The shared genetics of migraine and anxious depression

OBJECTIVES To investigate: - (1) whether shared genetic factors influence migraine and anxious depression; - (2) whether the genetic architecture of migraine depends on anxious depression; - (3) whether the association between migraine and anxious depression is causal. BACKGROUND Migraine and anxious depression frequently occur together, but little is known about the mechanisms causing this association. METHODS A twin study was conducted to model the genetic architecture of migraine and anxious depression and the covariance between them. Anxious depression was also added to the model as a moderator variable to examine whether anxious depression affects the genetic architecture of migraine. Causal models were explored with the co-twin control method. RESULTS Modest but significant phenotypic (rP=0.28), genetic (rG=0.30), and nonshared environmental (rE=0.26) correlations were found between the 2 traits. Interestingly, the heritability of migraine depended on the level of anxious depression: the higher the anxious depression score, the lower the relative contribution of genetic factors to the individual differences in migraine susceptibility. The observed risk patterns in discordant twins are most consistent with a bidirectional causal relationship. CONCLUSIONS These findings confirm the genetic association between migraine and anxious depression and are consistent with a syndromic association between the 2 traits. This highlights the importance of taking comorbidity into account in genetic studies of migraine, especially in the context of selection for large-scale genotyping efforts. Genetic studies may be most effective when migraine with and without comorbid anxious depression are treated as separate phenotypes.

Molecular Pathways of Disturbed Sleep and Depression: Studies on Adenosine and Gene Expression Patterns

Background: Adenosine is a potent sleep-promoting substance, and one of its targets is the basal forebrain. Fairly little is known about its mechanism of action in the basal forebrain and about the receptor subtype mediating its regulating effects on sleep homeostasis. Homeostatic deficiency might be one of the causes of the profoundly disturbed sleep pattern in major depressive disorder, which could explain the reduced amounts of delta-activity-rich stages 3 and 4. Since major depression has a relatively high heritability, and on the other hand adenosine regulates sleep homeostasis and might also be involved in mood modulation, adenosine-related genes should be considered for their possible contribution to a predisposition for depression and disturbed sleep in humans. Depression is a complex disorder likely involving the abnormal functioning of several genes. Novel target genes which could serve as the possible common substrates for depression and comorbid disturbed sleep should be identified. In this way specific brain areas related to sleep regulation should be studied by using animal model of depression which represents more homogenous phenotype as compared to humans. It is also important to study these brain areas during the development of depressive-like features to understand how early changes could facilitate pathophysiological changes in depression. Aims and methods: We aimed to find out whether, in the basal forebrain, adenosine induces recovery non-rapid eye movement (NREM) sleep after prolonged waking through the A1 or/and A2A receptor subtype. A1 and A2A receptor antagonists were perfused into the rat basal forebrain during 3 h of sleep deprivation, and the amount of NREM sleep and delta power during recovery NREM sleep were analyzed. We then explored whether polymorphisms in genes related to the metabolism, transport and signaling of adenosine could predispose to depression accompanied by signs of disturbed sleep. DNA from 1423 individuals representative of the Finnish population and including controls and cases with depression, depression accompanied by early morning awakenings and depression accompanied by fatigue, was used in the study to investigate the possible association between polymorphisms from adenosine-related genes and cases. Finally to find common molecular substrates of depression and disturbed sleep, gene expression changes were investigated in specific brain areas in the rat clomipramine model of depression. We focused on the basal forebrain of 3-week old clomipramine-treated rats which develop depressive-like symptoms later in adulthood and on the hypothalamus of adult female clomipramine-treated rats. Results: Blocking of the A1 receptor during sleep deprivation resulted in a reduction of the recovery NREM sleep amount and delta power, whereas A2A receptor antagonism had no effect. Polymorphisms in adenosine-related genes SLC29A3 (equilibrative nucleoside transporter type 3) in women and SLC28A1 (concentrative nucleoside transporter type 1) in men associated with depression alone as well as when accompanied by early morning awakenings and fatigue. In Study III the basal forebrain of postnatal rats treated with clomipramine displayed disturbances in gamma-aminobutyric acid (GABA) receptor type A signaling, in synaptic transmission and possible epigenetic changes. CREB1 was identified as a common transcription denominator which also mediates epigenetic regulation. In the hypothalamus the major changes included the expression of genes in GABA-A receptor pathway, K+ channel-related, glutamatergic and mitochondrial genes, as well as an overexpression of genes related to RNA and mRNA processing. Conclusions: Adenosine plays an important role in sleep homeostasis by promoting recovery NREM sleep via the A1 receptor subtype in the basal forebrain. Also adenosine levels might contribute to the risk of depression with disturbed sleep, since the genes encoding nucleoside transporters showed the strongest associations with depression alone and when accompanied by signs of disturbed sleep in both women and men. Sleep and mood abnormalities in major depressive disorder could be a consequence of multiple changes at the transcriptional level, GABA-A receptor signaling and synaptic transmission in sleep-related basal forebrain and the hypothalamus.

Numerical study on the surface depression of the concrete runway pavement under impact load

Airport runway pavement always subjected to huge impact loading due to the hard landing of aircraft on the pavement surface. Therefore runway pavements should have sufficient impact resistance capability to avoid damage causing by hard impact like surface deflection in downward or penetration since the repair works is cumbersome within the operating condition of airport and also increases the service life cost of the pavement structure. Several research works have been carried out on airport runway pavement to measure the present condition of pavement and also to predict future performance of it. However, most of the works are confined by pavement response under moving aircraft loading. Nevertheless, no comprehensive research work is yet conducted to identify the controlling factors which might have significant effect in changing the common pavements damage like surface penetration depth under impact of aircraft. Therefore, a 3D FE study is conducted to determine some effective factors in controlling the top surface penetration depth of runway pavement. Among the exterior factors, mass of the impactor, velocity of the impactor, impact angle and boundary conditions are selected and as interior factors, thickness of the runway pavement, compressive strength and density of materials used in the runway pavement are selected.

Metacognitions mediate HIV stigma and depression/anxiety in men who have sex with men living with HIV

The study examined whether the relationships between HIV stigma and depression and anxiety would be mediated by metacognitive beliefs and thought control strategies in men who have sex with men living with HIV. Men who have sex with men living with HIV completed an online survey that measured 30-item Metacognitions Questionnaire, thought control strategies (Thought Control Questionnaire), as well as symptoms of depression (Patient Health Questionnaire-9) and anxiety (generalized anxiety disorder-7). The relationships between internalised and anticipated HIV stigma with depressive symptoms were mediated by Negative Metacognitive Beliefs and the use of Worry and Social thought control strategies. Negative Metacognitive Beliefs mediated the association between internalised HIV stigma and anxiety symptoms.

Depression, Anxiety, Psychiatric Comorbidity and Dimensions of Temperament and Personality

This study is part of the Mood Disorders Project conducted by the Department of Mental Health and Alcohol Research, National Public Health Institute, and consists of a general population survey sample and a major depressive disorder (MDD) patient cohort from Vantaa Depression Study (VDS). The general population survey study was conducted in 2003 in the cities of Espoo and Vantaa. The VDS is a collaborative depression research project between the Department of Mental Health and Alcohol Research of the National Public Health Institute and the Department of Psychiatry of the Peijas Medical Care District (PMCD) beginning in 1997. It is a prospective, naturalistic cohort study of 269 secondary-level care psychiatric out- and inpatients with a new episode of Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) MDD. In the general population survey study, a total of 900 participants (300 from Espoo, 600 from Vantaa) aged 20 70 years were randomly drawn from the Population Register Centre in Finland. A self-report booklet, including the Eysenck Personality Inventory (EPI), the Temperament and Character Inventory Revised (TCI-R), the Beck Depression Inventory and the Beck Anxiety Inventory was mailed to all subjects. Altogether 441 participants responded (94 returned only the shortened version without TCI-R) and gave their informed consent. VDS involved screening all patients aged 20-60 years (n=806) in the PMCD for a possible new episode of DSM-IV MDD. 542 consenting patients were interviewed with a semi-structured interview (the WHO Schedules for Clinical Assessment in Neuropsychiatry, version 2.0). 269 patients with a current DSM-IV MDD were included in the study and further interviewed with semi-structured interviews to assess all other axis I and II psychiatric diagnoses. Exclusion criteria were DSM-IV bipolar I and II, schizoaffective disorder, schizophrenia or another psychosis, organic and substance-induced mood disorders. In the present study are included those 193 (139 females, 54 males) individuals who could be followed up at both 6 and 18 months, and their depression had remained unipolar. Personality was investigated with the EPI. Personality dimensions associated not only to the symptoms of depression, but also to the symptoms of anxiety among general population and in depressive patients, as well as to comorbid disorders in MDD patients, supporting the dimensional view of depression and anxiety. Among the general population High Harm Avoidance and low Self-Directedness associated moderately, whereas low extraversion and high neuroticism strongly with the depressive and anxiety symptoms. The personality dimensions, especially high Harm Avoidance, low Self-Directedness and high neuroticism were also somewhat predictive of self-reported use of health care services for psychiatric reasons, and lifetime mental disorder. Moreover, high Harm Avoidance associated with a family history of mental disorder. In depressive patients, neuroticism scores were found to decline markedly and extraversion scores to increase somewhat with recovery. The predictive value of the changes in symptoms of depression and anxiety in explaining follow-up neuroticism was about 1/3 of that of baseline neuroticism. In contrast to neuroticism, the scores of extraversion showed no dependence on the symptoms of anxiety, and the change in the symptoms of depression explained only 1/20 of the follow-up extraversion compared with baseline extraversion. No evidence was found of the scar effect during a one-year follow-up period. Finally, even after controlling for symptoms of both depression and anxiety, depressive patients had a somewhat higher level of neuroticism (odds ratio 1.11, p=0.001) and a slightly lower level of extraversion (odds ratio 0.92, p=0.003) than subjects in the general population. Among MDD patients, a positive dose-exposure relationship appeared to exist between neuroticism and prevalence and number of comorbid axis I and II disorders. A negative relationship existed between level of extraversion and prevalence of comorbid social phobia and cluster C personality disorders. Personality dimensions are associated with the symptoms of depression and anxiety. Futhermore these findings support the hypothesis that high neuroticism and somewhat low extraversion might be vulnerability factors for MDD, and that high neuroticism and low extraversion predispose to comorbid axis I and II disorders among patients with MDD.

Balance of growth factors in the human perinatal lung : Implications for physiological lung development and link to bronchopulmonary dysplasia

The aims of this Thesis was to evaluate the role of proangiogenic placental growth factor (PlGF), antiangiogenic endostatin and lymphangiogenic vascular endothelial growth factor (VEGF) -C as well as the receptors vascular endothelial growth factor receptor (VEGFR) -2 and VEGFR-3 during lung development and in development of lung injury in preterm infants. The studied growth factors were selected due to a close relationship with VEGF-A; a proangiogenic growth factor important in normal lung angiogenesis and lung injury in preterm infants. The thesis study consists of three analyses. I: Lung samples from fetuses, preterm and term infants without lung injury, as well as preterm infants with acute and chronic lung injury were stained by immunohistochemistry for PlGF, endostatin, VEGF-C, VEGFR-2 and VEGFR-3. II: Tracheal aspirate fluid (TAF) was collected in the early postnatal period from a patient population consisting of 59 preterm infants, half developing bronchopulmonary dysplasia (BPD) and half without BPD. PlGF, endostatin and VEGF-C concentrations were measured by commercial enzyme-linked immunosorbent assay (ELISA). III: Cord plasma was collected from very low birth weight (VLBW) (n=92) and term (n=48) infants in conjuncture with birth and endostatin concentrations were measured by ELISA. I: All growth factors and receptors studied were consistently stained in immunohistochemistry throughout development. For endostatin in early respiratory distress syndrome (RDS), no alveolar epithelial or macrophage staining was seen, whereas in late RDS and BPD groups, both alveolar epithelium and macrophages stained positively in approximately half of the samples. VEGFR-2 staining was fairly consistent, except for the fact that capillary endothelial staining in the BPD group was significantly decreased. II: During the first postnatal week in TAF mean PlGF concentrations were stable whereas mean endostatin and VEGF-C concentrations decreased. Higher concentrations of endostatin and VEGF-C correlated with lower birth weight (BW) and associated with administration of antenatal betamethasone. Parameters reflecting prenatal lung inflammation associated with lower PlGF, endostatin and VEGF-C concentrations. A higher mean supplemental fraction of inspired oxygen during the first 2 postnatal weeks (FiO2) correlated with higher endostatin concentrations. III: Endostatin concentrations in term infants were significantly higher than in VLBW infants. In VLBW infants higher endostatin concentrations associated with the development of BPD, this association remained significant after logistic regression analysis. We conclude that PlGF, endostatin and VEGF-C all have a physiological role in the developing lung. Also, the VEGFR-2 expression profile seems to reflect the ongoing differentiation of endothelia during development. Both endostatin and VEGFR-2 seem to be important in the development of BPD. During the latter part of the first postnatal week, preterm infants developing BPD have lower concentrations of VEGF-A in TAF. Our findings of disrupted VEGFR-2 staining in capillary and septal endothelium seen in the BPD group, as well as the increase in endostatin concentrations both in TAF and cord plasma associated with BPD, seem to strengthen the notion that there is a shift in the angiogenic balance towards a more antiangiogenic environment in BPD. These findings support the vascular hypothesis of BPD.

Investigation of a suicide ideation risk profile in people with co-occurring depression and substance use disorder

Disengagement from services is common before suicide, hence identifying factors at treatment presentation that predict future suicidality is important. This article explores risk profiles for suicidal ideation among treatment seekers with depression and substance misuse. Participants completed assessments at baseline and 6 months. Baseline demographics, psychiatric history, and current symptoms were entered into a decision tree to predict suicidal ideation at follow-up. Sixty-three percent of participants at baseline and 43.5% at follow-up reported suicidal ideation. Baseline ideation most salient when psychiatric illness began before adulthood, increasing the rate of follow-up ideation by 16%. Among those without baseline ideation, dysfunctional attitudes were the most important risk factor, increasing rates of suicidal ideation by 35%. These findings provide evidence of factors beyond initial diagnoses that increase the likelihood of suicidal ideation and are worthy of clinical attention. In particular, providing suicide prevention resources to those with high dysfunctional attitudes may be beneficial.

12-weeks supervised exercise training is a feasible and efficacious treatment for reducing depression in youth with major depressive disorder

Introduction: Major Depressive Disorder (MDD) has high prevalence among adolescents and young adults. Evidence of any effective treatments is limited. Exercise as an effective treatment for adults has some support but studies in younger populations are lacking. Therefore the aim of this study was to investigate the feasibility and preliminary efficacy of brief motivational interviewing (MI) plus 12-weeks exercise training as a treatment for MDD in youth...

Alcohol and depression

"A large proportion of people who experience drug problems also experience a range of mental health problems. Similarly, many people who experience mental health problems engage in hazardous drug use. The experience of these co-occurring disorders increases use of treatment services, but is associated with poorer prognosis. The implementation of effective responses has been hindered by the disaggregated systems of care that have been adopted in many countries; many problems are the outcome of poorly organised systems of care that do not reflect the needs of a large proportion of clients who experience various problems. There is a dearth of quality research to guide the development of evidence-based responses to co-occurring drug and mental health problems. This book introduces the reader to the issues, guided by a series of questions. These encourage the reader to consider the evidence about the nature and prevalence of co-occurring disorders and the challenges they create for individuals, the community and service providers. The diverse range of expertise of the contributors provides the opportunity to consider the challenges of navigating the various systems of care from the perspective of consumers, parents and clinicians. Researchers and clinicians examine the available evidence about the links between the various disorders and discuss the implications for treatment through a series of case studies. The reader is guided through evidence-based clinical decision-making. The editor and contributors argue that, while our knowledge and expertise is improving, there is a need to better resource and integrate treatment services to foster the adoption of evidence-based and effective responses. Poor systems of care don’t necessarily cause co-occurring mental health and drug problems, but they can contribute to poor outcomes."--Publisher website

Depression in / by / for women : agency, feminism and self-help in groups

Depression in / by / for Women: Agency, Feminism and Self-Help in Groups on ensimmäinen väitöstasoinen tutkimus feministisestä terapiasta Suomessa sijoittuen psykologian, sosiaalitieteellisen mielenterveystutkimuksen sekä feministisen tutkimuksen alueille. Perinteisen näkemyksen mukaan feministisen tutkimuksen tulee olla ”naisista, naisten tekemää ja naisille kohdistettua”. Naiset ja masennus -projektitutkimus keskittyy naisten kokemaan masennukseen sisältäen mahdollisen miesten sekä patriarkaalisen hyvinvointivaltion osuuden masennukseen. Masennusta kokevat naiset ovat tutkimuksessa sekä tutkimuksen kohteena että aktiivisia osanottajia, mikä tuo heidän äänensä kuuluville. Tutkimus perustuu vuosien 1994-2000 välisenä aikana kerättyyn 11 ryhmän osallistujia koskevaan kvalitatiivisiin ja kvantitatiivisiin aineistoon. Irmeli Laitinen on ollut suunnittelemassa, keräämässä ja analysoimassa sitä yhdessä projektin muiden jäsenten kanssa. Tutkimuksessa mitattiin kuinka ryhmiin osallistuvien seka masennuksen tunteet että toiminnat muuttuivat yhden vuoden aikana. Tutkimuksen tavoitteena oli sekä masennuksesta kärsivien naisten osallistuminen feministiseen toimintatutkimukseen että ammatillisesti ohjatun oma-apuryhmämenetelmän kehittäminen suomalaiseen mielenterveyspalveluun. Projektin tutkimustulosten mukaan siihen osallistuneet naiset voimaantuivat ymmärtämään itseään sekä saivat luottamusta sosiaaliisiin taitoihinsa. Pidemmällä aikavälillä naisten tunteet muuttuivat myönteisiksi, heidän suhteensa itseensä positiivisemmaksi ja he aktivoituivat fyysisesti. Lisäksi tutkimustulokset viittaavat siihen, että masennus voi johtua näkymättömästä, sukupuolisesti virittyneestä jännitteestä naisystävällisessä hyvinvointivaltiossa paljastaen ”hyvinvointimasennusoireilun”. Suomalaisen sosiologi Erik Allardtin hyvinvointitypologian - having, loving, being – mukaisesti nämä ryhmään osallistuvat naiset eivät koe puutteita niinkään materiaalisessa hyvinvoinnissa (having) vaan pikeminkin suhteiden, sosiaalisen ja emotionaalisen hyvinvoinnin ulottuvuuksilla (loving ja being). Se, että masentuneet naiset pystyvät tuomaan esille pitkään vaiennettuja kokemuksiaan, voi merkitä paljon heidän paranemisessaan ja voimaantumisessaan. Ammatillisesti ohjatut oma-apuryhmät ja naisystävälliset hoitokäytännöt mahdollistivat tämänkaltaisen paranemisprosessin alkamisen tutkimukseen osallistuneissa ryhmissä.

Depression and Cognition in Type 2 Diabetes from a Life Course Perspective

Background: Type 2 diabetes is linked to several complications which add to both physical and mental distress. Depression is a common co-morbidity of diabetes which can occur both as a cause and a consequence of type 2 diabetes. Depression has been shown to correlate with glucose regulation and treating depression might prove beneficial for glucose regulation as well as for mental well being. Another complication which might affect diabetes management is cognitive decline. Several risk factors and complications of diabetes might modify the risk for developing cognitive impairment, which is increased 1.5 times among subjects with type 2 diabetes. Type 2 diabetes, depression and impaired cognitive performance have all been linked to low birth weight. This thesis aimed to explore the effects and interactions of birth weight, depression and cognitive ability in relation to type 2 diabetes from a life course perspective. Subjects and methods: Studies I, II and V were part of the Helsinki Birth Cohort Study. 2003 subjects participated in an extensive clinical examination at an average age of 61 years. A standard glucose tolerance test (OGTT) was performed and depressive symptoms were assessed using the Beck Depression Inventory (BDI). In addition data was obtained from child welfare clinics and national registers. A subset of the cohort (n=1247) also performed a test on cognitive performance (CogState ®) at the average age of 64. Studies III and IV were randomised clinical trials where mildly depressed diabetic subjects were treated with paroxetine or placebo and the effect on metabolic parameters and quality of life was assessed. The first trial included 14 women and lasted 10 weeks, while the second trial included 43 subjects, both men and women, and lasted 6 months. Results: Type 2 diabetes was positively associated with the occurrence of depressive symptoms. Among diabetic subjects 23.6% had depressive symptoms, compared to 16.7% of subjects with normal glucose tolerance (OR = 1.77, p<0.001). Formal mediation analysis revealed that cardiovascular disease (CVD) is likely to act as a mediator in the association. Furthermore, low birth weight was found to modify the association between type 2 diabetes, CVD and depression. The association between BDI score and having type 2 diabetes or CVD was twice as strong in the subgroup with low birth weight (≤ 2500g) compared with the group with birth weight > 2500g (p for interaction 0.058). In the six months long randomised clinical trial (study IV) paroxetine had a transient beneficial effect on glycosylated haemoglobin A1c (GHbA1c) and quality of life when compared to placebo after three months of treatment. In study V we found that subjects with known diabetes had a consistently poorer level of cognitive performance than subjects with normal glucose tolerance in most of the tested cognitive domains. This effect was further amplified among those born with a small birth weight (p for interaction 0.002). Conclusions: Type 2 diabetes is associated with a higher occurrence of depressive symptoms compared to subjects with normal glucose tolerance. This association is especially strong among subjects with CVD and those born with a low birth weight. Treating depressed diabetic subjects with paroxetine has no long term effect on glucose regulation. Physicians should be aware of depression as an important co-morbidity of type 2 diabetes. Both depression and the cognitive decline often seen among diabetic subjects are increased if the subject is born with a low birth weight. Physicians should recognise low birth weight as an additional risk factor and modifier of diabetic complications.