Browsing by Subject "MOOD DISORDERS"

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  • Lainiola, Mira; Linden, Anni-Maija (2017)
    Neuroinflammation may play an important role in the development of alcohol addiction. Recent pre-clinical reports suggest that enhanced innate immune system signaling increases consumption of alcohol. Our aim was to study whether consequences of lipopolysaccharide (LPS)-induced sickness reaction increase long-term alcohol intake. Adult male C57BL/6j mice, housed in individually ventilated cages, were injected with LPS intraperitoneally (i.p.) and allowed to recover from an acute sickness reaction for 1 week before analysis of their alcohol intake in two different drinking models. Effects of LPS challenge were tested in a continuous two-bottle free choice test with increasing concentrations of alcohol and in a drinking in the dark (DID) binge model. In addition, the effect of repeatedly administered LPS during abstinence periods between binge drinking was analyzed in the DID model. In addition, the DID model was used to study the effects of the microglia inhibitor minocycline (50 mg/kg/day, 4 days) and purinergic P2X7 receptor antagonist Brilliant Blue G (75 mg/kg/day, 7 days) on alcohol intake. In contrast to previous findings, pretreatment with a 1-mg/kg dose of LPS did not significantly increase ethanol consumption in the continuous two-bottle choice test. As a novel finding, we report that increasing the LPS dose to 1.5 mg/kg reduced consumption of 18 and 21% (v/v) ethanol. In the DID model, pretreatment with LPS (0.2-1.5 mg/kg) did not significantly alter 15% or 20% ethanol consumption. Neither did repeated LPS injections affect binge alcohol drinking. Minocycline reduced alcohol, but also water, intake regardless of LPS pretreatment. No data on effects of P2X7 antagonists on alcohol consumption have been previously published; therefore, we report here that subchronic Brilliant Blue G had no effect on alcohol intake in the DID model. As a conclusion, further studies are needed to validate this LPS model of the interaction between immune system activation and alcohol consumption. (C) 2017 Elsevier Inc. All rights reserved.
  • Vincent, John; Hovatta, Iiris; Frissa, Souci; Goodwin, Laura; Hotopf, Matthew; Hatch, Stephani L.; Breen, Gerome; Powell, Timothy R. (2017)
    Background: Studies have provided evidence that both childhood maltreatment and depressive disorders are associated with shortened telomere lengths. However, as childhood maltreatment is a risk factor for depression, it remains unclear whether this may be driving shortened telomere lengths observed amongst depressed patients. Furthermore, it's unclear if the effects of maltreatment on telomere length shortening are more pervasive amongst depressed patients relative to controls, and consequently whether biological ageing may contribute to depression's pathophysiology. The current study assesses the effects of childhood maltreatment, depression case/control status, and the interactive effect of both childhood maltreatment and depression case/control status on relative telomere length (RTL). Method: DNA samples from 80 depressed subjects and 100 control subjects were utilized from a U.K. sample (ages 20-84), with childhood trauma questionnaire data available for all participants. RTL was quantified using quantitative polymerase chain reactions. Univariate linear regression analyses were used to assess the effects of depression status, childhood maltreatment and depression by childhood maltreatment interactions on RTL. The false discovery rate (q <0.05) was used for multiple testing correction. Results: Analysis of depression case/control status showed no significant main effect on RTL. Four subtypes of childhood maltreatment also demonstrated no significant main effect on RTL, however a history of physical neglect did significantly predict shorter RTL in adulthood (F(1, 174)=7.559, p=0.007, q=0.042, Variance Explained=4.2%), which was independent of case/control status. RTL was further predicted by severity of physical neglect, with the greatest differences observed in older maltreated individuals ( > 50 years old). There were no significant depression case/control status by childhood maltreatment interactions. Limitations: A relatively small sample limited our power to detect interaction effects, and we were unable to consider depression chronicity or recurrence. Conclusion: Shortened RTL was specifically associated with childhood physical neglect, but not the other subtypes of maltreatment or depression case/control status. Our results suggest that the telomere-eroding effects of physical neglect may represent a biological mechanism important in increasing risk for ageing-related disorders. As physical neglect is more frequent amongst depressed cases generally, it may also represent a confounding factor driving previous associations between shorter RTL and depression case status.
  • Bauer, Michael; Glenn, Tasha; Alda, Martin; Andreassen, Ole A.; Angelopoulos, Elias; Ardau, Raffaella; Ayhan, Yavuz; Baethge, Christopher; Bauer, Rita; Baune, Bernhard T.; Becerra-Palars, Claudia; Bellivier, Frank; Belmaker, Robert H.; Berk, Michael; Bersudsky, Yuly; Bicakci, Sule; Birabwa-Oketcho, Harriet; Bjella, Thomas D.; Cabrera, Jorge; Cheung, Eric Y. Wo; Del Zompo, Maria; Dodd, Seetal; Donix, Markus; Etain, Bruno; Fagiolini, Andrea; Fountoulakis, Kostas N.; Frye, Mark A.; Gonzalez-Pinto, Ana; Gottlieb, John F.; Grof, Paul; Harima, Hirohiko; Henry, Chantal; Isometsä, Erkki T.; Janno, Sven; Kapczinski, Flavio; Kardell, Mathias; Khaldi, Slim; Kliwicki, Sebastian; Konig, Barbara; Kot, Timur L.; Krogh, Rikke; Kunz, Mauricio; Lafer, Beny; Landen, Mikael; Larsen, Erik R.; Lewitzka, Ute; Licht, Rasmus W.; Lopez-Jaramillo, Carlos; MacQueen, Glenda; Manchia, Mirko; Marsh, Wendy; Martinez-Cengotitabengoa, Monica; Melle, Ingrid; Meza-Urzua, Fatima; Ming, Mok Yee; Monteith, Scott; Morken, Gunnar; Mosca, Enrica; Mozzhegorova, Anton A.; Munoz, Rodrigo; Mythri, Starlin V.; Nacef, Fethi; Nadella, Ravi K.; Nery, Fabiano G.; Nielsen, Rene E.; O'Donovan, Claire; Omrani, Adel; Osher, Yamima; Sorensen, Helle Ostermark; Ouali, Uta; Ruiz, Yolanda Pica; Pilhatsch, Maximilian; Pinna, Marco; da Ponte, Francisco D. R.; Quiroz, Danilo; Ramesar, Raj; Rasgon, Natalie; Reddy, M. S.; Reif, Andreas; Ritter, Philipp; Rybakowski, Janusz K.; Sagduyu, Kemal; Raghuraman, Bharathram Sathur; Scippa, Angela M.; Severus, Emanuel; Simhandl, Christian; Stackhouse, Paul W.; Stein, Dan J.; Strejilevich, Sergio; Subramaniam, Mythily; Sulaiman, Ahmad Hatim; Suominen, Kirsi; Tagata, Hiromi; Tatebayashi, Yoshitaka; Tondo, Leonardo; Torrent, Carla; Vaaler, Arne E.; Vares, Edgar; Veeh, Julia; Vieta, Eduard; Viswanath, Biju; Yoldi-Negrete, Maria; Zetina, Mark; Zgueb, Yosra; Whybrow, Peter C. (2019)
    In many international studies, rates of completed suicide and suicide attempts have a seasonal pattern that peaks in spring or summer. This exploratory study investigated the association between solar insolation and a history of suicide attempt in patients with bipolar I disorder. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area on Earth. Data were collected previously from 5536 patients with bipolar I disorder at 50 collection sites in 32 countries at a wide range of latitudes in both hemispheres. Suicide related data were available for 3365 patients from 310 onset locations in 51 countries. 1047 (31.1%) had a history of suicide attempt. There was a significant inverse association between a history of suicide attempt and the ratio of mean winter solar insolation/mean summer solar insolation. This ratio is smallest near the poles where the winter insolation is very small compared to the summer insolation. This ratio is largest near the equator where there is relatively little variation in the insolation over the year. Other variables in the model that were positively associated with suicide attempt were being female, a history of alcohol or substance abuse, and being in a younger birth cohort. Living in a country with a state-sponsored religion decreased the association. (All estimated coefficients p <0.01). In summary, living in locations with large changes in solar insolation between winter and summer may be associated with increased suicide attempts in patients with bipolar disorder. Further investigation of the impacts of solar insolation on the course of bipolar disorder is needed.
  • Markkula, Niina; Lindgren, Maija; Yolken, Robert H.; Suvisaari, Jaana (2020)
    Background Some prevalent infections have been associated with common mental disorders, but there are few longitudinal studies, and results are inconsistent. We aimed to assess whether serological evidence of exposure to Toxoplasma gondii (T. gondii), Epstein-Barr Virus (EBV), Herpes Simplex virus Type 1 (HSV-1) and Cytomegalovirus (CMV) predict development of new-onset depressive and anxiety disorders. Methods In a nationally representative sample of the Finnish adult population aged 30 and over (BRIF8901, n = 8028), IgG antibodies for T. gondii, EBV, HSV-1 and CMV were measured in plasma samples. The population was followed up for 11 years and new-onset depressive and anxiety disorders were diagnosed with the Composite International Diagnostic Interview. Associations were analysed controlling for sex, age, educational level, region of residence and marital status, and in separate analyses also for C-reactive protein level. Results Seropositivity and serointensity of the four infectious agents were not associated with an increased risk of new-onset depressive or anxiety disorders. Seropositivity for CMV at baseline was associated with a lower risk of new-onset generalized anxiety disorder (adjusted OR 0.43, 95% CI 0.22–0.86 for CMV positive persons). Conclusion The results of this large, nationally representative longitudinal study suggest that common viral infections are not significant risk factors for common mental disorders. The association of CMV with a lower risk of generalized anxiety disorder warrants further investigation.
  • Kovanen, Leena; Donner, Kati; Kaunisto, Mari; Partonen, Timo (2016)
    Cryptochromes are key components of the circadian clocks that generate and maintain seasonal variations. The aim of our study was to analyze the associations of CRY1 and CRY2 genetic variants with the problematicity of seasonal variations, and whether the problematicity of seasonal variations changed during the follow-up of 11 years. Altogether 21 CRY1 and 16 CRY2 single-nucleotide polymorphisms (SNPs) were genotyped and analyzed in 5910 individuals from a Finnish nationwide population-based sample who had filled in the self-report on the seasonal variations in mood and behavior in the year 2000. In the year 2011, 3356 of these individuals filled in the same self-report on the seasonal variations in mood and behavior. Regression models were used to test whether any of the SNPs associated with the problematicity of seasonal variations or with a change in the problematicity from 2000 to 2011. In the longitudinal analysis, CRY2 SNP rs61884508 was protective from worsening of problematicity of seasonal variations. In the cross-sectional analysis, CRY2 SNP rs72902437 showed evidence of association with problematicity of seasonal variations, as did SNP rs1554338 (in the MAPK8IP1 and downstream of CRY2). (C) 2016 Elsevier Ireland Ltd. All rights reserved.
  • Kovanen, Leena; Kaunisto, Mari; Donner, Kati; Saarikoski, Sirkku T.; Partonen, Timo (2013)
  • Savilahti, Emma M.; Haravuori, Henna; Rytilä-Manninen, Minna; Lindberg, Nina; Kettunen, Kirsi; Marttunen, Mauri (2018)
    Beck Depression Inventory (BDI) is widely used in assessing adolescents' psychological wellbeing, but occasionally the result diverges from diagnostics. Our aim was to identify factors associated with discrepancies between BDI scores and diagnostic assessment in adolescent psychiatric patients and general population. The study comprised 206 inpatients (13-17 years old) and 203 age and gender matched non -referred adolescents. Study subjects filled self-reports on depression symptoms (BDI-21), alcohol use (AUDIT), defense styles (DSQ-40) and self-image (OSIQ-11), and on background information and adverse life events. Diagnostics was based on K-SADS-PL interview, and/or clinical interview and clinical records when available. We compared subjects who scored in BDI-21 either 0-15 points or 16-63 points firstly among subjects without current unipolar depression (n = 284), secondly among those with unipolar depression (n = 105). High BDI-21 scores in subjects without depression diagnosis (n = 48) were associated with female sex, adverse life events, parents' psychiatric problems, higher comorbidity, higher AUDIT scores, worse self-image and more immature defense styles. Low BDI-21 scores among subjects with depression diagnosis (n = 23) were associated with male sex, more positive self-image and less immature defense style. In conclusion, high BDI-21 scores in the absence of depression may reflect a broad range of challenges in an adolescent's psychological development.
  • Markkula, Niina; Lehti, Venla; Gissler, Mika; Suvisaari, Jaana (2017)
    Migrants appear to have a higher risk of mental disorders, but findings vary across country settings and migrant groups. We aimed to assess incidence and prevalence of mental disorders among immigrants and Finnish-born controls in a register-based cohort study. A register-based cohort study of 184.806 immigrants and 185.184 Finnish-born controls (1.412.117 person-years) was conducted. Information on mental disorders according to ICD-10 was retrieved from the Hospital Discharge Register, which covers all public health care use. The incidence of any mental disorder was lower among male (adjusted HR 0.82, 95% CI 0.77-0.87) and female (aHR 0.76, 95% CI 0.72-0.81) immigrants, being lowest among Asian and highest among North African and Middle Eastern immigrants. The incidence of bipolar, depressive and alcohol use disorders was lower among immigrants. Incidence of psychotic disorders was lower among female and not higher among male immigrants, compared with native Finns. Incidence of PTSD was higher among male immigrants (aHR 4.88, 95% CI 3.38-7.05). The risk of mental disorders varies significantly across migrant groups and disorders and is generally lower among immigrants than native Finns.
  • Passos, Ives C.; Ballester, Pedro L.; Barros, Rodrigo C.; Librenza-Garcia, Diego; Mwangi, Benson; Birmaher, Boris; Brietzke, Elisa; Hajek, Tomas; Lopez Jaramillo, Carlos; Mansur, Rodrigo B.; Alda, Martin; Haarman, Bartholomeus C. M.; Isometsa, Erkki; Lam, Raymond W.; McIntyre, Roger S.; Minuzzi, Luciano; Kessing, Lars V.; Yatham, Lakshmi N.; Duffy, Anne; Kapczinski, Flavio (2019)
    Objectives The International Society for Bipolar Disorders Big Data Task Force assembled leading researchers in the field of bipolar disorder (BD), machine learning, and big data with extensive experience to evaluate the rationale of machine learning and big data analytics strategies for BD. Method A task force was convened to examine and integrate findings from the scientific literature related to machine learning and big data based studies to clarify terminology and to describe challenges and potential applications in the field of BD. We also systematically searched PubMed, Embase, and Web of Science for articles published up to January 2019 that used machine learning in BD. Results The results suggested that big data analytics has the potential to provide risk calculators to aid in treatment decisions and predict clinical prognosis, including suicidality, for individual patients. This approach can advance diagnosis by enabling discovery of more relevant data-driven phenotypes, as well as by predicting transition to the disorder in high-risk unaffected subjects. We also discuss the most frequent challenges that big data analytics applications can face, such as heterogeneity, lack of external validation and replication of some studies, cost and non-stationary distribution of the data, and lack of appropriate funding. Conclusion Machine learning-based studies, including atheoretical data-driven big data approaches, provide an opportunity to more accurately detect those who are at risk, parse-relevant phenotypes as well as inform treatment selection and prognosis. However, several methodological challenges need to be addressed in order to translate research findings to clinical settings.
  • Lahti-Pulkkinen, Marius; Girchenko, Polina; Robinson, Rachel; Lehto, Soili M.; Toffol, Elena; Heinonen, Kati; Reynolds, Rebecca M.; Kajantie, Eero; Laivuori, Hannele; Villa, Pia M.; Hamalainen, Esa; Lahti, Jari; Raikkonen, Katri (2020)
    Background Maternal depression during pregnancy increases the risk for adverse developmental outcomes in children. However, the underpinning biological mechanisms remain unknown. We tested whether depression was associated with levels of and change in the inflammatory state during pregnancy, if early pregnancy overweight/obesity or diabetes/hypertensive pregnancy disorders accounted for/mediated these effects, and if depression added to the inflammation that typically accompanies these conditions. Methods We analyzed plasma high-sensitivity C-reactive protein (hsCRP) and glycoprotein acetyls at three consecutive stages during pregnancy, derived history of depression diagnoses before pregnancy from Care Register for Healthcare (HILMO) (N= 375) and self-reports (N= 347) and depressive symptoms during pregnancy using the Center for Epidemiological Studies Depression Scale completed concurrently to blood samplings (N= 295). Data on early pregnancy body mass index (BMI) and diabetes/hypertensive pregnancy disorders came from medical records. Results Higher overall hsCRP levels, but not change, during pregnancy were predicted by history of depression diagnosis before pregnancy [HILMO: mean difference (MD) = 0.69 standard deviation (s.d.) units; 95% confidence interval (CI) 0.26-1.11, self-report: MD = 0.56s.d.; 95% CI 0.17-0.94] and higher depressive symptoms during pregnancy (0.06s.d.pers.d.increase; 95% CI 0.00-0.13). History of depression diagnosis before pregnancy also predicted higher overall glycoprotein acetyls (HILMO: MD = 0.52s.d.; 95% CI 0.12-0.93). These associations were not explained by diabetes/hypertensive disorders, but were accounted for and mediated by early pregnancy BMI. Furthermore, in obese women, overall hsCRP levels increased as depressive symptoms during pregnancy increased (p= 0.006 for interaction). Conclusions Depression is associated with a proinflammatory state during pregnancy. These associations are mediated by early pregnancy BMI, and depressive symptoms during pregnancy aggravate the inflammation related to obesity.
  • Vehviläinen, Juho; Skrifvars, Markus B.; Reinikainen, Matti; Bendel, Stepani; Marinkovic, Ivan; Ala-Kokko, Tero; Hoppu, Sanna; Laitio, Ruut; Siironen, Jari; Raj, Rahul (2021)
    Background Psychiatric sequelae after traumatic brain injury (TBI) are common and may impede recovery. We aimed to assess the occurrence and risk factors of post-injury psychotropic medication use in intensive care unit (ICU)-treated patients with TBI and its association with late mortality. Methods We conducted a retrospective multi-centre observational study using the Finnish Intensive Care Consortium database. We included adult TBI patients admitted in four university hospital ICUs during 2003-2013 that were alive at 1 year after injury. Patients were followed-up until end of 2016. We obtained data regarding psychotropic medication use through the national drug reimbursement database. We used multivariable logistic regression models to assess the association between TBI severity, treatment-related variables and the odds of psychotropic medication use and its association with late all-cause mortality (more than 1 year after TBI). Results Of 3061 patients, 2305 (75%) were alive at 1 year. Of these, 400 (17%) became new psychotropic medication users. The most common medication types were antidepressants (61%), antipsychotics (35%) and anxiolytics (26%). A higher Glasgow Coma Scale (GCS) score was associated with lower odds (OR 0.93, 95% CI 0.90-0.96) and a diffuse injury with midline shift was associated with higher odds (OR 3.4, 95% CI 1.3-9.0) of new psychotropic medication use. After adjusting for injury severity, new psychotropic medication use was associated with increased odds of late mortality (OR 1.19, 95% CI 1.19-2.17, median follow-up time 6.4 years). Conclusions Psychotropic medication use is common in TBI survivors. Higher TBI severity is associated with increased odds of psychotropic medication use. New use of psychotropic medications after TBI was associated with increased odds of late mortality. Our results highlight the need for early identification of potential psychiatric sequelae and psychiatric evaluation in TBI survivors.
  • Kraus, Christoph; Castrén, Eero; Kasper, Siegfried; Lanzenberger, Rupert (2017)
    Serotonin modulates neuroplasticity, especially during early life, and dysfunctions in both systems likewise contribute to pathophysiology of depression. Recent findings demonstrate that serotonin reuptake inhibitors trigger reactivation of juvenile-like neuroplasticity. How these findings translate to clinical antidepressant treatment in major depressive disorder remains unclear. With this review, we link preclinical with clinical work on serotonin and neuroplasticity to bring two pathophysiologic models in clinical depression closer together. Dysfunctional developmental plasticity impacts on later-life cognitive and emotional functions, changes of synaptic serotonin levels and receptor levels are coupled with altered synaptic plasticity and neurogenesis. Structural magnetic resonance imaging in patients reveals disease-state-specific reductions of gray matter, a marker of neuroplasticity, and reversibility upon selective serotonin reuptake inhibitor treatment. Translational evidence from magnetic resonance imaging in animals support that reduced densities and sizes of neurons and reduced hippocampal volumes in depressive patients could be attributable to changes of serotonergic neuroplasticity. Since ketamine, physical exercise or learning enhance neuroplasticity, combinatory paradigms with selective serotonin reuptake inhibitors could enhance clinical treatment of depression. (C) 2017 Elsevier Ltd. All rights reserved.
  • Santangeli, Olena; Porkka-Heiskanen, Tarja; Virkkala, Jussi; Castaneda, Anu E.; Marttunen, Mauri; Paunio, Tiina; Urrila, Anna S. (2017)
    Objective: Adolescence is a vulnerable period of life that is characterized by increasing incidence of depression. Sleep disturbance is one of the diagnostic symptoms of depressive disorder. Adolescence is also characterized by dramatic maturational changes in sleep and its regulation. The goal of this study was to assess sleep macroarchitecture and slow-wave activity (SWA) in depressed adolescent boys. Methods: Eight non-medicated adolescent boys meeting the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for depressive disorder and 10 age-matched healthy controls (average age 16.0 years) underwent polysomnography in their home environment for two consecutive nights. Sleep macroarchitecture, SWA, and SWA dissipation were assessed in all subjects. Results: Depressed boys showed a flattened pattern of SWA dissipation through the night. SWA power was lower during the first non-rapid eye movement (NREM) episode in the frontal derivation and higher during the third NREM episode in the central derivation in the group of depressed boys as compared to healthy boys. The SWA dissipation pattern correlated with the severity of depressive symptoms, and the correlation was strongest in the frontal derivation. In addition, total sleep time was shorter in patients as compared to the control group, but no other differences were found in the macroarchitecture of sleep. Conclusion: Depression in adolescent boys is characterized by more evenly distributed SWA through the night as compared to healthy subjects, and we showed for the first time that this pattern of SWA distribution is associated with severity of depressive symptoms. These findings suggest that homeostatic regulation of sleep may be impaired in adolescent depression. (C) 2017 Elsevier B.V. All rights reserved.
  • Utge, Siddheshwar; Soronen, Pia; Loukola, Anu; Kronholm, Erkki; Ollila, Hanna M.; Pirkola, Sami; Porkka-Heiskanen, Tarja; Partonen, Timo; Paunio, Tiina (2010)