Ciaran Pier

Correlates of ante- and postnatal depression in fathers: A systematic review

BACKGROUND Contemporary research findings suggest that depression during the ante- and postnatal periods is a significant problem not only for women but also for many men. This paper provides a conceptual and methodological review of the literature on cross-sectional and prospective correlates of depressive symptoms in men during both pregnancy and the postpartum period. METHODS The search, via several electronic databases, was limited to English papers published between January 1996 and August 2009, and identified 30 relevant articles. RESULTS The most common correlate of paternal depressive symptoms pre- and post birth was having a partner with elevated depressive symptoms or depression; poor relationship satisfaction was also frequently associated with elevated depressive symptoms or depression in men. LIMITATIONS There were significant methodological limitations of existing studies, including small sample sizes; the use of cross-sectional designs; varied measures of depression; focus on depression in the postpartum only; and in the few longitudinal gestational studies, the inclusion of only one assessment point. The limitations of the current systematic review include the inclusion of only papers written in English and potential publication bias, where studies with null findings are less likely to be published. CONCLUSION The scientific study of predictors of mens depressive symptoms pre and post birth remains in its infancy. Given the implications of clinical depression in men both during the gestational and postpartum periods, further systematic investigation of direct and indirect predictors of elevated depressive symptoms in men during this time is warranted.

Chronic mental stress is a cause of essential hypertension: Presence of biological markers of stress

1 In searching for biological evidence that essential hypertension is caused by chronic mental stress, a disputed proposition, parallels are noted with panic disorder, which provides an explicit clinical model of recurring stress responses. 2 There is clinical comorbidity; panic disorder prevalence is increased threefold in essential hypertension. Plasma cortisol is elevated in both. 3 In panic disorder and essential hypertension, but not in health, single sympathetic nerve fibres commonly fire repeatedly within an individual cardiac cycle; this appears to be a signature of stress exposure. For both conditions, adrenaline cotransmission is present in sympathetic nerves. 4 Tissue nerve growth factor is increased in both (nerve growth factor is a stress reactant). There is induction of the adrenaline synthesizing enzyme, phenylethanolamine‐N‐methyltransferase, in sympathetic nerves, an explicit indicator of mental stress exposure. 5 The question of whether chronic mental stress causes high blood pressure, still hotly debated, has been reviewed by an Australian Government body, the Specialist Medical Review Council. Despite the challenging medicolegal implications, the Council determined that stress is one proven cause of hypertension, this ruling being published in the 27 March 2002 Australian Government Gazette. This judgement was reached after consideration of the epidemiological evidence, but in particular after review of the specific elements of the neural pathophysiology of essential hypertension, described above.

Internet-based treatment for panic disorder: does frequency of therapist contact make a difference?

Internet‐based interventions with therapist support have proven effective for treating a range of mental health conditions. This study examined whether frequency of therapist contact affected treatment outcomes. Fifty‐seven people with panic disorder (including 32 with agoraphobia) were randomly allocated to an 8‐week Internet‐based cognitive behavioural treatment intervention (Panic Online) with either frequent (three e‐mails per week) or infrequent (one e‐mail per week) support from a psychologist. Posttreatment, intention‐to‐treat analyses revealed that both treatments were effective at improving panic disorder and agoraphobia severity ratings, panic‐related cognitions, negative affect, and psychological and physical quality of life domains, with no differences between conditions. High end‐state functioning was achieved by 28.6% of the frequent and infrequent participants, respectively. Therapist alliance, treatment credibility, and satisfaction also did not differ between groups, despite significantly greater therapist time invested in the frequent contact condition. The results provide evidence that the effectiveness of Internet‐based mental health interventions may be independent of the frequency of therapist support and may, therefore, be more cost‐effective than previously reported.

Therapist-Assisted, Internet-Based Treatment for Panic Disorder: Can General Practitioners Achieve Comparable Patient Outcomes to Psychologists?

Background Mental illness is an escalating concern worldwide. The management of disorders such as anxiety and depression largely falls to family doctors or general practitioners (GPs). However, GPs are often too time constrained and may lack the necessary training to adequately manage the needs of such patients. Evidence-based Internet interventions represent a potentially valuable resource to reduce the burden of care and the cost of managing mental health disorders within primary care settings and, at the same time, improve patient outcomes. Objective The present study sought to extend the efficacy of a therapist-assisted Internet treatment program for panic disorder, Panic Online, by determining whether comparable outcomes could be achieved and maintained when Panic Online was supported by either GPs or psychologists. Methods Via a natural groups design, 96 people with a primary diagnosis of panic disorder (with or without agoraphobia) completed the Panic Online program over 12 weeks with the therapeutic assistance of their GP (n = 53), who had received specialist training in cognitive behavioral therapy, or a clinical psychologist (n = 43). Participants completed a clinical diagnostic telephone interview, conducted by a psychologist, and a set of online questionnaires to assess panic-related symptoms at three time periods (pretreatment, posttreatment, and 6 month follow-up). Results Both treatments led to clinically significant improvements on measures of panic and panic-related symptomatology from pretreatment to posttreatment. Both groups were shown to significantly improve over time. Improvements for both groups were maintained at follow-up; however, the groups did differ significantly on two quality of life domains: physical (F1,82 = 9.13, P = .00) and environmental (F1,82 = 4.41, P = .04). The attrition rate was significantly higher among those being treated by their GP (χ 2 1 = 4.40, P = .02, N = 96). Conclusions This study provides evidence that Internet-based interventions are an effective adjunct to existing mental health care systems. Consequently, this may facilitate and enhance the delivery of evidence-based mental health treatments to increasingly large segments of the population via primary care systems and through suitably trained health professionals.

Human Sympathetic Nerve Biology

Patients with panic disorder provide a clinical model of stress. On a “good day,” free from a panic attack, they show persistent stress‐related changes in sympathetic nerve biology, including abnormal sympathetic nerve single‐fiber firing (“salvos” of multiple firing within a cardiac cycle) and release of epinephrine as a cotransmitter. The coreleased epinephrine perhaps originates from in situ synthesis by phenylethanolamine N‐methyltransferase (PNMT). In searching for biological evidence that essential hypertension is caused by mental stress—a disputed proposition—we note parallels with panic disorder, which provides an explicit clinical model of stress: (1) There is clinical comorbidity; panic disorder prevalence is increased threefold in essential hypertension. (2) For both, epinephrine cotransmission is present in sympathetic nerves. (3) In panic disorder and essential hypertension, but not in health, single‐fiber sympathetic nerve firing salvos occur. (4) Tissue nerve growth factor is increased in both conditions (nerve growth factor is a stress reactant). (5) There is induction of PNMT in sympathetic nerves. Essential hypertension exhibits a further manifestation of mental stress: there is activation of noradrenergic brain stem neurons projecting to the hypothalamus and amygdala. These pathophysiological findings strongly support the view that chronic mental stress is important in the pathogenesis of essential hypertension. A hypothesis now under test is whether in both disorders, under prevailing conditions of ongoing stress, PNMT induced in sympathetic nerves acts as a DNA methylase, causing the norepinephrine transporter (NET) gene silencing that is present in both conditions. PNMT can have an intranuclear distribution, binding to DNA. We have demonstrated that the reduced neuronal noradrenaline reuptake present in both disorders does have an epigenetic mechanism, with demonstrable reduction in the abundance of the transporter protein, the NET gene silencing being associated with DNA binding by the methylation‐related inhibitory transcription factor MeCP2.

The neuronal noradrenaline transporter, anxiety and cardiovascular disease

Panic disorder can serve as a clinical model for testing whether mental stress can cause heart disease. Potential neural mechanisms of cardiac risk are the sympathetic activation during panic attacks, continuing release of adrenaline as a co-transmitter in the cardiac sympathetic nerves, and impairment of noradrenaline neuronal reuptake, augmenting sympathetic neural respnses. The phenotype of impaired neuronal reuptake of noradrenaline: an epigenetic mechanism? We suspect that this phenotype, in sensitizing people to heart symptom development, is a cause of panic disorder, and by magnifying the sympathetic neural signal in the heart, underlies increased cardiac risk. No loss of function mutations of the coding region of the norepinephrine transporter (NET) are evident, but we do detect hypermethylation of CpG islands in the NET gene promoter region. Chromatin immunoprecipitation methodology demonstrates binding of the inhibitory transcription factor, MeCP2, to promoter region DNA in panic disorder patients. Cardiovascular illnesses co-morbid with panic disorder. Panic disorder commonly coexists with essential hypertension and the postural tachycardia syndrome. In both of these cardiovascular disorders the impaired neuronal noradrenaline reuptake phenotype is also present and, as with panic disorder, is associated with NET gene promoter region DNA hypermethylation. An epigenetic ‘co-morbidity’ perhaps underlies the clinical concordance. Brain neurotransmitters. Using internal jugular venous sampling, in the absence of a panic attack we find normal norepinephrine turnover, but based on measurements of the overflow of the serotonin metabolite, 5HIAA, a marked increase (six to sevenfold) in brain serotonin turnover in patients with panic disorder. This appears to represent the underlying neurotransmitter substrate for the disorder. Whether this brain serotonergic activation is a prime mover, or consequential on other primary causes of panic disorder, including cardiac sensitization by faulty neuronal noradrenaline reuptake leading to cardiac symptoms and the enhanced vigilance which accompanies them, is unclear at present.

Single-unit analysis of sympathetic nervous discharges in patients with panic disorder.

Patients with panic disorder are at increased cardiac risk. While the mechanisms responsible remain unknown, activation of the sympathetic nervous system may be implicated. Using isotope dilution methodology, investigations of whole‐body and regional sympathetic nervous activity have failed to show any differences between patients with panic disorder and healthy subjects. Using direct recording of single unit efferent sympathetic vasoconstrictor nerve activity by microneurography we examined sympathetic nervous function in patients with panic disorder more precisely than previously reported. The activity of multiunit and single unit vasoconstrictor sympathetic nerves was recorded at rest at the level of the peroneal nerve in 10 patients diagnosed with panic disorder and in nine matched healthy volunteers. Multiunit sympathetic activity was not different between the two groups (26 ± 3 bursts min−1 in patients with panic disorder and 28 ± 3 bursts min−1 in controls). The firing frequency of single unit vasoconstrictor neurones was also similar between the two groups (0.38 ± 0.09 versus 0.22 ± 0.03 Hz). However, the probability of firing during a sympathetic burst was higher in patients with panic disorder compared with healthy controls (45 ± 5%versus 32 ± 3%, P < 0.05). When only the neural bursts during which the vasoconstrictor neurone was active were considered, we found that in patients with panic disorder the neurones tended to fire more often in a ‘multiple spike’ pattern than in the controls (i.e. the probability of the neurone firing twice was 25 ± 3% in patients with panic disorder compared with 14 ± 3% in controls). Quantification from single vasoconstrictor unit recording provides evidence of a disturbed sympathetic firing pattern in patients with panic disorder.

Increased brain serotonin turnover in panic disorder patients in the absence of a panic attack : reduction by a selective serotonin reuptake inhibitor

Since the brain neurotransmitter changes characterising panic disorder remain uncertain, we quantified brain noradrenaline and serotonin turnover in patients with panic disorder, in the absence of a panic attack. Thirty-four untreated patients with panic disorder and 24 matched healthy volunteers were studied. A novel method utilising internal jugular venous sampling, with thermodilution measurement of jugular blood flow, was used to directly quantify brain monoamine turnover, by measuring the overflow of noradrenaline and serotonin metabolites from the brain. Radiographic depiction of brain venous sinuses allowed differential venous sampling from cortical and subcortical regions. The relation of brain serotonin turnover to serotonin transporter genotype and panic disorder severity were evaluated, and the influence of an SSRI drug, citalopram, on serotonin turnover investigated. Brain noradrenaline turnover in panic disorder patients was similar to that in healthy subjects. In contrast, brain serotonin turnover, estimated from jugular venous overflow of the metabolite, 5-hydroxyindole acetic acid, was increased approximately 4-fold in subcortical brain regions and in the cerebral cortex (P < 0.01). Serotonin turnover was highest in patients with the most severe disease, was unrelated to serotonin transporter genotype, and was reduced by citalopram (P < 0.01). Normal brain noradrenaline turnover in panic disorder patients argues against primary importance of the locus coeruleus in this condition. The marked increase in serotonin turnover, in the absence of a panic attack, possibly represents an important underlying neurotransmitter substrate for the disorder, although this point remains uncertain. Support for this interpretation comes from the direct relationship which existed between serotonin turnover and illness severity, and the finding that SSRI administration reduced serotonin turnover. Serotonin transporter genotyping suggested that increased whole brain serotonin turnover most likely derived not from impaired serotonin reuptake, but from increased firing in serotonergic midbrain raphe neurons projecting to both subcortical brain regions and the cerebral cortex.

GP registrar well-being: a cross-sectional survey.

ObjectivesTo investigate the major stressors affecting GP registrars, how those at risk can be best identified and the most useful methods of managing or reducing their stress.Design, setting and participantsCross-sectional postal questionnaire of all GP registrars in one large regional training providers catchment area.Main outcome measuresThe Depression, Anxiety and Stress Scale (DASS), a specifically developed Registrar Stressor Scale consisting of five subscales of potential stressors, plus closed questions on how to identify and manage stress in GP registrars.ResultsSurvey response rate of 51% (102/199). Rural difficulties followed by achieving a work/life balance were the principal stressors. Ten percent of registrars were mildly or moderately depressed or anxious (DASS) and 7% mild to moderately anxious (DASS). Registrars preferred informal means of identifying those under stress (a buddy system and talks with their supervisors); similarly, they preferred to manage stress by discussions with family and friends, debriefing with peers and colleagues, or undertaking sport and leisure activities.ConclusionsThis study supports research which confirms that poor psychological well-being is an important issue for a significant minority of GP trainees. Regional training providers should ensure that they facilitate formal and informal strategies to identify those at risk and assist them to cope with their stress.

Does GPs' use of an internet-based treatment protocol in CBT for panic disorder lead to positive patient outcomes?

This study was undertaken to develop and evaluate the efficacy of an early intervention for children who had been injured in an accident. The aim of the intervention was to prevent the development of longterm psychological consequences. Brochures were developed for children, adolescents, and their parents. These brochures detailed common responses to trauma (and normalized such responses), and suggestions for minimizing any post-trauma distress. Participants were children aged 7-15 admitted to hospital for traumatic injury. The intervention was delivered to one of two hospitals, within 72 hours of the trauma. 103 children and parents participated in the study. The parents and children completed structured interviews and questionnaires 2 weeks, 4-6 weeks and 6 months post-trauma. Outcome analyses also indicated that the intervention reduced parental distress at 4-6 weeks post-trauma. The intervention did not impact significantly on child adjustment over this time period. Results of the 6 month follow-up suggested that the intervention resulted in an amelioration of child anxiety from one to six months post-trauma, whereas the controls exhibited an increase in anxiety over this time period. Overall, it was concluded that the early intervention is a simple, practical, and cost-effective method of reducing child and parent distress post-trauma.