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  • Cesta, Carolyn E, et al. (författare)
  • Polycystic ovary syndrome and psychiatric disorders: Co-morbidity and heritability in a nationwide Swedish cohort.
  • 2016
  • Ingår i: Psychoneuroendocrinology. - 1873-3360. ; 73, s. 196-203
  • Tidskriftsartikel (refereegranskat)abstract
    • Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting 5-15% of reproductive-aged women and characterized by high levels of circulating androgens. Given that androgens have been implicated in the aetiology of several psychiatric disorders, it was hypothesized that women with PCOS have high risk for psychiatric comorbidity. We aimed to investigate this risk amongst women with PCOS, as well as in their siblings, to elucidate if familial factors underlie any potential associations. Using the Swedish national registers, we identified all women diagnosed with PCOS between 1990 and 2013 (n=24,385), their full-siblings (n=25,921), plus matched individuals (1:10/100) from the general population and their full-siblings. Psychiatric disorder diagnoses were identified including schizophrenia, bipolar disorder, depressive and anxiety disorders, eating disorders, personality and gender identity disorder, autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), tics, attempted and completed suicide. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression and adjusted ORs (AOR) were determined by adjustment for comorbid psychiatric disorders. Overall, women with PCOS had an increased odds of having at least one psychiatric disorder (OR=1.56 [95CI%, 1.51-1.61]). Crude ORs showed associations with nearly all psychiatric disorders included in this study. Following adjustment for comorbid psychiatric disorders, women with PCOS were still at a significantly increased risk for bulimia, schizophrenia, bipolar disorder, depressive and anxiety disorders, personality disorders, with the highest AORs for ASD (AOR=1.55 [95%CI, 1.32-1.81]) and tics (AOR=1.65 [95%CI, 1.10-2.47]). Significantly higher AORs were found for ASD in both brothers and sisters of women with PCOS, and for depressive, anxiety, and schizophrenia spectrum disorders in the sisters only. Notably, the crude ORs for attempted suicide were 40% higher in women with PCOS and 16% higher in their unaffected sisters. However, the AORs were greatly attenuated indicating that underlying psychiatric comorbidity is important for this association. Women with PCOS had higher risks for a range of psychiatric disorders not shown before. Elevated risk in their siblings suggests shared familial factors between PCOS and psychiatric disorders. This study is an important first step towards identifying the underlying mechanisms for risk of psychiatric disorders in women with PCOS. Health professionals treating women with PCOS should be aware that these patients - as well as their family members - are important targets for mental health care.
  • Ekman, Carl Johan, et al. (författare)
  • A History of Psychosis in Bipolar Disorder is Associated With Gray Matter Volume Reduction.
  • 2017
  • Ingår i: Schizophrenia bulletin. - 1745-1701. ; 43:1, s. 99-107
  • Tidskriftsartikel (refereegranskat)abstract
    • Psychotic symptoms are prevalent in schizophrenia, bipolar disorder, and other psychiatric and neurological disorders, yet the neurobiological underpinnings of psychosis remain obscure. In the last decade, a large number of magnetic resonance imaging studies have shown differences in local gray matter volume between patients with different psychiatric syndromes and healthy controls. Few studies have focused on the symptoms, which these syndromes are constituted of. Here, we test the association between psychosis and gray matter volume by using a sample of 167 subjects with bipolar disorder, with and without a history of psychosis, and 102 healthy controls. Magnetic resonance images were analyzed on group level using a voxel-wise mass univariate analysis (Voxel-Based Morphometry). We found that patients with a history of psychosis had smaller gray matter volume in left fusiform gyrus, the right rostral dorsolateral prefrontal cortex, and the left inferior frontal gyrus compared with patients without psychosis and with healthy controls. There was no volume difference in these areas between the no-psychosis group and healthy controls. These areas have previously been structurally and functionally coupled to delusions and hallucinations. Our finding adds further evidence to the probability of these regions as key areas in the development of psychotic symptoms.
  • Hughes, Timothy, et al. (författare)
  • A Loss-of-Function Variant in a Minor Isoform of ANK3 Protects Against Bipolar Disorder and Schizophrenia.
  • 2016
  • Ingår i: Biological psychiatry. - 1873-2402. ; 80:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Ankyrin-3 (ANK3) was one of the first genes to reach significance in a bipolar disorder genome-wide association study. Many subsequent association studies confirmed this finding and implicated this gene in schizophrenia. However, the exact nature of the role of ANK3 in the pathophysiology remains elusive. In particular, the specific isoforms involved and the nature of the imbalance are unknown.
  • Isgren, Anniella, et al. (författare)
  • Increased cerebrospinal fluid interleukin-8 in bipolar disorder patients associated with lithium and antipsychotic treatment.
  • 2015
  • Ingår i: Brain, behavior, and immunity. - 1090-2139. ; 43
  • Tidskriftsartikel (refereegranskat)abstract
    • Inflammation has been linked to the pathophysiology of bipolar disorder based on studies of inflammation markers, such as cytokine concentrations, in plasma and serum samples from cases and controls. However, peripheral measurements of cytokines do not readily translate to immunological activity in the brain. The aim of the present study was to study brain immune and inflammatory activity. To this end, we analyzed cytokines in cerebrospinal fluid from 121 euthymic bipolar disorder patients and 71 age and sex matched control subjects. Concentrations of 11 different cytokines were determined using immunoassays. Cerebrospinal fluid IL-8 concentrations were significantly higher in patients as compared to controls. The other cytokines measured were only detectable in part of the sample. IL-8 concentrations were positively associated to lithium- and antipsychotic treatment. The findings might reflect immune aberrations in bipolar disorder, or be due to the effects of medication.
  • Joas, Erik, 1983-, et al. (författare)
  • Pharmacological treatment and risk of psychiatric hospital admission in bipolar disorder
  • 2017
  • Ingår i: British Journal of Psychiatry. - 0007-1250. ; 210:3, s. 197-202
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Clinical trials have examined the efficacy of drugs to prevent relapse in patients with bipolar disorder, however, their design often limits generalisation to routine clinical practice. To estimate the effectiveness of drugs used for maintenance treatment in bipolar disorder. We used national registers to identify 35 022 individuals diagnosed with bipolar disorder and information on lithium, valproate, carbamazepine, lamotrigine, quetiapine and olanzapine treatment from 2006 to 2009. The main outcome was psychiatric hospital admissions. We used stratified cox regression to compare periods on and off medication within the same individual. Medication with lithium, valproate, lamotrigine, olanzapine and quetiapine was associated with reduced rates of admission to hospital. Lithium was more effective than quetiapine and olanzapine. The effects of specific drugs depended on the polarity of the mood episode. Our findings complement results from randomised controlled trails, but suggest that lithium is more effective than both quetiapine and olanzapine in routine clinical practice.
  • Johansson, Viktoria, et al. (författare)
  • Cerebrospinal fluid microglia and neurodegenerative markers in twins concordant and discordant for psychotic disorders.
  • 2017
  • Ingår i: European archives of psychiatry and clinical neuroscience. - 1433-8491. ; 267:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Schizophrenia and bipolar disorder are debilitating psychiatric disorders with partially shared symptomatology including psychotic symptoms and cognitive impairment. Aberrant levels of microglia and neurodegenerative cerebrospinal fluid (CSF) markers have previously been found in schizophrenia and bipolar disorder. We aimed to analyze familial and environmental influences on these CSF markers and their relation to psychiatric symptoms and cognitive ability. CSF was collected from 17 complete twin pairs, nine monozygotic and eight dizygotic, and from one twin sibling. Two pairs were concordant for schizophrenia, and 11 pairs discordant for schizophrenia, schizoaffective disorder or bipolar disorder, and four pairs were not affected by psychotic disorders. Markers of microglia activation [monocyte chemoattractant protein-1 (MCP-1), chitinase 3-like protein 1 (YKL-40), and soluble cluster of differentiation 14 (sCD14)], markers of β-amyloid metabolism (AβX-38, AβX-40, AβX-42 and Aβ1-42), soluble amyloid precursor proteins (sAPP-α and sAPP-β), total tau (T-tau), phosphorylated tau (P-tau), and CSF/serum albumin ratio were measured in CSF using immunoassays. Heritability of the CSF markers was estimated, and associations to psychiatric and cognitive measurements were analyzed. Heritability estimates of the microglia markers were moderate, whereas several neurodegenerative markers showed high heritability. In contrast, AβX-42, Aβ1-42, P-tau and CSF/serum albumin ratio were influenced by dominant genetic variation. Higher sCD14 levels were found in twins with schizophrenia or bipolar disorder compared to their not affected co-twins, and higher sCD14-levels were associated with psychotic symptoms. The study provides support for a significant role of sCD14 in psychotic disorders and a possible role of microglia activation in psychosis.
  • Johansson, V., et al. (författare)
  • Twin study shows association between monocyte chemoattractant protein-1 and kynurenic acid in cerebrospinal fluid
  • 2019
  • Ingår i: European Archives of Psychiatry and Clinical Neuroscience. - 0940-1334.
  • Tidskriftsartikel (refereegranskat)abstract
    • Preclinical studies indicate a link between the kynurenine pathway and monocyte chemoattractant protein-1 (MCP-1), but there is a lack of clinical studies examining this further. We here perform a secondary analysis of kynurenine metabolites and MCP-1 in cerebrospinal fluid of 23 twins affected from schizophrenia, bipolar disorder or unaffected. We show an association between MCP-1 and kynurenic acid (KYNA), driven by unique environmental influences and a less pronounced association between MCP-1 and tryptophan. No association was detected between MCP-1 and quinolinic acid. Further studies on the mechanism behind the putative relationship between KYNA and MCP-1 are needed. © 2019, The Author(s).
  • Kegel, Magdalena E, et al. (författare)
  • Kynurenic acid and psychotic symptoms and personality traits in twins with psychiatric morbidity.
  • 2017
  • Ingår i: Psychiatry research. - 1872-7123. ; 247, s. 105-112
  • Tidskriftsartikel (refereegranskat)abstract
    • Increased cytokines and kynurenic acid (KYNA) levels in cerebrospinal fluid (CSF) have been reported in patients with schizophrenia and bipolar disorder. The aim of the present study was to investigate cytokines and kynurenines in the CSF of twin pairs discordant for schizophrenia or bipolar disorder and to study these CSF markers in relation to psychotic symptoms and personality traits. CSF levels of tryptophan (TRP), KYNA, quinolinic acid (QUIN), interleukin (IL)-6, IL-8 and tumor necrosis factor-alpha (TNF-α) were analyzed in 23 twins with schizophrenia or bipolar disorder, and in their not affected co-twins. Ratings of psychotic symptoms and personality traits were made using the Scales for Assessment of Negative and Positive symptoms, the Structured Clinical Interview for DSM-IV - Axis II Disorders, and the Schizotypal Personality Questionnaire - Brief. A total score for psychotic symptoms and personality traits was constructed for analysis. CSF KYNA was associated with the score for psychotic symptom and personality traits. TNF-α and IL-8 were associated, and the intra-pair differences scores of TNF-α and IL-8 were highly correlated. Intraclass correlations indicated genetic influences on CSF KYNA, TRP, IL-8 and TNF-α. The association between KYNA and psychotic symptoms further supports a role of KYNA in psychotic disorders.
  • Kyaga, S., et al. (författare)
  • Bipolar disorder and leadership - a total population study
  • 2015
  • Ingår i: Acta Psychiatrica Scandinavica. - 0001-690X. ; 131:2, s. 111-119
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveTo investigate whether persons with bipolar disorder and their siblings have leadership traits and are overrepresented in executive professions. MethodA nested case-control study based on longitudinal Swedish total population registries. Data from officer suitability interviews (n=1126519), and information on occupations were collected. Bipolar patients (n=68915) and their healthy siblings were compared with controls. ResultsBipolar patients without comorbidity (pure; n=22980) were overrepresented in both the highest and lowest strata of officer suitability; their healthy siblings in the highest strata only. Patients with pure bipolar disorder were underrepresented in executive professions, whereas their siblings were overrepresented in these professions (particularly political professions). Patients with general bipolar disorder (including those with comorbidities) and their healthy siblings were overrepresented only in the lowest strata of officer suitability ratings. General bipolar patients were underrepresented in executive professions, whereas their siblings had similar rates of executive professions as controls. Adjusting results for IQ slightly attenuated point estimates, but resulted in pure bipolar patients and their siblings no longer being significantly overrepresented in superior strata of officer suitability, and siblings no longer being overrepresented in executive professions. ConclusionResults support that traits associated with bipolar disorder are linked to superior leadership qualities.
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