Efficacy of a cognitive and behavioural psychotherapy applied by primary care psychologists in patients with mixed anxiety-depressive disorder: a research protocol

Background: In contrast with the recommendations of clinical practice guidelines, the most common treatment for anxiety and depressive disorders in primary care is pharmacological. The aim of this study is to assess the efficacy of a cognitive-behavioural psychological intervention, delivered by primary care psychologists in patients with mixed anxiety-depressive disorder compared to usual care. Methods/Design: This is an open-label, multicentre, randomized, and controlled study with two parallel groups. A random sample of 246 patients will be recruited with mild-to-moderate mixed anxiety-depressive disorder, from the target population on the lists of 41 primary care doctors. Patients will be randomly assigned to the intervention group, who will receive standardised cognitive-behavioural therapy delivered by psychologists together with usual care, or to a control group, who will receive usual care alone. The cognitive-behavioural therapy intervention is composed of eight individual 60-minute face-to face sessions conducted in eight consecutive weeks. A follow-up session will be conducted over the telephone, for reinforcement or referral as appropriate, 6 months after the intervention, as required. The primary outcome variable will be the change in scores on the Short Form-36 General Health Survey. We will also measure the change in the frequency and intensity of anxiety symptoms (State-Trait Anxiety Inventory) and depression (Beck Depression Inventory) at baseline, and 3, 6 and 12 months later. Additionally, we will collect information on the use of drugs and health care services. Discussion: The aim of this study is to assess the efficacy of a primary care-based cognitive-behavioural psychological intervention in patients with mixed anxiety-depressive disorder. The international scientific evidence has demonstrated the need for psychologists in primary care. However, given the differences between health policies and health services, it is important to test the effect of these psychological interventions in our geographical setting.

Novel roles for the GABAB receptor in anxiety and cocaine addiction

The GABAB receptor has been postulated as a possible drug target in the treatment of anxiety disorders and cocaine addiction. Indeed, a wealth of preclinical data is emerging that has shown that mice lacking functional GABAB receptors display a highly anxious behaviour across a range of behavioural models of anxiety. Additionally, novel compounds that act by altering the allosteric conformation of the GABAB receptor to a more active state; the GABAB receptor positive modulators, have been repeatedly demonstrated to have anxiolytic effects in animals. In addition to being a putative anxiolytic drug target, the GABAB receptor has been identified as a novel target for antiaddictive therapies. Indeed GABAB receptor positive modulators have been demonstrated to have anti-addictive properties across a broad variety of behavioural paradigms. Despite these findings, several gaps in our knowledge of the role played by the GABAB receptor in both anxiety and drug abuse disorder exist. The aim of this thesis was to use preclinical animal models in an effort to further probe the role played by the GABAB receptor in anxiety and addiction. Our studies initially examined the role played by the GABAB receptor in the neurodevelopmental processes underpinning of anxiety. Our studies demonstrated that treating mouse pups in early life with the GABAB receptor agonist baclofen produced an anxious phenotype in adult life, whereas treatment with the GABAB receptor antagonist CGP52432 produced no effects on adult behaviour. Further to this, we examined whether the anxious behaviour induced by early life blockade of the serotonin reuptake transporter was dependant on alterations in GABAB receptor function. Our studies however revealed no effect of early life selective serotonin reuptake inhibitor treatment on adult life baclofen sensitivity. The next issue addressed in this thesis is the characterization of the effects of a GABAB receptor positive modulator and a GABAB receptor antagonist in a behavioural model of conditioned fear behaviour. These novel classes of GABAB receptor ligands have been considerably less well characterized in this facet of preclinical anxiety behaviour than in terms of innate anxiety behaviour. Our study however revealed that the GABAB receptor positive modulator GS39783 and the GABAB receptor antagonist CGP52432 were without effect on the acquisition, expression or extinction of conditioned fear in our model. The next element of this thesis dealt with the characterization of a novel mouse model, the GABAB(2)- S892A mouse. This mouse has been engineered to express a form of the GABAB(2) receptor subunit wherein the function determining serine phosphorylation site cannot be phosphorylated. We initially tested this mouse in terms of its GABAB receptor function in adult life, followed by testing it in a battery of tests of unconditioned and learned anxiety behaviour. We also examined the behavioural and molecular responses of the GABAB(2)-S892A mouse to cocaine. All of our studies appear to show that the GABAB(2)-S892A mouse is indistinguishable from wildtype controls. The final aim of the thesis was to investigate the behavioural and molecular sensitivity of the GABAB(1) subunit isoform null mice, the GABAB(1a) -/- and GABAB(1b) -/- mice to cocaine. Our studies revealed that these mice display differing behavioural responses to cocaine, with the GABAB(1a) -/- mouse displaying a hypersensitivity to the acute locomotor effects of cocaine, while the GABAB(1b) -/- displayed blunted locomotor sensitisation to cocaine.

The role of knowledge in the contraceptive behaviour of sexually active young people in state care

Aim: To analyse the role of sex-focused knowledge in the contraceptive behaviour of sexually active young people in state care.

Methods: The sample consisted of 19 care leavers (young people previously in state care) aged 18-22 years, 16 females and 3 males. In-depth interviewing was the method of data collection, and a qualitative strategy resembling modified analytical induction was used to analyse data.

Findings: Findings indicated that a lack of information was not the sole, or even the primary reason for engaging in unsafe sexual practices. Other factors such as ambivalence to becoming pregnant also featured in participants’ accounts. Several participants conveyed a relatively weak sense of agency about consistently using contraception. A small number of participants expressed a strong determination to avoid pregnancy, and these appeared to have a level of anxiety about becoming pregnant that motivated them to engage with knowledge about contraception and its use.

Conclusion: Lack of sex-focused information is just one aspect of a myriad of complex factors, including socioeconomic disadvantage and/or emotional deprivation, that influences contraceptive behaviour.

Somatic pedagogies: Critiquing and resisting the affective discourse of the neoliberal state from an embodied anarchist perspective.

This paper takes as its context widespread feelings of anxiety within neoliberal society caused by a combination of material and discursive factors including precarious access to work and resources. It is argued that the state uses ‘discourses of affect’ to produce compliant subjects able to deal with (and unable to desire beyond) neoliberal precarity and anxiety. Critical education theorists have argued that discourses of ‘well-being’, emotional support and self-help have gained increasing purchase in mainstream education and in popular culture. These discourses are dangerous because they are individualized and depoliticized, and undermine collective political struggle. At the same time there has been a ‘turn to affect’ in critical academia, producing critical pedagogies that resist state affective discourse. I argue that these practices are essential for problematizing neoliberal discourse, yet existing literature tends to elide the role of the body in effective resistance, emphasising intellectual aspects of critique. The paper sketches an alternative, drawing on psychoanalytic and practiced pedagogies that aim to transgress the mind-body dualism and hierarchy, in particular Roberto Freire’s work on Somatherapy.

The Impact of Thought Speed and Variability on Psychological State and Threat Perception: Further Exploration of the Theory of Mental Motion

Thought speed and variability are purportedly common features of specific psychological states, such as mania and anxiety. The present study explored the independent and combinational influence of these variables upon condition-specific symptoms and affective state, as proposed by Pronin and Jacobs’ (Perspect Psychol Sci, 3:461–485, 2008) theory of mental motion. A general population sample was recruited online (N = 263). Participants completed a thought speed and variability manipulation task, inducing a combination of fast/slow and varied/repetitive thought. Change in mania and anxiety symptoms was assessed through direct self-reported symptom levels and indirect, processing bias assessment (threat interpretation). Results indicated that fast and varied thought independently increased self-reported mania symptoms. Affect was significantly less positive and more negative during slow thought. No change in anxiety symptoms or threat interpretation was found between manipulation conditions. No evidence for the proposed combinational influence of speed and variability was found. Implications and avenues for therapeutic intervention are discussed.

The Role of Orexin-A in Anxiety and the Emission of Ultrasonic Vocalizations in Rats

Central administration of orexin-A has been shown to activate autonomic arousal in rats, reliably inducing anxiety-like behaviours in the open field. To date, there has yet to be a study investigating the role of orexin-A in the communication of such negative affective state. In the current study, forty-six adult male rats were chronically cannulated and administered orexin-A into the medial preoptic area/anterior hypothalamic area to determine the effect of this neuropeptide on anxiety-like behaviour and the production of 22 kHz aversive ultrasonic vocalizations. It was found that intracerebral administration of orexin-A increased autonomic arousal as measured by a significant increase in fecal boli output, however orexin-A did not significantly affect locomotor activity or induce 22 kHz calling. These data suggest that orexin-A is involved in the regulation of the autonomic aspect of anxiety-like behaviour but not in the vocal communication of such negative affect

Treatment response in child anxiety is differentially related to the form of maternal anxiety disorder

An examination was made of the extent to which maternal anxiety predicted response to treatment of children presenting with an anxiety disorder. In a sample of 55 children referred to a local NHS CAMH service for treatment of an anxiety disorder, systematic mental state interview assessment was made of both mothers and children, and both completed self-report questionnaires to assess aspects of anxiety, both immediately before the children received treatment and following treatment. Children of mothers with anxiety disorder overall responded less well to treatment than children of mothers with no anxiety disorder. There was some diagnostic specificity in this in that children of mothers with GAD did as well in treatment as children whose mothers had no anxiety, whereas children of mothers with social phobia did poorly. The outcome for children with anxiety appears to be related to the presence and nature of maternal anxiety. It would seem prudent that treatment of children with anxiety involves assessment of maternal anxiety. It is important to establish in systematic investigation whether treatment of maternal anxiety improves the outcome for child anxiety.

Affective disorder in the parents of a clinic sample of children with anxiety disorders

Background: Family history studies in adults reveal strong familiality for the anxiety disorders with some specificity. The aim of the current study was to establish whether there was an elevated rate of anxiety disorders in the parents of children with anxiety disorders, and whether there was intergenerational specificity in the form of disorder. Methods: The mental state of a clinic sample of 85 children with anxiety disorder and their parents was systematically assessed, together with a comparison sample of 45 children with no current disorder and their parents. Results: Compared to the rate of anxiety disorder amongst parents of comparison children, the rate of current anxiety disorder in mothers of anxious children was significantly raised, as was the lifetime rate of anxiety disorder for both mothers and fathers. The mothers of children with generalised anxiety disorder, social phobia, specific phobia and separation anxiety disorder all had raised lifetime rates of the corresponding disorder, but also raised rates of others disorders. Limitations: Only 60% of the fathers of the anxious children were assessed. Conclusions: Strong familiality of anxiety disorders was confirmed, especially between child and maternal anxiety disorder. All child anxiety disorders were associated with several forms of anxiety disorder in the mother. Some specificity in the form of anxiety disorder in the child and the mother was apparent for social phobia and separation anxiety disorder. The findings have implications for the management of child anxiety. (c) 2006 Elsevier B.V. All rights reserved.

The influence of anxiety on the initial selection of emotional faces presented in binocular rivalry

Neurocognitive theories of anxiety predict that threat-related information can be evaluated before attentional selection, and can influence behaviour differentially in high anxious compared to low anxious individuals. We investigate this further by presenting emotional and neutral faces in an adapted binocular rivalry paradigm. We show that the initial selection of emotional faces presented in binocular rivalry is highly influenced by self-reported state and trait anxiety-level. Heightened anxiety was correlated with increased perception of angry and fearful faces, and decreased perception of happy expressions. These results are consistent with recent evidence of involuntary selection of threat in anxiety.

Thyroid hormones regulate anxiety in the male mouse

Thyroid hormone levels are implicated in mood disorders in the adult human but the mechanisms remain unclear partly because, in rodent models, more attention has been paid to the consequences of perinatal hypo and hyperthyroidism. Thyroid hormones act via the thyroid hormone receptor (TR) alpha and beta isoforms, both of which are expressed in the limbic system. TR's modulate gene expression via both unliganded and liganded actions. Though the thyroid hormone receptor (TR) knockouts and a transgenic TRalpha1 knock-in mouse have provided us valuable insight into behavioral phenotypes such as anxiety and depression, it is not clear if this is because of the loss of unliganded actions or liganded actions of the receptor or due to locomotor deficits. We used a hypothyroid mouse model and supplementation with tri-iodothyronine (T3) or thyroxine (T4) to investigate the consequences of dysthyroid hormone levels on behaviors that denote anxiety. Our data from the open field and the light-dark transition tests suggest that adult onset hypothyroidism in male mice produces a mild anxiogenic effect that is possibly due to unliganded receptor actions. T3 or T4 supplementation reverses this phenotype and euthyroid animals show anxiety that is intermediate between the hypothyroid and thyroid hormone supplemented groups. In addition, T3 but not T4 supplemented animals have lower spine density in the CA1 region of the hippocampus and in the central amygdala suggesting that T3-mediated rescue of the hypothyroid state might be due to lower neuronal excitability in the limbic circuit.

Impact of chronic disease on quality of life among the elderly in the state of Sao Paulo, Brazil: a population-based study

Objectives. To assess the impact of chronic disease and the number of diseases on the various aspects of health-related quality of life (HRQOL) among the elderly in Sao Paulo, Brazil. Methods. The SF-36 (R) Health Survey was used to assess the impact of the most prevalent chronic diseases on HRQOL. A cross-sectional and population-based study was carried out with two-stage stratified cluster sampling. Data were obtained from a multicenter health survey administered through household interviews in several municipalities in the state of Sao Paulo. The study evaluated seven diseases-arthritis, back-pain, depression/anxiety, diabetes, hypertension, osteoporosis, and stroke-and their effects on quality of life. Results. Among the 1958 elderly individuals (60 years of age or older), 13.6% reported not having any of the illnesses, whereas 45.7% presented three or more chronic conditions. The presence of any of the seven chronic illnesses studied had a significant effect on the scores Of nearly all the SF-36 (R) scales. HRQOL achieved lower scores when related to depression/anxiety, osteoporosis, and stroke. The higher the number of diseases, the greater the negative effect on the SF-36 (R) dimensions. The presence of three or more diseases significantly affected HRQOL in all areas. The bodily pain, general health, and vitality scales were the most affected by diseases. Conclusions. The study detected a high prevalence of chronic diseases among the elderly population and found that the degree of impact on HRQOL depends on the type of disease. The results highlight the importance of preventing and controlling chronic diseases in order to reduce the number of comorbidities and lessen their impact on HRQOL among the elderly.

Expression of alpha-synuclein is increased in the hippocampus of rats with high levels of innate anxiety

A genomic region neighboring the alpha-synuclein gene, on rat chromosome 4, has been associated with anxiety- and alcohol-related behaviors in different rat strains. In this study, we have investigated potential molecular and physiological links between alpha-synuclein and the behavioral differences observed between Lewis (LEW) and Spontaneously Hypertensive (SHR) inbred rats, a genetic model of anxiety. As expected, LEW rats appeared more fearful than SHR rats in three anxiety models: open field, elevated plus maze and light/dark box. Moreover, LEW rats displayed a higher preference for alcohol and consumed higher quantities of alcohol than SHR rats. alpha-Synuclein mRNA and protein concentrations were higher in the hippocampus, but not the hypothalamus of LEW rats. This result inversely correlated with differences in dopamine turnover in the hippocampus of LEW and SHR rats, supporting the hypothesis that alpha-synuclein is important in the downregulation of dopamine neurotransmission. A novel single nucleotide polymorphism was identified in the 30-untranslated region (3`-UTR) of the alpha-synuclein cDNA between these two rat strains. Plasmid constructs based on the LEW 3`-UTR sequence displayed increased expression of a reporter gene in transiently transfected PC12 cells, in accordance with in-vivo findings, suggesting that this nucleotide exchange might participate in the differential expression of alpha-synuclein between LEW and SHR rats. These results are consistent with a novel role for alpha-synuclein in modulating rat anxiety- like behaviors, possibly through dopaminergic mechanisms. Since the behavioral and genetic differences between these two strains are the product of independent evolutionary histories, the possibility that polymorphisms in the alpha-synuclein gene may be associated with vulnerability to anxiety- related disorders in humans requires further investigation. Molecular Psychiatry (2009) 14, 894-905; doi: 10.1038/mp.2008.43; published online 22 April 2008

Dental anxiety and trait anxiety: an investigation of their relationship

Background Anxiety related to dental treatment is a fairly common phenomenon. Some studies have shown that there is an association between dental anxiety and general fears and anxiety, neuroticism and general psychological distress. Aim This study was designed to examine the relationship between dental anxiety and trait anxiety. Subjects and methods The sample consisted of 1,030 individuals (688 women; 342 men), aged 30.8 +/- 11.7 years. The Portuguese version of Corah`s Dental Anxiety Scale (DAS) and State-Trait Anxiety Inventory (STAI-T) were used. Results A statistically significant association between high DAS and high STAI-T, but not between high STAI-T and high DAS, was found. The data indicated that subjects with high dental anxiety tend to present with high trait anxiety, but high trait anxiety seems not to predispose to high dental anxiety. Conclusions Our results indicate that dental anxiety is specific, with its own features, and its development is not necessarily associated with trait anxiety.

Impact of chronic disease on quality of life among the elderly in the state of Sao Paulo, Brazil: A population-based study

Objectives. To assess the impact of chronic disease and the number of diseases on the various aspects of health-related quality of life (HROOL) among the elderly in Såo Paulo, Brazil. Methods. The SF-36® Health Survey was used to assess the impact of the most prevalent chronic diseases on HRQOL. A cross-sectional and population-based study was carried out with two-stage stratified cluster sampling. Data were obtained from a multicenter health survey administered through household interviews in several municipalities in the state of São Paulo. The study evaluated seven diseases - arthritis, back-pain, depression/anxiety, diabetes, hypertension, osteoporosis, and stroke - and their effects on quality of life. Results. Among the 1 958 elderly individuals (60 years of age or older), 13.6% reported not having any of the illnesses, whereas 45.7% presented three or more chronic conditions. The presence of any of the seven chronic illnesses studied had a significant effect on the scores of nearly all the SF-36® scales. HROOL achieved lower scores when related to depression/ anxiety, osteoporosis, and stroke. The higher the number of diseases, the greater the negative effect on the SF-36® dimensions. The presence of three or more diseases significantly affected HROOL in all areas. The bodily pain, general health, and vitality scales were the most affected by diseases. Conclusions. The study detected a high prevalence of chronic diseases among the elderly population and found that the degree of impact on HROOL depends on the type of disease. The results highlight the importance of preventing and controlling chronic diseases in order to reduce the number of comorbidities and lessen their impact on HROOL among the elderly.

Medicinal plants in pregnancy and lactation: perception of the health risk and practical educational group in Araraquara, São Paulo State, Brazil

The use of medicinal plants among pregnant women and lactating is a common practice in diverse countries. However, many medicinal plants are contraindicated during pregnancy and lactating, due to various adverse effects, such as teratogenic, embryotoxic and abortive effects, exposing these women, their fetus and babies to health unknown risks. Thus, the purpose of this commentary, was to analyze the perception about the use of medicinal plants by pregnant women and lactating registered in the "baby on board" NGO, Araraquara, São Paulo state, Brazil, between 2010 at 2013. The group was constituted by 48 women, between the first and last trimester of pregnancy or whilst breastfeeding. Information was collected during group meetings by oral interview, using a questionnaire, as script. The nature of the study was a qualitative analysis. The results were based on reports about the use of medicinal plants by pregnant women during group meetings: use, indication of use, knowledge about risks. All participants received written and oral information about the study and they gave a written informed consent. The use of medicinal plants is a reality among pregnant and lactating women of the "baby on board" NGO. They reported that they feel that "natural" products are not harmful for their health. The primary information sources for the majority of women about medicinal plants during pregnancy are family, neighbors and herbalists. The plants most cited (in popular name in Brazil) were: senna, chamomile, boldo, lemon balm, lemon grass. They were used mainly for: nausea, heartburn, indigestion, flatulence, intestinal and abdominal pain, anxiety, intestinal constipation and low milk production. The pregnant and lactating women lacked knowledge about the health risks of the use of medicinal plants and herbal medicines in pregnancy and lactation. They also reported difficulties in clarifying some questions about the use of medicinal plants with their doctors. The results of the present study showed that educative actions about the rational use of medicinal plants in pregnancy and breastfeeding could be part of the operating protocols to promote the maternal and child health programs in Araraquara. Thus, our results also suggest the importance of creating institutionalized places, to the implementation of continued education programs about rational use of medicinal plants in pregnancy and lactation. These targeted programs are not only for health professionals, but also for community members, pregnant women and breastfeeding. Our results pointed out the importance of guidance of doctors and healthcare professionals on the scientific studies about medicinal plants and herbal medicines and the risk/benefit of using herbs during pregnancy. Finally, it is noted the importance of the health professionals to inform women of childbearing on risks to their health, as well as on possibilities of utilization of herbs during fertile period, giving special attention to the potential risk of self-medication.