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1.  Food policies for physical and mental health 
BMC Psychiatry  2014;14:132.
Noncommunicable diseases (NCDs) account for the largest burden of early mortality and are predicted to cost the global community more than US $30 trillion over the next 20 years. Unhealthy dietary habits, in large part driven by substantial changes to global food systems, are recognised as major contributors to many of the common NCDs, including cardiovascular disease, cancer and diabetes. Recent evidence now indicates that unhealthy diets are also risk factors for mental disorders, particularly depression and dementia. This affords substantial scope to leverage on the established and developing approaches to the nutrition-related NCDs to address the large global burden of these mental disorders and reinforces the imperative for governments take substantial actions in regards to improving the food environment and consequent population health via policy initiatives.
PMCID: PMC4026829  PMID: 24884515
2.  Lifestyle medicine for depression 
BMC Psychiatry  2014;14:107.
The prevalence of depression appears to have increased over the past three decades. While this may be an artefact of diagnostic practices, it is likely that there are factors about modernity that are contributing to this rise. There is now compelling evidence that a range of lifestyle factors are involved in the pathogenesis of depression. Many of these factors can potentially be modified, yet they receive little consideration in the contemporary treatment of depression, where medication and psychological intervention remain the first line treatments. “Lifestyle Medicine” provides a nexus between public health promotion and clinical treatments, involving the application of environmental, behavioural, and psychological principles to enhance physical and mental wellbeing. This may also provide opportunities for general health promotion and potential prevention of depression. In this paper we provide a narrative discussion of the major components of Lifestyle Medicine, consisting of the evidence-based adoption of physical activity or exercise, dietary modification, adequate relaxation/sleep and social interaction, use of mindfulness-based meditation techniques, and the reduction of recreational substances such as nicotine, drugs, and alcohol. We also discuss other potential lifestyle factors that have a more nascent evidence base, such as environmental issues (e.g. urbanisation, and exposure to air, water, noise, and chemical pollution), and the increasing human interface with technology. Clinical considerations are also outlined. While data supports that some of these individual elements are modifiers of overall mental health, and in many cases depression, rigorous research needs to address the long-term application of Lifestyle Medicine for depression prevention and management. Critically, studies exploring lifestyle modification involving multiple lifestyle elements are needed. While the judicious use of medication and psychological techniques are still advocated, due to the complexity of human illness/wellbeing, the emerging evidence encourages a more integrative approach for depression, and an acknowledgment that lifestyle modification should be a routine part of treatment and preventative efforts.
PMCID: PMC3998225  PMID: 24721040
Lifestyle; Depression; Exercise; Diet; Smoking; Alcohol; Prevention; Treatment
3.  Stress, Inflammation, and Cellular Vulnerability during Early Stages of Affective Disorders: Biomarker Strategies and Opportunities for Prevention and Intervention 
The mood disorder prodrome is conceptualized as a symptomatic, but not yet clinically diagnosable stage of an affective disorder. Although a growing area, more focused research is needed in the pediatric population to better characterize psychopathological symptoms and biological markers that can reliably identify this very early stage in the evolution of mood disorder pathology. Such information will facilitate early prevention and intervention, which has the potential to affect a person’s disease course. This review focuses on the prodromal characteristics, risk factors, and neurobiological mechanisms of mood disorders. In particular, we consider the influence of early-life stress, inflammation, and allostatic load in mediating neural mechanisms of neuroprogression. These inherently modifiable factors have known neuroadaptive and neurodegenerative implications, and consequently may provide useful biomarker targets. Identification of these factors early in the course of the disease will accordingly allow for the introduction of early interventions which augment an individual’s capacity for psychological resilience through maintenance of synaptic integrity and cellular resilience. A targeted and complementary approach to boosting both psychological and physiological resilience simultaneously during the prodromal stage of mood disorder pathology has the greatest promise for optimizing the neurodevelopmental potential of those individuals at risk of disabling mood disorders.
PMCID: PMC3988376  PMID: 24782789
prodrome; depression; bipolar; biomarker; stress; inflammation; cellular resilience; plasticity
4.  Risk stratification using data from electronic medical records better predicts suicide risks than clinician assessments 
BMC Psychiatry  2014;14:76.
To date, our ability to accurately identify patients at high risk from suicidal behaviour, and thus to target interventions, has been fairly limited. This study examined a large pool of factors that are potentially associated with suicide risk from the comprehensive electronic medical record (EMR) and to derive a predictive model for 1–6 month risk.
7,399 patients undergoing suicide risk assessment were followed up for 180 days. The dataset was divided into a derivation and validation cohorts of 4,911 and 2,488 respectively. Clinicians used an 18-point checklist of known risk factors to divide patients into low, medium, or high risk. Their predictive ability was compared with a risk stratification model derived from the EMR data. The model was based on the continuation-ratio ordinal regression method coupled with lasso (which stands for least absolute shrinkage and selection operator).
In the year prior to suicide assessment, 66.8% of patients attended the emergency department (ED) and 41.8% had at least one hospital admission. Administrative and demographic data, along with information on prior self-harm episodes, as well as mental and physical health diagnoses were predictive of high-risk suicidal behaviour. Clinicians using the 18-point checklist were relatively poor in predicting patients at high-risk in 3 months (AUC 0.58, 95% CIs: 0.50 – 0.66). The model derived EMR was superior (AUC 0.79, 95% CIs: 0.72 – 0.84). At specificity of 0.72 (95% CIs: 0.70-0.73) the EMR model had sensitivity of 0.70 (95% CIs: 0.56-0.83).
Predictive models applied to data from the EMR could improve risk stratification of patients presenting with potential suicidal behaviour. The predictive factors include known risks for suicide, but also other information relating to general health and health service utilisation.
PMCID: PMC3984680  PMID: 24628849
Suicide risk; Electronic medical record; Predictive models
5.  Do Comorbid Anxiety Disorders Moderate the Effects of Psychotherapy for Bipolar Disorder? Results From STEP-BD 
The American journal of psychiatry  2014;171(2):178-186.
At least 50% of individuals with bipolar disorder have a lifetime anxiety disorder. Individuals with both bipolar disorder and a co-occurring anxiety disorder experience longer illness duration, greater illness severity, and poorer treatment response. The study explored whether comorbid lifetime anxiety in bipolar patients moderates psychotherapy treatment outcome.
In the Systematic Treatment Enhancement Program randomized controlled trial of psychotherapy for bipolar depression, participants received up to 30 sessions of intensive psychotherapy (family-focused therapy, interpersonal and social rhythm therapy, or cognitive-behavioral therapy) or collaborative care, a three-session comparison treatment, plus pharmacotherapy. Using the number needed to treat, we computed effect sizes to analyze the relationship between lifetime anxiety disorders and rates of recovery across treatment groups after 1 year.
A total of 269 patients (113 women) with a comorbid lifetime anxiety disorder (N=177) or without a comorbid lifetime anxiety disorder (N=92) were included in the analysis. Participants with a lifetime anxiety disorder were more likely to recover with psychotherapy than with collaborative care (66% compared with 49% recovered over 1 year; number needed to treat=5.88, small to medium effect). For patients without a lifetime anxiety disorder, there was no difference between rates of recovery in psychotherapy compared with collaborative care (64% compared with 62% recovered; number needed to treat=50, small effect). Participants with one lifetime anxiety disorder were likely to benefit from intensive psychotherapy compared with collaborative care (84% compared with 53% recovered; number needed to treat=3.22, medium to large effect), whereas patients with multiple anxiety disorders exhibited no difference in response to the two treatments (54% compared with 46% recovered; number needed to treat=12.5, small effect).
Depressed patients with bipolar disorder and comorbid anxiety may be in particular need of additional psychotherapy for treating acute depression. These results need to be replicated in studies that stratify bipolar patients to treatments based on their anxiety comorbidity status.
PMCID: PMC3946300  PMID: 24077657
6.  Depression following fracture in women: a study of age-matched cohorts 
BMJ Open  2014;4(2):e004226.
High levels of disability, functional impairment and mortality are independently associated with fracture and depression, however the relationship between fracture and depression is uncertain. The aim of this study was to investigate whether fracture is associated with subsequent depressive symptoms in a population-based sample of women.
A study of age-matched fracture versus non-fracture cohorts of women.
Barwon Statistical Division, southeastern Australia.
Two samples of women aged ≥35 years were drawn from the Geelong Osteoporosis Study (GOS). The fracture cohort included women with incident fracture identified from radiology reports and the non-fracture cohort were randomly selected from the electoral roll during 1994–1996.
Outcome measure
Symptoms of depression for women with and without fracture during the 12-month period 2000–2001 were identified by self-report questionnaire based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria.
A total of 296 women with fracture (12 hip, 48 vertebral, 91 wrist/forearm, 17 upper arm, 7 pelvis, 11 rib, 62 lower leg and 48 other fractures) and 590 women without fracture were included. Associations between fracture and depression differed between younger (≤65 years) and older (>65 years) women. Age and weight-adjusted odds ratio for depression following fracture among younger women was 0.62 (0.35 to 1.11, p=0.12) and 3.33 (1.24 to 8.98, p=0.02) for older women. Further adjustment for lifestyle factors did not affect the results.
This study demonstrated that differences in mood status exist between older and younger women following fracture and that fracture is associated with increased depression in older women. Assessment of mood status in both the short and long term following fracture in the elderly seems justified, with early detection and treatment likely to result in improved outcomes.
PMCID: PMC3931986  PMID: 24561497
Epidemiology; Geriatric Medicine
7.  Caspase 1-mediated regulation of fibrogenesis in diet-induced steatohepatitis 
Nonalcoholic steatohepatitis (NASH) is typically associated with pro-apoptotic caspase activation. A potential role for pro-inflammatory caspases remains incompletely understood. Our aims were to examine a potential role of caspase 1 in the development of liver damage and fibrosis in NASH. C57BL/6 wild-type (WT), developed marked steatohepatitis, HSC activation, fibrosis, and increased hepatic caspase 1 and IL-1β expression when placed on the methioninecholine deficient (MCD) diet. Marked caspase 1 activation was detected in the liver of MCD-fed mice. Hepatocyte and non-parenchymal fractionation of the livers further demonstrated that caspase 1 activation after MCD feeding was mainly localized to non-parenchymal cells. Caspase 1-knockout (Casp1−/−) mice on the MCD diet showed marked reduction in mRNA expression of genes involved in inflammation and fibrogenesis (TNFα was 7.6-fold greater in WT vs. Casp1−/−MCD-fed mice; F4/80 was 1.5-fold greater in WT vs. Casp1−/− MCD-fed mice; α-SMA was 3.2-fold greater in WT vs. Casp1−/− MCD-fed mice; Collagen 1-alpha was 7.6–fold greater in WT vs. Casp1−/− MCD-fed mice; TGFβ was 2.4-fold greater in WT vs. Casp1−/− MCD-fed mice; CRP2 was 3.2-fold greater in WT vs. Casp1−/− MCD-fed mice). Furthermore, Sirius red staining for hepatic collagen deposition was significantly reduced in Casp1−/− mice MCD-fed mice compared to WT MCD-fed animals. However, serum aminotransferase (ALT) levels, caspase 3 activity and TUNEL positive cells were similar in Casp1−/− and WT mice on the MCD diet. Selective Kupffer cell depletion by clodronate injection markedly suppressed MCD-induced caspase 1 activation and protected mice from fibrogenesis and fibrosis associated with this diet. Conclusion: this study uncovers a novel role for caspase 1 in inflammation and fibrosis during NASH development.
PMCID: PMC3808241  PMID: 22411067
Nonalcoholic fatty liver disease (NAFLD); nonalcoholic steatohepatitis (NASH); inflammasome; caspases; inflammation; fibrosis
8.  Emerging pharmacotherapy for cancer patients with cognitive dysfunction 
BMC Neurology  2013;13:153.
Advances in the diagnosis and multi-modality treatment of cancer have increased survival rates for many cancer types leading to an increasing load of long-term sequelae of therapy, including that of cognitive dysfunction. The cytotoxic nature of chemotherapeutic agents may also reduce neurogenesis, a key component of the physiology of memory and cognition, with ramifications for the patient’s mood and other cognition disorders. Similarly radiotherapy employed as a therapeutic or prophylactic tool in the treatment of primary or metastatic disease may significantly affect cognition. A number of emerging pharmacotherapies are under investigation for the treatment of cognitive dysfunction experienced by cancer patients. Recent data from clinical trials is reviewed involving the stimulants modafinil and methylphenidate, mood stabiliser lithium, anti-Alzheimer’s drugs memantine and donepezil, as well as other agents which are currently being explored within dementia, animal, and cell culture models to evaluate their use in treating cognitive dysfunction.
PMCID: PMC4015674  PMID: 24156319
Cancer; Cognitive impairment; Chemotherapy; Cognitive dysfunction; Pharmacotherapy
9.  Lowering dietary linoleic acid reduces bioactive oxidized linoleic acid metabolites in humans 
Linoleic acid (LA) is the most abundant polyunsaturated fatty acid in human diets, a major component of human tissues, and the direct precursor to the bioactive oxidized LA metabolites (OXLAMs), 9- and 13 hydroxy-octadecadienoic acid (9- and 13-HODE) and 9- and 13-oxo-octadecadienoic acid (9- and 13-oxoODE). These four OXLAMs have been mechanistically linked to pathological conditions ranging from cardiovascular disease to chronic pain. Plasma OXLAMs, which are elevated in Alzheimer’s dementia and non-alcoholic steatohepatitis, have been proposed as biomarkers useful for indicating the presence and severity of both conditions. Because mammals lack the enzymatic machinery needed for de novo LA synthesis, the abundance of LA and OXLAMs in mammalian tissues may be modifiable via diet. To examine this issue in humans, we measured circulating LA and OXLAMs before and after a 12-week LA lowering dietary intervention in chronic headache patients. Lowering dietary LA significantly reduced the abundance of plasma OXLAMs, and reduced the LA content of multiple circulating lipid fractions that may serve as precursor pools for endogenous OXLAM synthesis. These results show that lowering dietary LA can reduce the synthesis and/or accumulation of oxidized LA derivatives that have been implicated in a variety of pathological conditions. Future studies evaluating the clinical implications of diet-induced OXLAM reductions are warranted.
PMCID: PMC3467319  PMID: 22959954
Linoleic acid; HODE; hydroxy-octadecadienoic acid; oxoODE; oxo-octadecadienoic acid; oxidation; OXLAM; PUFA; polyunsaturated fatty acid
10.  DSM-5: a collection of psychiatrist views on the changes, controversies, and future directions 
BMC Medicine  2013;11:202.
The recent release of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) by the American Psychiatric Association has led to much debate. For this forum article, we asked BMC Medicine Editorial Board members who are experts in the field of psychiatry to discuss their personal views on how the changes in DSM-5 might affect clinical practice in their specific areas of psychiatric medicine. This article discusses the influence the DSM-5 may have on the diagnosis and treatment of autism, trauma-related and stressor-related disorders, obsessive-compulsive and related disorders, mood disorders (including major depression and bipolar disorders), and schizophrenia spectrum disorders.
PMCID: PMC3846446  PMID: 24229007
DSM-5; Psychiatry; Autism; PTSD; Mood disorders; Bipolar; Obsessive-compulsive disorders; Depression; Schizophrenia
11.  So depression is an inflammatory disease, but where does the inflammation come from? 
BMC Medicine  2013;11:200.
We now know that depression is associated with a chronic, low-grade inflammatory response and activation of cell-mediated immunity, as well as activation of the compensatory anti-inflammatory reflex system. It is similarly accompanied by increased oxidative and nitrosative stress (O&NS), which contribute to neuroprogression in the disorder. The obvious question this poses is ‘what is the source of this chronic low-grade inflammation?’
This review explores the role of inflammation and oxidative and nitrosative stress as possible mediators of known environmental risk factors in depression, and discusses potential implications of these findings. A range of factors appear to increase the risk for the development of depression, and seem to be associated with systemic inflammation; these include psychosocial stressors, poor diet, physical inactivity, obesity, smoking, altered gut permeability, atopy, dental cares, sleep and vitamin D deficiency.
The identification of known sources of inflammation provides support for inflammation as a mediating pathway to both risk and neuroprogression in depression. Critically, most of these factors are plastic, and potentially amenable to therapeutic and preventative interventions. Most, but not all, of the above mentioned sources of inflammation may play a role in other psychiatric disorders, such as bipolar disorder, schizophrenia, autism and post-traumatic stress disorder.
PMCID: PMC3846682  PMID: 24228900
Depression; Inflammation; Cytokines; Diet; Obesity; Exercise; Smoking; Vitamin D; Dental cares; Sleep; Atopic; Gut; Oxidative stress
12.  Extreme Attributions Predict the Course of Bipolar Depression: Results from the STEP-BD Randomized Controlled Trial of Psychosocial Treatment 
Little is known about predictors of recovery from bipolar depression or moderators of treatment response. In the present study we investigated attributional style (a cognitive pattern of explaining the causes of life events) as a predictor of recovery from episodes of bipolar depression and as a moderator of response to psychotherapy for bipolar depression.
106 depressed outpatients with DSM-IV bipolar I or II disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) were randomized to intensive psychotherapy for depression (n=62), or collaborative care (n=44), a minimal psychoeducational intervention. The primary outcome was recovery status at each study visit as measured by the Clinical Monitoring Form. Attributional style was measured at baseline using the Attributional Style Questionnaire. Data were collected between 1998 and 2005.
All analyses were by intention to treat. Extreme attributions predicted a lower likelihood of recovery (p=.01, OR=0.93, 95% CI=.88-.98) and longer time until recovery (p<.01, OR=0.96, 95% CI=.93-.99), independent of the effects of initial depression severity. Among individuals with more pessimistic attributional styles, initial depression severity predicted a lower likelihood of recovery (p=.01, OR=0.64, 95% CI=.45-.91) and longer time until recovery (p<.001, OR=0.76, 95% CI=.66-.88). There was no difference in recovery rates between intensive psychotherapy and collaborative care (OR=0.90, 95% CI=0.40-2.01) in the full sample.
These results suggest that extreme, rigid attributions may be associated with a more severe course of depression, and that evaluating attributional style may help clinicians to identify patients who are at risk for experiencing a more severe course of depression.
PMCID: PMC3646511  PMID: 23561230
13.  Gastro oesophageal reflux disease (GORD)-related symptoms and its association with mood and anxiety disorders and psychological symptomology: a population-based study in women 
BMC Psychiatry  2013;13:194.
Psychopathology seems to play a role in reflux pathogenesis and vice versa, yet few population-based studies have systematically investigated the association between gastro-oesophageal reflux disease (GORD) and psychopathology. We thus aimed to investigate the relationship between GORD-related symptoms and psychological symptomatology, as well as clinically diagnosed mood and anxiety disorders in a randomly selected, population-based sample of adult women.
This study examined data collected from 1084 women aged 20-93 yr participating in the Geelong Osteoporosis Study. Mood and anxiety disorders were identified using the Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition (SCID-I/NP), and psychological symptomatology was assessed using the General Health Questionnaire (GHQ-12). GORD-related symptoms were self-reported and confirmed by medication use where possible and lifestyle factors were documented.
Current psychological symptomatology and mood disorder were associated with increased odds of concurrent GORD-related symptoms (adjusted OR 2.1, 95% CI 1.3-3.5, and OR 3.0, 95% CI 1.7-5.6, respectively). Current anxiety disorder also tended to be associated with increased odds of current GORD-related symptoms (p = 0.1). Lifetime mood disorder was associated with a 1.6-fold increased odds of lifetime GORD-related symptoms (adjusted OR 1.6, 95% CI 1.1-2.4) and lifetime anxiety disorder was associated with a 4-fold increased odds of lifetime GORD-related symptoms in obese but not non-obese participants (obese, age-adjusted OR 4.0, 95% CI 1.8-9.0).
These results indicate that psychological symptomatology, mood and anxiety disorders are positively associated with GORD-related symptoms. Acknowledging this common comorbidity may facilitate recognition and treatment, and opens new questions as to the pathways and mechanisms of the association.
PMCID: PMC3751862  PMID: 23883104
Mood disorder; Anxiety disorder; Gastro-oesophageal reflux disease (GORD); Psychological symptoms; Comorbidity; Depression; Gastrointestinal tract; Somatic; Comorbidity
14.  Evaluation of the acceptability and usefulness of an information website for caregivers of people with bipolar disorder 
BMC Medicine  2013;11:162.
Bipolar disorder is associated with extreme mood symptoms, disability and suicide risk. Close family or friends often have a primary role in supporting an adult with bipolar disorder. However, not all support is helpful and there is little publicly accessible evidence-based information to guide caregivers. Caregiver burden increases the risk of caregiver depression and health problems. To help fill the information gap, expert clinicians, caregivers and consumers contributed to the development of guidelines for caregivers of adults with bipolar disorder using the Delphi consensus method. This paper reports on an evaluation of the acceptability and usefulness of the online version of the guidelines,
Visitors to the website responded to an initial online survey about the usefulness of the information (N = 536). A more detailed follow-up feedback survey was emailed to web users who were adult caregivers of adults with bipolar disorder a month later (N = 121). The feedback was analyzed quantitatively and qualitatively to establish user appraisals of the online information, whether and how caregivers applied the information and ways it could be improved.
The majority of users (86.4% to 97.4%) found the various sections of the website useful. At follow-up, nearly 93% of caregivers reported that the information was relevant to them and 96% thought it would help others. Most respondents said that the information was supportive and encouraged adaptive control appraisals. However, a few respondents who were experiencing complex family problems, or who cared for a person with severe chronic bipolar disorder did not appraise it as positively. Nevertheless, over two-thirds of the caregivers reported using the information. Optional interactive features were recommended to maximize benefits.
Overall, was appraised positively and used. It appears useful to close family and friends seeking basic information and reassurance, and may be an inexpensive way to disseminate guidelines for caregivers. Those who care for people with more severe and chronic bipolar disorder, or who have complex family problems might benefit from more specialized interventions, suggesting the importance of a stepped-care approach to supporting caregivers. The potential of evidence-based, collaboratively developed information websites to enhance caregiver and consumer outcomes merits further investigation.
PMCID: PMC3717000  PMID: 23844755
Bipolar disorder; Caregiver burden; Caregivers; Control appraisals; Disseminate guidelines; Evaluation by users; Guidelines for caregivers; Information website; Website evaluation; Website for caregivers
15.  Altered cardiac autonomic nervous function in depression 
BMC Psychiatry  2013;13:187.
Depression is an independent risk factor for coronary artery disease. Autonomic instability may play a mediating or moderating role in this relationship; however this is not well understood. The objective of this study was to explore cardiac autonomic function and cardiac arrhythmia in depression, the correlation between depression severity and Heart Rate Variability (HRV) related indices, and the prevalence of arrhythmia.
Individuals (n = 53) with major depression as assessed by the Diagnostic and Statistical Manual of Mental Disorders, who had a Hamilton Rating Scale for Depression (HAMD) score ≥20 and a Zung Self-Rating Depression Scale score > 53 were compared to 53 healthy individuals, matched for age and gender. Multichannel Electrocardiograph ECG-92C data were collected over 24 hours. Long-term changes in HRV were used to assess the following vagally mediated changes in autonomic tone, expressed as time domain indices: Standard deviation of the NN intervals (SDNN), standard deviation of 5 min averaged NN intervals (SDANN), Root Mean Square of the Successive Differences (RMSSD) and percentage of NN intervals > 50 ms different from preceding interval (pNN50). Pearson’s correlations were conducted to explore the strength of the association between depression severity (using the SDS and HRV related indices, specifically SDNN and low frequency domain / high frequency domain (LF/HF)).
The values of SDNN, SDANN, RMSSD, PNN50 and HF were lower in the depression group compared to the control group (P<.05). The mean value of the LF in the depression group was higher than the in control group (P<.05). Furthermore the ratio of LF/HF was higher among the depression group than the control group (P<.05). A linear relationship was shown to exist between the severity of the depression and HRV indices. In the depression group, the prevalence of arrhythmia was significantly higher than in the control group (P<.05), particularly supraventricular arrhythmias.
Our findings suggest that depression is accompanied by dysfunction of the cardiac autonomic nervous system, and further, that depression severity is linked to severity of this dysfunction. Individuals with depression appear to be susceptible to premature atrial and/or ventricular disease.
PMCID: PMC3710510  PMID: 23842138
Depression; Cardiac autonomic nervous system; Heart rate variability; Arrhythmia; Vagus; Cardiovascular disorders
16.  The association between diet quality, dietary patterns and depression in adults: a systematic review 
BMC Psychiatry  2013;13:175.
Recent evidence suggests that diet modifies key biological factors associated with the development of depression; however, associations between diet quality and depression are not fully understood. We performed a systematic review to evaluate existing evidence regarding the association between diet quality and depression.
A computer-aided literature search was conducted using Medline, CINAHL, and PsycINFO, January 1965 to October 2011, and a best-evidence analysis performed.
Twenty-five studies from nine countries met eligibility criteria. Our best-evidence analyses found limited evidence to support an association between traditional diets (Mediterranean or Norwegian diets) and depression. We also observed a conflicting level of evidence for associations between (i) a traditional Japanese diet and depression, (ii) a “healthy” diet and depression, (iii) a Western diet and depression, and (iv) individuals with depression and the likelihood of eating a less healthy diet.
To our knowledge, this is the first review to synthesize and critically analyze evidence regarding diet quality, dietary patterns and depression. Further studies are urgently required to elucidate whether a true causal association exists.
PMCID: PMC3706241  PMID: 23802679
Depression; Diet; Food habits; Adults; Systematic review
17.  Molecular hydrogen: an overview of its neurobiological effects and therapeutic potential for bipolar disorder and schizophrenia 
Medical Gas Research  2013;3:11.
Hydrogen gas is a bioactive molecule that has a diversity of effects, including anti-apoptotic, anti-inflammatory and anti-oxidative properties; these overlap with the process of neuroprogression in major psychiatric disorders. Specifically, both bipolar disorder and schizophrenia are associated with increased oxidative and inflammatory stress. Moreover, lithium which is commonly administered for treating bipolar disorder has effects on oxidative stress and apoptotic pathways, as do valproate and some atypical antipsychotics for treating schizophrenia. Molecular hydrogen has been studied pre-clinically in animal models for the treatment of some medical conditions including hypoxia and neurodegenerative disorders, and there are intriguing clinical findings in neurological disorders including Parkinson’s disease. Therefore, it is hypothesized that administration of hydrogen molecule may have potential as a novel therapy for bipolar disorder, schizophrenia, and other concurrent disorders characterized by oxidative, inflammatory and apoptotic dysregulation.
PMCID: PMC3680337  PMID: 23742229
18.  Tobacco smoking predicts depression and poorer quality of life in heart disease 
We report on the prospective association between smoking and depression and health-related quality of life (HRQOL) in patients with coronary artery disease (CAD).
Prospective study of 193 patients with assessment of depression occurring 3-, 6- and 9- months (T1, 2, and 3, respectively) following discharge from hospital for a cardiac event. HRQOL was assessed at T3. T1 depression was assessed by clinical interview; T2 and T3 depression was assessed by self-report. Smoking at time of cardiac event was assessed by self-report. Multivariate analyses controlled for known demographic, psychosocial and clinical correlates of depression.
Smoking at the time of index cardiac event increased the likelihood of being diagnosed with Major Depressive Disorder (MDD) at T1 by 4.30 [95% CI, 1.12-16.46; p < .05]. The likelihood of receiving a diagnosis of minor depression, dysthymia or MDD as a combined group was increased by 8.03 [95% CI, 2.35-27.46; p < .01]. Smoking did not reliably predict depression at T2 or T3 and did not reliably predict persistent depression. Smoking increased the likelihood of being classified as depressed according to study criteria at least once during the study period by 5.19 [95% CI, 1.51-17.82; p < .01]. Smoking independently predicted worse mental HRQOL.
The findings support a role for smoking as an independent predictor of depression in CAD patients, particularly in the first 3 months post-cardiac event. The well-established imperative to encourage smoking cessation in these patients is augmented and the findings may add to the evidence for smoking cessation campaigns in the primary prevention of depression.
PMCID: PMC3666905  PMID: 23705944
Coronary artery disease; Depression; Smoking; Quality of life
19.  The Impact of Smoking in Adolescence on Early Adult Anxiety Symptoms and the Relationship between Infant Vulnerability Factors for Anxiety and Early Adult Anxiety Symptoms: The TOPP Study 
PLoS ONE  2013;8(5):e63252.
Cigarette smoking is increased in people with trait anxiety and anxiety disorders, however no longitudinal data exist illuminating whether smoking in adolescence can influence the developmental trajectory of anxiety symptoms from early vulnerability in infancy to adult anxiety expression. Using The Tracing Opportunities and Problems in Childhood and Adolescence (TOPP) Study, a community-based cohort of children and adolescents from Norway who were observed from the age of 18months to age 18–19years, we explored the relationship between adolescent smoking, early vulnerability for anxiety in infancy (e.g. shyness, internalizing behaviors, emotional temperaments) and reported early adult anxiety.
Structural equation modeling demonstrated that adolescent active smoking was positively associated with increased early adulthood anxiety (β = 0.17, p<0.05), after controlling for maternal education (proxy for socioeconomic status). Adolescent anxiety did not predict early adult smoking. Adolescent active smoking was a significant effect modifier in the relationship between some infant vulnerability factors and later anxiety; smoking during adolescence moderated the relationship between infant internalizing behaviors (total sample: active smokers: β = 0.85,p<0.01, non-active smokers: ns) and highly emotional temperament (total sample: active smokers: β = 0.55,p<0.01,non-active smokers: ns), but not shyness, and anxiety in early adulthood. The results support a model where smoking acts as an exogenous risk factor in the development of anxiety, and smoking may alter the developmental trajectory of anxiety from infant vulnerability to early adult anxiety symptom expression. Although alternative non-mutually exclusive models may explain these findings, the results suggest that adolescent smoking may be a risk factor for adult anxiety, potentially by influencing anxiety developmental trajectories. Given the known adverse health effects of cigarette smoking and significant health burden imposed by anxiety disorders, this study supports the importance of smoking prevention and cessation programs targeting children and adolescence.
PMCID: PMC3655993  PMID: 23696803
20.  The DSM-5: Hyperbole, Hope or Hypothesis? 
BMC Medicine  2013;11:128.
The furore preceding the release of the new edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) is in contrast to the incremental changes to several diagnostic categories, which are derived from new research since its predecessor’s birth in 1990. While many of these changes are indeed controversial, they do reflect the intrinsic ambiguity of the extant literature. Additionally, this may be a mirror of the frustration of the field’s limited progress, especially given the false hopes at the dawn of the “decade of the brain”. In the absence of a coherent pathophysiology, the DSM remains no more than a set of consensus based operationalized adjectives, albeit with some degree of reliability. It does not cleave nature at its joints, nor does it aim to, but neither does alternate systems. The largest problem with the DSM system is how it’s used; sometimes too loosely by clinicians, and too rigidly by regulators, insurers, lawyers and at times researchers, who afford it reference and deference disproportionate to its overt acknowledged limitations.
PMCID: PMC3653753  PMID: 23672603
DSM-V; Diagnosis; Pathophysiology; DSM-V; Symptoms; Classification
21.  How cigarette smoking may increase the risk of anxiety symptoms and anxiety disorders: a critical review of biological pathways 
Brain and Behavior  2013;3(3):302-326.
Multiple studies have demonstrated an association between cigarette smoking and increased anxiety symptoms or disorders, with early life exposures potentially predisposing to enhanced anxiety responses in later life. Explanatory models support a potential role for neurotransmitter systems, inflammation, oxidative and nitrosative stress, mitochondrial dysfunction, neurotrophins and neurogenesis, and epigenetic effects, in anxiety pathogenesis. All of these pathways are affected by exposure to cigarette smoke components, including nicotine and free radicals. This review critically examines and summarizes the literature exploring the role of these systems in increased anxiety and how exposure to cigarette smoke may contribute to this pathology at a biological level. Further, this review explores the effects of cigarette smoke on normal neurodevelopment and anxiety control, suggesting how exposure in early life (prenatal, infancy, and adolescence) may predispose to higher anxiety in later life. A large heterogenous literature was reviewed that detailed the association between cigarette smoking and anxiety symptoms and disorders with structural brain changes, inflammation, and cell-mediated immune markers, markers of oxidative and nitrosative stress, mitochondrial function, neurotransmitter systems, neurotrophins and neurogenesis. Some preliminary data were found for potential epigenetic effects. The literature provides some support for a potential interaction between cigarette smoking, anxiety symptoms and disorders, and the above pathways; however, limitations exist particularly in delineating causative effects. The literature also provides insight into potential effects of cigarette smoke, in particular nicotine, on neurodevelopment. The potential treatment implications of these findings are discussed in regards to future therapeutic targets for anxiety. The aforementioned pathways may help mediate increased anxiety seen in people who smoke. Further research into the specific actions of nicotine and other cigarette components on these pathways, and how these pathways interact, may provide insights that lead to new treatment for anxiety and a greater understanding of anxiety pathogenesis.
PMCID: PMC3683289  PMID: 23785661
Anxiety; anxiety disorder; cigarette; epigenetic; inflammation; mitochondria; neurodevelopment; neurotransmitters; neurotrophins; nicotine; nitrosative stress; oxidative stress
22.  Physical comorbidities in men with mood and anxiety disorders: a population-based study 
BMC Medicine  2013;11:110.
The mind-body nexus has been a topic of growing interest. Further data are however required to understand the specific relationship between mood and anxiety disorders and individual physical health conditions, and to verify whether these psychiatric disorders are linked to overall medical burden.
This study examined data collected from 942 men, 20 to 97 years old, participating in the Geelong Osteoporosis Study. A lifetime history of mood and anxiety disorders was identified using the Structured Clinical Interview for DSM-IV-TR Research Version, Non-patient edition (SCID-I/NP). The presence of medical conditions (lifetime) was self-reported and confirmed by medical records, medication use or clinical data. Anthropometric measurements and socioeconomic status (SES) were determined and information on medication use and lifestyle was obtained via questionnaire. Logistic regression models were used to test the associations.
After adjustment for age, socioeconomic status, and health risk factors (body mass index, physical activity and smoking), mood disorders were associated with gastro oesophageal reflux disease (GORD), recurrent headaches, blackouts and/or epilepsy, liver disorders and pulmonary disease in older people, whilst anxiety disorders were significantly associated with thyroid, GORD and other gastrointestinal disorders, and psoriasis. Increased odds of high medical burden were associated with both mood and anxiety disorders.
Our study provides further population-based evidence supporting the link between mental and physical illness in men. Understanding these associations is not only necessary for individual management, but also to inform the delivery of health promotion messages and health care.
PMCID: PMC3648485  PMID: 23618390
Mood disorder; Anxiety disorder; Comorbidity; Medical burden; Population-based study; Physical illness
23.  A randomised, controlled trial of a dietary intervention for adults with major depression (the “SMILES” trial): study protocol 
BMC Psychiatry  2013;13:114.
Despite increased investment in its recognition and treatment, depression remains a substantial health and economic burden worldwide. Current treatment strategies generally focus on biological and psychological pathways, largely neglecting the role of lifestyle. There is emerging evidence to suggest that diet and nutrition play an important role in the risk, and the genesis, of depression. However, there are limited data regarding the therapeutic impact of dietary changes on existing mental illness. Using a randomised controlled trial design, we aim to investigate the efficacy and cost-efficacy of a dietary program for the treatment of Major Depressive Episodes (MDE).
One hundred and seventy six eligible participants suffering from current MDE are being randomised into a dietary intervention group or a social support group. Depression status is assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS) and Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (Non Patient Edition) (SCID-I/NP). The intervention consists of 7 individual nutrition consulting sessions (of approximately 60 minutes), delivered by an Accredited Practising Dietitian (APD). Sessions commence within one week of baseline assessment. The intervention focuses on advocating a healthy diet based on the Australian Dietary Guidelines and the Dietary Guidelines for Adults in Greece. The control condition comprises a befriending protocol using the same visit schedule and length as the diet intervention. The study is being conducted at two locations in Victoria, Australia (a metropolitan and regional centre). Data collection occurs at baseline (pre-intervention), 3-months (post-intervention) and 6– months. The primary endpoint is MADRS scores at 3 months. A cost consequences analysis will determine the economic value of the intervention.
If efficacious, this program could provide an alternative or adjunct treatment strategy for the management of this highly prevalent mental disorder; the benefits of which could extend to the management of common co-morbidities including cardiovascular disease (CVD), obesity, and type 2 diabetes.
Trial registration
PMCID: PMC3636120  PMID: 23587364
Diet; Nutrition; Depression; Mental health; Social support
24.  Aspirin: a review of its neurobiological properties and therapeutic potential for mental illness 
BMC Medicine  2013;11:74.
There is compelling evidence to support an aetiological role for inflammation, oxidative and nitrosative stress (O&NS), and mitochondrial dysfunction in the pathophysiology of major neuropsychiatric disorders, including depression, schizophrenia, bipolar disorder, and Alzheimer's disease (AD). These may represent new pathways for therapy. Aspirin is a non-steroidal anti-inflammatory drug that is an irreversible inhibitor of both cyclooxygenase (COX)-1 and COX-2, It stimulates endogenous production of anti-inflammatory regulatory 'braking signals', including lipoxins, which dampen the inflammatory response and reduce levels of inflammatory biomarkers, including C-reactive protein, tumor necrosis factor-α and interleukin (IL)--6, but not negative immunoregulatory cytokines, such as IL-4 and IL-10. Aspirin can reduce oxidative stress and protect against oxidative damage. Early evidence suggests there are beneficial effects of aspirin in preclinical and clinical studies in mood disorders and schizophrenia, and epidemiological data suggests that high-dose aspirin is associated with a reduced risk of AD. Aspirin, one of the oldest agents in medicine, is a potential new therapy for a range of neuropsychiatric disorders, and may provide proof-of-principle support for the role of inflammation and O&NS in the pathophysiology of this diverse group of disorders.
PMCID: PMC3751197  PMID: 23506529
aspirin; depression; schizophrenia; dementia; inflammation; cytokines; neuroprogression; treatment; COX
25.  Gender differences in first episode psychotic mania 
BMC Psychiatry  2013;13:82.
The aim of this paper was to delineate the impact of gender on premorbid history, onset, and 18 month outcomes of first episode psychotic mania (FEPM) patients.
Medical file audit assessment of 118 (male = 71; female = 47) patients with FEPM aged 15 to 29 years was undertaken on clinical and functional measures.
Males with FEPM had increased likelihood of substance use (OR = 13.41, p <.001) and forensic issues (OR = 4.71, p = .008), whereas females were more likely to have history of sexual abuse trauma (OR = 7.12, p = .001). At service entry, males were more likely to be using substances, especially cannabis (OR = 2.15, p = .047), had more severe illness (OR = 1.72, p = .037), and poorer functioning (OR = 0.96, p = .045). During treatment males were more likely to decrease substance use (OR = 5.34, p = .008) and were more likely to be living with family (OR = 4.30, p = .009). There were no gender differences in age of onset, psychopathology or functioning at discharge.
Clinically meaningful gender differences in FEPM were driven by risk factors possibly associated with poor outcome. For males, substance use might be associated with poorer clinical presentation and functioning. In females with FEPM, the impact of sexual trauma on illness course warrants further consideration.
PMCID: PMC3602146  PMID: 23497439
Gender; Mania; Psychosis; Bipolar disorder

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