Genetic contribution to disease-course severity and progression in the SUPER-Finland study, a cohort of 10,403 individuals with psychotic disorders.

Genetic factors contribute to the susceptibility of psychotic disorders, but less is known how they affect psychotic disease-course development. Utilizing polygenic scores (PGSs) in combination with longitudinal healthcare data with decades of follow-up we investigated the contributing genetics to psychotic disease-course severity and diagnostic shifts in the SUPER-Finland study, encompassing 10 403 genotyped individuals with a psychotic disorder. To longitudinally track the study participants' past disease-course severity, we created a psychiatric hospitalization burden metric using the full-coverage and nation-wide Finnish in-hospital registry (data from 1969 and onwards). Using a hierarchical model, ranking the psychotic diagnoses according to clinical severity, we show that high schizophrenia PGS (SZ-PGS) was associated with progression from lower ranked psychotic disorders to schizophrenia (OR = 1.32 [1.23-1.43], p = 1.26e-12). This development manifested already at psychotic illness onset as a higher psychiatric hospitalization burden, the proxy for disease-course severity. In schizophrenia (n = 5 479), both a high SZ-PGS and a low educational attainment PGS (EA-PGS) were associated with increased psychiatric hospitalization burden (p = 1.00e-04 and p = 4.53e-10). The SZ-PGS and the EA-PGS associated with distinct patterns of hospital usage. In individuals with high SZ-PGS, the increased hospitalization burden was composed of longer individual hospital stays, while low EA-PGS associated with shorter but more frequent hospital visits. The negative effect of a low EA-PGS was found to be partly mediated via substance use disorder, a major risk factor for hospitalizations. In conclusion, we show that high SZ-PGS and low EA-PGS both impacted psychotic disease-course development negatively but resulted in different disease-course trajectories.

Implementation of CYP2D6 copy-number imputation panel and frequency of key pharmacogenetic variants in Finnish individuals with a psychotic disorder.

We demonstrate that CYP2D6 copy-number variation (CNV) can be imputed using existing imputation algorithms. Additionally, we report frequencies of key pharmacogenetic variants in individuals with a psychotic disorder from the genetically bottle-necked population of Finland. We combined GWAS chip and CYP2D6 CNV data from the Breast Cancer Pain Genetics study to construct an imputation panel (n = 902) for CYP2D6 CNV. The resulting data set was used as a CYP2D6 CNV imputation panel in 9262 non-related individuals from the SUPER-Finland study. Based on imputation of 9262 individuals we confirm the higher frequency of CYP2D6 ultrarapid metabolizers and a 22-fold enrichment of the UGT1A1 decreased function variant rs4148323 (UGT1A1*6) in Finland compared with non-Finnish Europeans. Similarly, the NUDT15 variant rs116855232 was highly enriched in Finland. We demonstrate that imputation of CYP2D6 CNV is possible and the methodology enables studying CYP2D6 in large biobanks with genome-wide data.

Variants in regulatory elements of PDE4D associate with major mental illness in the Finnish population.

We have previously reported a replicable association between variants at the PDE4D gene and familial schizophrenia in a Finnish cohort. In order to identify the potential functional mutations underlying these previous findings, we sequenced 1.5 Mb of the PDE4D genomic locus in 20 families (consisting of 96 individuals and 79 independent chromosomes), followed by two stages of genotyping across 6668 individuals from multiple Finnish cohorts for major mental illnesses. We identified 4570 SNPs across the PDE4D gene, with 380 associated to schizophrenia (p ≤ 0.05). Importantly, two of these variants, rs35278 and rs165940, are located at transcription factor-binding sites, and displayed replicable association in the two-stage enlargement of the familial schizophrenia cohort (combined statistics for rs35278 p = 0.0012; OR = 1.18, 95% CI: 1.06-1.32; and rs165940 p = 0.0016; OR = 1.27, 95% CI: 1.13-1.41). Further analysis using additional cohorts and endophenotypes revealed that rs165940 principally associates within the psychosis (p = 0.025, OR = 1.18, 95% CI: 1.07-1.30) and cognitive domains of major mental illnesses (g-score p = 0.044, ß = -0.033). Specifically, the cognitive domains represented verbal learning and memory (p = 0.0091, ß = -0.044) and verbal working memory (p = 0.0062, ß = -0.036). Moreover, expression data from the GTEx database demonstrated that rs165940 significantly correlates with the mRNA expression levels of PDE4D in the cerebellum (p-value = 0.04; m-value = 0.9), demonstrating a potential functional consequence for this variant. Thus, rs165940 represents the most likely functional variant for major mental illness at the PDE4D locus in the Finnish population, increasing risk broadly to psychotic disorders.

Long-term cognitive functioning is impaired in ICU-treated COVID-19 patients: a comprehensive controlled neuropsychological study.

BACKGROUND: Cognitive impairment has emerged as a common post-acute sequela of coronavirus disease 2019 (COVID-19). We hypothesised that cognitive impairment exists in patients after COVID-19 and that it is most severe in patients admitted to the intensive care unit (ICU). METHODS: This prospective controlled cohort study of 213 participants performed at the Helsinki University Hospital and the University of Helsinki, Finland, comprised three groups of patients-ICU-treated (n = 72), ward-treated (n = 49), and home-isolated (n = 44)-with confirmed COVID-19 between March 13 and December 31, 2020, participating in a comprehensive neuropsychological evaluation six months after the acute phase. Our study included a control group with no history of COVID-19 (n = 48). Medical and demographic data were collected from electronic patient records and interviews carried out four months after the acute phase. Questionnaires filled six months after the acute phase provided information about change in cognitive functioning observed by a close informant, as well as the presence of self-reported depressive and post-traumatic symptoms. RESULTS: The groups differed (effect size η2p = 0.065, p = 0.004) in the total cognitive score, calculated from neuropsychological measures in three domains (attention, executive functions, and memory). Both ICU-treated (p = 0.011) and ward-treated patients (p = 0.005) performed worse than home-isolated patients. Among those with more than 12 years of education, ICU-treated patients performed worse in the attention domain than ward-treated patients (p = 0.021) or non-COVID controls (p = 0.045); ICU-treated male patients, in particular, were impaired in executive functions (p = 0.037). CONCLUSIONS: ICU-treated COVID-19 patients, compared to patients with less severe acute COVID-19 or non-COVID controls, showed more severe long-term cognitive impairment. Among those with more than 12 years of education, impairment existed particularly in the domains of attention and for men, of executive functions. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT04864938, retrospectively registered February 9, 2021.

Mortality in individuals with childhood ADHD or subthreshold symptoms - a prospective perinatal risk cohort study over 40 years.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with negative life outcomes and recent studies have linked it to increased mortality. These studies have examined nationwide registers or clinic-referred samples and mostly included participants up until the age of 30. No studies have investigated mortality associated with subthreshold levels of ADHD symptoms. Our aim was to analyze mortality in a perinatal risk cohort of 46-year-old adults with childhood ADHD (cADHD) and milder childhood attention problems (including hyperactivity and inattention; cAP) compared with a group with similar birth risks but no or low levels of childhood ADHD symptoms (Non-cAP). Causes of death obtained from a national register were examined. METHODS: Mortality was analyzed with Cox proportional hazard models for all-cause mortality, cause-specific mortality (natural and unnatural causes), and age-specific mortality (under and over age 30). All models were adjusted with gender. The total n in the study was 839 (cADHD n = 115; cAP n = 216; Non-cAP n = 508). RESULTS: By the age of 46, 11 (9.6%) deaths occurred in the cADHD group, 7 (3.2%) in the cAP group, and 20 (3.9%) in the Non-cAP group. The cADHD group had the highest mortality risk (adjusted hazard ratio = 2.15; 95% CI 1.02, 4.54). Mortality was not elevated in the cAP group (adjusted hazard ratio = 0.72; 95% CI .30, 1.72). Mortality in the cADHD group was mainly attributed to unnatural causes of death (adjusted hazard ratio = 2.82; 95% CI 1.12, 7.12). The mortality risk in the cADHD group was sixfold before age 30 (adjusted hazard ratio = 6.20; 95% CI 1.78, 21.57). CONCLUSIONS: Childhood ADHD was associated with a twofold risk of premature death by the age of 46 in this prospective longitudinal cohort study. Our results corroborate previous findings and the morbidity of ADHD. Subthreshold levels of childhood ADHD symptoms were not linked to increased mortality. Our results suggest that mortality risk is higher in young than middle adulthood. Future studies should examine mortality associated with ADHD in different ages in adulthood to identify those in greatest risk of premature death.

Consumption of psychotropic drugs among disability pension applicants with mental disorders: comparing awarded and rejected applicants in Finland.

PURPOSE: Psychotropic drug consumption as a proxy measure of mental health problems during a disability pension process has only been studied among awarded applicants. This study examined psychotropic drug purchase trajectories among awarded and rejected disability pension applicants. Analyses were conducted in different diagnostic and sociodemographic groups. METHODS: A representative 70% sample of Finnish adults applying for disability pension due to a mental disorder in 2009-2011 (N = 18,087) was followed for 4 years in 3-month periods both before and after the pension decision. Register data on purchased drugs measured in defined daily doses (DDDs), gender, age, occupational class, unemployment history, and diagnostic group were used. The DDD levels and trends were analyzed using growth curve models. RESULTS: Psychotropic drug purchases increased before the pension decision and decreased gradually thereafter among both awarded and rejected applicants. The average DDD level was higher for rejected than awarded applicants before the decision but lower thereafter. The high pre-decision level for rejected applicants was explicit with a lower socioeconomic status. The pre-decision increase in DDDs was steeper for awarded applicants. Changes in DDDs before and after the decision were most prominent for depression, bipolar disorders, schizophrenia, and anxiety disorders. CONCLUSION: Awarded and rejected disability pension applicants differed partly in their trajectories of psychotropic drug consumption. For awarded applicants, the steep rise of consumption prior to the award possibly reflects worsening occupational capacity. Early high consumption for rejected applicants signals long running mental health problems and calls for earlier support.

Intergenerational transmission of psychiatric disorders: the 1987 Finnish Birth Cohort study.

The causes of mental disorders are multifactorial including genetic and environmental exposures, parental psychopathology being the greatest risk factor for their offspring. We set out to quantify the risk of parental psychiatric morbidity with the incidence of mental disorders among their offspring before the age of 22 years and study the sex- and age-specific associations. The present study utilises the 1987 Finnish Birth Cohort (FBC) data, which is a register-based follow-up of all 60,069 children born in Finland 1987 and followed-up until 2008. Data on psychiatric morbidity are based on inpatient care episodes of parents and both inpatient and outpatient visits of offspring and were collected from the Finnish Hospital Discharge Register which covers all Finnish citizens accessing specialized care. Altogether 7.6% of the cohort members had a parent or both parents treated at psychiatric inpatient care during the follow-up. Parental psychiatric morbidity increased the offspring's risk for psychiatric diagnoses two to threefold versus those children without parental psychiatric hospitalization, mother's morbidity comprising a greater risk than that of father's. The risk was prominent for both sexes of the offspring throughout childhood and adolescence. Psychiatric disorders possess significant intergenerational continuum. It is essential to target preventive efforts on the high-risk population that comprises families with a parent or both having mental disorders. It also implies developing appropriate social and health care interventions to support the whole family.

Predictive Association of Smoking with Depressive Symptoms: a Longitudinal Study of Adolescent Twins.

Longitudinal, genetically informative studies of the association between cigarette smoking and depressive symptoms among adolescents are limited. We examined the longitudinal association of cigarette smoking with subsequent depressive symptoms during adolescence in a Finnish twin cohort. We used prospective data from the population-based FinnTwin12 study (maximum N = 4152 individuals, 1910 twin pairs). Current smoking status and a number of lifetime cigarettes smoked were assessed at the age of 14 and depressive symptoms at the age of 17. Negative binomial regression was conducted to model the association between smoking behavior and subsequent depressive symptoms among individuals, and within-pair analyses were conducted to control for unmeasured familial confounding. Analyses were adjusted for age, sex, school grades, drinking alcohol to intoxication, health status, family structure, parental education, and smoking, as well as for pre-existing depressiveness. The results of the individual-level analyses showed that cigarette smoking at the age of 14 predicted depressive symptoms at the age of 17. Compared to never smokers, those who had smoked over 50 cigarettes (incidence rate ratio, IRR = 1.43, 95% CI 1.28-1.60) and regular smokers (IRR = 1.46, 95% CI 1.32-1.62) had higher depression scores. The associations were attenuated when adjusted for measured covariates and further reduced in within-pair analyses. In the within-pair results, the estimates were lower within monozygotic (MZ) pairs compared to dizygotic (DZ) pairs, suggesting that shared genetic factors contribute to the associations observed in individual-based analyses. Thus, we conclude that cigarette smoking is associated with subsequent depressive symptoms during adolescence, but the association is not independent of measured confounding factors and shared genetic influences.

Trends in the long-term use of benzodiazepine anxiolytics and hypnotics: A national register study for 2006 to 2014.

PURPOSE: Long-term benzodiazepine (BZD) treatment continues to be a debated topic. Because individual BZDs have different clinical profiles, we assessed the nationwide trends of long-term BZD use at active substance level during years 2006 to 2014. METHODS: This study covered all reimbursed BZD purchases (n = 408 572-521 823 annually) for adults recorded in the Finnish Prescription Register. We assessed long-term use (annual cumulative purchase of ≥180 defined daily doses) in general, and at active substance level with the most commonly used BZD anxiolytics (oxazepam, diazepam, alprazolam, and clonazepam for nonepilepsy indications) and hypnotics (zopiclone, zolpidem, and temazepam) included. The persistence rates for each substance were assessed separately. RESULTS: The prevalence of long-term BZD use among Finnish adults declined significantly from 5.3% to 3.6%, during years 2006 to 2014. Despite this decline, there was a significant increase in the long-term use of clonazepam for nonepilepsy indications and zolpidem (28.0% and 17.5%, respectively). Long-term use was common in the aged population, as well as among the users of hypnotics or clonazepam. Persistent use of 9 consecutive calendar years varied between 7.5% for incident alprazolam users and 21.0% for incident clonazepam users. CONCLUSIONS: We found a declining trend in long-term BZD use, but the decline was not uniform between the substances-the long-term use of clonazepam and zolpidem even increased. Follow-up research is needed to assess whether the decline in BZD use is accompanied by an increased use of other types of anxiolytic or hypnotic drugs or other forms of treatment.

Sickness allowance histories among disability retirees due to mental disorders: A retrospective case-control study.

OBJECTIVES: The aim was to describe sickness allowance histories before disability retirement due to mental disorders and to examine whether receiving sickness allowance due to mental disorders and somatic conditions predicts future disability retirement. METHOD: Pre-retirement sickness allowance histories were traced backwards for 7 years among Finnish residents aged 25-64 years who had retired due to mental disorders in 2011 (n=5.544). For each retiree, five sex- and age-matched controls were drawn from the non-retired population. Conditional logistic regression was used to calculate the risk for disability retirement by sickness allowance history and to control for the effects of educational level, social class, marital status and the urbanisation level of the municipality. RESULTS: The proportion of sickness allowance recipients increased steadily during the years preceding disability retirement, and was highest among those who retired due to bipolar disorders or depression. Those who had received sickness allowance due to mental disorders 6-7 years earlier had 6.5 times higher risk and those with sickness allowance 1-2 years earlier 11.7 times higher risk for disability retirement. Sickness allowance due to somatic conditions increased the risk for disability retirement 1.6-1.9 times. Sickness allowance most strongly predicted retirement due to bipolar disorders and depression. Adjustment for covariates had little effect. CONCLUSION: Those who retired due to mental disorders more often had sickness allowance due to both mental disorders and somatic conditions, but in particular sickness allowance due to mental disorders predicted disability retirement due to mental disorders.

Common variants conferring risk of schizophrenia.

Schizophrenia is a complex disorder, caused by both genetic and environmental factors and their interactions. Research on pathogenesis has traditionally focused on neurotransmitter systems in the brain, particularly those involving dopamine. Schizophrenia has been considered a separate disease for over a century, but in the absence of clear biological markers, diagnosis has historically been based on signs and symptoms. A fundamental message emerging from genome-wide association studies of copy number variations (CNVs) associated with the disease is that its genetic basis does not necessarily conform to classical nosological disease boundaries. Certain CNVs confer not only high relative risk of schizophrenia but also of other psychiatric disorders. The structural variations associated with schizophrenia can involve several genes and the phenotypic syndromes, or the 'genomic disorders', have not yet been characterized. Single nucleotide polymorphism (SNP)-based genome-wide association studies with the potential to implicate individual genes in complex diseases may reveal underlying biological pathways. Here we combined SNP data from several large genome-wide scans and followed up the most significant association signals. We found significant association with several markers spanning the major histocompatibility complex (MHC) region on chromosome 6p21.3-22.1, a marker located upstream of the neurogranin gene (NRGN) on 11q24.2 and a marker in intron four of transcription factor 4 (TCF4) on 18q21.2. Our findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition.

Enhancing sense of coherence via early intervention among depressed occupational health care clients.

BACKGROUND: Research on interventions improving psychological adjustment has suggested that sense of coherence (SOC) could be improved. AIMS: In the present study, we measured the impact of an intervention on the SOC among adults with first-episode depression. We also examined whether rehabilitation, depression, occupational stressors, life situation stressors and socio-demographic characteristics are associated with a change in the SOC. METHODS: Occupational health care clients were screened for depression using the Beck Depression Inventory (BDI) and a structured clinical interview (the The Structured Clinical Interview for DSM-IV: SCID-I). The participating subjects were randomized into a rehabilitation group (n = 134) and control group (n = 100) receiving treatment as usual. The Sense of Coherence Scale (SOC-13) was used at the baseline and in a 1-year follow-up to compare the change of the SOC between the groups. RESULTS: The increase in the mean SOC score was statistically significant both in the rehabilitation group (54.91 compared with 62.85, P < 0.001) and in the control group (55.29 compared with 61.64, P < 0.001). There was no significant difference in the mean SOC scores between the groups at the follow-up. The improved SOC was associated with less severe depression (P = 0.003) and greater decreasing in BDI (P = 0.041) in the rehabilitation group. CONCLUSIONS: The results suggest that both rehabilitation and conventional depression treatment in a first episode of depression may enhance the SOC and that rehabilitation itself enhances the SOC more effectively among those with less severe depression or those whose BDI scores had further decreased at the 1-year follow-up.

[Family-based psychosocial interventions for children with attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder, and conduct disorder]. / Psykososiaaliset perheinterventiot lapsen aktiivisuuden ja tarkkaavuuden häiriön sekä uhmakkuus--ja käytöshäiriöiden hoidossa.

Psychosocial family-based interventions--family therapy, cognitive-behavioral parent training and family-based treatment protocols--are empirically supported treatments for children with attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder, and conduct disorder. Well-researched interventions such as remote and group-based parent training programs relate to improvements in parenting quality, positive parenting, and the child's decreased ADHD and conduct behavioral problems, whereas individual family-based treatments are sometimes required, depending on symptom severity. Specific family-based treatment protocols are tailored for older children and adolescents with severe behavioral and emotional problems. Considering the above, empirically supported programs are used more in Finland, compared to licensed Anglo-American treatment protocols.

[Cognitive functions in severe psychotic disorders]. / Kognitiiviset toiminnot vaikeissa psykoottisissa häiriöissä.

Cognitive functions in schizophrenia exhibit a widely mixed nature. A specific neuropsychological core disturbance typical of schizophrenia still remains to be defined. Disturbances of cognitive function that do not qualitatively differ from those associated with schizophrenia are observed also in other severe psychotic disorders. Cognitive disturbances may even be more significant than other symptoms of disease for the patient's overall condition and coping with daily life. Neuropsychological examination is an essential part of assessment of the total care and rehabilitation of a patient with psychosis.

Childhood motor difficulties and cognitive impairment in midlife: A 40-year cohort study.

OBJECTIVE: We aimed to examine the association of childhood motor difficulties (MD) with cognitive impairment in midlife. METHOD: We studied 357 participants from a cohort born in 1971-1975. At age 9, they had completed the Test of Motor Impairment, which classified them into three groups: childhood MD (cMD), borderline cMD (bcMD), or no cMD. Participants with attention-deficit/hyperactivity disorder were excluded. At age 40, participants comprised 18 (5.0%) with cMD, 43 (12.0%) with bcMD, and 296 (82.9%) with no cMD. They underwent neuropsychological assessment covering six domains: executive functions, processing speed, attention and working memory, learning and memory, verbal symbolic abilities, and visuoperceptual and visuospatial abilities. A participant was considered to have an impairment if their performance was in the 15th percentile of a normative group. RESULTS: Participants with cMD were more likely than those with no cMD to have an impairment in executive functions (OR = 6.73, p < .01), processing speed (OR = 3.85, p < .05), attention and working memory (OR = 4.79, p < .01), and a cross-domain impairment (OR = 3.62, p < .01). These differences remained significant after adjusting for parents' occupation, sex, and low birth weight and after multiple imputation. No consistent difference emerged between participants with bcMD and no cMD. CONCLUSIONS: Childhood MD are associated with midlife cognitive impairment, which underscores their long-term implications. In the neuropsychological assessment of an adult patient, information on childhood motor development is of value. The assessment may help adapt the patient's physical or occupational therapy to the patient's cognitive profile. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Motor difficulties from childhood to midlife: A 40-year cohort study.

BACKGROUND: There are few studies of the persistence of childhood motor difficulties (MD) into adulthood. AIMS: To investigate the association of childhood MD with motor skills and body mass index (BMI) in midlife. METHODS AND PROCEDURES: We studied 324 adults aged 40 from a cohort born in 1971-1974. At age 9, they had undergone the Test of Motor Impairment, used to classify them into groups: childhood MD (cMD), borderline cMD (bcMD), or no cMD. At age 40, participants comprised 23 with cMD, 47 with bcMD, and 254 with no cMD. Participants completed motor tests of balance, manual dexterity, and visuomotor speed, followed by recording of their BMI. OUTCOMES AND RESULTS: At age 40, the cMD group performed worse than the no-cMD group on all motor tests (p < .001-.008). The bcMD group had slower visuomotor speed than the no-cMD group (p = .025). The groups differed in BMI (p = .002). Having cMD was associated with obesity in midlife (p < .001). After adjusting for sex, childhood socioeconomic status, and BMI at age 9, both cMD and bcMD were associated with obesity in midlife (p = .015). CONCLUSIONS AND IMPLICATIONS: Childhood MD are associated with poor motor skills, overweight, and obesity in midlife. This emphasises the importance of early intervention and follow-up when a child exhibits MD. WHAT THIS PAPER ADDS: This prospective longitudinal study presents novel evidence that individuals with a history of comprehensively and objectively assessed childhood motor difficulties (MD) have worse motor skills and a higher risk of obesity in midlife than do those with no childhood MD. There is a growing literature on adults with developmental coordination disorder or a history of MD. There is, however, a scarcity of longitudinal studies of childhood MD that continue beyond early adulthood, into midlife. In a systematic search, we could identify only one longitudinal study of objectively measured childhood MD with a reassessment of motor skills in those same participants in adulthood, and no study with a reassessment after age 20. Furthermore, longitudinal studies of the association of comprehensively and objectively assessed childhood MD with BMI in midlife have been lacking.

Association of antidepressant and benzodiazepine use, and anticholinergic burden with cognitive performance in schizophrenia.

Schizophrenia is characterized by cognitive impairment affecting everyday functioning. Earlier research has hypothesized that antidepressants may associate with better cognitive functioning, but results are mixed. This study explored the association between antidepressant use and cognitive performance in terms of reaction time and visual learning in a clinical sample. In addition, we examined benzodiazepine use and anticholinergic burden. Study participants were drawn from the SUPER-Finland cohort, collected among patients with psychotic illnesses in 2016-2018 throughout Finland (n = 10,410). The analysis included adults with a schizophrenia diagnosis (F20) and results from a cognitive assessment (n = 3365). Information about medications and psychosocial factors were gathered through questionnaire and interview. Cognitive performance was assessed with the Cambridge Neuropsychological Test Automated Battery (CANTAB) with two subtests measuring reaction time and visual learning. Almost 36 % of participants used at least one antidepressant. The use of antidepressants in general was not associated with performance in the reaction time and visual learning tasks. However, the use of SNRI antidepressants was associated with a faster reaction time. Benzodiazepine use and a higher anticholinergic burden were associated with poorer performance in both tests. The results strengthen earlier findings that there is no association between antidepressant use in general and cognitive performance in schizophrenia. However, the association of SNRI medications with a faster reaction time warrants further research. Moreover, the results suggest that more attention should be paid to the anticholinergic burden of the medications used by patients with schizophrenia, as well as avoiding continuous benzodiazepine use.

Common variants at VRK2 and TCF4 conferring risk of schizophrenia.

Common sequence variants have recently joined rare structural polymorphisms as genetic factors with strong evidence for association with schizophrenia. Here we extend our previous genome-wide association study and meta-analysis (totalling 7 946 cases and 19 036 controls) by examining an expanded set of variants using an enlarged follow-up sample (up to 10 260 cases and 23 500 controls). In addition to previously reported alleles in the major histocompatibility complex region, near neurogranin (NRGN) and in an intron of transcription factor 4 (TCF4), we find two novel variants showing genome-wide significant association: rs2312147[C], upstream of vaccinia-related kinase 2 (VRK2) [odds ratio (OR) = 1.09, P = 1.9 × 10(-9)] and rs4309482[A], between coiled-coiled domain containing 68 (CCDC68) and TCF4, about 400 kb from the previously described risk allele, but not accounted for by its association (OR = 1.09, P = 7.8 × 10(-9)).

Depressive symptoms, major depressive episodes and cognitive test performance-what is the role of physical activity?

BACKGROUND: Positive associations between physical activity and cognitive test performance in depressed subjects have been proposed in clinical studies. The contribution of severity and recency of depressive symptoms at the population level is not known. AIMS: This study aims to examine whether regular physical activity associates with better verbal fluency and psychomotor speed in depressed subjects using a large population-based sample. METHODS: Data was obtained from the population-based Finnish Health 2000 Study, gathered in 2000-2001. Depressive symptoms and depressive disorders were assessed by the Beck Depression Inventory (BDI) and the Composite International Diagnostic Interview (CIDI), correspondingly. Cognitive test performance was assessed by the animal naming test and psychomotor speed with a simple and multi-choice reaction time test. Physical activity (Gothenburg scale) was self-reported. Complete data were obtained from 3658 subjects aged 30-64 years. Socio-demographic factors, health behaviours and use of antidepressants and anxiolytics were used as covariates in the linear regression models. Adjusted means were calculated using the predictive margins method. RESULTS: Regular physical activity associated with better performance in reaction time tests and better verbal fluency among men with depressive symptoms or with a major depressive episode. Physical activity also associated with cognitive test performance among non-depressed men and women, but among them the differences between the physical activity groups were smaller. CONCLUSION: Regular physical activity may be a useful tool in supporting neurocognitive functioning among depressed subjects.

Associations of subjective and objective cognitive functioning after COVID-19: A six-month follow-up of ICU, ward, and home-isolated patients.

Background: Subjective and objective cognitive dysfunction are reported after COVID-19 but with limited data on their congruence and associations with the severity of the acute disease. The aim of this cohort study is to describe the prevalence of subjective and objective cognitive dysfunction at three and six months after COVID-19 and the associations of subjective cognitive symptoms and psychological and disease-related factors. Methods: We assessed a cohort of 184 patients at three and six months after COVID-19: 82 patients admitted to the Intensive Care Unit (ICU), 53 admitted to regular hospital wards, and 49 isolated at home. A non-COVID control group of 53 individuals was included. Demographic and clinical data were collected. Subjective cognitive symptoms, objective cognitive impairment, and depressive and post-traumatic stress disorder (PTSD) symptoms were assessed. Results: At six months, subjective cognitive impairment was reported by 32.3% of ICU-treated, 37.3% of ward-treated, and 33.3% of home-isolated patients and objective cognitive impairment was observed in 36.1% of ICU-treated, 34.7% of ward-treated, and 8.9% of home-isolated patients. Subjective cognitive symptoms were associated with depressive and PTSD symptoms and female sex, but not with objective cognitive assessment or hospital metrics. Conclusions: One-third of COVID-19 patients, regardless of the acute disease severity, reported high levels of subjective cognitive dysfunction which was not associated with results from objective cognitive screening but with psychological and demographic factors. Our study stresses the importance of thorough assessment of patients reporting long-term subjective symptoms, screening for underlying mental health related factors such as PTSD or depression.