Food anthocyanins decrease concentrations of TNF-α in older adults with mild cognitive impairment: A randomized, controlled, double blind clinical trial.

BACKGROUND & AIMS: Vascular function, blood pressure and inflammation are involved in the pathogenesis of major chronic diseases, including both cardiovascular disease (CVD) and mild cognitive impairment (MCI). This study investigated the effects of food anthocyanins on microvascular function, 24-h ambulatory blood pressure (ABP) and inflammatory biomarkers in older adults with MCI. METHODS AND RESULTS: Thirty-one participants with MCI [19 female, 12 male, mean age 75.3 (SD 6.9) years and body mass index 26.1 (SD 3.3) kg/m2], participated in a randomized, controlled, double-blind clinical trial (Australian New Zealand Clinical Trials Registry: ACTRN12618001184268). Participants consumed 250 mL fruit juice daily for 8 weeks, allocated into three groups: a) high dose anthocyanins (201 mg); b) low dose anthocyanins (47 mg); c) control. Microvascular function (Laser Speckle Contrast Imaging combined with a post-occlusive reactive hyperaemia test), 24h ABP and serum inflammatory biomarkers were assessed before and after the nutritional intervention. RESULTS: Participants in the high anthocyanins group had a reduction in serum tumor necrosis factor alpha (TNF-α) (P = 0.002) compared to controls and the low anthocyanins group (all P's > 0.05). Serum IL-6, IL-1ß, c-reactive protein, and parameters of microvascular function and 24h ABP were not altered by any treatment. CONCLUSION: A daily high dose of fruit-based anthocyanins for 8 weeks reduced concentrations of TNF-α in older adults with MCI. Anthocyanins did not alter other inflammatory biomarkers, microvascular function or blood pressure parameters. Further studies with a larger sample size and longer period of follow-up are required to elucidate whether this change in the immune response will alter CVD risk and progression of cognitive decline.

Suprasensory phenomena in those with a bipolar disorder.

OBJECTIVES: To increase awareness of the sensory changes experienced during hypo/manic and depressive states by those with a bipolar disorder and determine if the prevalence of such features is similar across differing bipolar sub-types. METHODS: We interviewed 66 patients who acknowledged sensory changes during hypo/manic states. They were allocated to bipolar I, bipolar II and soft bipolar diagnostic categories and the prevalence of 10 differing sensory changes was quantified during hypo/manic and depressive phases. RESULTS: Bipolar I patients were just as likely, if not more likely, to report suprasensory changes which typically involved enhancement of senses during hypo/manic phases and muting or blunting during depressive phases. The high prevalence of changes in intuition, empathy, appreciation of danger and predictive capacities suggests that these are more part of the intrinsic bipolar mood domain states and not necessarily suprasensory, while changes in primary senses of smell, taste, vision, touch and hearing appear to more commonly define the suprasensory domain. CONCLUSIONS: It is important for clinicians and patients with a bipolar disorder to be aware of non-psychotic, suprasensory phenomena. Identification of such features may aid diagnosis and also explain the recognised increased creativity in those with a bipolar condition.

Melancholia and catatonia: disorders or specifiers?

The fifth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 defines mental disorders as syndromes and also introduced disorder "specifiers" with the aim of providing increased diagnostic specificity by defining more homogeneous subgroups of those with the disorder and who share certain features. While the majority of specifiers in DSM-5 define a specific aspect of the disorder such as age at onset or severity, some define syndromes that appear to meet the DSM-5 definition of a mental disorder. Specifically, melancholia is positioned in DSM-5 as a major depressive disorder (non-coded) specifier, while catatonia is listed as both a disorder secondary to a medical condition and as a specifier associated with other mental disorders such as schizophrenia, major depressive disorder, and bipolar disorder. Despite decades of research supporting melancholia's status as a categorical "disorder" (a higher-order construct than a specifier), failure to provide convincing support for its disorder status has contributed to its current positioning in DSM-5. As DSM-5 has similar symptom criteria for major depression and for its melancholia specifier, research seeking to differentiate melancholic and non-melancholic depression according to DSM-5 criteria will have limited capacity to demonstrate "melancholia" as a separate disorder and risks melancholia continuing to be reified as a low-order specifier and thus clinical marginalization. There have been few advances in catatonia research in recent years with its positioning largely relying on opinion and clinical observation rather than on empirical studies.

Construct validity of the Experiences of Therapy Questionnaire (ETQ).

BACKGROUND: The Experiences of Therapy Questionnaire (ETQ) is a reliable measure of adverse effects associated with psychotherapy. The measure has not been subject to validity analyses. This study sought to examine the validity of the ETQ by comparison against a measure of therapist satisfaction. METHODS: Participants were recruited from the Black Dog Institute's website and completed all measures online, at two time points (two weeks apart). Correlational analyses compared scale scores on the ETQ with related constructs of the Therapist Satisfaction Scale (TSS). To exclude any impact of current depression on ratings, we examined correlations between salient ETQ and TSS scales after controlling for depression severity. RESULTS: Forty-six participants completed all the measures at both time points. Hypothesised associations between the ETQ and TSS scales were supported, irrespective of current depression severity. CONCLUSIONS: The validity of the ETQ is supported; however limitations of the study are noted, including generalizability due to sample characteristics.

Is cognitive behaviour therapy of benefit for melancholic depression?

OBJECTIVE: This paper seeks to determine the relevance and likely salience of cognitive behaviour therapy (CBT) as a treatment for melancholic depression. METHODS: The findings of a randomised trial comparing 12-week outcome of 18 patients with melancholic depression receiving antidepressant medication and 11 receiving CBT were evaluated, and qualitative explanations for the outcomes were provided principally by the treating CBT practitioners. RESULTS: In the trial, CBT showed no improvement in depression severity in the first four weeks and then some level of improvement over the subsequent eight weeks. Outcome was superior for those receiving antidepressant medication at 12 weeks and was first demonstrated at four weeks. The benefits of CBT appeared to be in settling anxiety, dealing with cognitive processing of having a melancholic depression and addressing any personality vulnerabilities. CONCLUSION: While a pilot study, our qualitative reports indicate that CBT may provide a useful role in managing melancholia as an adjunct to antidepressant medication. Future studies examining such a combination treatment model should seek to determine if indicative data provided here argue for a sequencing model of CBT being introduced after medication has addressed core biological underpinnings.

Paradigms lost and gained: has psychiatry in Australasia lost its voice?

OBJECTIVE: The evolution of views about causes and management models in psychiatry is of keen interest to those who respect the field's history. The objective of this study was to identify international paradigm shifts since 1950 in psychiatric theorising and management models. METHOD: Multiple methods were used, including citation analysis, qualitative judgments by highly cited researchers and obtaining the views of historians of psychiatry. RESULTS: The quantitative citation analysis was of low yield, seemingly reflecting limitations intrinsic to such an approach, but it did identify some 'signals' to broader domain shifts, such as the progressive loss of salience of psychoanalysis and a contrasting emphasis on a science-weighted model. Also, the highly cited researchers tend to nominate narrow exemplars. Nominations by the historians were more panoramic and, while capturing the domains identified by the two other strategies, went further in proposing a wide set of additional candidates for consideration. CONCLUSION: Of the three strategies employed, the qualitative approach (canvassing the views of historians and of highly cited authors) captured the paradigm changes, or at least theoretical or research trends, more accurately than the quantitative citation analysis. Changes in Australasian psychiatry would appear to generally mirror such international changes, rather than evidence a distinctive voice.

Beyond the baby blues: perspectives of women diagnosed with a mood disorder on children, pregnancy and medication.

OBJECTIVE: The aim of this study was to explore the views of women diagnosed with a mood disorder about children, medication and pregnancy. METHOD: Female patients from the Black Dog Institute were invited to complete a questionnaire regarding their views about pregnancy, children and medication during pregnancy. Diagnostic groupings were derived by assessing DSM-IV criteria for mood disorders. Unipolar and bipolar patient responses were analysed to determine any differences between groups. RESULTS: Women with bipolar disorder were more concerned than those with a unipolar condition about the impact pregnancy would have on their mood, as well as the potential for their offspring to inherit a mood condition. Both groups of women expressed concerns regarding the child-rearing environment, and stated that knowing the risk their child could have of developing a mood disorder would encourage them to be more vigilant parents. CONCLUSION: While both groups were concerned about the environment in which they would raise their child and wanted to be vigilant parents, women diagnosed with a bipolar condition expressed stronger opinions regarding the impact that their pregnancy could have on their mood disorder, and passing the mood disorder onto their children.

The Mood Assessment Program is now on the Australian map.

OBJECTIVE: To report on the wide uptake and utility of the freely available Mood Assessment Program (MAP) since its introduction as a tool to assist diagnosis and management of mood disorders. METHOD: By mid-2012, some 16,000 patients had completed the MAP. We analyse data derived from such a sample. RESULTS: The majority of patients utilizing this service were referred by general practitioners, psychologists and psychiatrists from within New South Wales (NSW). The great majority across age bands found the MAP easy to complete and judged that it covers issues relating to their mood disorder very well or completely. CONCLUSION: The MAP is available for use Australia-wide with ready referral access for patients of mental health practitioners in general practice, psychiatry, psychology and social work. The online availability of the service makes it ideal for use in areas where access to health services is limited.

Do practitioners managing mood disorders work to a sub-typing or a 'one size fits all' model?

OBJECTIVE: To assess whether psychiatrists in the community operate to a sub-typing model of mood disorders when choosing psychotropic medications. METHOD: Patients assessed through the Black Dog Institute depression clinic provided information on their previously prescribed and current medications, on how effective they found them and whether they had to be ceased due to side-effects. The prevalence of each medication trialled was analysed according to diagnosis (bipolar I, bipolar II, unipolar melancholic depression or unipolar non-melancholic depression). RESULTS: Analyses indicate that psychiatrists prescribe medications differentially in line with diagnosis. This effect was found in both previously prescribed and currently prescribed medications, and was most distinct for mood stabiliser and antipsychotic medications. Several medications, in contrast, appeared to have been trialled by the majority of patients, regardless of diagnosis. Analyses of effectiveness and cessation due to side-effects were compromised by small sub-sample sizes. CONCLUSIONS: Psychiatrists in the community appear to operate to a sub-typing model of mood disorders, preferentially prescribing many medications according to mood disorder sub-type.

Out of the darkness: the impact of a mood disorder over time.

OBJECTIVE: Being diagnosed with depression or bipolar disorder has a significant impact on an individual's life. This paper reports data examining how patients view having had such a condition. METHOD: Patients attending the Black Dog Institute Depression Clinic were asked to complete questionnaires examining the impact of being diagnosed with a mood disorder and dealing with that condition over time. RESULTS: Patient responses were analysed qualitatively (in terms of positive, negative and neutral responses) and their quantitative distribution was examined. Themes were relatively consistent across unipolar and bipolar patients. Negative themes included family and work consequences, social impairment and a loss of self-confidence. Positive themes included the development of stronger familial bonds, the provision of relief and hope, positive treatment outcomes and the explanatory benefits of receiving a diagnosis. CONCLUSIONS: Findings indicate quite contrasting courses reported by patients with mood disorders (irrespective of polarity), ranging from negative to very positive evaluations.

How well does a wellbeing measure predict psychiatric 'caseness' as well as suicide risk and self-harm in adolescents?

Screening for psychiatric disorders may be hampered by traditional measures that increase participant burden and elicit negative responses via denial and social desirability biases. This study examined the utility of a wellbeing measure to identify psychopathology and suicide risk in adolescent participants. 1,579 students from Sydney schools participated in a survey which assessed wellbeing using the Satisfaction With Life Scale (SWLS) as well as psychiatric disorders and suicide risk. Results showed that low scores on the SWLS discriminated adolescents who had experienced a psychiatric condition or suicidality from those not so assigned. Specifically, students with no psychiatric diagnosis yielded a mean SWLS score of 28.0 while for those assigned a diagnosis, mean scores ranged from 19.4-3.0 across the various psychiatric conditions. Students who reported any suicidal ideation yielded a mean SWLS score of 22.7, and those with a current suicidal plan yielded a mean score of 17.7. We derived SWLS cut-off scores for predicting psychiatric caseness and suicidality but established that they had low positive predictive power. The SWLS therefore appears to provide a limited proxy measure of the chance of a psychiatric disorder or psychological distress, and might usefully complement more direct measures of such states.

Lithium and cognition in those with bipolar disorder.

Although a percentage of patients report cognitive side-effects when taking lithium, it can be difficult to determine from the literature whether any cognitive changes reflect lithium itself, the lithium serum level, residual mood symptoms, the underlying nature of bipolar disorder, or biological alterations such as hypothyroidism. This review was carried out to synthesize and evaluate relevant literature examining any cognitive impact of lithium in those with bipolar disorder. The effect of lithium in those with bipolar disorder was examined across the cognitive domains of attention, psychomotor speed, processing speed, working memory, intellectual functioning, verbal memory, visual memory, and executive functioning by reviewing the published empirical literature. Any impact of hypothyroidism and lithium toxicity was also examined. The literature supports the conclusion that lithium has a distinct impact on psychomotor speed in participants with bipolar disorder. In contrast, there appears to be no impact on attention. Any impact of lithium on memory in patients with bipolar disorder is unclear as the literature is contradictory and any such effect may be overshadowed by the greater impact of residual mood symptoms. The impact on processing speed, intellectual abilities, and executive functioning also remains unclear. Several clinical management strategies are recommended.

Clinical features distinguishing grief from depressive episodes: A qualitative analysis.

BACKGROUND: The independence or interdependence of grief and major depression has been keenly argued in relation to recent DSM definitions and encouraged the current study. METHODS: We report a phenomenological study seeking to identify the experiential and phenomenological differences between depression and grief as judged qualitatively by those who had experienced clinical (n=125) or non-clinical depressive states (n=28). RESULTS: Analyses involving the whole sample indicated that, in contrast to grief, depression involved feelings of hopelessness and helplessness, being endless and was associated with a lack of control, having an internal self-focus impacting on self-esteem, being more severe and stressful, being marked by physical symptoms and often lacking a justifiable cause. Grief was distinguished from depression by the individual viewing their experience as natural and to be expected, a consequence of a loss, and with an external focus (i.e. the loss of the other). Some identified differences may have reflected the impact of depressive "type" (e.g. melancholia) rather than depression per se, and argue for a two-tiered model differentiating normative depressive and grief states at their base level and then "clinical" depressive and 'pathological' grief states by their associated clinical features. LIMITATIONS: Comparative analyses between the clinical and non-clinical groups were limited by the latter sub-set being few in number. The provision of definitions may have shaped subjects׳ nominated differentiating features. CONCLUSION: The study identified a distinct number of phenomenological and clinical differences between grief and depression and few shared features, but more importantly, argued for the development of a two-tiered model defining both base states and clinical expressions.

Emotional response patterns of depression, grief, sadness and stress to differing life events: a quantitative analysis.

BACKGROUND: In clarifying the clinical definition of an episode of major depression, DSM-5 equates bereavement with a number of other loss-related stressors (e.g. financial ruin, serious medical problems) and infers differences between such loss-related and non-loss-related responses. We undertook a study with the aim of examining the likelihood of varying life stressors leading to depression or to other emotional responses, and so allowing consideration as to whether bereavement might be equivalent to other loss-related stressful triggers. METHODS: We studied a sample comprising sub-sets of those likely to have either experienced or never experienced a clinical depressive episode and report data for both the whole sample and the separate sub-sets. Participants were asked to report their exposure to 16 differing stressors and, given definitions of depression, grief, sadness and stress, to rate (in order of importance) their primary and secondary reactions if so experienced. RESULTS: Only one event (i.e. the individual being left by their partner) generated depression as the most likely response within the sample. A grief reaction was nominated as the most likely primary response to the death of a first-degree relative (52%) and was also a relatively common primary response to the death of a more distant relative or close family friend (36%). While one-fourth (24%) nominated grief as the primary response to being left by one's partner, it was rarely nominated as a primary response to all other events, including the DSM-5 'loss-related' exemplars of a financial crisis and of a medical illness (rates of 3% and 2%, respectively). LIMITATIONS: As participants were given a definition of the emotional responses and candidate contexts, their responses may have been a reflection of the definitions provided. Additionally, a retrospective, self-report design was used which may have impacted on the veracity of responses. CONCLUSIONS: Findings position a grief response as showing relative specificity to bereavement events and that bereavement is unlikely to induce a depressive response.

Predictors of post-natal depression are shaped distinctly by the measure of 'depression'.

BACKGROUND: Many variables have been proposed as predictive of post-natal depression (PND). AIMS: To investigate and refine PND risk variables. METHOD: We recruited a large sample and employed two measures of PND (the dimensional Edinburgh Postnatal Depression Scale or EPDS, and DSM-defined major depression). RESULTS: High levels of stress in the post-natal period, previous depression and higher depression scores during pregnancy were the only consistent predictors across measures. Those exceeding the EPDS cut-off had additional psychosocial risk factors while those meeting criteria for major depression were strongly predicted by a past history of depression as well as higher pre-natal state depression scores. LIMITATIONS: The EPDS has been used with variable cut off scores across multiple studies. We used only nine of the 10 EPDS items, electing to exclude the self-harm related question, but preserving the recommended EPDS cut-off score, and which might have impacted on predictions. CONCLUSIONS: Study results generated a refined set of predictors of PND but, more importantly, identified that predictors of PND status are distinctly influenced by the measure of PND. Such inconsistencies are intrinsically noteworthy and of potential key importance in shaping intervention strategies.

Anhedonia in melancholic and non-melancholic depressive disorders.

BACKGROUND: Anhedonia represents a core symptom of major depression and may be a potential marker for melancholia. However, current understanding of this construct in depressive sub-types is limited. METHOD: Participants were recruited from the Black Dog Institute (Sydney) and Massachusetts General Hospital (Boston). Diagnostic groups were derived on the basis of agreement between clinician and DSM-IV diagnosis from structured interviews. Currently depressed unipolar melancholic, non-melancholic and healthy control participants were administered a probabilistic reward task (PRT) to assess a behavioural correlate of anhedonia-blunted reward-based learning. Self-reported measures of anhedonia, approach and avoidance motivation were completed by the Sydney sample. RESULTS: Relative to healthy controls and non-melancholic participants, melancholic depressed participants had reduced response bias, highlighting blunted reward learning. Moreover, although non-melancholic participants were characterized by a delayed response bias, melancholic depressed participants failed to develop a bias throughout blocks. Response bias showed no associations with self-report measures of hedonic tone in depressed participants. Positive associations were observed between response bias, approach and avoidance motivation in non-melancholic participants only. LIMITATIONS: Possible medication, fatigue and anxiety effects were not controlled; small sample sizes; inclusion criteria may have excluded those with severe melancholia and led to underestimation of group differences. CONCLUSIONS: Melancholia is characterised by a reduced ability to modulate behaviour as a function of reward, and the motivational salience of rewarding stimuli may differ across depressive sub-types. Results support the view that melancholia is a distinct sub-type. Further exploration of reward system functioning in depressive sub-types is warranted.

Melancholia: definition and management.

PURPOSE OF REVIEW: To overview historical ascriptions and the current nosological status of melancholia, before reporting diagnostic strategy, biological marker and treatment studies. RECENT FINDINGS: As melancholia has never been satisfactorily differentiated by reliance on symptoms, strategies that adopt a more prototypic approach and incorporate illness correlates in conjunction with symptoms appear to provide greater precision in differentiating melancholic and nonmelancholic depression. An early indicative biological marker--hyperactive Hypothalamic-Pituitary-Adrenal axis functioning--remains supported, whereas a number of other recently proposed candidate markers require clarification. Implications for treatment from recent clinical trials are also discussed. SUMMARY: We note that the Diagnostic and Statistical Manual 5 (DSM-5) definition of melancholia [as for Diagnostic and Statistical Manual IV (DSM-IV)] may be limited in its differentiating capacity and so compromise research into melancholia's causes and treatments. Clarifying melancholia's status, primary causes and differential treatment responsiveness awaits more precise definition of this depressive condition.

Emotion regulation strategies in bipolar II disorder and borderline personality disorder: differences and relationships with perceived parental style.

BACKGROUND: Bipolar II disorder (BP II) and Borderline Personality Disorder (BPD) share common features and can be difficult to differentiate, contributing to misdiagnosis and inappropriate treatment. Research contrasting phenomenological features of both conditions is limited. The current study sought to identify differences in emotion regulation strategies in BP II and BPD in addition to examining relationships with perceived parental style. METHOD: Participants were recruited from a variety of outpatient and community settings. Eligible participants required a clinical diagnosis of BP II or BPD, subsequently confirmed via structured diagnostic interviews assessing DSM-IV criteria. Participants completed a series of self-reported questionnaires assessing emotion regulation strategies and perceived parental style. RESULTS: The sample comprised 48 (n=24 BP II and n=24 BPD) age and gender-matched participants. Those with BPD were significantly more likely to use maladaptive emotion regulation strategies, less likely to use adaptive emotion regulation strategies, and scored significantly higher on the majority of (perceived) dysfunctional parenting sub-scales than participants with BP II. Dysfunctional parenting experiences were related to maladaptive emotion regulation strategies in participants with BP II and BPD, however differential associations were observed across groups. LIMITATIONS: Relatively small sample sizes; lack of a healthy control comparator group; lack of statistical control for differing sociodemographic and clinical characteristics, medication and psychological treatments; no assessment of state or trait anxiety; over-representation of females in both groups limiting generalisability of results; and reliance on self-report measures. CONCLUSIONS: Differences in emotion regulation strategies and perceived parental style provide some support for the validity of distinguishing BP II and BPD. Development of intervention strategies targeting the differing forms of emotion regulatory pathology in these groups may be warranted.

Gender differences in depression severity and symptoms across depressive sub-types.

BACKGROUND: Lifetime rates of depression are distinctly higher in women reflecting both real and artefactual influences. Most prevalence studies quantifying a female preponderance have examined severity-based diagnostic groups such as major depression or dysthymia. We examined gender differences across three depressive sub-type conditions using four differing measures to determine whether any gender differences emerge more from severity or symptom prevalence, reflect nuances of the particular measure, or whether depressive sub-type is influential. METHODS: A large clinical sample was recruited. Patients completed two severity-weighted depression measures: the Depression in the Medically Ill 10 (DMI-10) and Quick Inventory of Depressive Symptoms-Self-Report (QIDS-SR) and two measures weighting symptoms and illness correlates of melancholic and non-melancholic depressive disorders - the Severity of Depressive Symptoms (SDS) and Sydney Melancholia Prototype Index (SMPI). Analyses were undertaken of three diagnostic groups comprising those with unipolar melancholic, unipolar non-melancholic and bipolar depressive conditions. RESULTS: Women in the two unipolar groups scored only marginally (and non-significantly) higher than men on the depression severity measures. Women in the bipolar depression group, did however, score significantly higher than men on depression severity. On measures weighted to assessing melancholic and non-melancholic symptoms, there were relatively few gender differences identified in the melancholic and non-melancholic sub-sets, while more gender differences were quantified in the bipolar sub-set. The symptoms most commonly and consistently differentiating by gender were those assessing appetite/weight change and psychomotor disturbance. CONCLUSION: Our analyses of several measures and the minimal differentiation of depressive symptoms and symptom severity argues against any female preponderance in unipolar depression being contributed to distinctly by these depression rating measures. Our analyses indicated that gender had minimal if any impact on depression severity estimates. Gender differences in depressive symptoms and severity were more distinctive in bipolar patients, a finding seemingly not previously identified or reported. LIMITATIONS: The study had considerable power reflecting large sample sizes and thus risks assigning significant differences where none truly exist, although we repeated analyses after controlling for the type I error rate.

Suggested early onset of true action of antidepressant drugs may be artefactual: a heuristic study.

In recent decades, there have been many studies reporting that antidepressants have a rapid onset of action, with improvement occurring in the first week. The current pilot study questions whether such findings reflect an artefact emerging from high rates of 'nonspecific' improvement and evaluates the phenomenon in a small sample of melancholic patients seemingly lacking nonspecific improvement propensities. Twenty-nine patients with a well-defined melancholic depression completed a 12-week treatment study comparing drug therapy versus cognitive behaviour therapy. The primary outcome measure was the Hamilton Rating Scale for Depression, and a self-report measure of depressed mood severity (the Daily Rating Scale) was completed daily. Analyses seeking time till onset of action were limited to those receiving drug therapies. The lack of improvement in the first 4 weeks for those receiving cognitive behaviour therapy argued for the melancholic patients lacking the capacity for a nonspecific response to therapy. Formal 12-week responder status in those receiving the antidepressant could not be predicted from improvement status until day 12 of the study, and not in the first week as reported in most previous studies of those with major depression. This pilot study argues for any study seeking to quantify the specific interval for onset of action of antidepressant drugs focusing on only those with well-defined melancholia.