Browsing by Subject "schizophrenia"

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  • Mäntylä, Teemu; Nummenmaa, Lauri; Rikandi, Eva; Lindgren, Maija; Kieseppä, Tuula; Hari, Riitta; Suvisaari, Jaana; Raij, Tuukka T. (2018)
    BACKGROUND: Functional magnetic resonance imaging studies of psychotic disorders have reported both hypoactivity and hyperactivity in numerous brain regions. In line with the dysconnection hypothesis, these regions include cortical integrative hub regions. However, most earlier studies focused on a single cognitive function at a time, assessed by delivering artificial stimuli to patients with chronic psychosis. Thus, it remains unresolved whether these findings are present already in early psychosis and whether they translate to real-life-like conditions that require multisensory processing and integration. METHODS: Scenes from the movie Alice in Wonderland (2010) were shown to 51 patients with first-episode psychosis (16 women) and 32 community-based control subjects (17 women) during 3T functional magnetic resonance imaging. We compared intersubject correlation, a measure of similarity of brain signal time courses in each voxel, between the groups. We also quantified the hubness as the number of connections each region has. RESULTS: Intersubject correlation was significantly lower in patients with first-episode psychosis than in control subjects in the medial and lateral prefrontal, cingulate, precuneal, and parietotemporal regions, including the default mode network. Regional magnitude of between-group difference in intersubject correlation was associated with the hubness. CONCLUSIONS: Our findings provide novel evidence for the dysconnection hypothesis by showing that during complex real-life-like stimulation, the most prominent functional alterations in psychotic disorders relate to integrative brain functions. Presence of such abnormalities in first-episode psychosis rules out long-term effects of illness or medication. These methods can be used in further studies to map widespread hub alterations in a single functional magnetic resonance imaging session and link them to potential downstream and upstream pathways.
  • Terevnikov, Viacheslav; Stenberg, Jan-Henry; Tiihonen, Jari; Burkin, Mark; Joffe, Grigori (2017)
    Aim: Sexual dysfunction, common in schizophrenia, may be further exaggerated by antipsychotics, especially those of First Generation (FGAs), and antidepressants, such as Selective Serotonin Reuptake Inhibitors (SSRs). Mirtazapine, an antidepressant characterized by its different action mechanism compared with that of the majority of other antidepressants, may improve SSRI-induced sexual dysfunction in patients with depression. It is unknown, however, whether mirtazapine improves sexual functioning in schizophrenia.Methods: This study randomly assigned FGA-treated patients with schizophrenia to receive either an add-on mirtazapine (n=20) or a placebo (n=19) for 6 weeks. Sexual functioning was prospectively measured using five relevant items from the Udvalg for Kliniske Undersogelser side-effect rating scale (UKU-SERS).Results: Orgasmic function improved with statistical significance in the mirtazapine group (p=.03), with no changes in any other sexual functions in either group.Conclusion: Add-on mirtazapine appears to relieve orgasmic dysfunction in FGA-treated patients with schizophrenia.
  • Mäkipelto, Ville (Helsingin yliopisto, 2021)
    Aims: Schizophrenia is characterized by cognitive impairment that associates with many problems in everyday life and functioning. Earlier research has hypothesized that antidepressant medication may associate with better cognitive functioning among schizophrenia patients, but empirical results are mixed. This study explored the profile of schizophrenia patients that use antidepressants and asked whether there is an association between antidepressant use and cognitive performance in a clinical patient sample. Because of effects on the central nervous system, benzodiazepines and anticholinergic medications were also considered. Methods: Study participants were drawn from the SUPER-Finland cohort, which was collected among patients with psychotic illnesses in 2016–2018 from all university hospital districts across Finland (n=10474). The analysis included working-age (18–70) patients with a schizophrenia diagnosis (F20) and complete results from the brief cognitive assessment (n=3411). Information about regular medications and psychosocial factors were gathered through questionnaire and interview. Cognition was assessed with CANTAB (Cambridge Neuropsychological Test Automated Battery), out of which the subtests measuring reaction time (RTI) and visual learning (PAL) were included. The association of antidepressants on cognition was examined using both pooled antidepressants and various antidepressant groups as predictors in linear regression models. Gender, age, age of diagnosis, living status, relationship, education, and psychological distress were controlled in the models. Results: Over 35% of schizophrenia patients regularly used at least one antidepressant. On average, schizophrenia patients using antidepressants experienced lower well-being and more psychological distress than patients without antidepressants. The use of antidepressants was not generally associated with better or poorer cognitive performance. However, the use of SNRI antidepressants was associated with a significantly faster reaction time. The use of benzodiazepines was associated with poorer cognitive performance in both reaction time and visual learning. Conclusions: The results support the conclusion that there is generally no meaningful association between antidepressants and better cognitive performance in schizophrenia. However, the association of SNRI-medicines with a slightly faster reaction time is promising and warrants further research. Several psychosocial factors were associated with the cognitive performance of schizophrenia patients, which underlines the need for supporting psychosocial well-being in cognitive rehabilitation.
  • HUNT All-in Headache; Bahrami, Shahram; Hindley, Guy; Winsvold, Bendik Slagsvold; O'Connell, Kevin S.; Frei, Oleksandr; Shadrin, Alexey; Cheng, Weiqiu; Bettella, Francesco; Rodevand, Linn; Odegaard, Ketil J.; Fan, Chun C.; Pirinen, Matti J.; Hautakangas, Heidi M.; Dale, Anders M.; Djurovic, Srdjan; Smeland, Olav B.; Andreassen, Ole A. (2022)
    Migraine is three times more prevalent in people with bipolar disorder or depression. The relationship between schizophrenia and migraine is less certain although glutamatergic and serotonergic neurotransmission are implicated in both. A shared genetic basis to migraine and mental disorders has been suggested but previous studies have reported weak or non-significant genetic correlations and five shared risk loci. Using the largest samples to date and novel statistical tools, we aimed to determine the extent to which migraine's polygenic architecture overlaps with bipolar disorder, depression and schizophrenia beyond genetic correlation, and to identify shared genetic loci. Summary statistics from genome-wide association studies were acquired from large-scale consortia for migraine (n cases = 59 674; n controls = 316 078), bipolar disorder (n cases = 20 352; n controls = 31 358), depression (n cases = 170 756; n controls = 328 443) and schizophrenia (n cases = 40 675, n controls = 64 643). We applied the bivariate causal mixture model to estimate the number of disorder-influencing variants shared between migraine and each mental disorder, and the conditional/conjunctional false discovery rate method to identify shared loci. Loci were functionally characterized to provide biological insights. Univariate MiXeR analysis revealed that migraine was substantially less polygenic (2.8 K disorder-influencing variants) compared to mental disorders (8100-12 300 disorder-influencing variants). Bivariate analysis estimated that 800 (SD = 300), 2100 (SD = 100) and 2300 (SD = 300) variants were shared between bipolar disorder, depression and schizophrenia, respectively. There was also extensive overlap with intelligence (1800, SD = 300) and educational attainment (2100, SD = 300) but not height (1000, SD = 100). We next identified 14 loci jointly associated with migraine and depression and 36 loci jointly associated with migraine and schizophrenia, with evidence of consistent genetic effects in independent samples. No loci were associated with migraine and bipolar disorder. Functional annotation mapped 37 and 298 genes to migraine and each of depression and schizophrenia, respectively, including several novel putative migraine genes such as L3MBTL2, CACNB2 and SLC9B1. Gene-set analysis identified several putative gene sets enriched with mapped genes including transmembrane transport in migraine and schizophrenia. Most migraine-influencing variants were predicted to influence depression and schizophrenia, although a minority of mental disorder-influencing variants were shared with migraine due to the difference in polygenicity. Similar overlap with other brain-related phenotypes suggests this represents a pool of 'pleiotropic' variants that influence vulnerability to diverse brain-related disorders and traits. We also identified specific loci shared between migraine and each of depression and schizophrenia, implicating shared molecular mechanisms and highlighting candidate migraine genes for experimental validation.
  • Karmila, Nelli (Helsingin yliopisto, 2022)
    Schizophrenia is a debilitating psychiatric disorder associated with reduced life expectancy. The biological mechanism of schizophrenia is nebulous; however, many findings point to the central nervous system and neurons, where a reduction in dendritic spines has been indicated by previous research. The genetic findings support the involvement of synapses in the pathogenesis of schizophrenia. To study the biological properties stemming from genetics, relevant model systems and efficient methods are needed. Induced pluripotent stem cell (iPSC) technology offers a robust method for modeling the biological processes underlying schizophrenia. Somatic cells, e.g. fibroblasts, can be reprogrammed back to a pluripotent state resembling embryonic stem cells, and further differentiated into any cell type of the body, which might not be otherwise accessible. This allows establishing and characterizing neuronal cultures from patient and control cell lines, potentially revealing biological differences associated to the disease phenotype. The field of schizophrenia research has adopted iPSC technology and multiple studies have been conducted. These include assessments of synaptic density in the produced neuronal cultures, many of which reported decreased density associated with schizophrenia. In this thesis, a modified version of Nehme et al. (2018) protocol was used to differentiate iPSCs into neurons in co-cultures with human iPSC-derived astrocytes. The overarching aim was to construct an immunocytochemistry (ICC) -based assay to measure synaptic density in the produced co-cultures. First, suitable markers for characterization by ICC were tested and selected. The markers were selected to inform about neuronal identity, maturity, and synapses of the differentiated neurons. Next, the culturing conditions were optimized regarding the cell density and coating of the culturing wells. Finally, to estimate the utility of the assay, a pilot study was performed with three cell lines derived from a healthy control and a monozygotic twin pair discordant for schizophrenia. iPSCs from these cell lines were differentiated into neurons in co-cultures with astrocytes, and then characterized with ICC using selected markers and image analysis software. The synaptic density was quantified for each cell line. The performance of the assay was evaluated with analysis of variance (ANOVA) and restricted maximum likelihood model (RELM). An assay to quantify synaptic structures in mature neurons was established. The average synaptic density for all cell lines was approximately 1 synapse per 100μm of neurite. Analysis of the data produced with the assay revealed a notable batch effect and technical variation. This suggests that further optimization is needed to reduce variance from undesired sources. The pilot data suggests that the differences in synaptic density between cases and controls may be modest, further highlighting the need for minimizing noise in the assay to improve signal to noise ratio. However, indicated by power analysis, large sample sizes are needed to identify meaningful differences between cases and controls. In light of these results, more attention should be drawn to the methodology in the field of iPSC-based studies, as the principals of the assay constructed here were similar to other synaptic assays used in previous publications.
  • Oliveira, Aline A.; Rog, Tomasz; da Silva, Alberico B. F.; Amaro, Rommie E.; Johnson, Mark S.; Postila, Pekka A. (2022)
    The outer mitochondrial membrane (OMM) is involved in multiple cellular functions such as apoptosis, inflammation and signaling via its membrane-associated and -embedded proteins. Despite the central role of the OMM in these vital phenomena, the structure and dynamics of the membrane have regularly been investigated in silico using simple two-component models. Accordingly, the aim was to generate the realistic multi-component model of the OMM and inspect its properties using atomistic molecular dynamics (MD) simulations. All major lipid components, phosphatidylinositol (PI), phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS), were included in the probed OMM models. Because increased levels of anionic PS lipids have potential effects on schizophrenia and, more specifically, on monoamine oxidase B enzyme activity, the effect of varying the PS concentration was explored. The MD simulations indicate that the complex membrane lipid composition (MLC) behavior is notably different from the two-component PC-PE model. The MLC changes caused relatively minor effects on the membrane structural properties such as membrane thickness or area per lipid; however, notable effects could be seen with the dynamical parameters at the water-membrane interface. Increase of PS levels appears to slow down lateral diffusion of all lipids and, in general, the presence of anionic lipids reduced hydration and slowed down the PE headgroup rotation. In addition, sodium ions could neutralize the membrane surface, when PI was the main anionic component; however, a similar effect was not seen for high PS levels. Based on these results, it is advisable for future studies on the OMM and its protein or ligand partners, especially when wanting to replicate the correct properties on the water-membrane interface, to use models that are sufficiently complex, containing anionic lipid types, PI in particular.
  • Laine, Anna; Välimäki, Maritta; Pekurinen, Virve; Löyttyniemi, Eliisa; Marttunen, Mauri; Anttila, Minna (2019)
    Background: Web-based interventions are promising tools for increasing the understanding of illness and treatment among patients with serious mental disorders. Objective: This study aimed to test the feasibility and acceptability of a Web-based patient education intervention using a quasi-experimental cluster design to report feedback on patient education sessions and the website used and to report preliminary evidence of the intervention's impact on patients with schizophrenia spectrum disorder. Methods: A single-blind, parallel, quasi-experimental cluster study over a 6-month period comparing Web-based education (n=33) with a nonequivalent control group (treatment as usual, n=24) for people with schizophrenia spectrum disorder was conducted. Participants (N=57) were recruited from one psychiatric hospital (6 wards). Feasibility was assessed by participants' commitment (refusal rate, dropout rate) to the study. Acceptability was assessed as participants' commitment to the intervention. Patient education sessions and website feedback were assessed by the patients and health care professionals. The preliminary impact of the sessions on patients' self-efficacy, self-esteem, illness cognition, and knowledge level was measured at baseline and follow-ups (8 weeks, 6 months) with self-rated questionnaires. Results: The refusal rate among patients was high with no statistically significant difference (69% [74/107] in the intervention group, 76% [76/100] in the control group; P =.21). The same result was found for the dropout rates (48% [16/33] vs 58% [14/24]; P=. 46). The acceptability of the intervention was good; 31 participants out of 33 (94%) completed all five sessions. Feedback on the intervention was mainly positive; three out of four subscales of session were rated above the midpoint of 4.0. Feedback on the website was also positive, with a grade of good for content (69%, 20/29 patients; 75%, 21/28 professionals), layout (62%, 18/29 patients; 61%, 17/28 professionals), and usability (62%, 18/29 patients; and 68%, 19/28 professionals). The patients using the intervention had significantly higher scores 6 months after the sessions in self-efficacy (baseline mean 26.12, SD 5.64 vs 6-month mean 29.24, SD 6.05; P=.003) and regarding knowledge level about schizophrenia (mean 11.39, SD 4.65 vs 6-month mean 15.06, SD 5.26; P=. 002), and lower scores in the subscale of helplessness in illness cognition (mean 2.26, SD 0.96 vs 6-month mean 1.85, SD 0.59; P=.03). Differences from the control group were not significant. No differences were found in patients' self-esteem or other subscales in illness cognition. Conclusions: The patients were reluctant to participate in the study and tended to drop out before the follow-ups. Once they had participated, their acceptance of the intervention was high. A more effective recruitment strategy and monitoring method will be needed in future studies. To assess the impact of the intervention, a more rigorous study design with an adequately powered sample size will be used in cooperation with outpatient mental health services.
  • Hartung, Henrike; Cichon, Nicole; De Feo, Vito; Riemann, Stephanie; Schildt, Sandra; Lindemann, Christoph; Mulert, Christoph; Gogos, Joseph A.; Hanganu-Opatz, Ileana L. (2016)
    Cognitive deficits represent a major burden of neuropsychiatric disorders and result in part from abnormal communication within hippocampal-prefrontal circuits. While it has been hypothesized that this network dysfunction arises during development, long before the first clinical symptoms, experimental evidence is still missing. Here, we show that pre-juvenile mice mimicking genetic and environmental risk factors of disease (dual-hit GE mice) have poorer recognition memory that correlates with augmented coupling by synchrony and stronger directed interactions between prefrontal cortex and hippocampus. The network dysfunction emerges already during neonatal development, yet it initially consists in a diminished hippocampal theta drive and consequently, a weaker and disorganized entrainment of local prefrontal circuits in discontinuous oscillatory activity in dual-hit GE mice when compared with controls. Thus, impaired maturation of functional communication within hippocampal-prefrontal networks switching from hypo- to hyper-coupling may represent a mechanism underlying the pathophysiology of cognitive deficits in neuropsychiatric disorders.
  • Bolhuis, Koen; Lång, Ulla; Gyllenberg, David; Kääriälä, Antti; Veijola, Juha; Gissler, Mika; Kelleher, Ian (2021)
    Expanding clinical strategies to identify high risk groups for psychotic and bipolar disorders is a research priority. Considering that individuals diagnosed with psychotic and bipolar disorder are at high risk of self-harm, we hypothesised the reverse order relationship would also be true (ie, self-harm would predict psychotic/bipolar disorder). Specifically, we hypothesised that hospital presentation for self-harm would be a marker of high risk for subsequent development of psychotic/bipolar disorder and sought to test this hypothesis in a large population sample. This prospective register-based study included everyone born in Finland in 1987, followed until age 28 years (N = 59 476). We identified all hospital records of self-harm presentations, as well as all ICD-10 healthcare registrations of first diagnoses of psychotic and bipolar disorders. Cox proportional hazards models were used to assess the relationship between self-harm and psychotic/bipolar disorders. Of all individuals who presented to hospital with self-harm (n = 481), 12.8% went on to receive a diagnosis of psychosis (hazard ratio [HR] = 6.03, 95% confidence interval [CI] 4.56-7.98) and 9.4% a diagnosis of bipolar disorder (HR = 7.85, 95% CI 5.73-10.76) by age 28 years. Younger age of first self-harm presentation was associated with higher risk-for individuals who presented before age 18 years, 29.1% developed a psychotic or bipolar disorder by age 28 years. Young people who present to hospital with self-harm are at high risk of future psychotic and bipolar disorders. They represent an important cohort for the prevention of serious mental illness.
  • Kallio, Mika; Korkeila, Jyrki; Malmberg, Markus; Gunn, Jarmo; Rautava, Päivi; Korhonen, Paivi; Kytö, Ville (2022)
    Background Patients with schizophrenia spectrum disorder have increased risk of coronary artery disease. Aims To investigate long-term outcomes of patients with schizophrenia spectrum disorder and coronary artery disease after coronary artery bypass grafting surgery (CABG). Method Data from patients with schizophrenia spectrum disorder (n = 126) were retrospectively compared with propensity-matched (1:20) control patients without schizophrenia spectrum disorder (n = 2520) in a multicentre study in Finland. All patients were treated with CABG. The median follow-up was 7.1 years. The primary outcome was all-cause mortality. Results Patients with diagnosed schizophrenia spectrum disorder had an elevated risk of 10-year mortality after CABG, compared with control patients (42.7 v. 30.3%; hazard ratio 1.56; 95% CI 1.13-2.17; P = 0.008). Schizophrenia spectrum diagnosis was associated with a higher risk of major adverse cardiovascular events during follow-up (49.9 v. 32.6%, subdistribution hazard ratio 1.59; 95% CI 1.18-2.15; P = 0.003). Myocardial infarction (subdistribution hazard ratio 1.86; P = 0.003) and cardiovascular mortality (subdistribution hazard ratio 1.65; P = 0.017) were more frequent in patients with versus those without schizophrenia spectrum disorder, but there was no difference for stroke. Psychiatric ward admission, antipsychotic medication, antidepressant use and benzodiazepine use before CABG were not associated with outcome differences. After CABG, patients with schizophrenia spectrum disorder received statin therapy less often and had lower doses; the use of other cardiovascular medications was similar between schizophrenia spectrum and control groups. Conclusions Patients with schizophrenia spectrum disorder have higher long-term risks of death and major adverse cardiovascular events after CABG. The results underline the vulnerability of these patients and highlight the importance of intensive secondary prevention and risk factor optimisation.
  • Kuusimäki, Tomi; Al-Abdulrasul, Haidar; Kurki, Samu; Hietala, Jarmo; Hartikainen, Sirpa; Koponen, Marjaana; Tolppanen, Anna-Maija; Kaasinen, Valtteri (2021)
    Background PD comorbid with schizophrenia has been considered rare because these diseases associate with opposite alterations in the brain dopamine system. The objective of this study was to investigate the risk of PD after a diagnosis of a schizophrenia spectrum disorder. Methods Regionally, this was a retrospective record-based case-control study. The cohort included 3045 PD patients treated 2004-2019 in southwestern Finland. Nationally this was a nested case-control study using registers to examine Finnish patients who received a clinically confirmed PD diagnosis 1996-2015 (n = 22,189). PD patients with previously diagnosed schizophrenia spectrum disorder (separate analysis for schizophrenia) were included. Comparable non-PD control groups were derived from both data sets. All PD diagnoses were based on individual clinical examinations by certified neurologists. Results In PD patients, the prevalence of earlier schizophrenia spectrum disorder was 0.76% in regional data and 1.50% in nationwide data. In age-matched controls, the prevalence in the regional and national data was 0.16% and 1.31%, respectively. The odds ratio for PD after schizophrenia spectrum disorder diagnosis was 4.63 (95% CI, 1.76-12.19; P <0.01) in the regional data and 1.17 (95% CI, 1.04-1.31; P <0.01) in the national data. Conclusions Schizophrenia spectrum disorder increases the risk of PD later in life. This association was observed in both individual patient data and nationwide register data. Therefore, despite the opposite dopaminergic disease mechanisms, schizophrenia spectrum disorder increases rather than decreases the risk of PD. The increased PD risk could be related to risk-altering effects of dopamine receptor antagonists or to the increased vulnerability of the dopamine system induced by illness phase-dependent dopamine dysregulation in schizophrenia/schizophrenia spectrum disorder. (c) 2021 International Parkinson and Movement Disorder Society
  • Komulainen, Emilia; Zdrojewska, Justyna; Freemantle, Erika; Mohammad, Hasan; Kulesskaya, Natalia; Deshpande, Prasannakumar; Marchisella, Francesca; Mysore, Raghavendra; Hollos, Patrik; Michelsen, Kimmo A.; Magard, Mats; Rauvala, Heikki; James, Peter; Coffey, Eleanor T. (2014)
  • Holi, Matti M.; Eronen, Markku; Toivonen, Kari; Toivonen, Päivi; Marttunen, Mauri; Naukkarinen, Hannu (2004)
    In a double-blind, controlled study, we examined the therapeutic effects of high-frequency left prefrontal repetitive transcranial magnetic stimulation (rTMS) on schizophrenia symptoms. A total of 22 chronic hospitalized schizophrenia patients were randomly assigned to 2 weeks (10 sessions) of real or sham rTMS. rTMS was given with the following parameters: 20 trains of 5-second 10-Hz stimulation at 100 percent motor threshold, 30 seconds apart. Effects on positive and negative symptoms, self-reported symptoms, rough neuropsychological functioning, and hormones were assessed. Although there was a significant improvement in both groups in most of the symptom measures, no real differences were found between the groups. A decrease of more than 20 percent in the total PANSS score was found in 7 control subjects but only 1 subject from the real rTMS group. There was no change in hormone levels or neuropsychological functioning, measured by the MMSE, in either group. Left prefrontal rTMS (with the used parameters) seems to produce a significant nonspecific effect of the treatment procedure but no therapeutic effect in the most chronic and severely ill schizophrenia patients.
  • Mattila-Holappa, Pauliina (Kela, 2018)
    Studies in social security and health 152
    Mental disorders are the leading cause of work disability among young adults. This study examined the background of young adults who were granted temporary work disability pension due to mental disorders in Finland, their clinical profile, the interventions targeted at them, and employment outcomes over five years. The data comprised people aged 18–34 (n = 1,163) who were granted a fixed-term work disability pension in 2008 due to a mental disorder (ICD-10 codes F10–69, F80–99) by an occupational pension institute. The data included patients’ pension applications and attached medical certifications, which were linked to employment data from the Finnish Centre for Pensions. The most common diagnoses were depressive mood disorders (39%), schizophrenia, schizotypal and delusional disorders (34%), and mania or bipolar disorder (14%). Half of the young adults were attached to the labour market or education prior to the granted pension. Three clinical profiles were identified: ‘Childhood (including adolescence) adversity’, associated with depressive disorders; ‘Comorbidity’, associated with bipolar disorder; and ‘Undefined’, associated with psychotic disorders. Half of the non-student young adults had received work-oriented interventions or had them in their treatment and rehabilitation plan. Forty per cent had received psychotherapy or had a plan for it. A total of 22% of the sample were employed at the end of the 5.6-year follow-up, whereas 48% had been employed at some time during this period. Having planned psychotherapeutic intervention or rehabilitative courses and training at baseline was associated with quicker entry into the labour market. Having both planned psychotherapeutic and work-oriented interventions was associated with being employed at the end of the follow-up. Both psychotherapy and work-oriented interventions are likely to be beneficial for the future employment of young adults on disability pension.
  • Robinson, Rachel; Lahti-Pulkkinen, Marius; Schnitzlein, Daniel; Voit, Falk; Girchenko, Polina; Wolke, Dieter; Lemola, Sakari; Kajantie, Eero; Heinonen, Kati; Räikkönen, Katri (2020)
    Preterm birth research is poised to explore the mental health of adults born very preterm(VP;1970) included VP/VLBW individuals with controls born at term(≥37+0 weeks) or with normal birth weight(NBW; ≥2500g). Thirteen studies were included. Studies consistently showed an increased risk for psychotropic medication use for VP/VLBW adults in comparison to NBW/term controls, but whether VP/VLBW adults have an increased risk for mental health disorders or symptoms appearing in adulthood remains uncertain. The quality of the evidence was moderate (65.8%) to high (34.2%). Further research in larger samples is needed.
  • M-RESIST Grp; Seppala, Jussi; De Vita, Ilaria; Miettunen, Jouko; Isohanni, Matti; Rubinstein, Katya; Feldman, Yoram; Grasa, Eva; Corripio, Iluminada; Berdun, Jesus; D'Amico, Enrico; Bulgheroni, Maria (2019)
    Background: Mobile Therapeutic Attention for Patients with Treatment-Resistant Schizophrenia (m-RESIST) is an EU Horizon 2020-funded project aimed at designing and validating an innovative therapeutic program for treatment-resistant schizophrenia. The program exploits information from mobile phones and wearable sensors for behavioral tracking to support intervention administration. Objective: To systematically review original studies on sensor-based mHealth apps aimed at uncovering associations between sensor data and symptoms of psychiatric disorders in order to support the m-RESIST approach to assess effectiveness of behavioral monitoring in therapy. Methods: A systematic review of the English-language literature, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, was performed through Scopus, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials databases. Studies published between September 1, 2009, and September 30, 2018, were selected. Boolean search operators with an iterative combination of search terms were applied. Results: Studies reporting quantitative information on data collected from mobile use and/or wearable sensors, and where that information was associated with clinical outcomes, were included. A total of 35 studies were identified; most of them investigated bipolar disorders, depression, depression symptoms, stress, and symptoms of stress, while only a few studies addressed persons with schizophrenia. The data from sensors were associated with symptoms of schizophrenia, bipolar disorders, and depression. Conclusions: Although the data from sensors demonstrated an association with the symptoms of schizophrenia, bipolar disorders, and depression, their usability in clinical settings to support therapeutic intervention is not yet fully assessed and needs to be scrutinized more thoroughly.
  • Aitta-aho, Teemu (Helsingfors universitet, 2003)
    Epidemiological data suggest an important role of perinatal viral infections in the etiology of schizophrenia. In this thesis the connection between neonatal viral brain infection and its consequences to the development of central nervous system was studied. In schizophrenia the symptoms are divided into three categories as positive, negative and cognitive ones. Positive symptoms refer to hallucinations and delusions, negative symptoms are defined as social withdrawal, apathy and poor motivation and cognitive symptoms include deficits in abstraction and paying attention into subjects. Symptoms suggest that in schizophrenia the received information can not be filtered properly in central nervous system, but comes into patients senses in excess i.e. there are defects in sensorimotor gating. Sensorimotor gating was studied by prepulse inhibition of acoustic startle -phenomenon. Prepulse inhibition refers to the inhibition of the startle reflex by weak prepulse presented before the startling stimulus. In schizophrenic patients prepulse inhibition is decreased and in addition to that psychotomimetic drugs disrupt prepulse inhibition in humans as well as in experimental animals. Sensorimotor gating ability is developed under neuronal development and it can be affected by several neurodevelopmental disturbances. In the present study rats were infected with herpes simplex type 1 virus at neonatal age and later challenged to dopaminergic and glutamatergic systems. Results show controversial data of effects on prepulse inhibition, still some attenuation can be seen. Challenge studies did not show clear and persistent effect either in dopaminergic or glutamatergic tests. Corticosterone, naturally occurring hormone in rats, was administered to rat mothers under gestation until weaning in terms to clarify its effects to neuronal development. Administration was carried out by implanted pellet as well as by drinking water. The latter was found to work out better as it releases corticosterone in pulsatile manner. Corticosterone was administered also in acute test to drug naïve animals. This test showed significant decrease on prepulse inhibition. The same could not be repeated in corticosterone challenge test after perinatal treatments. Nitric oxide synthase inhibitor L-NMMA was administered to neonates under days 5-9 after partus. This was supposed to prevent neonates from neurodevelopmental disturbances affected by virus and corticosterone. Despite various dose levels used, any clear effect could not be seen. In summary, the studies show some effect of treatments on neuronal development and sensorimotor gating measured by prepulse inhibition. In the test groups inspected many treatments showed effect at first, but those effects disappeared at later tests as rats grew up. This might be an outcome of the potential compensatory mechanisms of the central nervous system to counteract harmful neurodevelopmental events.
  • Castrén, Eero (2014)
    Increasing number of studies has during the last decade linked neurotrophic factors with the pathophysiology of neuropsychiatric disorders and with the mechanisms of action of drugs used for the treatment of these disorders. In particular, brain-derived neurotrophic factor BDNF and its receptor TrkB have been connected with the pathophysiology in mood disorders and there is strong evidence that BDNF signaling is critically involved in the recovery from depression with both pharmacological and psychological means. Neurotrophins play a central role in neuronal plasticity and network connectivity in developing and adult brain and recent evidence links plasticity and network rewiring with mood disorders and their treatment. Therefore, neurotrophins should not be seen as happiness factors, but as critical tools in the process where brain networks are optimally tuned to environment and it is against this background that the effects of neurotrophins on neuropsychiatric disorders should be looked at.
  • Savolainen, Mari (Helsingfors universitet, 2011)
    Neuronal nicotinic receptors are widely expressed throughout the brain and they facilitate fast synaptic neurotransmission. They are also involved in regulation of the release of other neurotransmitters like GABA, dopamine and glutamate. The most common subtypes are alfa4beta2 and alfa7 subunits containing receptors. Neuronal nicotinic receptors are involved in nicotine addiction but also in many neurological diseases like Alzheimer's disease, schizophrenia, depression and attention deficit/hyperactivity disorder. The cholinergic stimulation enhances cognition in vivo and in human. There is not many drugs on the market that act via nicotinic receptors but many drug companies have new nicotinic agonists and antagonist under clinical research. When using nicotinic receptor agonists the problem is desensitization, which occurs in alfa7 nicotinic receptor rapidly after agonist exposure. When desensitized the receptor no longer responds to agonist even if it is there available to bind to receptor. The desensitization may lead to tachyphylaxis and losing of the clinical effect. Conventional agonists, like acetylcholine, bind to the binding site located in the extracellular part on nicotinic receptor subunit. There is also some other binding sites, which are called allosteric binding sites. It has been found out, that allosterically binding ligands, for example PNU-120596, can cause potentiation of agonist induced responses and/or prevent desensitization of receptor. These kinds of agents are called positive allosteric modulators and they are considered to be a new therapeutic option for CNS diseases containing cholinergic deficits. The mechanism of action of positive allosteric modulators is so far unclear. The purpose of my study was to characterize positive allosteric modulators on alfa7 nicotinic receptor. It had been found out earlier in the Millar laboratory that mutation L247T in the transmembrane domain converts positive allosteric modulators to agonists. The aim was to use site-directed mutagenesis to generate mutation in the agonist-binding site of alfa7 and alfa7L247T receptors and see how it effects on the ability of PNU-120596 to act as an agonist on the receptor. Second aim was to generate a mutation in the transmembrane part of the receptor to an assumed binding site of allosteric potentiators' and test how it effects on allosteric potentiator's ability to act as an agonist on the alfa7L247T. Mutated receptors were expressed on oocytes by microinjeting the mRNA into oocyte. The function of receptors was studied with electrophysiology using two-electrode voltageclamp technique. All the mutations were successfully inserted in nicotinic receptor alfa7 and alfa7L247T. Mutation in orthosteric agonist binding site had a very profound effect on wild type alfa7 receptor; it had an effect on either acetylcholine binding or receptor gating. It was not possible to record any proper responses neither with acetylcholine nor with PNU-120596. In the double-mutated receptor alfa7W149M/L247T the W149M mutation had a much greater effect on dose-response curves than it had on PNU-120596 curves compared with alfa7L247T. The transmembrane domain mutation M253L did not have much effect on PNU-120596's ability to act as an agonist to alfa7L247T and either it did not effect on acetylcholine dose-response curves. The results from this study support the previous results that the binding site of positive allosteric modulators is located in the transmembrane domain of the alfa7 receptor. The results are little controversial with the M253L mutation but because the L247T mutation has so profound effect on the function on alfa7 receptor it might be that it masks the other mutation which is located quite close to it. On the other hand it might be so that the amino acid M253 has only effect on the receptor's ability to be potentiated not the allosteric binding.
  • Latvala, Reetta (Helsingin yliopisto, 2014)
    Objective. Based on previous studies, foster care adolescents placed due to behavioral problems have an elevated risk to psychosis. In this large register based longitudinal study we aimed to investigate the prevalence of psychosis among Finnish reform school adolescents compared to matched peers in general population. We also intended to assess the possible differences in psychosis liability among five cohorts of reform school adolescents and examined the possible correlation between instability of out-of-home placements or the age at the time of first out-of-home placement with later psychosis. It was hypothesized that reform school adolescents had greater risk for psychosis, the number of adolescents with psychosis in reform schools was increasing and that instability of placements and early age at the time of fist out-of-home placement would be associated with an elevated risk for psychosis. Methods. The subjects (N=1159, M/F=749/410) were chosen from the Finnish welfare registry by status "placement in reform school" the last day of the years 1991, 1996, 2001, 2006 or (/and?) 2011. A control group (N=5676) matched on age, gender and place of birth was obtained from the Population Register Centre, Finland. The information about child's involvement in child welfare services and out-of-home placements was collected from the Finnish welfare register, and the data from schizophrenia spectrum disorders was collected from the Finnish hospital discharge register. Results. Prevalence of psychosis among reform adolescents was 7.1%, which was significantly higher than among general population controls (0.8%) (χ² = 205.550, df =1, P<.000). After controlling for gender and cohort, reform school adolescents had a 9.44 fold risk for psychosis compared to controls (OR=9.440, p<.000). There was no difference in psychosis liability between the five study cohorts after controlling for the difference in cohorts' follow-up times. The instability of out-of-home placements and the age at the time of first out-of-home placement were not associated with an elevated risk to psychosis. Conclusions. Results of this study show clearly that psychosis is a common problem among reform school adolescents, and indicates that reform school adolescents are a population, where the identification of early psychosis should be readily and reliable accessible. Only by recognizing early psychotic symptoms it is possible to offer intervention procedures, which in turn might prevent psychosis from becoming a chronic illness, decrease other mental health and substance abuse problems and thus enhance the overall functioning and quality of life of reform school adolescents.