Gender differences in the relationship between depression and suicidal ideation in young adolescents

Objective: This study examined the risk relationship between depressive symptomatology and suicidal ideation for young adolescent males and females. Method: A large cohort of students in their first year of high school completed the Center for Epidemiological Studies Depression Scale (CES-D) and the Adolescent Suicide Questionnaire. The risk relationship between depressive symptomatology and suicidal ideation was modelled using non-parametric kernel-smoothing techniques. Results: Suicidal ideation was more frequently reported by females compared with males which was partly explained by females having higher mean depression scores. At moderate levels of depression females also had a significantly higher risk of suicidal ideation compared with males and this increased risk contributed to the overall higher levels of female ideation. Conclusions: The risk relationship between depressive symptomatology and suicidal ideation is different for young adolescent males and females. The results indicate that moderate levels of depressive symptomatology can be associated with suicidal ideation (especially among young females) and that for these young people a suicide risk assessment is required.

Decreased perinatal sunshine duration is associated with increased non-affective but not affective psychosis birth rates

We have previously found an association between variations in schizophrenia birth rates and varyinglevels of perinatal sunshine duration. This study examines whether such an association can also be found for Ža. affective psychosis, and Žb. broadly defined nonaffective psychoses. Data for individuals born between 1931 and 1970 in Australia with ICD9 Other PsychosisŽ295–299.were obtained from the Queensland Mental Health Statistical System. ‘Affective psychosis’ included affective psychosis, schizo-affective psychosis, and depressive and excitative non-organic psychoses. ‘Non-affective psychosis’ included chizophrenia, paranoid disorders and other non-organic psychoses. Those receiving both affective and non-affective psychotic diagnoses were excluded. Rates per 10,000 live monthly general population births were calculated. For each month, we assessed the agreementŽusing the kappa statistic. between trends in Ža. birth rates and Žb. long-term trends in seasonally adjusted perinatal sunshine duration. The analyses were performed separately for males and females. There were 6265 with non-affective psychosis ŽMs3964 rate 66r10,000; Fs2299 44r10,000. and 2858 with affective psychosisŽMs1392 24r10,000; Fs1466 28r10,000.. There were no significant associations between Ža. affective psychosis birth rates for either males or females and Žb. sunshine duration. There was a significant association between nonaffective psychosis birth rates for males only and Žb. sunshine duration Žkappas0.15 p-0.001.. This suggests that, as a risk factor, the effect of reduced perinatal sunshine is specifically associated with males who develop non-affective psychosis. The Stanley Foundation supported this project.

Response selection deficits in melancholic but not nonmelancholic unipolar major depression

One consistent functional imaging finding from patients with major depression has been abnormality of the anterior cingulate cortex (ACC). Hypoperfusion has been most commonly reported, but some studies suggest relative hyperperfusion is associated with response to somatic treatments. Despite these indications of the possible importance of the ACC in depression there have been relatively few cognitive studies ACC function in patients with major depression. The present study employed a series of reaction time (RT) tasks involving selection with melancholic and nonmelancholic depressed patients, as well as age-matched controls. Fifteen patients with unipolar major depression (7 melancholic, 8 nonmelancholic) and 8 healthy age-matched controls performed a series of response selection tasks (choice RT, spatial Stroop, spatial stimulus-response compatibility (SRC), and a combined Stroop + SRC condition). Reaction time and error data were collected. Melancholic patients were significantly slower than controls on all tasks but were slower than nonmelancholic patients only on the Stroop and Stroop + SRC conditions. Nonmelancholic patients did not differ from the control group on any task. The Stroop task seems crucial in differentiating the two depressive groups, they did not differ on the choice RT or SRC tasks. This may reflect differential task demands, the SRC involved symbolic manipulation that might engage the dorsal ACC and dorsolateral prefrontal cortex (DLPFC) to a greater extent than the, primarily inhibitory, Stroop task which may engage the ventral ACC and orbitofrontal cortex (OFC). This might suggest the melancholic group showed a greater ventral ACC-OFC deficit than the nonmelancholic group, while both groups showed similar dorsal ACC-DLPFC deficit.

Assessing cost-effectiveness - Mental health: introduction to the study and methods

Objective: The Assessing Cost-Effectiveness - Mental Health (ACE-MH) study aims to assess from a health sector perspective, whether there are options for change that could improve the effectiveness and efficiency of Australia's current mental health services by directing available resources toward 'best practice' cost-effective services. Method: The use of standardized evaluation methods addresses the reservations expressed by many economists about the simplistic use of League Tables based on economic studies confounded by differences in methods, context and setting. The cost-effectiveness ratio for each intervention is calculated using economic and epidemiological data. This includes systematic reviews and randomised controlled trials for efficacy, the Australian Surveys of Mental Health and Wellbeing for current practice and a combination of trials and longitudinal studies for adherence. The cost-effectiveness ratios are presented as cost (A$) per disability-adjusted life year (DALY) saved with a 95% uncertainty interval based on Monte Carlo simulation modelling. An assessment of interventions on 'second filter' criteria ('equity', 'strength of evidence', 'feasibility' and 'acceptability to stakeholders') allows broader concepts of 'benefit' to be taken into account, as well as factors that might influence policy judgements in addition to cost-effectiveness ratios. Conclusions: The main limitation of the study is in the translation of the effect size from trials into a change in the DALY disability weight, which required the use of newly developed methods. While comparisons within disorders are valid, comparisons across disorders should be made with caution. A series of articles is planned to present the results.

Cost-effectiveness of cognitive behavioural therapy and selective serotonin reuptake inhibitors for major depression in children and adolescents

Objective: To assess from a health sector perspective the incremental cost-effectiveness of cognitive behavioural therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) for the treatment of major depressive disorder (MDD) in children and adolescents, compared to 'current practice'. Method: The health benefit is measured as a reduction in disability-adjusted life years (DALYs), based on effect size calculations from meta-analysis of randomised controlled trials. An assessment on second stage filter criteria ('equity'; 'strength of evidence', 'feasibility' and 'acceptability to stakeholders') is also undertaken to incorporate additional factors that impact on resource allocation decisions. Costs and benefits are tracked for the duration of a new episode of MDD arising in eligible children (age 6-17 years) in the Australian population in the year 2000. Simulation-modelling techniques are used to present a 95% uncertainty interval (UI) around the cost-effectiveness ratios. Results: Compared to current practice, CBT by public psychologists is the most cost-effective intervention for MDD in children and adolescents at A$9000 per DALY saved (95% UI A$3900 to A$24 000). SSRIs and CBT by other providers are less cost-effective but likely to be less than A$50 000 per DALY saved (> 80% chance). CBT is more effective than SSRIs in children and adolescents, resulting in a greater total health benefit (DALYs saved) than could be achieved with SSRIs. Issues that require attention for the CBT intervention include equity concerns, ensuring an adequate workforce, funding arrangements and acceptability to various stakeholders. Conclusions: Cognitive behavioural therapy provided by a public psychologist is the most effective and cost-effective option for the first-line treatment of MDD in children and adolescents. However, this option is not currently accessible by all patients and will require change in policy to allow more widespread uptake. It will also require 'start-up' costs and attention to ensuring an adequate workforce.

Homocysteine, Alzheimer genes and proteins, and measures of cognition and depression in older men

The epsilon4 allele of apolipoprotem E (APOE), and the plasma levels of APOE, amyloid beta-protein precursor, arnyloid beta1-40 (Abeta40) and homocysteine, (Hcy) have all been correlated with the presence of dementia. Mutations in the methylnetetrahydrofolate reductase enzyme (MTHFR) have been associated with elevated levels of Hcy. This study explored the association of these factors with cognition and depression in community dwelling older men. Two hundred and ninety-nine men, mean age 78.9 years (SD 2.8), were studied in this cross-sectional survey. Mean plasma Hcy was 13.5 (SD 5.3) mumol/L. The MTHFR genotype had no obvious impact on Hey levels. Ln Hcy and Ln Abeta40 were both inversely correlated with calculated glomerular filtration rate (cGFR), r = -0.41 (p < 0.001) and r = -0.28 (p < 0.001), respectively. There was a positive correlation between Ln Hey and Ln Abeta40, r = 0.19 (p < 0.001), which remained significant after adjusting for cGFR, with a doubling of Hcy associated with a 24% increase of Abeta40. The e4 allele was associated with increased depressive symptoms as measured by the Geriatric Depression Scale-15, Odds ratio (OR) = 2.59 (95% CI 1.06-6.34) and poorer performance on the Clock Drawing Test, OR = 2.32 (95% CI: 1.25-4.29). There was a positive association between Abeta40 and Hcy, even after adjustment for cGFR in this sample of well, community dwelling older men. This association may help elucidate the link between elevated levels of Hey and Alzheimer's disease.

Age-at-first-registration for affective psychosis and schizophrenia

We compared the age-at-first-registration for patients with schizophrenia and affective psychosis in a statewide mental health register. After excluding those receiving (1) a diagnosis of both schizophrenia (ICD-9 295.x) and affective psychosis (ICD-9 296.x), or (2) a diagnosis of ICD-9 296.1 (which can cover major depressive episode), we adjusted the distributions for the age structure of the background general population. We found that all distributions showed a wide age range of onset, with a similar male modal age group of 20-24 for schizophrenia and 25-29 for affective psychosis. The female modal age group was 50-54 for both diagnoses. Although more individuals were diagnosed with schizophrenia (males = 2,434, females = 1,609) than with affective psychosis (males = 670, females = 913), the shape of the two distributions was similar. This finding suggests that factors influencing age-at-first-registration for schizophrenia and affective psychosis may be similar, especially for females.

Pindolol potentiates the panicolytic effect of paroxetine in the elevated T-maze

Aims: The beta-adrenergic and 5-HT(1A) receptor antagonist pindolol has been used in combination with antidepressant drugs, to shorten the time of onset of clinical efficacy and/or increase the proportion of responders in depressive and anxiety disorders. The aim of this study was to examine the interaction between pindolol and the selective serotonin reuptake inhibitor (SSRI), paroxetine in rats submitted to the elevated T-maze (ETM). Main methods: For assessing the drug combination effect, rats were administered with pindolol before paroxetine, using oral or intraperitoneal (i.p.) routes of acute administration, and were submitted to the ETM model. Key findings: The highest dose of pindolol used (15.0 mg/kg, i.p.) increased both inhibitory avoidance and escape latencies in the ETM, probably due to nonspecific motor deficit, since locomotion in a circular arena was also significantly decreased. The highest dose of paroxetine (3.0 mg/kg, i.p.) selectively impaired escape, considered a panicolytic effect. Combination of pindolol (5.0 mg/kg, i.p.) with an ineffective dose of paroxetine (1.5 mg/kg, i.p.) impaired escape, indicating a potentiation of the panicolytic effect of paroxetine. By the oral route, neither paroxetine (3.0 mg/kg) nor pindolol (5.0 mg/kg) alone were effective, but the combination treatment had a marked panicolytic effect, again indicating drug potentiation. Significance: The present results show that the combination of the ineffective doses of pindolol and paroxetine significantly increased escape latency, indicating a selective panicolytic effect. These findings give preclinical support for the use of this drug combination in the treatment of panic disorder (PD). (C) 2010 Elsevier Inc. All rights reserved.

Antidepressant-Like Effects of Medial Prefrontal Cortex Deep Brain Stimulation in Rats

Background: Subcallosal cingulate gyrus (SCG) deep brain stimulation (DBS) is being investigated as a treatment for major depression. We report on the effects of ventromedial prefrontal cortex (vmPFC) DBS in rats, focusing on possible mechanisms involved in an antidepressant-like response in the forced swim test (FST). Methods: The outcome of vmPFC stimulation alone or combined with different types of lesions, including serotonin (5-HT) or nore-pineprhine (NE) depletion, was characterized in the FST. We also explored the effects of DBS on novelty-suppressed feeding, learned helplessness, and sucrose consumption in animals predisposed to helplessness. Results: Stimulation at parameters approximating those used in clinical practice induced a significant antidepressant-like response in the FST. Ventromedial PFC lesions or local muscimol injections did not lead to a similar outcome. However, animals treated with vmPFC ibotenic acid lesions still responded to DBS, suggesting that the modulation of fiber near the electrodes could play a role in the antidepressant-like effects of stimulation. Also important was the integrity of the serotonergic system, as the effects of DBS in the FST were completely abolished in animals bearing 5-HT, but not NE, depleting lesions. In addition, vmPFC stimulation induced a sustained increase in hippocampal 5-HT levels. Preliminary work with other models showed that DBS was also able to influence specific aspects of depressive-like states in rodents, including anxiety and anhedonia, but not helplessness. Conclusions: Our study suggests that vmPFC DES in rats maybe useful to investigate mechanisms involved in the antidepressant effects of SCG DBS.

Serotonin-1A receptors in the dorsal periaqueductal gray matter mediate the panicolytic-like effect of pindolol and paroxetine combination in the elevated T-maze

The beta-adrenergic blocker and 5-HT(1A) receptor antagonist pindolol has been combined with selective serotonin reuptake inhibitors (SSRIs) in patients with depressive and anxiety disorders to shorten the onset of the clinical action and/or increase the proportion of responders. The results of a previous study have shown that pindolol potentiates the panicolytic effect of paroxetine in rats submitted to the elevated T-maze (ETM). Since reported evidence has implicated the 5-HT(1A) receptors of the dorsal periaqueductal gray matter (DPAG) in the panicolytic effect of antidepressants, rats treated with pindolol (5.0 mg/kg, i.p.) and paroxetine (1.5 mg/kg, i.p.) received a previous intra-DPAG injection of the selective 5-HT(1A) antagonist, WAY-100635 (0.4 mu g) and were submitted to the ETM. Pretreatment with WAY-100635 reversed the increase in escape latency, a panicolytic effect, determined by the pindolol-paroxetine combination. These results implicate the 5-HT(1A) receptors of the DPAG in the panicolytic effect of the pindolol-paroxetine combination administered systemically. They also give further preclinical support for the use of this drug combination in the treatment of panic disorder. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Psychosocial pathways to inconsistent condom use among male sex workers: personality, drug misuse and criminality

Background: This research compared street male sex workers in Santo Andre, Brazil, that reported consistent condom use with those that revealed inconsistent condom use with their clients, concerning personality aspects, impulsiveness, alcohol and drug consumption, depressive symptoms, sociodemographic data and criminal involvement. Methods: Eighty-six male sex workers were evaluated in face-to-face interviews at their place of work. A `snowball` sampling procedure was used to access this hard-to-reach population. Findings: Male sex workers with inconsistent condom use showed greater involvement with criminal activities, higher reward dependence level and more frequent self-report of being HIV-positive. Conclusions: Conceptualisation of male sex workers` psychological characteristics may be required where HIV risk is not only attributed to sex work per se, but to other aspects such as personality-related factors and negative identity.

Sertraline vs. ELectrical Current Therapy for Treating Depression Clinical Trial - SELECT TDCS: Design, rationale and objectives

Background: Despite significant advancements in psychopharmacology, treating major depressive disorder (MDD) is still a challenge considering the efficacy, tolerability, safety, and economical costs of most antidepressant drugs. One approach that has been increasingly investigated is modulation of cortical activity with tools of non-invasive brain stimulation - such as transcranial magnetic stimulation and transcranial direct current stimulation (tDCS). Due to its profile, tDCS seems to be a safe and affordable approach. Methods and design: The SELECT TDCS trial aims to compare sertraline vs. tDCS in a double-blinded, randomized, factorial trial enrolling 120 participants to be allocated to four groups to receive sertraline + tDCS, sertraline, tDCS or placebo. Eligibility criteria are moderate-to-severe unipolar depression (Hamilton Depression Rating Scale >17) not currently on sertraline treatment. Treatment will last 6 weeks and the primary outcome is depression change in the Montgomery-Asberg Depression Rating Score (MADRS). Potential biological markers that mediate response, such as BDNF serum levels, Val66Met BDNF polymorphism, and heart rate variability will also be examined. A neuropsychological battery with a focus on executive functioning will be administered. Discussion: With this design we will be able to investigate whether tDCS is more effective than placebo in a sample of patients free of antidepressants and in addition, we will be able to secondarily compare the effect sizes of sertraline vs. tDCS and also the comparison between tDCS and combination of tDCS and sertraline. (C) 2010 Elsevier Inc. All rights reserved.

Neural activity changes to emotional stimuli in healthy individuals under chronic use of clomipramine

Previous functional magnetic resonance imaging (fMRI) studies examined neural activity responses to emotive stimuli in healthy individuals after acute/subacute administration of antidepressants. We now report the effects of repeated use of the antidepressant clomipramine on fMRI data acquired during presentation of emotion-provoking and neutral stimuli on healthy volunteers. A total of 12 volunteers were evaluated with fMRI after receiving low doses of clomipramine for 4 weeks and again after 4 weeks of washout. Fear-, happiness-, anger-provoking and neutral pictures from the International Affective Picture System (IAPS) were used. Data analysis was performed with statistical parametric mapping (P < 0.05). Paired t-test comparisons for each condition between medicated and unmedicated states showed, to negative valence paradigms, decrease in brain activity in the amygdala when participants were medicated. We also demonstrated, across both positive and negative valence paradigms, consistent decreases in brain activity in the medicated state in the anterior cingulate gyrus and insula. This is the first report of modulatory effects of repeated antidepressant use on the central representation of somatic states in response to emotions of both negative and positive valences in healthy individuals. Also, our results corroborate findings of antidepressant-induced temporolimbic activity changes to emotion-provoking stimuli obtained in studies of subjects treated acutely with such agents.

Common mental disorders during pregnancy and adverse obstetric outcomes

Methods. A prospective cohort study was conducted with 831 pregnant women from antenatal clinics in primary healthcare in Sao Paulo, Brazil. The clinical interview schedule-revised and demographic questionnaires were administered between the 20th and 30th weeks of gestation. Information on infant weight and gestational age at birth were obtained from hospital records. Univariate analyses were used to examine the association between the main exposure and main outcomes. Statistical associations were examined with chi

Common mental disorders during pregnancy: prevalence and associated factors among low-income women in Sao Paulo, Brazil

To estimate the prevalence of common mental disorders (CMD) and factors associated with these disorders among pregnant women of low socio-economic status (SES) in Sao Paulo. We performed a cross-sectional study with 831 women in their 20th to 30th weeks of pregnancy, who were attending antenatal clinics in primary care in Sao Paulo, Brazil. CMD were assessed with the Clinical Interview Schedule-Revised. Crude and adjusted prevalence ratios and 95% CI were calculated to examine the association between CMD and exposure variables. The prevalence of CMD was 20.2% (95% CI 17.5 to 23.0). Age at current pregnancy and at first delivery, current obstetric complications, not having friends in the community, living in a crowded household, lower occupational status and history of previous psychiatric treatment were all independently associated with increased prevalence of CMD. CMD is highly prevalent among pregnant women of low SES seen in primary care settings in Sao Paulo. A combination of distal and proximal psychosocial factors increase the risk for CMD. Primary health care professionals need to be aware of how common CMD in such settings and properly trained to deal with CMD during pregnancy.