Journal of Affective Disorders

Editorial Board

2010-10-01

Symptoms and signs of the initial prodrome of bipolar disorder: A systematic review

Dag V. Skjelstad, Ulrik F. Malt, Arne Holte — 2010-10-01

Abstract: Background: Systematic studies addressing symptoms, signs and temporal aspects of initial bipolar prodrome are reviewed to identify potential clinical targets for early intervention.Methods: The databases PsycINFO, PubMed, EMBASE and British Nursing Index were searched for original studies.Results: Eight studies were identified. Irritability and aggressiveness, sleep disturbances, depression and mania symptoms/signs, hyperactivity, anxiety, and mood swings are clusters representing common symptoms and signs of the distal prodrome of bipolar disorder (BD). As time to full BD onset decreases, symptoms of mania and depression seem to increase gradually in strength and prevalence. The specificity of prodromal symptoms and signs appears to be low. Not every person who develops BD experiences a prolonged initial prodrome to the full illness. Current data on the mean duration of the prodrome are contradictory, ranging from 1.8 to 7.3years. No qualitative studies were found.Limitations: Because of the scarcity of data, studies that did not explicitly investigate bipolar prodrome were included when thematically relevant. The selected studies are methodologically diverse and the validity of some findings is questionable. Findings must be interpreted cautiously.Conclusions: The initial prodrome of BD is characterized by dysregulation of mood and energy. Because of the apparently low specificity of prodromal symptoms and signs of BD, it is currently neither possible nor advisable to predict the development of BD based solely on early phenomenology. More well-designed in-depth studies, including qualitative ones, are needed to characterize the initial bipolar prodrome.

Genetic and environmental influences on psychiatric comorbidity: A systematic review

M. Cerdá, A. Sagdeo, J. Johnson, S. Galea — 2010-10-01

Abstract: Background: The purpose of this review is to systematically appraise the peer-reviewed literature about the genetic and environmental determinants of psychiatric comorbidity, focusing on four of the most prevalent types of psychopathology: anxiety disorders, depression, conduct disorder and substance abuse.Methods: We summarize existing empirical research on the relative contribution that genetic, nonshared and shared environmental factors make to the covariance between disorders, and evidence about specific genes and environmental characteristics that are associated with comorbidity.Results: Ninety-four articles met the inclusion criteria and were assessed. Genetic factors play a particularly strong role in comorbidity between major depression and generalized anxiety disorder or posttraumatic stress disorder, while the non-shared environments make an important contribution to comorbidity in affective disorders. Genetic and non-shared environmental factors also make a moderate-to-strong contribution to the relationship between CD and SA. A range of candidate genes, such as 5HTTLPR, MAOA, and DRD1–DRD4, as well as others implicated in the central nervous system, has been implicated in psychiatric comorbidity. Pivotal social factors include childhood adversity/life events, family and peer social connections, and socioeconomic and academic difficulties.Limitations: Methodological concerns include the use of clinical case–control samples, the focus on a restricted set of individual-level environmental risk factors, and restricted follow-up times.Conclusions: Given the significant mental health burden associated with comorbid disorders, population-based research on modifiable risk factors for psychiatric comorbidity is vital for the design of effective preventive and clinical interventions.

Electroconvulsive therapy-induced persistent retrograde amnesia: Could it be minimised by ketamine or other pharmacological approaches?

Emily M. Gregory-Roberts, Sharon L. Naismith, Karen M. Cullen, Ian B. Hickie — 2010-10-01

Abstract: Background: Certain pharmacological agents administered during electroconvulsive therapy may have the potential to prevent persistent retrograde amnesia induced during electroconvulsive therapy. This review examines mechanisms for electroconvulsive therapy-induced retrograde amnesia, and evaluates the suitability of the anaesthetic ketamine for preventing this amnestic outcome.Methods: A review of human studies, animal models and theoretical models in light of memory dysfunction following electroconvulsive therapy was conducted. MEDLINE was searched from 1950 to April 2009 using the MeSH terms “electroconvulsive therapy”, “memory”, “memory short term”, “memory disorders”, “excitatory amino acid antagonists”, and “ketamine”. PREMEDLINE was searched using the terms “electroconvulsive therapy”, “amnesia” and “ketamine”. Additional keyword and reference list searches were performed. No language, date constraints or article type constraints were used.Results: Disruption of long term potentiation as a mechanism for electroconvulsive therapy-induced retrograde amnesia is well supported. Based on this putative mechanism, an N-methyl-D-aspartate receptor antagonist would appear suitable for preventing the retrograde amnesia. Available evidence in animals and humans supports the prediction that ketamine, an anaesthetic agent and N-methyl-D-aspartate receptor antagonist, could effectively prevent electroconvulsive therapy-induced persistent retrograde amnesia. Whilst there are concerns about the use of ketamine with electroconvulsive therapy, such as possible psychotomimetic effects, on balance this anaesthetic agent may improve or hasten clinical response to electroconvulsive therapy.Conclusions: A clinical trial is warranted to determine if ketamine anaesthesia during electroconvulsive therapy can lessen persistent retrograde amnesia and improve therapeutic response. Electroconvulsive therapy with ketamine anaesthesia may provide effective antidepressant action with minimal side effects.

A factor analysis of different temperament domains in a border region in rural Southern California

2010-10-01

Abstract: Background: Temperament has been described as an oligogenic model that confers attributes to individuals in their daily functioning. Understanding of these temperaments can help understanding psychiatric status and therapeutic needs of a patient population. As the Latino population grows providers need to become more familiar with their psychiatric status.Objective: To describe how the characteristics of different temperament domains in a community vs a private practice clinic of patients being treated for a mood disorder.Methodology: Retrospective record review was conducted in 117 patients with mood disorders who received the Temperament Scale (TEMPS). Forty nine were from a community clinic (CM) and 68 from a private practice (PP).Results: The following temperament domains were found. In PP: depressed 17/69 (25%); cyclothymic 18/69 (26%); hyperthymic 16/69 (23%); anxious 14/68 (20%); irritable 4/69 (5%). Among CM: depressed 10/49 (20%); cyclothymic 14/49 (28%); hyperthymic 8/49 (16%); anxious 15/49 (30%); irritable 2/49 (5%). Using factor analysis to determine the significant domains among clinics, cyclothima (0.82) and irritability (0.81) were the most relevant, regardless of psychosocial background and language differences.Limitations: Cross-sectional retrospective study without longitudinal follow up.Conclusion: This study elucidates how temperament domains could be considered a valuable tool in evaluating patients in mood disorders clinic. The tool elucidates valuable characteristics that could be applied for guidance in diagnosis and treatment without being biased by different socio-cultural background or language differences. The factor analysis helps elucidate the pertinence of TEMPS scores that may not be the focus of clinical intervention although they contribute significantly to the structure of an individual's temperament, specifically emotional labiality (i.e., cyclothima and irritability).

Emotional and affective temperament in 23 professional areas

A. Schmidt, R.S. Rodrigues, C.C. Pipa, L.N. Brandalise, T.M. Lorenzi, D.R. Lara — 2010-10-01

Abstract: Background: Preliminary data has shown temperament differences in workers of a few professions, particularly in artists.Methods: 3805 subjects (75.5% female, mean 32.4±9.8years) of 23 broad professional areas answered a web-survey with the Combined Emotional and Affective Temperament Scale (CEATS).Results: Educational level was correlated with drive and control, was lower in depressives and apathetics and higher in euthymics and hyperthymics. Fear was lower in administration and communications and higher in computing and office workers. Drive was lower in those unemployed and at home and higher in fitness and administration. Control was lower in arts and higher in teaching and health caring. Anger was lower in subjects in the areas of teaching and health caring and higher in human studies and unemployed. For affective temperament scores: depressive was lower in fitness and higher in human studies; anxious and apathetic scores were lower in fitness and higher in unemployed subjects; cyclothymic was lower in health caring and higher in unemployed; euthymic score was lower in human studies and higher in fitness; irritable was lower in religion and higher in unemployed; labile was lower in health caring and higher in unemployed; disinhibited was lower in engineering and higher in communications and arts; hyperthymic was lower in human studies and high in fitness.Limitation: Convenience sample by the internet and most subjects assessed the instruments through a psychoeducational website for bipolar spectrum disorders, which may have biased the absolute scores of emotional temperaments.Conclusions: Professional areas and educational level are associated with distinct emotional and affective profiles.

Psychotic versus non-psychotic bipolar II disorder

2010-10-01

Abstract: Introduction: Psychotic symptoms in bipolar II disorder, allowed by definition only during a depressive episode, are present in a range between 3% and 45%. Little is known regarding the impact of psychotic symptoms on the clinical course of bipolar II patients. Findings from previous reports are controversial and focused specifically on bipolar I disorder. The aim of this study was to ascertain the clinical characteristics of individuals with bipolar II disorder with and without lifetime history of psychotic symptoms.Methods: The sample consisted of 164 DSM-IV Bipolar II patients consecutively recruited from the Barcelona Bipolar Disorder Program. Patients were divided in Bipolar II patients with (N=32) and without (N=132) lifetime history of psychotic symptoms. Clinical and sociodemographic features were compared.Results: Thirty-two out of 164 patients with bipolar II disorder had a history of psychosis during depression (19.5%). Bipolar II patients with a history of psychotic symptoms showed a higher number of hospitalizations than patients without such a history (p<0.001). They were also older but were less likely to have a family history of bipolar illness and any mental disorder than non-psychotic bipolar II patients. Melancholic and catatonic features were significantly more frequent in psychotic bipolar II patients (p<0.001).Conclusions: Our findings confirm that the presence of psychotic symptoms in bipolar II disorder is not rare. Psychotic bipolar II disorder may be a different phenotype from non-psychotic bipolar disorder.

Postpartum bipolar episodes are not distinct from spontaneous episodes: Implications for DSM-V

2010-10-01

Abstract: Introduction: DSM course modifiers should be based on enough evidence on his impact in the clinical prognosis of patients presenting with a certain clinical feature. The presence of postpartum onset of a mood episode in bipolar disorders has not been sufficiently studied. This is the first prospective clinical study comparing female bipolar patients with and without lifetime history of postpartum mood episode.Methods: Systematic prospective follow-up (12years) of 200 female bipolar I or II patients with or without history of postpartum episodes. Postpartum mood episode was defined according to DSM-IV criteria. Patients with and without postpartum onset of a mood episode were compared regarding clinical and sociodemographic variables.Results: Lifetime history of postpartum episode was present in 43 patients and absent in 137 patients. Twenty patients were excluded from the study because lack of agreement of the two independent psychiatrist. Both groups showed almost no differences regarding clinical features, functioning or severity.Limitations: The present study does not take account of potential factors that may influence the outcome of a postpartum episode, including obstetric complications and social support before delivery. Similarly, dimensional and qualitative aspects of bipolar disorder were not included in our analysis.Conclusion: The role of postpartum onset as a DSM course modifier should be reconsidered, as it seems to have no impact on prognosis or functioning.

Bipolar disorder with frequent mood episodes in the New Zealand Mental Health Survey

J. Elisabeth Wells, Magnus A. McGee, Kate M. Scott, Mark A. Oakley Browne — 2010-10-01

Abstract: Background: Rapid cycling bipolar disorder has been studied almost exclusively in clinical samples.Methods: A national cross-sectional survey in 2003–2004 in New Zealand used the Composite International Diagnostic Interview (CIDI 3.0). Diagnosis was by DSM-IV. Depression severity was assessed with the Quick Inventory of Depressive Symptoms (QIDS) and role impairment using Sheehan Scales. Complex survey analyses compared percentages and means, and used logistic regression and discrete-time survival analyses. Frequent mood episodes (FMEs) in the past 12months (4+) were used as an indicator of rapid cycling.Results: The lifetime prevalence of bipolar disorder (I + II) was 1.7%. Twelve-month prevalence was 1.0%: 0.3% with FME and 0.7% with No FME (1–3 episodes). Another 0.7% had no episodes in that period. Age of onset was earliest for FME (16.0years versus 19.5 and 20.1, p<.05). In the past 12months, weeks in episode, total days out of role and role impairment in the worst month were all worse for the FME group (p<.0001) but both the FME and No-FME groups experienced severe and impairing depression. Lifetime suicidal behaviours and comorbidity were high in all three bipolar groups but differed little between them. About three-quarters had ever received treatment but only half with twelve-month disorder made treatment contact.Limitations: Recall, not observation of episodes.Conclusions: Even in the community the burden of bipolar disorder is high. Frequent mood episodes in bipolar disorder are associated with still more disruption of life than less frequent episodes. Treatment is underutilized and could moderate the distress and impairment experienced.

Access to weight loss counseling services among patients with bipolar disorder

2010-10-01

Abstract: Background: Cardiovascular disease is the leading cause of mortality in persons with bipolar disorder but little is known about utilization of services for risk reduction. We assessed determinants of access to weight counseling in a sample of patients with bipolar disorder.Methods: Patients enrolled in the Continuous Improvement for Veterans in Care: Mood Disorders (CIVIC-MD), a prospective study conducted from July 2004–July 2006. Patient data were obtained from a baseline questionnaire and chart review.Results: Out of 298 patients, 73% received some weight counseling, with utilization more likely for those with higher BMI (OR=1.12, p<0.001) or prescribed a second generation antipsychotic (SGA) (OR=1.80, p=0.05). About 41% received 2≥ dietary consultations with consults more likely for those reporting illicit substance use (OR=1.9, p<0.05) or SGA treatment (OR=2.4, p<0.05). In approximately 25% of patients, increased BMI (OR=1.06, p=0.04) and SGA treatment (OR=2.13, p=0.04) were associated with greater likelihood of receiving ≥ 2 exercise consultations. Zero-inflated Poisson regression found SGA treatment was associated with more diet consultations (β=35, p<0.05) while SGA treatment (β=29, p<0.05) and women (β=76, p<0.001) were associated with more exercise consultations. Illicit substance use (β=−0.36, p<0.05), binge drinking (β=32, p<0.05) and other ethnicity (β=−0.57, p<0.05) were associated with fewer exercise consults.Limitations: Single-site study and limited chart detail.Conclusion: The majority of patients received some weight counseling, with obesity and SGA predicting service use over time. However, low utilization patterns underscore the need for research into determinants of long-term counseling utilization to improve patient health outcomes.

How effective is a psychological intervention program for patients with refractory bipolar disorder? A randomized controlled trial

Ana González Isasi, Enrique Echeburúa, José María Limiñana, Ana González-Pinto — 2010-10-01

Abstract: Background: The aim of this research was to evaluate the short-term and long-term efficacy of a combined treatment (pharmacological + psychoeducational and cognitive-behavioral therapy) as compared with a standard pharmacological treatment in patients with refractory bipolar disorder.Method: 40 patients were randomly assigned to one of the following: Experimental group under combined treatment, and Control group under pharmacological treatment. We used an analysis of variance (ANOVA), including one or two factors, with repeated measures at different evaluation times: baseline, post-treatment, 6-month follow-up and 12-month follow-up.Results: We found significant between-group differences at all evaluation times after the treatment. The experimental group showed less hospitalizations than the control group in the 12-month evaluation (p=0.007) as well as lower rates of depression and anxiety in the 6-month valuation (p=0.015; p=0.027) and the 12-month evaluation (p=0.001; p<0.001). Significant differences in relation to mania and inadaptation emerged in the post-treatment evaluation (p=0.004; p<0.001) and were sustained throughout the study (p=0.002, p<0.001; p<0.001, p<0.001). Analysis of within-group differences in the Experimental group showed reduction of mania (p<0.001), depression (p=0.001), anxiety (p=0.003) and inadaptation (p<0.001) throughout the study; while in the Control group, it showed increased numbers of hospitalizations (p=0.016), as well as higher rates of mania (p=0.030), anxiety (p<0.001) and inadaptation (p=0.003).Conclusions: Our results suggest that a combined treatment is effective in patients with refractory bipolar disorder. Suggestions for future research are commented on.

Pre-morbid and outcome correlates of first episode mania with psychosis: Is a distinction between schizoaffective and bipolar I disorder valid in the early phase of psychotic disorders?

2010-10-01

Abstract: Objectives: The validity of schizoaffective disorder (SA) diagnosis has for long been a matter of controversy and its delineation from bipolar I disorders (BD) has often been questioned. However, most studies have been conducted in chronic samples and have therefore been biased towards patients with poorer outcome, which may have hampered the possibility to identify significant differences between both diagnoses.Methods: 108 subjects presenting a first DSM-III-R manic episode with psychotic features were assessed at baseline and 12months after stabilisation on symptoms and functional characteristics, and patients with BD (n=87) were compared with those with SA bipolar subtype (SAB) (n=21).Results: SAB patients had a higher prevalence of first degree relatives with schizophrenia and a lower premorbid functional level. They had a longer prodromal phase, a longer duration of untreated psychosis and remained symptomatic for a longer period. They also had higher levels of positive symptoms in the acute manic phase; however, with two exceptions, the type of psychotic symptoms were similar in both groups. At stabilisation and 12months after stabilisation, SA patients had higher levels of negative symptoms, with poorer functional level at 12months.Conclusions: These data suggest SA is a valid diagnosis in the early phase of psychotic disorders considering it defines a subgroup of first episode psychotic mania patients with distinct characteristics compared to BD. While a dimensional approach to diagnosis may be more adapted to this phase of illness, SA disorder offers, in the context of categorical classifications, a useful intermediate category that reflects a clinical reality.

The educational patterning of health-related adversities in individuals with major depression

2010-10-01

Abstract: Background: Major depressive disorder and depression severity are socially patterned, disfavouring individuals from lower socioeconomic groups. Depressive disorders are associated with several adverse health-related outcomes. We examined the educational patterning of somatic health, lifestyles, psychological function and treatment modalities in individuals suffering from major depressive disorder.Methods: We used cross-sectional medical and psychiatric data from 992 participants of The Netherlands Study of Depression and Anxiety (NESDA) with a diagnosed current major depressive disorder. Associations of education with somatic, lifestyle-related, and psychological outcomes, and with treatment modalities, adjusted for depression severity, were examined by means of (multinomial and binary) logistic and linear regression analyses.Results: In addition to and independent of major depressions being more severe in the less educated patients, metabolic syndrome, current smoking, low alcohol consumption, hopelessness and low control were more prevalent in a group of less educated individuals suffering from major depression, compared with their more highly educated peers. The less educated persons were more likely to be treated with antidepressant medication and less likely to receive psychotherapy treatment. None of these observations were explained by a higher depression severity in the less educated group.Limitations: The cross-sectional design does not allow us to make direct causal inferences regarding the mutual influences of the different health-related outcomes.Conclusions: Further research should explore the necessity and feasibility of routine screening for additional health risk, particularly among less educated depressed individuals.

The specificity of childhood adversities and negative life events across the life span to anxiety and depressive disorders

2010-10-01

Abstract: Background: Although several studies have shown that life adversities play an important role in the etiology and maintenance of both depressive and anxiety disorders, little is known about the relative specificity of several types of life adversities to different forms of depressive and anxiety disorder and the concurrent role of neuroticism. Few studies have investigated whether clustering of life adversities or comorbidity of psychiatric disorders critically influence these relationships.Methods: Using data from the Netherlands Study of Depression and Anxiety (NESDA), we analyzed the association of childhood adversities and negative life experiences across the lifespan with lifetime DSM-IV-based diagnoses of depression or anxiety among 2288 participants with at least one affective disorder.Results: Controlling for comorbidity and clustering of adversities the association of childhood adversity with affective disorders was greater than that of negative life events across the life span with affective disorders. Among childhood adversities, emotional neglect was specifically associated with depressive disorder, dysthymia, and social phobia. Persons with a history of emotional neglect and sexual abuse were more likely to develop more than one lifetime affective disorder. Neuroticism and current affective disorder did not affect the adversity–disorder relationships found.Limitations: Using a retrospective study design, causal interpretations of the relationships found are not warranted.Conclusions: Emotional neglect seems to be differentially related to depression, dysthymia and social phobia. This knowledge may help to reduce underestimation of the impact of emotional abuse and lead to better recognition and treatment to prevent long-term disorders.

Regional brain metabolic correlates of self-reported depression severity contrasted with clinician ratings

2010-10-01

Abstract: Background: We compared brain-map correlations of relative cerebral glucose metabolism (rCMRglu) with psychopathologic factors derived from the self-rated Beck Depression Inventory (BDI) and factors from the clinician-rated Hamilton Depression Rating Scale (HDRS) factors, seeking an anatomic basis for differences in self and clinician ratings.Methods: [18F]-FDG Positron Emission Tomography generated rCMRglu, SPM-estimated, voxel-level, brain correlation maps with BDI factor scores and HDRS factor scores in medication-free major depressive disorder.Results: Regional brain correlates of BDI are more extensive than HDRS, even when adjusting for variance accounted for by the HDRS. Factors comprising the BDI were associated with distinct cortical and subcortical regions. The degree of overlap in factor correlation brain maps is explained by the variance shared by BDI and HDRS factor scores.Conclusion: Self and clinician-rated aspects of depression have common and distinct neuroanatomic correlates that reflect correlations between rating scales, but correlations between glucose metabolism and self-rated depression were anatomically more extensive in this sample. Findings highlight the importance and biological underpinnings of these subjective features of major depression.

Evidence for the 2008 economic crisis exacerbating depression in Hong Kong

2010-10-01

Abstract: Background: There is a lack of population-level research on the relationship between economic contraction and specific mental disorders and how individual-level variables may mediate such a relationship.Methods: Two cross-sectional surveys using identical random sampling and diagnostic methods were conducted among Hong Kong adults in 2007 (January–February) and 2009 (April–May). 3016 and 2011 Chinese speaking adults completed structured interviews based on the criteria of Diagnostic and Statistical Manual of Mental Disorders (4th edition) (DSM-IV).Results: The twelve-month prevalence of DSM-IV major depressive episode (MDE) was significantly higher in 2009 (12.5%) than 2007 (8.5%). A significant increase of prevalence was found in both male and female respondents, those in the highest (55–65years) age group, having secondary education level, were married/cohabited, divorced/widowed, employed, home-making, and in the lowest and high-middle income groups. Those with large investment loss had a significantly higher prevalence of MDE (20.3%) than those with less or no-investment loss (9.2–13.7%). The symptom pattern and severity of depression in 2007 and 2009 were similar.Conclusion: Economic contraction triggered by a global financial crisis was associated with a significant increase in the risk of depression in the Hong Kong population. This increase was not explained primarily by unemployment and had a significant contribution from employed, home-making, high-middle income, and having married people. A holistic perspective that encompasses both ecological and individual levels of analysis is essential for studying the net impact of economic contraction on depression across communities and sociodemographic groups and for health policy planning.

Contribution of adenosine related genes to the risk of depression with disturbed sleep

2010-10-01

Abstract: Background: Most patients with major depression report problems in their sleep: insomnia, early morning awakenings and fatigue correlating with poor sleep quality. One of the key substances regulating sleep is adenosine. We hypothesized that variations in polymorphic sites of adenosine related genes may predispose to depression with sleep disturbances.Methods: We selected 117 single nucleotide polymorphisms from 13 genes and analyzed their association with depression and specific sleep problems (early morning awakenings and fatigue). Data were collected as part of the Health 2000 Study based on Finnish population and included 1423 adult subjects.Results: Our major finding herein was, among women, the association of SLC29A3 polymorphism rs12256138 with depressive disorder (p=0.0004, odds ratio=0.68, 95% CI 0.55–0.84, p<0.05 after Bonferonni correction for multiple testing). Only one gene showing any evidence for association was common to women and men (ADA).Limitations: Relatively small size of the case samples.Conclusions: Our results suggest that compromised adenosine transport due to variation in nucleoside transporter gene SLC29A3 in women, could predispose to depression, and could suggest new directions in treatment research. The shortage of overlapping genes between the genders indicates that the genetics of mood regulation may vary between the sexes.

Measures of temperament and character are differentially impacted on by depression severity

2010-10-01

Abstract: Background: Cloninger's Temperament and Character Inventory (TCI) is a widely used measure of personality. Two scales of the TCI, harm avoidance (HA) and self directedness (SD), have been shown to be influenced by depressed mood. We examined how the seven TCI scales and their subscales are correlated with depression severity before and after treatment. We also examined whether changes in personality measures could be attributed to changes in depression severity.Methods: Two clinical samples of depressed out-patients were recruited for trials to examine predictors of treatment response to antidepressants (N=195) and psychotherapies (N=177). Assessment included the Montgomery–Asberg depression rating scales (MADRS), Hopkins Symptom Checklist (SCL-90) and TCI at baseline and after treatment.Results: After treatment, in both samples, depression severity correlated significantly with HA and negatively with SD. Multiple regression analysis revealed that changes in SD and HA over treatment were related to improvement in depression. In the psychotherapy trial baseline MADRS scores correlated with low SD and high HA.Limitations: The trial results are applicable to mild-moderately depressed out-patients.Conclusions: Depression severity influences the total scales and most of the subscale measures of HA and SD. Some personality traits, as measured by the TCI, were not impacted upon by mood. Clinically mood should be taken into account when assessing personality measures of negative affect using the TCI.

Negative intrusive memories in depression: The role of maladaptive appraisals and safety behaviours

Jill M. Newby, Michelle L. Moulds — 2010-10-01

Abstract: Background: Evidence from non-clinical studies suggests that both negative appraisals of intrusive memories and the use of safety behaviours to manage these memories play a role in depression. This study extended this research by exploring its generalisability to a clinically depressed sample.Methods: 85 participants (25 depressed, 30 recovered depressed, 30 never-depressed) were administered the SCID-I/NP (First et al., 1996), mood measures, and self-report questionnaires that indexed intrusive memory frequency and avoidance, appraisals and strategies used to manage the memories.Results: Depressed participants endorsed higher ratings of negative appraisals of intrusive memories than the never-depressed group, with the recovered group reporting intermediate ratings across most appraisal themes. Depressed individuals reported more safety behaviours and passive strategies in response to their memories than the other two groups.Limitations: The cross-sectional design of this study prevents conclusions regarding the causal role of both appraisals and safety behaviours.Conclusions: These results highlight the importance of negative appraisals, safety behaviours and passive strategies that are used to manage intrusive memories in depression, and provide further support for the proposal that psychological interventions for depression could usefully incorporate components that aim to reduce intrusions and associated maintaining variables.

Concordance between telephone survey classification and face-to-face interview diagnosis of one-year major depressive episode in Hong Kong

Sing Lee, Adley Tsang, Arthur Mak, Athene Lee, Lisa Lau, K.L. Ng — 2010-10-01

Abstract: Background: Community-based telephone surveys of depression have generated reliable findings but their concordance with standardized clinical diagnostic interviews is uncommonly examined, especially in non-western populations.Method: 106 consenting participants from a previous telephone-based population survey of major depressive episode (MDE) using a structured questionnaire were re-assessed face-to-face by clinical interviewers using the Structured Clinical Interview for DSM-IV Axis I Disorder (SCID-I). Receiver operating characteristic and other predictive indicators were used to investigate the concordance between the telephone survey instrument and SCID interview.Result: The telephone survey instrument adequately classified MDE when the DSM-IV symptom number standard was fulfilled at moderate to severe levels of distress and impairment. It performed best when the cut-off was set at a severe level of distress or impairment in any one of four domains of functioning (AUC=0.76). Feeling useless, fatigue, loss of motivation and difficulty in concentration were the most prominent items for increasing the certainty of SCID-MDE diagnosis.Conclusion: Classification of MDE by telephone-based structured interview of MDE exhibited generally good agreement with face-to-face clinical interview diagnosis in the Chinese population of Hong Kong. Further research on the telephone-based methodology should address inter-rater reliability, specificity of diagnosis, and variability of concordance across different mental disorder diagnoses and criteria of clinically significant impairment.

Altered expression of circadian rhythm genes among individuals with a history of depression

2010-10-01

Abstract: Background: Depression has been associated with several circadian rhythm perturbations, suggesting a disruption of the circadian clock system in affective disorders. The interaction of several circadian clock genes generates these daily circadian rhythms.Methods: This cross-sectional study evaluated whether circadian gene expression differed between individuals with a history of depression and participants without a similar history. The participants were 60 healthy older adults. Half of the participants had a history of depression. Real-time quantitative polymerase chain reaction was used to measure the circadian gene Clock, BMAL1, Period1, and Period2 messenger RNA levels in peripheral blood leukocytes.Results: Individuals with a history of depression had higher Clock, Period1, and Bmal1 mRNA levels, compared to non-depressed participants.Limitations: Although circadian gene expression fluctuates throughout the day, clock gene mRNA levels were evaluated only in the morning.Conclusions: These results suggest that disruptions of the molecular mechanisms underlying the circadian clock system may be associated with depression.

SIRT1 gene is associated with major depressive disorder in the Japanese population

2010-10-01

Abstract: Background: Many studies including our previous ones as to PROKR2 and CLOCK have suggested that circadian genes may be involved in the mechanisms of mood disorders and their treatment responses. Also several recent investigations have reported that SIRT1 plays an important role in the circadian system as conventional circadian clock genes, and also have some relation to dopaminergic metabolism. So we considered the SIRT1 gene to be a good candidate gene for the pathophysiology for MDD and SSRI responses in MDD, and conducted a case–control study using four tagging SNPs (450 MDD patients, including 261 patients treated by SSRIs and 766 controls).Method: The MDD patients in this study had scores of 12 or higher on the 17 items of the Structured Interview Guide for Hamilton Rating Scale for Depression (SIGH-D). We defined a clinical response as a decrease of more than 50% in baseline SIGH-D within 8weeks, and clinical remission as an SIGH-D score of less than 7 at 8weeks. Marker-trait association analysis was used to evaluate allele and genotype association with the chi-square test, and haplotype association analysis was evaluated with a likelihood ratio test.Result: We found an association between rs10997875 in SIRT1 gene and MDD in the allele/genotype analysis. In addition, this significance of these associations survived Bonferroni correction. However, we did not find any association between SIRT1 gene and SSRI therapeutic response in MDD in the allele/genotype analysis or haplotype analysis.Limitations: A replication study using larger samples may be required for conclusive results, since our sample size was small.Conclusions: Our results suggest that rs10997875 in SIRT1 gene may play a role in the pathophysiology of MDD in the Japanese population.

Predictors of outcome in a multi-component treatment program for chronic fatigue syndrome

2010-10-01

Abstract: Background: Little is known about factors predicting treatment outcome in chronic fatigue syndrome (CFS).Methods: Based on cognitive–behavioral model of perpetuating factors in CFS, the predictive value of the following patient characteristics were examined in a sample of 178 CFS patients who followed a multi-component treatment program: (1) somatic attributions, (2) psychological attributions, (3) sense of control over symptoms, (4) physical activity, (5) functional impairment, (6) somatic focus, and (7) severity of depression.Results: Only pre-treatment severity of depression was associated with negative treatment outcome defined in terms of post-treatment fatigue and improvement in fatigue.Limitations: The study was conducted at a tertiary care centre and did not include a control group or a long-term follow-up.Conclusions: Level of depression may be the most important factor of the cognitive–behavioral model predicting post-treatment fatigue in CFS. Hence, findings suggest that treatment of CFS should include a focus on severity of depression.

The associations between health risk behaviors and suicidal ideation and attempts in an urban Chinese sample of adolescents

Wang Juan, Deng Xiao-Juan, Wang Jia-Ji, Wang Xin-Wang, Xu Liang — 2010-10-01

Abstract: Background: To investigate the prevalence of suicidal ideation and attempts among adolescents in Guangzhou, China, and to explore the associations between health risk behaviors and suicidal behaviors.Methods: A two-stage stratified cluster sample design produced a representative sample of 12–19-year-old students who attended public middle schools in Guangzhou. Prevalence estimates and standard errors (SEs) of suicidal ideation and attempts were calculated using SUDAAN statistical software. Logistic regression was used to examine the associations between health risk behaviors and suicidal behaviors.Results: Overall, 17.25% of students reported suicidal ideation, and 3.04% reported suicidal attempts during the past 12months. Almost all investigated health risk behaviors were significantly associated with suicidal ideation and attempts among adolescent females and males. In adjusted logistic regression analyses, physical fight was associated with suicidal attempts (adjusted odds ratio (AOR)=4.358; 95% confidence interval (CI)=1.080, 17.589), but not with suicidal ideation for females. Considering themselves overweight (AOR=1.257; 95%CI=1.082, 1.610) and current smoking (AOR=1.708; 95%CI=1.134, 4.605) were associated with suicidal ideation, but not with suicidal attempts for females. Among adolescent males, sad/hopeless (AOR=2.280; 95%CI=1.615, 3.219), current drinking (AOR=1.904; 95%CI=1.269, 2.857), and participating in vigorous physical activities ≥3times/week (AOR=0.639; 95%CI=0.477, 0.854) were associated with suicidal ideation, but not with suicidal attempts. Ever having had sexual intercourse was associated with suicidal attempts (AOR=2.588; 95%CI=1.125, 5.952), but not with suicidal ideation for males.Conclusions: The associations of health risk behaviors with suicidal ideation and attempts varied by gender, and the correlates of suicidal ideation and suicidal attempts were different.

P50 suppression, prepulse inhibition, and startle reactivity in the same patient cohort suffering from posttraumatic stress disorder

2010-10-01

Abstract: Background: Psychophysiological alterations like impaired gating and increased startle have been reported in patients with posttraumatic stress disorder (PTSD). However, findings are inconsistent, and potential relationships to symptomatology remain unclear.Aims: The present study investigates two distinct operational measures of gating and startle reactivity within the same patients suffering from PTSD and their relationship to PTSD symptomatology.Methods: Prepulse inhibition of the acoustic evoked startle reflex, P50 suppression of auditory event related potentials, and startle reactivity were assessed in three distinct experiments in 27 PTSD patients and compared to 25 healthy control subjects.Results: PTSD patients exhibited impaired P50 suppression and exaggerated startle. Lower P50 suppression was associated with higher levels of general psychopathology. Patients and control subjects did not differ in PPI.Limitations: Some of the limitations include, that the control group compromised of non-trauma exposure subjects and menstrual cycle in female participants potentially affecting PPI was not controlled.Conclusions: Deficient P50 gating, not related to specific trauma or distinct symptom clusters reflects a robust finding in PTSD patients. In contrast, further research is needed to clarify whether PPI is affected in PTSD.

Long-term follow-up of patients with obsessive–compulsive disorder treated by anterior capsulotomy: A neuropsychological study

K. Csigó, A. Harsányi, Gy. Demeter, Cs. Rajkai, A. Németh, M. Racsmány — 2010-10-01

Abstract: Background: For treatment-refractory Obsessive–Compulsive-Disorder (OCD) patients, anterior capsulotomy is a potential therapy. We investigated what kinds of cognitive deficits treatment-refractory patients have and how anterior capsulotomy modifies their clinical and cognitive profiles.Methods: Ten treatment-refractory OCD patients were examined in two groups (operated and non-operated) with 5 participants in each group, matched for symptom severity, gender, age and education. The operated group was treated with anterior capsulotomy; the non-operated group was treated only with pharmaco- and psychotherapy. The Yale–Brown Obsessive–Compulsive Rating Scale (Y-BOCS) was used to measure OCD symptoms, and ten neuropsychological tests were used to measure cognitive functioning.Results: In the operated group, the score of Y-BOCS score significantly decreased during the two-year follow-up period. Additionally, we found a significant increase in neuropsychological test scores on the Wechsler Intelligence Test (MAWI), California Sorting Test Part A (CST-A), Stroop Test Interference Score (STR-I), Verbal Fluency Test and Iowa Gambling Test. As a negative result, we observed intrusion errors in the Category Fluency Test. In the non-operated group significant improvement was found in Y-BOCS scores. At follow-up, we found significant differences between the operated and non-operated groups on three neuropsychological tests: Trail Making Test Part B, Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Attention Index and RBANS Language Index, with better performance in the non-operated group.Conclusions: Both treatment methods (i.e. anterior capsulotomy and pharmaco- and psychotherapy) seem effective in reducing OCD symptoms and cognitive deficits, but, importantly, to different degrees. The clinical and neuropsychological improvements were more impressive in the operated group.

Readmission: A useful indicator of the quality of inpatient psychiatric care

Shannon L. Byrne, Geoffrey R. Hooke, Andrew C. Page — 2010-10-01

Abstract: Background: The literature is unclear regarding the relationship between hospital outcome (i.e., symptom improvement during a hospital admission) and readmission, questioning the validity of readmission as an indicator of the quality of the previous hospitalization. Thus, the present aim was to examine if hospital outcome is a predictor of readmission and identify the factors that may mask any effects.Methods: A naturalistic historical study compared the predictors of readmission over the 30days, 6months and 5years following discharge for first-ever admitted inpatients with depression (n=478) to all inpatients regardless of prior hospitalisations and current diagnoses (n=1177).Results: Hospital outcome, as indicated by changes from admission to discharge in scores on symptom measures, during both first-ever admissions and admissions which are not the first, predicted readmissions over all time periods for all patients, not only those with depression. However, this finding was only significant when hospital outcome was assessed by improvements on a patient-reported symptom measure, and not a clinician-rated measure.Limitations: The sample included inpatients treated at a private psychiatric hospital and therefore it is unknown if these findings can be generalised to patients treated in a public system.Conclusions: These findings support that readmission may be a useful indicator of the quality of the previous hospitalization.

Selective breeding for dominant and submissive behavior in Sabra mice

2010-10-01

Abstract: Background: The Dominant–Submissive Relationship (DSR) model used here was developed for mood stabilizing and antidepressant drug testing. Treatment of submissive animals with known antidepressants significantly reduced submissive behavior in a dose-dependent manner. We hypothesized that if submissive behavior in DSR is a valid model of depression, it should be possible to show a genetic predisposition for this trait, since clinical studies support a genetic component for depression.Methods: To test this hypothesis, we applied selective breeding on outbred Sabra mice based on DSR paradigm.Results: Here we have demonstrated that the frequency of DSR formation gradually increased across four generations of outbred Sabra mice, when animals inbred for the dominant trait were paired with those inbred for the submissive trait. Chronic imipramine administration (10mg/kg) significantly reduced submissive behavior in the F2 generation consistent with the effect seen in unselected C57BL/6J mice.Conclusions: We conclude that increased frequency of DSR formation suggest a genetic component of these two phenotypes, and strengthens the predictive and face validity of the DSR test. Selective breeding may aid in a better understanding of the genetic basis of dominant and submissive behavior, important elements in the etiology of affective disorders.

Serotonin transporter and BDNF genetic variants interact to predict cognitive reactivity in healthy adults

Tony T. Wells, Christopher G. Beevers, John E. McGeary — 2010-10-01

Abstract: Background: Cognitive theory and empirical evidence both suggest that cognitive reactivity (the tendency to think more negatively when in a sad mood) is an important marker of depression vulnerability. Research has not yet determined whether genetic factors contribute to the expression of cognitive reactivity.Methods: The present study examined associations between the 5-HTTLPR polymorphism of the SLC6A4 gene, the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene, and cognitive reactivity in a never depressed, unmedicated, young adult sample (N=151).Results: The interaction between 5-HTTLPR and Val66Met polymorphisms significantly predicted change in dysfunctional thinking from before to after a standardized sad mood provocation. Cognitive reactivity increased among S/LG 5-HTTLPR homozygotes if they were also homozygous for the Val Val66Met allele. In contrast, presence of a Met Val66Met allele was associated with attenuated cognitive reactivity among S/LG 5-HTTLPR homozygotes.Limitations: The sample size of the current study is relatively small for modern genetic association studies. However, results are consistent with previous research demonstrating biological epistasis between SLC6A4 and BDNF for predicting connectivity among neural structures involved in emotion regulation.Conclusions: The BDNF Met allele may protect S/LG 5-HTTLPR homozygotes from increased dysfunctional thinking following a sad mood provocation. Study results are the first to demonstrate an epistatic genetic relationship predicting cognitive reactivity and suggest the need for more complex and integrative models of depression vulnerability.

Posttraumatic growth in Veterans of Operations Enduring Freedom and Iraqi Freedom

2010-10-01

Abstract: Objective: A growing body of research has examined the prevalence and correlates of psychopathology, mild traumatic brain injury, and related problems in Veterans of Operations Enduring Freedom and Iraqi Freedom (OEF-OIF). While these studies help characterize the deleterious effects of combat, no known study has examined factors that may enhance posttraumatic growth or positive changes experienced as a result of combat in this population.Method: A total of 272 predominantly older Reservist/National Guard OEF-OIF Veterans completed an anonymous mail survey that assessed combat exposure, psychopathology, psychosocial functioning, social support, and posttraumatic growth.Results: Seventy-two percent of the sample endorsed a significant degree of posttraumatic growth in at least one of the areas assessed, the most common of which were changing priorities about what is important in life (52.2%), being able to better appreciate each day (51.1%), and being better able to handle difficulties (48.5%). Hierarchical regression analysis revealed that younger age, greater posttraumatic stress disorder (PTSD) symptoms, and increased perceptions of unit member support and effort/perseverance were significantly associated with posttraumatic growth. Respondents with PTSD scored higher on an overall measure of posttraumatic growth and on items reflecting appreciation of life and personal strength.Limitations: This study is limited by a relatively low survey return rate and employment of an abbreviated measure of posttraumatic growth.Conclusions: Results of this study suggest that interventions to bolster unit member support and to enhance perceptions of effort and perseverance may help promote posttraumatic growth in OEF-OIF Veterans.

The effects of Brief Behavioral Activation Therapy for Depression on cognitive control in affective contexts: An fMRI investigation

Gabriel S. Dichter, Jennifer N. Felder, Moria J. Smoski — 2010-10-01

Abstract: Background: Unipolar major depressive disorder (MDD) is characterized by impaired cognitive control in affective contexts, but the potential for psychotherapy to affect the neural correlates of these functions has not been evaluated.Method: Twelve adults with and 15 adults without MDD participated in two identical functional magnetic resonance imaging (fMRI) scans that utilized a task requiring cognitive control in both sad and neutral contexts. Between scans, MDD outpatients received Behavioral Activation Therapy for Depression, a psychotherapy modality designed to increase engagement with positive stimuli and reduce avoidance behaviors.Results: Seventy-five percent of adults with MDD were treatment responders, achieving post-treatment Hamilton Rating Scale for Depression score of six or below. Consistent with predictions, psychotherapy resulted in decreased activation in response to cognitive control stimuli presented within a sad context in prefrontal structures, including the paracingulate gyrus, the right orbital frontal cortex, and the right frontal pole. Furthermore, the magnitude of pretreatment activation in the paracingulate gyrus cluster responsive to psychotherapy predicted the magnitude of depressive symptom change after psychotherapy.Limitations: Replication with larger samples is needed, as are follow-up studies that involve placebo control groups, wait-list control groups, and alternative forms of antidepressant intervention.Conclusions: Behavioral Activation Therapy for Depression improves depressive symptoms and concomitantly influences brain systems mediating cognitive control in affective contexts.

ICD-10 or DSM-IV? Anhedonia, fatigue and depressed mood as screening symptoms for diagnosing a current depressive episode in physically ill patients in general hospital

2010-10-01

Abstract: Objective: To explore the usefulness of “anhedonia”, “fatigue” and “depressed mood” as screening symptoms for predicting a depressive episode in physically ill patients.Method: 290 patients filled in a modified version of the Patient Questionnaire and were subsequently assessed by psychiatrists with the Composite International Diagnostic Interview (CIDI; ICD-10 version).Results: 63 patients suffered from a current depressive episode according to the CIDI. If at least two of the three symptoms were used for screening positively (ICD-10 algorithm), the sensitivity was 93.2% and the specificity 72.7%, while the simpler algorithm of DSM-IV – requiring depressed mood or anhedonia to be present – yielded a slightly higher sensitivity (95.2%) and a slightly lower specificity (66.5%). One in five patients with a depressive episode did not report “depressed mood”.Limitation: It remains unclear how relevant the three core symptoms of depression are for the diagnosis of an ICD-10 depression in people who are not physically ill.Conclusion: The fact that both diagnostic algorithms yielded comparable results suggests that the more parsimonious DSM-IV algorithm is preferable and “fatigue” could be left out as a screening symptom. Since “depressed mood” was absent in a substantial proportion of patients, special attention has to be paid to “anhedonia”. Medical students and non-psychiatric clinicians should be especially trained to ask for anhedonia, so that cases of depression will not be overlooked.

Manic symptoms in patients with depressive and/or anxiety disorders

Belinda van den Berg, Brenda W.J.H. Penninx, Frans G. Zitman, Willem A. Nolen — 2010-10-01

Abstract: Background: Previous studies found that patients with depressive disorders frequently have lifetime manic symptoms or even an unrecognized bipolar disorder and that these patients have more severe illness. In this study we investigated whether the presence of significant manic symptoms among patients presenting with depressive and/or anxiety disorders is associated with more severe illness, more comorbidity, more suicidality and more atypical symptoms.Methods: In a large cohort (n=2012) of persons with lifetime depressive and/or anxiety disorders (as confirmed with the Composite International Diagnostic interview (CIDI)) we used the 15-item Mood Disorder Questionnaire (MDQ) to assess the presence of lifetime manic symptoms. Patients with clinically recognized bipolar disorders were excluded from the study.Results: Lifetime manic symptoms were present among 6.3% of the persons with depressive or anxiety disorders. Persons with lifetime manic symptoms more frequently had comorbid social phobia, generalized anxiety disorder and alcohol dependence, more frequently reported previous serious suicide attempts and their current depressive symptoms were more severe. Atypical depression symptoms were not more prevalent in persons with lifetime manic symptoms.Limitations: The presence of a lifetime manic or hypomanic episode was not assessed with the CIDI.Conclusions: Identifying lifetime manic symptoms with the MDQ in persons presenting with (unipolar) depressive or anxiety disorders, can not only help the recognition of actual bipolar disorder (as described in previous studies), but also the identification of a subgroup of patients with more severe symptomatology, more comorbid anxiety and alcohol dependence disorders, and more suicidality.

Influence of age on the efficacy of electroconvulsive therapy in major depression: A retrospective study

2010-10-01

Abstract: Background: Several variables have been studied as possible predictors for the efficacy of ECT, results from the few studies assessing the influence of age on the efficacy of ECT were inconsistent. In older patients suffering from severe depression, ECT is often the treatment of choice, therefore, investigating the influence of age on ECT response is considered relevant.Method: At two depression units, 141 patients meeting DSM-IV criteria for major depression and scores of at least 18 on the 17-item Hamilton Rating Scale for Depression (HAM-D) were treated with bilateral ECT, twice weekly. Clinical evaluation of depressive symptoms was performed each week; scores on the HAM-D were obtained 1–3days prior to ECT and 1–3days after termination of the ECT course. The primary outcome criterion was defined a priori as the mean change on the HAM-D score. The influence of age on mean change on the HAM-D score was analyzed with multiple linear regression analysis, adjusted for three covariables: center, duration of the index episode and presence of psychotic features.Results: Age as a continuous variable had no significant effect on the efficacy of ECT as measured by mean change on the HAM-D score (SE 0.057, p=0.84).Limitations: The disproportionate distribution of patients among the three age groups appears to be the major limitation of the present study.Conclusion: This study suggests that the efficacy of ECT in elderly depressed patients is at least equal to that in younger depressed patients.

Exercise-induced release of cytokines in patients with major depressive disorder

2010-10-01

Abstract: Background: Patients with major depressive disorder (MDD) may display elevated plasma levels of pro-inflammatory substances. Although the underlying mechanisms are unknown, inflammation has been proposed to play a direct role in the generation of depressive symptoms. Skeletal muscle is a potent producer of cytokines, and physical exercise has been suggested to alleviate symptoms of depression. In this study we therefore addressed the question of whether MDD patients display altered levels of pro-, anti-inflammatory and regulatory factors in the blood in response to acute exercise.Methods: Eighteen MDD patients and 18 healthy controls performed a maximal-workload exercise challenge. Blood samples were taken before the test, at sub-maximal and maximal workload, as well as 30 and 60min after testing. The plasma levels of SAA, TNF-α, S-VCAM, S-ICAM, CRP, IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 and IL-13 were assayed using multiplex sandwich ELISA.Results: Exercise-induced significant changes in the plasma levels of inflammatory substances in both MDD patients and controls. IL-8, IL-6 and TNF-α increased, and IL-4 decreased during the challenge in both groups. In addition, IFN-γ decreased in the controls. There was a significant difference in IL-6 reactivity between the groups at the sub-max timepoint.Limitations: Group sizes are comparably limited.Conclusion: Exercise induces changes in the blood levels of cytokines in unmedicated MDD patients. Whether these changes affect symptoms of depression should be evaluated in long-term studies of the anti-depressive effects of exercise.

Risk factors of treatment resistance in major depression: Association with bipolarity

2010-10-01

Abstract: Background: An undiagnosed and therefore inadequately treated bipolarity may be an important cause of drug resistance in depression diagnosed as unipolar. The study aimed to detect clinical and demographic characteristics, with a special interest in bipolarity features which could be risk factors for treatment resistance in unipolar depression.Method: One-thousand and fifty-one patients recruited from 150 outpatient psychiatric clinics and fulfilling DSM-IV criteria for major depressive episodes, single or recurrent, were studied. Among them, 569 patients with treatment-resistant depression (TR) were compared with 482 patients with non-treatment-resistant depression (NTR). All patients were assessed using the structured demographic and clinical data interviews, Mood Disorder Questionnaire (MDQ) and Hypomania Checklist (HCL-32).Results: Independent risk factors of treatment resistance were: scoring 6 or higher on MDQ, scoring 14 or higher in HCL-32, age at first onset ≤20years, more than three previous depressive episodes, and lack of remission or partial remission after the previous depressive episode.Limitation: A retrospective assessment of treatment resistance.Conclusions: Bipolarity features as assessed by MDQ and HCL-32 were identified as significant factors of treatment resistance. Some other clinical variables connected with treatment resistance may be also be associated with bipolarity features.

Subregional hippocampal deformations in major depressive disorder

2010-10-01

Abstract: Background: Hippocampal atrophy is a well reported feature of major depressive disorder, although the evidence has been mixed. The present study sought to examine hippocampal volume and subregional morphology in patients with major depressive disorder, who were all medication-free and in an acute depressive episode of moderate severity.Methods: Structural magnetic resonance imaging scans were acquired in 37 patients (mean age 42years) and 37 age, gender and IQ-matched healthy individuals. Hippocampal volume and subregional structural differences were measured by manual tracings and identification of homologous surface points to the central core of each hippocampus.Results: Both right (P=0.001) and left (P=0.005) hippocampal volumes were reduced in patients relative to healthy controls (n=37 patients and n=37 controls), while only the right hippocampus (P=0.016) showed a reduced volume in a subgroup of first-episode depression patients (n=13) relative to healthy controls. Shape analysis localised the subregional deformations to the subiculum and CA1 subfield extending into the CA2-3 subfields predominantly in the tail regions in the right (P=0.017) and left (P=0.011) hippocampi.Limitations: As all patients were in an acute depressive episode, effects associated with depressive state cannot be distinguished from trait effects.Conclusions: Subregional hippocampal deficits are present early in the course of major depression. The deformations may reflect structural correlates underlying functional memory impairments and distinguish depression from other psychiatric disorders.

Actions that young people can take to prevent depression, anxiety and psychosis: Beliefs of health professionals and young people

Anthony F. Jorm, Amy J. Morgan, Annemarie Wright — 2010-10-01

Abstract: Background: Members of the public know about actions they can take to prevent major physical diseases, but there has been less attention to the public's capacity to take action to prevent mental disorders. Since mental disorders often have first onset during youth, young people's beliefs about prevention are of particular relevance.Methods: Young people's prevention beliefs were assessed by a national telephone survey of 3746 Australian youth aged 12–25years. To allow a comparison with professional beliefs, postal surveys were carried out with 470 GPs, 591 psychiatrists, 736 psychologists and 522 mental health nurses. Respondents were asked to rate the helpfulness of 9 potential strategies in relation to the prevention of four disorders: depression, depression with alcohol misuse, social phobia and psychosis.Results: Both young people and professionals believed that mental disorders could be prevented by physical activity, keeping contact with family and friends, avoiding use of substances, and making time for relaxing activities. However, professionals disagreed with young people about the benefits of avoiding stressful situations, particularly for social phobia. Professionals were also less optimistic about the prevention of psychosis than depression and anxiety.Limitations: The surveys assessed beliefs, but not actual use of preventive strategies.Conclusions: Given the beliefs of young people and professionals that prevention is possible, there is fertile ground for health promotion in this area. However, young people need to be aware that avoiding stressful situations may not be helpful for anxiety.

Eicosapentaenoic acid as an add-on to antidepressant medication for co-morbid major depression in patients with diabetes mellitus: A randomized, double-blind placebo-controlled study

2010-10-01

Abstract: Background: Depression is common in individuals with diabetes. The present study is the first randomized controlled trial to test the efficacy of ω-3 ethyl-eicosapentaenoic acid (E-EPA) as adjuvant to antidepressant medication in the treatment of depression in adults with diabetes mellitus.Methods: In the VU University Medical Center, we conducted a 12-week, placebo-controlled, double-blind, parallel-group intervention study of E-EPA (1g/day) versus placebo in 25 diabetes patients meeting DSM-IV criteria for major depressive disorder, who were already using antidepressant medication. The primary outcome was severity of depressive symptoms, assessed by the Montgomery Åsberg Depression Rating Scale (MADRS) at baseline and 12-week follow-up at two-weekly intervals. Blood samples were collected at baseline and at 12-week follow-up to determine EPA levels in erythrocyte membranes. Data were analyzed with ANOVA for repeated measures.Results: Thirteen participants were randomly assigned to E-EPA; 12 participants were given placebo. At 12-week follow-up, erythrocyte membranes from patients receiving E-EPA contained tripled levels of EPA, while no changes were noted in participants receiving placebo. In both groups, depressive symptoms significantly decreased over time (F=21.14, p<0.001), yet no significant differences were found between those treated with E-EPA versus placebo (F=1.63, p=0.17).Limitations: Although having sufficient study power, this study had a relatively small sample size. Small effects could not be detected, and dose-dependent effects could not be studied.Conclusions: No evidence was found for the efficacy of adding E-EPA to antidepressants in reducing depressive symptoms in diabetic patients with co-morbid depression.

Impact of emotion on cognition in trauma survivors: What is the role of posttraumatic stress disorder?

2010-10-01

Abstract: Background: Cognitive theories of anxiety disorders postulate an increased attentional bias to environmental cues associated with threat that underlies the exaggerated fear response. The role of trauma, which may represent strong competitive advantage for attention, remains unclear. We investigated the influence of trauma exposure and the presence of anxiety/stress disorders on the impact of emotional distractors on cognitive performance.Methods: Fourteen trauma-exposed subjects with PTSD, 12 trauma-exposed subjects with anxiety disorders other than PTSD, 12 trauma-exposed healthy subjects and 19 non-trauma-exposed healthy controls participated in this study. The impact of emotion on cognition was determined by the Affective Stroop task that measures the effect of irrelevant emotional distractors on the speed of operant responding.Results: The speed of cognitive performance was significantly reduced in the presence of negative distractors versus neutral or positive distractors in subjects with PTSD, while there was no significant influence of the distractor type on performance in the other diagnostic groups (diagnosis-by-distractor type interaction, p<0.001). While negative distractors induced the same levels of anxiety and depersonalization in subjects with PTSD and subjects with other anxiety disorders, distractor-induced depersonalization was associated with slowing of cognitive performance in PTSD (p=0.02) but not in other groups.Limitations: Different types of anxiety disorders in the non-PTSD group might reduce the selectivity of the results; some subjects received medication possibly impacting on their cognitive functioning.Conclusions: The cognitive impairments in the presence of negative distractors specifically found in PTSD call for research into novel psychotherapeutic approaches, e.g. attentional training, for PTSD.

Benzodiazepine and cyclopyrrolone reduction in general practice — Does this lead to concomitant change in the use of antipsychotics? A study based on a Danish population

Viggo Rask Kragh Jørgensen — 2010-10-01

Abstract: Introduction: In the period 2004–2006, 15 doctors in the Danish municipality of Lemvig introduced a more restrictive approach to the prescription of benzodiazepines and cyclopyrrolones. A prescription could be renewed only following personal consultation, and prescriptions were issued for only a single month's usage. The intervention reduced the prescription of benzodiazepine anxiolytics by 50%, cyclopyrrolones by 57% and benzodiazepine hypnotics by 55% over a 1½ year period. There is a paucity of knowledge about whether such an intervention reduces drug consumption in general or merely shifts consumption to other drugs. Here especially antipsychotics (AP) are in the spotlight.Materials and methods: The current article describes the prescription of antipsychotics before and after the intervention. Consumption was followed via the Danish Medicines Agency's website Ordiprax, where the quantity of pharmacy-sold prescription drugs by individual medical practices can be monitored.Results: The overall increase in the prescription of antipsychotics during the intervention described here was not more than 3.1% of the reduction in prescriptions of benzodiazepine and cyclopyrrolone measured in defined daily doses (DDD).Conclusion: The intervention against benzodiazepine and cyclopyrrolone did not result in an uncontrollable increase in the prescription of antipsychotic drugs. It cannot be excluded that the intervention impacted individual prescriptions. For future interventions of a similar nature, it is recommended that GPs are trained in the use of antipsychotics.

Dissimilar morbidity following initial mania versus mixed-states in type-I bipolar disorder

Ross J. Baldessarini, Paola Salvatore, Hari-Mandir Kaur Khalsa, Mauricio Tohen — 2010-10-01

Abstract: Background: Mixed-states of bipolar disorders (BPD) may predict worse future illness and more depressive than manic morbidity, challenging a tendency to conflate mixed-states and mania.Methods: Patients (N=247) were followed-up systematically for 24months following hospitalization for initial major episodes of DSM-IV type-I BPD and scored for weekly interval morbidity-types.Results: Overall morbidity during follow-up was 1.6-times greater following mixed (n=97) versus manic (n=150) first-episodes of BPD (60.0 vs. 37.8%-of-weeks; p<0.0001). Patients with initial mixed-states had a nearly 12-fold later excess of mixed-states, 6.5-times more major depression, and 69% more dysthymia during follow-up than those presenting in mania. In contrast, manic first-episodes were followed by over 10-times more mania, 6-times more hypomania, and 35% more psychotic illness.Limitations: Estimates of longitudinal morbidity may be inaccurate, and ongoing treatment may distort them.Conclusions: Based on detailed, prospective assessments among first-episode BPD patients, those presenting in mixed-states were more ill, and much more likely to experience mixed, depressive and dysthymic morbidity during follow-up, versus much more mania, hypomania, and perhaps more psychosis following mania. The findings support two markedly dissimilar subtypes of BPD, and call for more explicit therapeutic studies of mixed-states.

Selective deficits in erythrocyte docosahexaenoic acid composition in adult patients with bipolar disorder and major depressive disorder

2010-10-01

Abstract: Background: Epidemiological and controlled intervention trials suggest that omega-3 (n-3) fatty acid deficiency represents a reversible risk factor for recurrent affective disorders. However, there is limited comparative information available regarding the n-3 fatty acid status and associated mood symptoms in medication-free patients with major depressive disorder (MDD) and bipolar disorder (BD).Methods: The fatty acid composition of erythrocyte membranes from adult male and female healthy controls (n=20) and medication-free patients with MDD (n=20) and BD (n=20) was determined by gas chromatography. Associations with depression and mania symptom severity scores were investigated.Results: After correction for multiple comparisons, both MDD (−20%) and BD (−32%) patients exhibited significantly lower erythrocyte docosahexaenoic acid (DHA, 22:6n-3) composition relative to healthy controls, and there was a trend for lower DHA in BD patients relative to MDD patients (−15%, p=0.09). There were no gender differences for DHA in any group. Other n-3 fatty acids, including eicosapentaenoic acid (EPA, 20:5n-3) and docosapentanoic acid (22:5n-3), and n-6 fatty acids, including arachidonic acid (AA, 20:4n-6), were not different. Erythrocyte DHA composition was inversely correlated with indices of delta-9 desaturase activity (18:1/18:0), and associated elevations in oleic acid (18:1n-9) composition, and delta-6 desaturase activity (20:3/18:2). DHA composition was not significantly correlated with depression or mania symptom severity scores.Limitations: Data regarding diet and life style factors (cigarette smoking) were not available to evaluate their contribution to the present findings.Conclusions: Male and female patients with MDD and BD exhibit selective erythrocyte DHA deficits relative to healthy controls, and this deficit was numerically greater in BD patients. Selective DHA deficits are consistent with impaired peroxisome function, which has implications for n-3 fatty acid interventions aimed at preventing or reversing this deficit.

A genome-wide association study of bipolar disorder in Norwegian individuals, followed by replication in Icelandic sample

2010-10-01

Abstract: Background: In the present study we investigated genetic variants associated with bipolar disorder in a homogenous Norwegian sample, and potential genetic overlap with schizophrenia, using the Affymetrix 6.0 array.Methods: We carried out a genome-wide association study (GWAS) by genotyping 620 390 single-nucleotide polymorphisms (SNPs) in a case-control sample of Norwegian origin (the TOP study) including bipolar disorder (n=194), healthy controls (n=336) and schizophrenia (n=230), followed by replication and combined analysis in a genetically concordant Icelandic sample of bipolar disorder (n=435), and healthy controls (n=10,258).Results: We selected 1000 markers with the lowest P values in the TOP discovery GWAS and tested these (or their surrogates) for association in the Icelandic replication sample. Polymorphisms on 35 loci were confirmed associated with bipolar disorder (nominal P value<0.05; not corrected for multiple testing) in the replication sample. The most significant markers were located in DLEU2, GUCY1B2, PKIA, CCL2, CNTNAP5, DPP10, and FBN1. The combined group of schizophrenia and bipolar disorder compared to controls did not provide additional significant findings.Limitations: Relatively small number of samples.Conclusions: We detected weak but reproducible association with markers in several genes, in proximity to susceptibility loci found in previous GWAS studies of bipolar disorder. Further work is required to study their localization, expression, and regulation and international meta-analytic efforts will help to further elucidate their role.

Affective temperament and personal identity

Giovanni Stanghellini, René Rosfort — 2010-10-01

Abstract: The complex relationship between temperament and personal identity, and between these and mental disorders, is of critical interest to both philosophy and psychopathology. More than other living creatures, human beings are constituted and characterized by the interplay of their genotype and phenotype. There appears to be an explanatory gap between the almost perfect genetic identity and the individual differences among humans. One reason for this gap is that a human being is a person besides a physiological organism. We propose an outline of a theoretical model that might somewhat mitigate the explanatory discrepancies between physiological mechanisms and individual human emotional experience and behaviour. Arguing for the pervasive nature of human affectivity, i.e., for the assumption that human consciousness and behaviour is characterised by being permeated by affectivity; to envisage the dynamics of emotional experience, we make use of a three-levelled model of human personal identity that differentiates between factors that are simultaneously at work in the constitution of the individual human person: 1) core emotions, 2) affective temperament types/affective character traits, and 3) personhood. These levels are investigated separately in order to respect the methodological diversity among them (neuroscience, psychopathology, and philosophy), but they are eventually brought together in a hermeneutical account of human personhood.

An fMRI study on mental pain and suicidal behavior

2010-10-01

Abstract: Background: Suicide is a poorly understood phenomenon. A clinical model of suicide conceptualizes suicidal behavior as a solution to an unbearable state of mind, experienced as mental pain.Methods: In order to investigate the neural correlates of suicidal behavior, we used fMRI during presentation of autobiographical scripts extracted from personal narratives reactivating patients' memories of a recent episode of attempted suicide. Brain activation was measured during three recalled conditions: mental pain, suicide action, and neutral activity.Results: Recall of suicidal episodes, that is, mental pain plus suicide action, compared to neutral activity, was associated with deactivation in the prefrontal cortex (BA 6, 10, and 46). Recall of suicide action, however, compared to mental pain, was associated with increased activity in the medial prefrontal cortex, the anterior cingulate cortex, and the hippocampus.Limitations: This is a pilot study with eight female subjects.Conclusions: Clinical and fMRI data suggest that mental pain triggering suicidal behavior may have the quality of traumatic stress, associated with decreased prefrontal activity. Planning and acting out suicidal impulses in response to mental pain, however, is associated with increased activity in the frontal cortex, suggesting that goal-directed suicidal behavior is associated with a reduction of mental pain.

Effect of treatment on serum glial cell line-derived neurotrophic factor in bipolar patients

2010-10-01

Abstract: Objective: Post-mortem studies have demonstrated various glial deficits in different brain areas of patients diagnosed with bipolar disorder (BD). Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic factor from the transforming growth factor β family which has been implicated in the pathophysiology of BD. This study aimed to determine whether GDNF in serum was abnormal in BD, and how it responded to drug treatment of BD.Method: Serum GDNF concentrations were measured in BD patients before treatment, after 8weeks of drug treatment, and in control subjects using a sandwich ELISA method.Results: Before treatment, serum GDNF was significantly lower in BD patients during both manic (P<0.001) and depressive (P<0.001) episodes than in control subjects. From baseline to remission after 8weeks of treatment, the increase in serum GDNF was statistically significant (P<0.001).Conclusions: The present study suggests that lower GDNF levels might be involved in the pathophysiology of BD and drug treatment increases the GDNF in BD.

Low dose lignocaine added to propofol does not attenuate the response to electroconvulsive therapy

2010-10-01

Abstract: Background: The addition of small amounts of lignocaine (50mg) to propofol (200mg) has been previously shown to reduce pain in injection, a common problem with this particular anaesthetic agent. The aim of this study was to investigate whether using the mixture of propofol plus lignocaine had any adverse effects on ECT seizure expression (duration, and ictal quality).Method: Ictal EEG records were retrospectively examined in 29 patients who underwent 80 pairs of ECT treatments, one given with propofol alone and one with propofol plus lignocaine. Ictal quality was manually rated for the transition from the polyspike phase to the slow wave phase, amplitude of the mid-ictal spike-and-wave phase, regularity of morphology of the predominant pattern of the slow wave phase, stereotypy, variability of the morphology and amplitude of the slow wave phase and post-ictal suppression.Results: There was no significant difference in seizure duration between the two groups (33.4±13.0s (propofol) vs. 33.6±11.2s (propofol plus lignocaine). Furthermore although the addition of lignocaine delayed the onset of the slow wave phase by about 1s, it resulted in an improvement in three of four of the other measures of ictal quality.Conclusion: The addition of a small dose of lignocaine to propofol during ECT treatment enhanced rather than reduced the quality of the seizures produced.