (Cl): 1.1–28.0), even though opioid use disorder had been diagnosed in the treatment system. According the available information the corresponding proportion among patients with opioid use disorder and using substance use disorder services was 30.4% (565/1860, 95% Cl: 28.3–32.5). The fraction of patients receiving opioid replacement therapy was significantly lower among patients with schizophrenia (p = 0.022). Conclusions Opioid replacement therapy was seldom used among schizophrenia patients who were later ordered to involuntary forensic psychiatric treatment. More attention should be paid to the possible use of opioids when planning treatment for patients with schizophrenia. Trial registration Our study is not a randomized controlled trial (but a register-based study); thus the trial registration is not applicable.
  • Ottensmann, Linda (Helsingin yliopisto, 2020)
    It is challenging to identify causal genes and pathways explaining the associations with diseases and traits found by genome-wide association studies (GWASs). To solve this problem, a variety of methods that prioritize genes based on the variants identified by GWASs have been developed. In this thesis, the methods Data-driven Expression Prioritized Integration for Complex Traits (DEPICT) and Multi-marker Analysis of GenoMic Annotation (MAGMA) are used to prioritize causal genes based on the most recently published publicly available schizophrenia GWAS summary statistics. The two methods are compared using the Benchmarker framework, which allows an unbiased comparison of gene prioritization methods. The study has four aims. Firstly, to explain what are the differences between the gene prioritization methods DEPICT and MAGMA and how the two methods work. Secondly, to explain how the Benchmarker framework can be used to compare gene prioritization methods in an unbiased way. Thirdly, to compare the performance of DEPICT and MAGMA in prioritizing genes based on the latest schizophrenia summary statistics from 2018 using the Benchmarker framework. Lastly, to compare the performance of DEPICT and MAGMA on a schizophrenia GWAS with a smaller sample size by using Benchmarker. Firstly, the published results of the Benchmarker analyses using schizophrenia GWAS from 2014 were replicated to make sure that the framework is run correctly. The results were very similar and both the original and the replicated results show that DEPICT and MAGMA do not perform significantly differently. Furthermore, they show that the intersection of genes prioritized by DEPICT and MAGMA outperforms the outersection, which is defined as genes prioritized by only one of these methods. Secondly, Benchmarker was used to compare the performance of DEPICT and MAGMA on prioritizing genes using the schizophrenia GWAS from 2018. The results of the Benchmarker analyses suggest that DEPICT and MAGMA perform similarly with the GWAS from 2018 compared to the GWAS from 2014. Furthermore, an earlier schizophrenia GWAS from 2011 was used to check if the performance of DEPICT and MAGMA differs when a GWAS with lower statistical power is used. The results of the Benchmarker analyses make clear that MAGMA performs better than DEPICT in prioritizing genes using this smaller data set. Furthermore, for the schizophrenia GWAS from 2011 the outersection of genes prioritized by DEPICT and MAGMA outperforms the intersection. To conclude, the Benchmarker framework is a useful tool for comparing gene prioritization methods in an unbiased way. For the most recently published schizophrenia GWAS from 2018 there is no significant difference between the performance of DEPICT and MAGMA in prioritizing genes according to Benchmarker. For the smaller schizophrenia GWAS from 2011, however, MAGMA outperformed DEPICT.
  • Mäntylä, Teemu; Kieseppä, Tuula; Suvisaari, Jaana; Raij, Tuukka T. (2021)
    Poor insight is a central characteristic of psychotic disorders, and it has been suggested to result from a general dysfunction in self-reflection. However, brain processing of clinical insight and more general self-reflection has not been directly compared. We compared tasks on (1) self-reflection on psychosis-related mental functioning (clinical insight, in patients only), (2) self-reflection on mental functioning unrelated to psychosis (general metacognition), and (3) semantic control during blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging with 19 first-episode psychosis patients and 24 control participants. Arterial-spin-labeling (ASL) images were collected at rest. Clinical insight was evaluated with the Schedule for the Assessment of Insight. In patients, posterosuperior precuneus showed stronger activation during the insight task than during the semantic control task, while anteroinferior precuneus and posterior cingulate cortex (PCC) showed stronger activation during the insight task than during the general metacognition task. No significant group differences in brain activation emerged during the general metacognition task. Although the BOLD measures did not correlate with clinical insight measures, ASL-measured cerebral blood flow (CBF) values did correlate when extracted from the task-selective precuneus/PCC areas: higher CBF correlated with higher clinical insight scores. These results suggest that regions in the posteromedial cortex are selective for clinical insight.
  • Alitalo, Okko; Rantamäki, Tomi; Huhtala, Tuulia (2020)
    Autoradiography (ARG) is a high-resolution imaging method for localization of radiolabeled biomarkers in ex vivo specimen. ARG using 2-deoxy-D-glucose (2-DG) method is used in to study drug actions on brain functional activity, as it provides results comparable to clinically used functional positron-emission tomography (PET). The requirement of slow analog detection methods and emerging advances in small animal PET imaging have, however, reduced the interest in ARG. In contrast to ARG, experimental animals need to be restrained or sedated/anesthetized for PET imaging, which strongly influence functional activity and thus complicate the interpretation of the results. Digital direct particle-counting ARG systems have gained attraction during the last decade to overcome the caveats of conventional ARG methods. Here we demonstrate that the well-established 2-DG imaging method can be adapted into use with contemporary digital detectors. This method readily and rapidly captures the characteristic effects of phencyclidine (5 mg/kg, i.p.), a dissociative agent targeting the NMDAR (N-methyl-D-aspartate receptor), on regional glucose utilization in the adult mouse brain. Pretreatment with antipsychotic drug clozapine (6 mg/kg, i.p.) essentially abolishes these effects of phencyclidine on brain functional activity. Digital ARG produces viable data for the regional analysis of functional activity in a fraction of time required for film development. These results support the use of digital ARG in preclinical drug research, where high throughput and response linearity are preferred and use of sedation/anesthesia has to be avoided.
  • Soininen, Paivi; Putkonen, Hanna; Joffe, Grigori; Korkeila, Jyrki; Puukka, Pauli; Pitkanen, Anneli; Valimaki, Maritta (2013)
  • Virtanen, Tomi; Eskelinen, Saana; Sailas, Eila; Suvisaari, Jaana (Helsingfors universitet, 2016)
    Background Constipation and dyspepsia are disturbing gastrointestinal symptoms that are often ignored in research on physical comorbidities of schizophrenia. Aims Our aim was to assess dyspepsia and constipation in a sample of outpatients with schizophrenia spectrum psychoses. Methods A general practitioner performed a thorough physical health check for 275 outpatients and diagnosed constipation and dyspepsia. We assessed the possible contribution of several sociodemographic, lifestyle, and clinical variables to constipation and dyspepsia using logistic regression analysis. We also assessed whether these symptoms were associated with abnormal laboratory findings. Results The prevalence of constipation was 31.3%, and of dyspepsia 23.6%. Paracetamol (OR=3.07, 95% CI 1.34–7.02) and clozapine use (OR=5.48, 95% CI 2.75–10.90), older age (OR=1.04, 95% CI 1.01–1.06), and living in sheltered housing (OR=2.49, 95% CI 1.16–5.33) were risk factors for constipation. For dyspepsia the risk factors were female sex (OR=2.10, 95% CI 1.15–3.83), non-steroidal anti-inflammatory drugs (OR=2.47, 95% CI 1.13–5.39), and diabetes medication (OR=2.42, 95% CI 1.12–5.25). Patients with dyspepsia had lower hemoglobin and hematocrit and higher glucose values than those without dyspepsia. Patients with constipation had lower thrombocyte values than patients without constipation. However, these findings were explained by factors predisposing to constipation and dyspepsia. Conclusions Clozapine use markedly increases the risk of constipation and may lead to life-threatening complications. In addition, analgesics and diabetes medication were related to gastrointestinal symptoms. These medications and their association to gastrointestinal symptoms should be kept in mind when treating patients with schizophrenia.
  • Ukkola-Vuoti, L.; Torniainen-Holm, M.; Ortega-Alonso, A.; Sinha, V.; Tuulio-Henriksson, A.; Paunio, T.; Lönnqvist, J.; Suvisaari, J.; Hennah, W. (2019)
    Schizophrenia is a heterogeneous disorder characterized by a spectrum of symptoms and many different underlying causes. Thus, instead of using the broad diagnosis, intermediate phenotypes can be used to possibly decrease the underlying complexity of the disorder. Alongside the classical symptoms of delusions and hallucinations, cognitive deficits are a core feature of schizophrenia. To increase our understanding of the biological processes related to these cognitive deficits, we performed a genome-wide gene expression analysis. A battery of 14 neuropsychological tests was administered to 844 individuals from a Finnish familial schizophrenia cohort. We grouped the applied neuropsychological tests into five factors for further analysis. Cognitive endophenotypes, whole blood mRNA, genotype, and medication use data were studied from 47 individuals. Expression level of several RNA probes were significantly associated with cognitive performance. The factor representing Verbal Working Memory was associated with altered expression levels of 11 probes, of which one probe was also associated with a specific sub-measure of this factor (WMS-R Digit span backward). While, the factor Processing speed was related to one probe, which additionally associated among 55 probes with a specific sub-measure of this factor (WAIS-R Digit symbol). Two probes were associated with the measure recognition memory performance. Enrichment analysis of these differentially expressed probes highlighted immunological processes. Our findings are in line with genome-wide genetic discoveries made in schizophrenia, suggesting that immunological processes may be of biological interest for future drug design towards schizophrenia and the cognitive dysfunctions that underlie it.
  • Liuhanen, Johanna; Suvisaari, Jaana; Kajantie, Eero; Miettunen, Jouko; Sarin, Antti-Pekka; Järvelin, Marjo-Riitta; Lönnqvist, Jouko; Veijola, Juha; Paunio, Tiina (2018)
    Schizophrenia is a highly heritable disease, but despite extensive study, its genetic background remains unresolved. The lack of environmental measures in genetic studies may offer some explanation. In recent Finnish studies, high birth weight was found to increase the risk for familial schizophrenia. We examined the interaction between a polygenic risk score for schizophrenia and high birth weight on social anhedonia and schizophrenia in a general population birth cohort. The study sample included 4223 participants from the 1966 Northern Finland Birth Cohort. As a replication sample we used 256 participants from a systematically collected sample of Finnish schizophrenia families. The polygenic risk score comprised of variants published in the large genome-wide meta analysis for schizophrenia. We found the association between the polygenic risk score and social anhedonia stronger among those with high birth weight, and the same phenomenon was seen for schizophrenia among women, suggesting a gene-environment interaction. Similar results were found within the replication sample. Our results suggest a role for gene-environment interactions in assessing the risk of schizophrenia. Failure to take environmental effects into account may be one of the reasons why identifying significant SNPs for schizophrenia in genome-wide studies has been challenging.
  • Terevnikov, Viacheslav; Stenberg, Jan-Henry; Joffe, Grigori (2017)
  • Hulkko, A. P.; Murray, G. K.; Moilanen, J.; Haapea, M.; Rannikko, I.; Jones, P. B.; Barnett, J. H.; Huhtaniska, S.; Isohanni, M. K.; Koponen, H.; Jaaskelainen, E.; Miettunen, J. (2017)
    Background: Higher lifetime antipsychotic exposure has been associated with poorer cognition in schizophrenia. The cognitive effects of adjunctive psychiatric medications and lifetime trends of antipsychotic use remain largely unclear. We aimed to study how lifetime and current benzodiazepine and antidepressant medications, lifetime trends of antipsychotic use and antipsychotic polypharmacy are associated with cognitive performance in midlife schizophrenia. Methods: Sixty participants with DSM-IV schizophrenia from the Northern Finland Birth Cohort 1966 were examined at 43 years of age with an extensive cognitive test battery. Cumulative lifetime and current use of psychiatric medications were collected from medical records and interviews. The associations between medication and principal component analysis-based cognitive composite score were analysed using linear regression. Results: Lifetime cumulative DDD years of benzodiazepine and antidepressant medications were not significantly associated with global cognition. Being without antipsychotic medication (for minimum 11 months) before the cognitive examination was associated with better cognitive performance (P = 0.007) and higher lifetime cumulative DDD years of antipsychotics with poorer cognition (P = 0.020), when adjusted for gender, onset age and lifetime hospital treatment days. Other lifetime trends of antipsychotic use, such as a long antipsychotic-free period earlier in the treatment history, and antipsychotic polypharmacy, were not significantly associated with cognition. Conclusions: Based on these naturalistic data, low exposure to adjunctive benzodiazepine and antidepressant medications does not seem to affect cognition nor explain the possible negative effects of high dose long-term antipsychotic medication on cognition in schizophrenia. (C) 2017 Elsevier Masson SAS. All rights reserved.
  • Cruz, Gabriela; Grent-'t-Jong, Tineke; Krishnadas, Rajeev; Palva, J. Matias; Palva, Satu; Uhlhaas, Peter J. (2021)
    Long-Range Temporal Correlations (LRTCs) index the capacity of the brain to optimally process information. Previous research has shown that patients with chronic schizophrenia present altered LRTCs at alpha and beta oscillations. However, it is currently unclear at which stage of schizophrenia aberrant LRTCs emerge. To address this question, we investigated LRTCs in resting-state magnetoencephalographic (MEG) recordings obtained from patients with affective disorders and substance abuse (clinically at low-risk of psychosis, CHR-N), patients at clinical high-risk of psychosis (CHR-P) (n = 115), as well as patients with a first episode (FEP) (n = 25). Matched healthy controls (n = 47) served as comparison group. LRTCs were obtained for frequencies from 4 to 40 Hz and correlated with clinical and neuropsychological data. In addition, we examined the relationship between LRTCs and transition to psychosis in CHR-P participants, and the relationship between LRTC and antipsychotic medication in FEP participants. Our results show that participants from the clinical groups have similar LRTCs to controls. In addition, LRTCs did not correlate with clinical and neurocognitive variables across participants nor did LRTCs predict transition to psychosis. Therefore, impaired LRTCs do not reflect a feature in the clinical trajectory of psychosis. Nevertheless, reduced LRTCs in the beta-band over posterior sensors of medicated FEP participants indicate that altered LRTCs may appear at the onset of the illness. Future studies are needed to elucidate the role of anti-psychotic medication in altered LRTCs.
  • Huhtaniska, Sanna; Jaaskelainen, Erika; Heikka, Tuomas; Moilanen, Jani S.; Lehtiniemi, Heli; Tohka, Jussi; Manjon, Jose V.; Coupe, Pierrick; Bjornholm, Lassi; Koponen, Hannu; Veijola, Juha; Isohanni, Matti; Kiviniemi, Vesa; Murray, Graham K.; Miettunen, Jouko (2017)
    High doses of antipsychotics have been associated with loss in cortical and total gray matter in schizophrenia. However, previous imaging studies have not taken benzodiazepine use into account, in spite of evidence suggesting adverse effects such as cognitive impairment and increased mortality. In this Northern Finland Birth Cohort 1966 study, 69 controls and 38 individuals with schizophrenia underwent brain MRI at the ages of 34 and 43 years. At baseline, the average illness duration was over 10 years. Brain structures were delineated using an automated volumetry system, volBrain, and medication data on cumulative antipsychotic and benzodiazepine doses were collected using medical records and interviews. We used linear regression with intracranial volume and sex as covariates; illness severity was also taken into account. Though both medication doses associated to volumetric changes in subcortical structures, after adjusting for each other and the average PANSS total score, higher scan-interval antipsychotic dose associated only to volume increase in lateral ventricles and higher benzodiazepine dose associated with volume decrease in the caudate nucleus. To our knowledge, there are no previous studies reporting associations between benzodiazepine dose and brain structural changes. Further studies should focus on how these observations correspond to cognition and functioning.
  • Lauerma, Hannu; Oksanen, Jorma K. (2016)
    Vaik­ka hyp­noosia pi­detään var­sin haitat­to­mana hoito­muo­tona, kirjal­li­suu­dessa on ku­vattu sen varo­mat­tomaan käyt­töön liitty­neitä kompli­kaa­tioita, ku­ten disso­sia­tii­visia ja lyhyt­kes­toisia psy­koot­tisia ti­loja. Yli 50-vuotiaan aiem­min ter­veen ja työelä­mässä menes­tyneen nai­sen akuutti skit­sof­ree­nis­tyyp­pinen ­psy­koot­tinen häi­riö al­koi varo­mat­to­masti käy­tetyn maallik­ko­hyp­noosin yhtey­dessä. Po­tilas ko­keili sel­laista ensim­mäistä ker­taa, ja hä­nen koke­mansa hallu­si­naatiot ja harha­luulot liit­tyivät yksi­nomaan hyp­noosiin. Po­tilaan oi­reistoon liit­tyi vaaral­lisia piir­teitä, ku­ten har­haääniä, jot­ka kehot­tivat hän­tä riski­käyt­täy­ty­miseen liiken­teessä. Ly­hyen sairaa­la­hoidon jäl­keen po­tilas voi seuran­nassa hy­vin. Hyp­noosia tu­lisi käyt­tää vain valvo­tusti tervey­den­huol­lossa.
  • Simoila, Laura; Isometsä, Erkki; Gissler, Mika; Suvisaari, Jaana; Sailas, Ella; Halmesmäki, Erja; Lindberg, Nina (2019)
    Schizophrenia may affect a mother's ability to parent. We investigated out-of-home placements among children with a biological mother having schizophrenia, and their relation to maternal characteristics and adverse perinatal health outcomes of the offspring. For each Finnish woman born between 1 JAN 1965 - 31 DEC 1980 and diagnosed with schizophrenia before 31 DEC 2013 (n = 5214), five matched controls were randomly selected from the Finnish Central Population Register. Children born to these women were identified and followed till 31 DEC 2013. The Child Welfare Register, the Medical Birth Register and the Register of Congenital Malformations were used to gather information. Altogether 35.1% of children with an affected mother and 3.2% of control children were placed out of home during the follow-up. The incidence rate ratio (IRR) of out-of-home placement among children with an affected mother was 12.6 (95% confidence interval (CI) 10.80-13.46) when children with a non-affected mother served as a reference. Single motherhood (IRR 2.2, 95% CI 1.88-2.60) and maternal smoking (IRR 1.9, 95% CL 1.68-2.16), but not an adverse perinatal outcome of the offspring, increased the risk of out-of-home placement. To conclude, maternal schizophrenia is a strong risk factor for placement of children in out-of-home care.