Journal of Affective Disorders

Medial prefrontal cortex and the self in major depression

2012-01-01

Abstract: Self-focus (i.e. the process by which one engages oneself in self-referential processing) is a core issue in the psychopathology of major depression. The cortical midline structures, including the medial prefrontal cortex (MPFC), play a key role in self-referential processing in healthy subjects. Four functional magnetic resonance imaging studies recently found either an increased or a decreased MPFC activation during self-referential processing in depressed patients compared to healthy controls. Building on critical differences in experimental settings, we argue that these conflicting results are indeed consistent with two modes of elevated MPFC activation in major depression. An elevated tonic ventral MPFC activation, as uncovered by an event-related design, may embody automatic aspects of depressive self-focus, such as attracting attention to self-relevant incoming information. An elevated phasic dorsal MPFC activation, as uncovered by a block-based design, may embody more strategic aspects of depressive self-focus, such as comparing the self with inner standards. Additionally, strategic self-focus in depression may recruit the anterior cingulate cortex and more lateral regions of the prefrontal cortex. An aberrant functional connectivity of the dorsal MPFC may underlie this lack of reciprocal inhibition between the cognitive control network and the default mode network. Altogether, these results suggest that self-focus in depression may emerge as a process competing for brain resources due to a lack of inhibition of the default mode network, resulting in detrimental effects on externally-oriented cognitive processes. Follow-up studies are warranted to determine the trait vs. state nature of these biomarkers and their ability to predict treatment outcome.

Bipolarity and inadequate response to antidepressant drugs: Clinical and psychopharmacological perspective

Janusz K. Rybakowski — 2012-01-01

Abstract: Objectives: The reason why depression may respond poorly to treatment with antidepressant drugs may be connected with the features of bipolarity. Evidence to this effect has accumulated in recent studies of various kinds of depression in mood disorders. Additional evidence for such a connection may be the efficacy of mood-stabilizing drugs in the augmentation of antidepressants in treatment-resistant depression.Methods: This review is based on clinical and psychopharmacological research performed over the past five years. The clinical investigation was based on the response to antidepressants of bipolar depression or to symptoms of hypomania, assessed mainly by the Mood Disorder Questionnaire (MDQ) and the Hypomania Checklist-32 (HCL-32). The psychopharmacological research tested the efficacy of augmentation of antidepressants in treatment-resistant depression by mood-stabilizing drugs of the 1st and 2nd generations.Results: A number of studies have pointed to an association between bipolar depression, or symptoms of hypomania and an inadequate response to antidepressants. Such a connection was also found in the Polish TRES-DEP study which included 1051 depressed patients. Pharmacological studies have demonstrated the efficacy of first generation mood-stabilizing drugs (lithium, carbamazepine) and second generation drugs (quetiapine, olanzapine, risperidone, ziprasidone, lamotrigine) for augmentation of antidepressants in treatment-resistant depression. Some evidence has been presented that mixed depressive episodes may also belong to this category.Conclusions: The results of these clinical and psychopharmacological studies appear to confirm an association between bipolarity and a poor response of depression to treatment with antidepressant drugs.

Pharmacogenomics of antidepressant induced mania: A review and meta-analysis of the serotonin transporter gene (5HTTLPR) association

2012-01-01

Abstract: Background: Antidepressants can trigger a rapid mood switch from depression to mania. Identifying genetic risk factors associated with antidepressant induced mania (AIM) may enable individualized treatment strategies for bipolar depression. This review and meta-analysis evaluates the evidence for association between the serotonin transporter gene promoter polymorphism (5HTTLPR) and AIM.Methods: Medline up to November 2009 was searched for key words bipolar, antidepressant, serotonin transporter, SLC6A4, switch, and mania.Results: Five studies have evaluated the SLC6A4 promoter polymorphism and AIM in adults (total N=340 AIM+ cases, N=543 AIM− controls). Although a random effects meta-analysis showed weak evidence of association of the S allele with AIM+ status, a test of heterogeneity indicated significant differences in estimated genetic effects between studies. A similar weak association was observed in a meta-analysis based on a subset of three studies that excluded patients on mood stabilizers; however the result was again not statistically significant.Limitations: Few pharmacogenomic studies of antidepressant treatment of bipolar disorder have been published. The completed studies were underpowered and often lacked important phenotypic information regarding potential confounders such as concurrent use of mood stabilizers or rapid cycling.Conclusions: There is insufficient published data to confirm an association between 5HTTLPR and antidepressant induced mania. Pharmacogenomic studies of antidepressant induced mania have high potential clinical impact provided future studies are of adequate sample size and include rigorously assessed patient characteristics (e.g. ancestry, rapid cycling, concurrent mood stabilization, and length of antidepressant exposure).

The efficacy of zinc supplementation in depression: Systematic review of randomised controlled trials

Jun Lai, Annette Moxey, Gabriel Nowak, Khanrin Vashum, Kylie Bailey, Mark McEvoy — 2012-01-01

Abstract: Background: Depression is a significant public health problem. Pre-clinical studies suggest a potential role of zinc in reducing or preventing depressive symptoms. Many epidemiological studies have examined the association of low zinc status with depression; however, clinical trials on the effect of zinc supplementation in depression are limited. This review aimed to synthesise results from all published randomised controlled trials on the efficacy of zinc supplementation for reducing or preventing depressive symptoms.Methods: Six databases were searched over all years of records until March 2011. All randomised controlled trials with a comparison group, that examined zinc supplementation as the intervention and depressive symptoms as the primary outcome were included. Pairs of reviewers extracted key information of study characteristics and outcomes, and assessed the quality of each study.Results: Four randomised controlled trials met inclusion criteria. In studies that examined the effects of zinc supplementation as an adjunct to antidepressants drug treatment, zinc significantly lowered depressive symptom scores of depressed patients. There is less clear evidence on the effectiveness of zinc supplementation alone on depressive symptoms of non-depressed healthy subjects. The overall study quality was rated ‘moderate’.Limitations: There are limited trials examining the effects of zinc supplementation on depressive symptoms. An overall pooled estimate of effect for all included studies could not be calculated and evidence was difficult to summarise because of substantial heterogeneity.Conclusion: Evidence suggests potential benefits of zinc supplementation as a stand-alone intervention or as an adjunct to conventional antidepressant drug therapy for depression. However, there are methodological limitations in existing studies and so further well-designed, adequately powered research is required.

The influence of affective temperaments and psychopathological traits on the definition of bipolar disorder subtypes: A study on Bipolar I Italian National sample

2012-01-01

Abstract: Affective temperament and psychopathological traits such as separation anxiety (SA) and interpersonal sensitivity (IPS) are supposed to impact on the clinical manifestation and on the course of Bipolar Disorder (BD); in the present study we investigated their influence on the definition of BD subtypes.Method:: Among 106 BD-I patients with DSM-IV depressive, manic or mixed episode included in a multi-centric Italian study and treated according to the routine clinical practice, 89 (84.0%) were in remission after a follow-up period ranging from 3 to 6months (Clinical Global Impression-BP [CGI-BP] <2). Remitting patients underwent a comprehensive evaluation including self-report questionnaires such as the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-A) scale, Separation Anxiety Symptom Inventory (SASI), Interpersonal Sensitivity Measure (IPSM) and the Semi-structured interview for Mood Disorder (SIMD-R) administered by experienced clinicians. Correlation and factorial analyses were conducted on temperamental and psychopathological measures. Comparative analyses were conducted on different temperamental subtypes based on the TEMPS-A, SASI and IPSM profile.Results:: Depressive, cyclothymic and irritable TEMPS-A score and SASI and IPSM total scores were positively and statistically correlated with each other. On the contrary, hyperthymic temperament score was negatively correlated with depressive temperament and not significantly correlated with the other temperamental and psychopathological dimensions. The factorial analysis of the TEMPS-A subscales and SASI and IPSM total scores allowed the extraction of 2 factors: the cyclothymic-sensitive (explaining 46% of the variance) that included, as positive components, depressive, cyclothymic, irritable temperaments and SASI and IPSM scores; the hyperthymic (explaining the 19% of the variance) included hyperthymic temperament as the only positive component and depressive temperament and IPSM, as negative components. Dominant cyclothymic-sensitive patients (n=49) were more frequently females and reported higher number of depressive, hypomanic and suicide attempts when compared to the dominant hyperthymic patients (n=40). On the contrary, these latter showed a higher number of manic episodes and hospitalizations than cyclothymic-sensitive patients. The rates of first-degree family history for both mood and anxiety disorders were higher in cyclothymic-sensitive than in hyperthymic patients. Cyclothymic sensitive patients also reported more axis I lifetime co-morbidities with Panic Disorder/Agoraphobia and Social Anxiety Disorder in comparison with hyperthymics. As concerns axis II co-morbidity the cyclothymic-sensitive patients met more frequently DSM-IV criteria 1, 5 and 7 for borderline personality disorder than the hyperthymics. On the contrary, antisocial personality disorder was more represented among hyperthymic than cyclothymic patients, in particular for DSM-IV criteria 1 and 6.Limitation:: No blind evaluation and uncertain validity of personality inventory.Conclusion:: Our results support the view that affective temperaments influence the clinical features of BD in terms of both clinical and course characteristics, family history and axis I and II co-morbidities. Hypothetical temperamental subtypes as measured by TEMPS-A presented important interrelationships that permit to reliably isolate two fundamental temperamental disposition: the first characterized by rapid fluctuations of mood and emotional instability, and the second by hyperactivity, high level of energy and emotional intensity. Dominant cyclothymic and hyperthymic bipolar I patients reported important differences in terms of gender distribution, number and polarity of previous episodes, hospitalizations, suicidality, rates of co-morbid anxiety and personality traits and disorders. Our data are consistent with the hypothesis that affective temperaments, and in particular cyclothymia, could be utilized as quantitative, intermediate phenotypes in order to identify BD susceptibility genes.

Evaluation of the efficacy and safety of paliperidone extended-release in the treatment of acute mania: A randomized, double-blind, dose-response study

Joris Berwaerts, Haiyan Xu, Isaac Nuamah, Pilar Lim, David Hough — 2012-01-01

Abstract: Background: Atypical antipsychotics are effective in the treatment of bipolar I disorder. In this 3-week double-blind study, the efficacy and safety of paliperidone extended-release (ER) tablets were assessed in patients with acute mania.Methods: Patients experiencing a manic or mixed episode (Young Mania Rating Scale [YMRS] total score ≥20), were randomly assigned to 1 of 3 fixed doses of once-daily paliperidone ER (3, 6, or 12-mg), or placebo (1:1:1:1 ratio).Results: In total, 469 patients were randomly assigned to treatment with paliperidone ER 3mg (n=112), 6mg (n=120), or 12mg (n=115); or placebo (n=122). Mean (SD) change in YMRS total score from baseline to the 3-week endpoint (primary variable) was statistically significantly different for the paliperidone ER 12mg group (−13.5 [9.17], p=0.025), but not the 6mg (−11.4 [9.98], p=0.57) or 3mg (−9.1 [11.18], p=0.79) groups compared with placebo (−10.1 [10.21]). Headache was the most common treatment-emergent adverse event (17% total paliperidone ER versus 12% placebo).Limitations: A statistically significant (p=0.0032) treatment-by-country interaction occurred, which confounded interpretation of study results. Paliperidone ER and placebo did not differ statistically for the primary efficacy variable among patients from the United States sites (74% of the intent-to-treat analysis set).Conclusions: Paliperidone ER 12mg/day was superior to placebo in the treatment of acute mania. Change from baseline in YMRS total score increased with the dose of paliperidone ER. Paliperidone ER was generally tolerated by patients with bipolar I disorder and no new safety signal was detected.

Two-year outcomes in first-episode psychotic depression: The McLean–Harvard first-episode project

2012-01-01

Abstract: Objective: Early assessment can guide accurate diagnosis, prognosis, and treatment-planning for patients with major mental illnesses. Longitudinal studies in psychotic depression from onset are rare, encouraging the present study.Method: We followed 56 DSM-IV MDD patients with psychotic features prospectively and systematically to assess course and predictors of operationally-defined syndromal remission, syndromal recovery, symptomatic remission, functional recovery, and new episodes, and to evaluate diagnostic stability.Results: Among 49/56 cases followed for ≥2years, 59% retained the initial diagnosis and most achieved syndromal remission (86%) and recovery (84%); 58% remitted symptomatically, and only 35% (17/49) recovered functionally. Syndromal recovery was earlier following subacute onset, lower initial depression scores, and lack of moodincongruent psychotic features. Within 2years, 45% (22/49) experienced new episodes — earlier with younger onset and higher CGI scores. DSM diagnosis changed in 41%, to bipolar (33%), or schizoaffective disorders (12%), which followed early mania-like or schizophrenia-like features, respectively.Conclusions: Within 2years of first-hospitalizations, 41% of patients initially diagnosed with psychotic-depression met criteria for DSM-IV bipolar or schizoaffective disorders. Of the 59% retaining the initial diagnosis for 2years, nearly half experienced new episodes, 42% remained symptomatic, and two-thirds failed to regain their own prior functional status.

Preference of lethal methods is not the only cause for higher suicide rates in males

2012-01-01

Abstract: Background: In most countries worldwide suicide rates are higher for males whereas attempted suicide rates are higher for females. The aim is to investigate if the choice of more lethal methods by males explains gender differences in suicide rates.Methods: Data on completed and attempted suicides were collected (n=3235, Nuremberg and Wuerzburg, years 2000–2004). The research question was analyzed by comparing the method-specific case fatality (= completed suicides/completed+attempted suicides) for males and females.Results: Among the events captured, men chose high-risk methods like hanging significantly more often than women (φ=−0.27; p<0.001). However, except for drowning, case fatalities were higher for males than for females within each method. This was most apparent in “hanging” (men 83.5%, women 55.3%; φ=−0.28; p<0.001) and “poisoning by drugs” (men 7.2%, women 3.4%; φ=−0.09; p<0.001).Limitations: The sample size (n=3235) was not enough for comparing method and gender specific case fatalities with a fine-meshed stratification regarding age.Conclusions: Higher suicide rates in males not only result from the choice of more lethal methods. Other factors have to be considered.

Perfectionism dimensions in major postpartum depression

2012-01-01

Abstract: Background: Although perfectionism from a multidimensional perspective has generally been associated with depressive illness, there are not many studies on its role in major depression in the postnatal period. The aim of the present study was to explore the relationship between perfectionism dimensions using the Frost Multidimensional Perfectionism Scale (FMPS) and major postpartum depression.Methods: One-hundred-twenty-two women with major postpartum depression (SCID-I; DSM-IV) and 115 healthy postpartum women were evaluated using the FMPS, an instrument for the assessment of six perfectionism dimensions: concern over mistakes, personal standards, parental expectations, parental criticism, doubt about actions and organisation. Other variables were also considered: neuroticism, psychiatric history, social support, life events and genotype combinations according to serotonin transporter expression (5-HTTLPR and Stin2 VNTR polymorphisms).Results: The prevalence of high-perfectionism was higher in major postpartum depression group than in control group (34% vs. 11%; p<0.001). Multivariate models confirmed high-perfectionism as an independent factor associated with major postpartum depression. Specifically, the high-concern over mistakes dimension increased over four-fold the odds of major depression in postpartum period. (OR=4.14; 95% CI=1.24–13.81) Neuroticism, personal psychiatric history and 5-HTT low-expressing genotypes at one of the loci were also identified as independent factors.Conclusions: High-perfectionism, and particularly high-concern over mistakes is a personality dimension associated with major postpartum depression. The inclusion of perfectionism assessment, together with others factors, may be considered in order to improve the detection of women at risk of postpartum depression, in whom early intervention may be of benefit.

Type D (distressed) personality is associated with poor quality of life and mental health among 3080 cancer survivors

2012-01-01

Abstract: Background: This study assessed the association between Type D personality (the conjoint effect of negative affectivity and social inhibition) and quality of life (QoL) and mental health of cancer survivors up to 10years post-diagnosis.Methods: All currently alive individuals diagnosed with endometrial or colorectal cancer between 1998 and 2007, or with lymphoma or multiple myeloma between 1999 and 2008 as registered in the Eindhoven Cancer Registry received a questionnaire on Type D personality (DS14), QoL (SF-36 or EORTC-QLQ-C30) and mental health (HADS).Results: Of the 3080 survivors who responded (69%), 572 (19%) had a Type D personality. Type D survivors had clinically meaningful lower levels of general health, social functioning, role-function emotional, mental health and vitality compared to non-Type D's (SF-36: all P's<0.001). They also reported clinically meaningful worse emotional and social functioning, global health status/QoL, and more fatigue (EORTC-QLQ-C30: all P's<0.001). This was also confirmed by multivariate logistic regression analyses showing that cancer survivors with a Type D personality were more likely to experience a decreased QoL on all SF-36 and EORTC-QLQ-C30 scales (all ORs ranging between 1.88 and 5.56). The proportion of survivors reporting an impaired QoL was higher among Type D (35–64%) than non-Type D's (20–36%). Finally, Type D's were more likely to be depressed (44% vs. 13%; P<0.0001) or anxious (51% vs. 14%; P<0.0001).Conclusions: Cancer survivors with a Type D personality are at increased risk of impaired QoL and mental health problems that cannot be explained by socio-demographic or clinical characteristics.

Sociodemographic and psychopathological risk factors in repeated suicide attempts: Gender differences in a prospective study

2012-01-01

Abstract: Background: The prevention of the repetition of suicide attempts is an important feature of the care of attempters but current data fail to give actual predictors of repetition. The aim of this study was to characterize sociodemographic and psychopathological features and risk factors associated with future repetition of suicide attempts in two years. The study focused on differences between men and women.Methods: 273 participants selected in psychiatric emergency units after their admission for a suicide attempt (index) were included in the study. Subsequent suicide attempts occurring within a two year follow-up were identified from the regional observatory of suicide attempts. At inclusion, sociodemographic variables and psychopathological data were collected. In particular, psychometric evaluations were performed using the following scales: BDI-SF, SIS, BIS and BDHI. The lifetime history of suicide attempt was also noted.Results: Repetition of suicide attempt in 2years was associated with current follow up and treatment, a personal history of multiple suicide attempt, post traumatic stress disorder, current recurrent psychotic syndrome and substance misuse. Specific features of men and women repeaters have been identified. Men repeaters were characterized by substance use disorders whereas the re-attempt in women was associated with current follow up and treatment, post traumatic stress disorder and higher BDI-SF score.Conclusions: Repeaters must be considered as a specific population among suicide attempters and gender differences must be taken into account in this particular population in order to promote more personalized prevention programs for suicidal recurrence and completed suicide.

Offspring of parents with recurrent depression: Which features of parent depression index risk for offspring psychopathology?

2012-01-01

Abstract: Background: Parental depression is associated with an increased risk of psychiatric disorder in offspring, although outcomes vary. At present relatively little is known about how differences in episode timing, severity, and course of recurrent depression relate to risk in children. The aim of this study was to consider the offspring of parents with recurrent depression and examine whether a recent episode of parental depression indexes risk for offspring psychopathology over and above these other parental depression features.Methods: Three hundred and thirty seven recurrently depressed parents and their offspring (aged 9–17) were interviewed as part of an ongoing study, the ‘Early Prediction of Adolescent Depression Study’. The Child and Adolescent Psychiatric Assessment was used to assess two child outcomes; presence of a DSM-IV psychiatric disorder and number of DSM-IV child-rated depression symptoms.Results: Children whose parents had experienced a recent episode of depression reported significantly more depression symptoms, and odds of child psychiatric disorder were doubled relative to children whose parents had not experienced a recent episode of depression. Past severity of parental depression was also significantly associated with child depression symptoms.Limitations: Statistical analyses preclude causal conclusions pertaining to parental depression influences on offspring psychopathology; several features of parental depression were recalled retrospectively.Conclusions: This study suggests that particular features of parental depression, specifically past depression severity and presence of a recent episode, may be important indicators of risk for child psychiatric disorder and depressive symptoms.

Impact on prisoners of participating in research interviews related to near-lethal suicide attempts

Adrienne Rivlin, Lisa Marzano, Keith Hawton, Seena Fazel — 2012-01-01

Abstract: Background: Prisoners have a high risk of suicide. Research studies have investigated factors contributing to this, some through interviews with survivors of suicide attempts, others with informants such as family and friends of suicide victims. However, there is little information regarding the effects of participating in such interviews.Aims: To investigate the effects on participants of taking part in detailed interviews about suicidal behaviour and contributory factors.Method: Case–control studies of 120 prisoners who made near-lethal suicide attempts (cases) and 120 prisoners who had never carried out near-lethal suicide attempts in prison (controls) were conducted. Information regarding effects on prisoners of participating in the interviews was collected using quantitative and qualitative methods.Results: For both male cases and controls, and female controls, self-reported mood levels improved significantly by the end of the interviews. For female cases, the interviews had no negative effect on their self-reported mood. Whilst some prisoners found the interviews upsetting, nearly all said they were pleased to have participated.Limitations: The same researchers carried out the interviews and collected data on the effects of participation. Also, several potential participants were excluded from the study and the likely effect of the interview on them is unknown.Conclusions: We found little evidence that participation of prisoners in interview-based research on suicidal behaviour has negative effects on them; indeed, it can be beneficial. Inclusion of similar instruments to measure the effects of research participation in future investigations could provide valuable feedback to researchers and ethics committees.

Screening for depression in a sample of Egyptian secondary school female students

A. El-Missiry, M. Soltan, M. Abdel Hadi, W. Sabry — 2012-01-01

Abstract: Background: Depression is common in female adolescents. Data on prevalence rates, socio-demographic correlates, and putative risk factors in Egyptian population are needed along with better screening tools to inform future research and service development. We aimed to estimate the point prevalence of depression in a representative sample of Egyptian female students; to detect the sensitivity and specificity of CDI as a screening tool, and to highlight some putative risk factors associated with depression.Method: Multistage random selection of 602 female students from public and private secondary schools in Eastern Cairo. All participants were subjected to screening using the Children Depression Inventory (CDI) and the Non-patient version of the Structured Clinical Interview for DSM-IV axis-I disorders.Results: Depression was estimated to be 15.3% by CDI in comparison to 13.3% by SCID-I/NP. The sensitivity and specificity of CDI were 74.8% and 97.6% respectively. Regression Analysis pointed to a number of predictive factors as; academic underachievement, quarrelsome family atmosphere, socioeconomic status, negative life events and family history of psychiatric disorders.Limitations: The cross-sectional design, the lack of collateral information and access to records precluded inference of casualty. The lack of the rural comparator and samples from other governorates limits the generalisation of results.Conclusion: Depression was prevalent in a sample of Egyptian female secondary school students. It correlated with some psychosocial factors and can be effectively screened using CDI. Hence, there is a need for better screening, Psychoeducational programmes, and services for better identification, early intervention and targeting for those at risk.

Principal domains of quantitative anxiety trait in subjects with lifetime history of mania

Javier Contreras, Elizabeth Hare, Michael Escamilla, Henriette Raventos — 2012-01-01

Abstract: Background: High comorbidity rates for anxiety have been documented in subjects with history of mania or hypomania. We explored the presence of latent constructs of quantitative anxiety in subjects who have a history of mania or hypomania.Methods: We conducted an exploratory factor analysis of anxiety trait in 212 subjects who have a lifetime history of at least one manic/hypomanic syndrome. Participants were originally recruited for a Costa Rican sibling pair genetic study of Bipolar Disorder. We used principal factors extraction method with squared multiple correlations (SAS/SAT Professional software) of the STAI (trait subscale).Results: A three-factor solution with a good simple structure and statistical adequacy was obtained with a KMO of 0.84 (>0.6) and Bartlett's Test of Sphericity of 2.4668E-162 (p<0.05). Items were grouped into anxiety-absent factor and the anxiety-present symptoms in two additional factors based on the nature of the symptoms, worry and rumination.Limitations: Comorbid disorders could affect the interaction of anxiety score with manic/hypomanic symptoms. Some statistical parameters (mood status independence, score distribution and correlation between trait score and quantitative mania/hypomania) were not taken into consideration to extract the factors. Because anxiety dimensions were explored on individuals with history of mania or hypomania and not in healthy subjects, comparison of our results with other studies can draw confusing conclusions.Conclusions: Two underlying constructs, worry and rumination may explain anxiety sub-syndromic symptoms in Costa Rican patients with history of mania or hypomania.

Ruminative response in clinical patients with major depressive disorder, bipolar disorder, and anxiety disorders

Sojung Kim, Bum Hee Yu, Dong Soo Lee, Ji-Hae Kim — 2012-01-01

Abstract: Background: There is a growing interest in the transdiagnostic trait of rumination. However, few studies have directly examined the ruminative response in the diagnosis of disorders other than major depression, such as anxiety disorders and bipolar disorders. Even fewer studies have done so in a large, clinical sample.Method: Patients with major depressive disorder (MDD), bipolar disorder (BPD), panic disorder with/without agoraphobia (PD), and generalized anxiety disorder or obsessive–compulsive disorder (GAD/OCD) were compared using the Ruminative Response Scale (RRS), Hamilton Rating Scale for Depression (HAM-D), and Hamilton Rating Scale for Anxiety (HAM-A).Results: The PD group displayed the lowest levels of rumination even when depression and anxiety symptoms were treated as a covariate. The BPD group displayed higher levels of rumination than the MDD group.Conclusions: A heightened ruminative response was not only found among individuals with MDD, but also among those with BPD and GAD/OCD; this might indicate ineffective thought control.

Dysregulated glutamate and dopamine transporters in postmortem frontal cortex from bipolar and schizophrenic patients

2012-01-01

Abstract: Background: Dysregulated glutamate, serotonin and dopamine neurotransmission has been reported in bipolar disorder (BD) and schizophrenia (SZ), but the underlying mechanisms of dysregulation are not clear. We hypothesized that they involve alterations in excitatory amino acid transporters (EAATs), the serotonin reuptake transporter (SERT), and the dopamine reuptake transporter (DAT).Methods: To test this hypothesis, we determined protein and mRNA levels of EAAT subtypes 1–4, of the SERT and of the DAT in postmortem frontal cortex from BD (n=10) and SZ (n=10) patients and from healthy control (n=10) subjects.Results: Compared to control levels, protein and mRNA levels of EAAT1 were increased significantly in cortex from both BD and SZ patients. EAAT2 protein and mRNA levels were decreased significantly in BD but not in SZ cortices. EAAT3 and EAAT 4 protein and mRNA levels were significantly higher in SZ but not in BD compared with control. DAT protein and mRNA levels were decreased significantly in both BD and SZ cortices. There was no significant change in SERT expression in either BD or SZ.Conclusions: The altered EAATs and DAT expression could result in altered glutamatergic and hyperdopaminergic function in BD and SZ. Differently altered EAATs involved in glutamatergic transmission could be therapeutic targets for treating BD and SZ.

The effects of blue-enriched light treatment compared to standard light treatment in seasonal affective disorder

M.C.M. Gordijn, D. 't Mannetje, Y. Meesters — 2012-01-01

Abstract: Background: One of the most frequently investigated hypotheses of the pathophysiology underlying Seasonal Affective Disorder (SAD) is a disturbance of circadian rhythms. Since the circadian system as well as other non-visual effects is especially sensitive to blue light, a new light therapy device with blue enriched polychromatic light was tested for its efficacy to treat SAD.Methods: Within one winter 52 patients were treated in one of three conditions: 30min full spectrum light (9000lx, 5000K), 30min blue-enriched light (9000lx, 17,000K), or 20min blue-enriched light. The study lasted 22days with 10days of morning-light treatment on weekdays during the first 2weeks.Results: Depressive symptoms (SIGH SAD) diminished over the 3-week period in all conditions, with no significant differences between conditions. The percentage responders were high, differing from 75%, 59% and 71% for the standard-LT, 30min blue-enriched-LT, and 20min blue-enriched-LT, respectively.Conclusion: The lack of superiority of high intensity blue-enriched light over standard bright light treatment does not clearly support nor rule out the possibility of an important role for the circadian system or the blue sensitive non-visual image forming system in general, in the pathophysiology of SAD. The lack of a difference between conditions may also be the result of a saturated response to the high light intensities used. Recent data indeed suggest that low intensity blue-enriched light may be as effective as standard bright light treatment. The possibility of improving light therapy for SAD patients by applying light of shorter duration or at lower light intensities is highly relevant for optimizing treatment and will help to clarify the role of the circadian system and/or the non-image forming photoreceptors in SAD pathophysiology.Clinical trial: https://register.clinicaltrials.gov: NCT01048294.

Empirically derived subgroups of bipolar I patients with different comorbidity patterns of anxiety and substance use disorders in Han Chinese population

2012-01-01

Abstract: Objective: Bipolar-I disorder (BPI) often co-occurred with anxiety (ANX) and substance use disorders (SUD), which poses challenges in public health and clinical treatment, and adds complexity in searching for relevant etiologic factors. The present study sought to identify subgroups of BPI patients using comorbidity patterns with ANX and SUD.Methods: Clinical patients (N=306) diagnosed with BPI were recruited and interviewed using the Composite International Diagnostic Interview to collect data on demographics and clinical features, including episodic information, impairments, and lifetime diagnoses of ANX (panic, agoraphobia, generalized anxiety disorder, specific and social phobia) and SUD (nicotine dependence, alcohol use and drug use disorder). We applied latent class analysis to empirically derive classes of BPI. A number of exogenous variables were examined for each class.Results: A three-class model provides excellent discriminability for subgrouping BPI patients with different comorbidity patterns. The BPI-LOW class (83.99%) had more pure mania without most lifetime comorbidity, higher numbers of last year mania episodes, and less suicidality and impairments. The BPI-ANX class (3.60%) was female predominant, tended to comorbid with multiple anxiety disorders but no SUD, and had early onset age. The BPI-SUD class (12.42%) was male predominant, had high prevalence of lifetime SUD and frequent mood episodes in the last year. Both the BPI-ANX and BPI-SUD classes had severe functional impairments and suicidal behaviors.Limitations: Clinical information was retrospectively collected. Besides, we did not comprehensively access lifetime comorbidity for all psychiatric disorders.Conclusion: The three empirically identified subgroups of BPI patients exhibited distinguished comorbidity patterns and clinical features, including suicidal behaviors, frequent mood episodes and functional impairments. Our findings have clinical implication in intervention and treatment as well as to explore their different underlying mechanisms.

Social anxiety in the general population: Introducing abbreviated versions of SIAS and SPS

Nina Kupper, Johan Denollet — 2012-01-01

Abstract: Background: Social anxiety is characterized by the experience of stress, discomfort and fear in social situations, and is associated with substantial personal and societal burden. Two questionnaires exist that assess the aspects of social anxiety, i.e. social interaction anxiety (SIAS) and social phobia (SPS). There is no agreement in literature on the dimensionality of social anxiety. Further, the length of a questionnaire may negatively affect response rates and participation at follow-up occasions.Aim: To explore the structure of social anxiety in the general population, and to examine psychosocial and sociodemographic correlates. Our second aim was to construct abbreviated versions of SIAS and SPS that can be easily used and with minimal burden.Method: A total of 1598 adults from the general Dutch population completed a survey asking information on social anxiety, mood and demographics. Exploratory and confirmatory factor analyses as well as reliability analysis with item-total statistics were performed.Results: Confirmatory factor analysis revealed a 3-factor structure for social phobia, and a 2-factor structure for the SIAS, with the second factor containing both reversely scored items. The abbreviated versions of SPS (11 items) and SIAS (10 items) show excellent discriminant and construct validity (Cronbach's α=.90 and .92), while specificity analysis showed that gender, marital status and educational level (SIAS10: p<.0005; SPS11: p<.0005) are important determinants of social anxiety.Conclusion: In the general population, social interaction anxiety and social phobia are two aspects of a higher-order factor of social anxiety. Social anxiety is validly captured by the short versions of SPS and SIAS, reducing the questionnaire burden for participants in epidemiological and biobehavioral research.

Decreased serotonin content and reduced agonist-induced aggregation in platelets of patients chronically medicated with SSRI drugs

2012-01-01

Abstract: Background: Chronic treatment with selective serotonin reuptake inhibitors (SSRIs) reduces the risk and severity of cardiovascular diseases. SSRIs block the serotonin transporter, thereby inhibiting serotonin (5-HT) uptake into presynaptic neurons as well as into platelets where 5-HT is stored in dense granules. When 5-HT is released in response to agonists it enhances platelet aggregation induced by injury-related signals. Chronic administration of SSRIs may thus reduce platelet aggregability secondary to depletion of platelets' serotonin stores.Methods: The study included ten DSM-IV-TR major depression (MDD) and four obsessive compulsive disorder (OCD) patients and fourteen healthy untreated age- and sex-matched controls. The patients were chronically medicated (6–108months) with various SSRIs. Platelet serotonin content was assessed in fresh samples of platelet rich plasma (PRP) using radioimmunoassay. ADP, collagen, arachidonic acid and epinephrine were used as inducers of platelet aggregation measured in PRP by turbometric method in a microplate reader.Results: Lower platelet serotonin content (66%; p<0.05) and lower ADP, collagen or epinephrine-induced platelet aggregation (10–52%; p<0.05) were detected in PRP of SSRI-medicated patients, while no such effect was obtained with arachidonic acid.Limitations: The small sample size and the co-treatment with non-SSRI drugs such as benzodiazepines.Conclusion: Patients chronically medicated with SSRIs exhibit lower platelet 5-HT content and reduced platelet aggregation induced by ADP, collagen and epinephrine, but not by arachidonic acid. Our observations may explain the increased bleeding risk associated with chronic SSRI treatment as well as the reported beneficial effect of SSRIs in prevention of recurrent myocardial infarction.

Validation of three psychometric instruments for screening for perinatal common mental disorders in men in the north of Vietnam

Thach Duc Tran, Tuan Tran, Jane Fisher — 2012-01-01

Abstract: Background: Perinatal non-psychotic common mental disorders (PCMDs) are less well recognised in men than in women. However, there are adverse consequences of PCMD for men, their partners and their infants. There is a need for simple, readily administered screening tools for use in research and primary health care for men, including in low income settings. The aim of this study was to validate three scales for screening PCMDs in men in northern Vietnam.Methods: Translated and culturally verified versions of the Edinburgh Postnatal Depression Scale (EPDS), Zung's Self-rated Anxiety Scale (Zung SAS), and the General Health Questionnaire 12 items (GHQ-12) were validated against a gold-standard diagnostic tool, the Structured Clinical Interview for DSM IV diagnoses in a community-based sample of 231 Vietnamese men who were partners of pregnant women or women who had recently given birth. Post-hoc analyses, Receiver Operating Characteristic (ROC) analyses, and Cronbach's alpha were performed to examine the validity and internal reliability of the three scales.Results: The prevalence of PCMDs in men was 17.8% (95%CI: 13.3–22.3). The AUROC of the EPDS 76.7% (95%CI: 67.9–85.5), the Zung SAS was 77.5% (95%CI: 68.9–86.0) and the GHQ-12 was 79.2% (95%CI: 71.2–87.1). The selected cut-off point to detect clinically significant symptoms in men using the EPDS was 4/5 (Sensitivity (Se) 68.3% and specificity (Sp) 77.4%), the Zung SAS was 35/36 (Se 70.7% and Sp 79.0%) and the GHQ-12 was 0/1 (Se 75.6% and Sp 74.7%).Conclusions: PCMDs in men are an unrecognised public health problem in northern Vietnam. Overall the cut off scores to detect clinically significant symptoms are lower than those reported in high income settings. Cut off scores on the EPDS and Zung SAS are slightly higher in men than in women in northern Vietnam, but these scales are suitable for use with men in this setting. Although not suitable to detect PCMD in women, the GHQ-12 is suitable to detect PCMD in men.

Inflammatory markers and their relationships with leptin and insulin from acute mania to full remission in bipolar disorder

2012-01-01

Abstract: Background: Weight gain and increased production of leptin may be associated with immuno-modulation and insulin resistance in bipolar disorder. The links among inflammatory markers, leptin, and insulin of bipolar patients from acute mania to full remission remain unclear.Methods: Thirty-three healthy, bipolar I patients under 45years of age were enrolled. We measured the circulating levels of high-sensitivity C-reactive protein (hs-CRP), anti-inflammatory mediators (interleukin-1 receptor antagonist [IL-1Ra] and soluble tumor necrosis factor receptor 1 [sTNF-R1]), leptin, and insulin during acute mania and subsequent partial and full remission. The results were compared with 33 age- and gender-matched healthy subjects.Results: The levels of IL-1Ra and hs-CRP of bipolar patients in both acute mania and partial remission were significantly higher than their levels of control subjects. The hs-CRP level of bipolar patients was also elevated in full remission. The elevation of IL-1Ra and hs-CRP levels in acute mania was independent of each other. They were also independent of the body mass index (BMI) and levels of leptin and insulin measurements. The levels of leptin were all positively associated with insulin levels in the normal subjects and bipolar patients in three phases. However, a significant relationship between leptin and immunoparameter was only seen in full remission with sTNF-R1 (r=0.51). Furthermore, IL-1Ra was inversely correlated with sTNF-R1 (r=−0.37, p<0.05) during partly remission, and while levels of IL-1Ra tended to normalize when patients remitted, levels of hs-CRP and sTNF-R1 showed the opposite trend.Conclusions: Activated inflammation was found in acute mania, as evidenced by high levels of IL-1Ra, hs-CRP, and sTNF-R1. The production of leptin may be more tightly linked to insulin than the immunomodulators. Chronic inflammation may exist in bipolar patients and is reflected by elevations of IL-1Ra and hs-CRP levels in acute mania and persistent higher hs-CRP in full remission.

The impact of the catastrophic earthquake in China's Sichuan province on the mental health of pregnant women

2012-01-01

Abstract: Background: On May 12, 2008, a magnitude 8.0 earthquake struck China's southwestern Sichuan province. Recent studies have identified mental health problems among the survivors, but little is known about the impact of the Sichuan earthquake on the mental health of pregnant women in the area. The main objective was to assess the impact of the Sichuan earthquake on the mental health of pregnant women in earthquake stricken areas.Methods: During November 2009 and January 2010, 311 pregnant women were interviewed. Symptoms of PTSD were measured using IES-R, while symptoms of antenatal depression were measured using EPDS.Results: The prevalence rate of PTSD symptoms was 12.2% (95% CI, 9.0–16.4). The rate of major depression was 40.8% (95% CI, 35.5–46.4). Living through an earthquake has been significantly correlated with PTSD but no significant correlation has been found with depression. The perceived stresses of pregnancy are significantly correlated with both depression and PTSD.Limitations: Lack of long term follow up data and comparison group from non earthquake struck area.Conclusions: 18months after the Sichuan earthquake, the incidence of depression and PTSD were still quite high among pregnant women in the earthquake stricken areas. Depression was more common than PTSD. Living through an earthquake has been significantly correlated with PTSD but not with depression.

Neural correlates of disbalanced motor control in major depression

2012-01-01

Abstract: Background: Motor retardation is a common symptom of major depressive disorder (MDD). Despite the existence of various assessment methods, little is known on the pathobiology of motor retardation. We aimed to elucidate aspects of motor control investigating the association of objective motor activity and resting state cerebral blood flow (CBF).Methods: Nineteen control subjects and 20 MDD patients were investigated using arterial spin labeling (ASL) at 3T in the morning to quantify resting state CBF. Afterwards wrist actigraphy was recorded for 24h. CBF, group and activity level (AL) were entered into a whole brain general linear model.Results: MDD patients had reduced AL. Both groups had linear associations of AL and CBF in bilateral rostral prefrontal cortex. Groups differed in four clusters associated with motor control. In controls a positive association was found in the left caudal cingulate zone (CCZ) and an inverse association in the right external globus pallidus (GPe). MDD patients had positive associations in the right orbitofrontal cortex and inverse associations in the left supplemental motor area.Limitations: Patients were on antidepressant medication.Conclusions: The pattern of associations between CBF and AL suggest disbalanced motor control in MDD. Findings are in line with the hypothesis of dopamine deficits contributing to motor retardation in MDD.

Promoter variants in IL18 are associated with onset of depression in patients previously exposed to stressful-life events

2012-01-01

Abstract: Background: Depression is accompanied by an inflammatory reaction and activation of cell mediated immunity (CMI) and stressors may induce the cytokine network in humans. The proinflammatory cytokine interleukin-18 (IL-18) is less investigated in depression but highly relevant since it is produced by activated macrophages and expressed in the brain.Methods: The distribution of six polymorphisms in IL10, IL18 and NF was compared between patients with a single episode of depression either preceded by a stressful life event (n=182), or occurring without a prior stressful life event (n=106) and a group of healthy control individuals (n=335).Results: The major C allele of the IL18 rs187238 and the major G allele of rs1946518 had a significantly higher prevalence among the patients with a stressful life event prior to onset of disease than both patients without a stressful life event and compared with the healthy controls individuals. None of the examined IL10 or NF alleles were differently distributed among these groups.Limitations: Data are nominally significant and not resistant to correction for multiple testing.Conclusion: The major C allele of the IL18 rs187238 and the major G allele rs1946518 have previously been associated with higher expression of IL-18 mRNA. Our data suggest that this genetic trend towards higher IL-18 production may increase the susceptibility to depression in response to stressful life events.

Developing a clinical typology of dysfunctional anger

2012-01-01

Abstract: Background: This study attempted to validate a clinical typology of dysfunctional anger proposed by DiGiuseppe and Tafrate (2007) using assessment data obtained from 197 participants assessed at an outpatient clinic for anger problems.Methods: Several self-report scales assessing anger, hostility, impulsivity and aggression, as well as a structured interview regarding anger experience and expression, were administered; Axis I and II comorbidity were assessed using clinical assessment and the SCID-II PQ.Results: We found support for four of the proposed eight types described by DiGiuseppe and Tafrate – Pervasive Dysfunctional Anger, Impulsive Type; Pervasive Dysfunctional Anger, Mixed Type; Impulsive Aggressive Dysfunctional Anger; and Suppressed Dysfunctional Anger – with significant, predicted group differences on self-report measures of anger, aggression, and impulsivity, as well as differences in Axis I and II diagnoses.Limitations: Patients were rarely assigned to the other four dysfunctional anger types and thus we could not examine the validity of these types. We relied heavily on self-report data.Conclusions: Anger is a common symptom in outpatient psychiatry clinics. It is associated with both mood and anxiety disorder diagnoses, and often co-occurs with substance use problems. Different types of angry patients will likely require different assessment and treatment approaches.

Episode cycles with increasing recurrences in first-episode bipolar-I disorder patients

2012-01-01

Abstract: Background: Preliminary review of a century of studies of the course of manic-depressive syndromes produced 40 reports, of which approximately one-third report evidence of shortening wellness intervals or cycle-lengths with more recurrences, and two-thirds did not.Methods: We evaluated inter-episode intervals (cycle-length) in 128 clinically-treated, DSM-IV bipolar-I disorder patients followed prospectively and systematically over 5.7years, with 6.5 episodes/person.Results: As expected, cycle-length varied inversely with total cycle-count/person; however, multivariate linear regression found only longer initial hospitalization and fewer total cycles to be associated with cycle-length, whereas cycle-number (1, 2, 3, etc.), sex, intake-age, and first-episode polarity were not. Regression of within-subject cycle-length versus cycle-number yielded individual slope-functions with pseudo-random distribution (28% fell within ±1month/cycle of the null [zero-slope]). Mean duration of early and late euthymic intervals (cycles 2 vs. 5) in patients with matched recurrence-counts was nearly identical.Conclusions: The course of bipolar-I disorder from onset was largely random or chaotic over nearly 6years from onset. Only a minority of patients showed either cycle-acceleration or slowing, without changes in wellness intervals. The findings may be influenced by treatment-effects, but seem to indicate that most current bipolar-I disorder patients are unlikely to show progressive shortening of recurrence-cycles.

A comparison of three screening tools to identify perinatal depression among low-income African American women

2012-01-01

Abstract: Background: The purpose of the current study was to determine the sensitivity, specificity, and positive predictive value of three depression screening tools among a low-income African American population of pregnant and recently delivered women enrolled in home visitation programs in a low-income urban community.Methods: Ninety-five women enrolled in home visitation programs—32 who were pregnant and 63 with a child <6months comprise the study sample. Each woman completed a structured clinical interview and three depression screening tools—the Edinburgh Postnatal Depression Scale (EPDS), Center for Epidemiologic Studies Depression Scale (CES-D), and Beck Depression Inventory II (BDI-II).Results: Over a quarter of women (28.4%) were experiencing major depression. Each screening tool was highly accurate in detecting major depression and major or minor depression among prenatal and postpartum women, with areas under the curve (AUCs) >0.90. Sensitivities of all screening tools were improved when using cutoffs lower than those considered standard by instrument developers.Limitations: Participants were recruited from home visitation programs in an urban context which may limit generalizability to other populations of low-income African American women. Given that no women during pregnancy met criteria for minor depression, it was not possible to determine optimal prenatal cutoff scores.Conclusions: Three depression screening tools—the EPDS, CES-D, and BDI-II—appear to be reliable and brief assessments of major and minor depression among low-income African American perinatal women. Providers using these tools should consider using lower cutoff scores to most effectively identify women in need of depression treatment.

The sustained mood-stabilizing effect of memantine in the management of treatment resistant bipolar disorders: Findings from a 12-month naturalistic trial

2012-01-01

Abstract: Background: We have recently provided preliminary clinical observations indicating that memantine, as augmenting agent, was associated with a meaningful antimanic and mood-stabilizing effect in treatment-resistant bipolar disorders. To further investigate the therapeutic and prophylactic action of the drug we administered memantine, as augmenting agent, to 40 treatment-resistant bipolar disorder patients, monitored and evaluated for 12months.Methods: The sample population encompassed 40 treatment-resistant bipolar disorder patients monitored for 12months. Memantine, at the dose of 10–30mg/day, was added to the ongoing treatment, which was left unmodified. The severity of the patients' condition before memantine and the changes after memantine addition were evaluated on the Clinical Global Impression Bipolar (CGI-BP) Overall Bipolar Illness Scale. The severity of patients' condition was scored before memantine and the change was evaluated after memantine addition at 6 and 12months.Limitations: The present study has the limitations of an open clinical study and the observed effects require testing in a blinded, randomized, controlled trial which is planned.Results: The average CGI-BP score of the patients was 6.7 (SD=0.58, range: 5–7) before the addition of memantine. After 6months of memantine treatment, 72.5% of patients were very much or much improved. Among the rapid cyclers 68.4% of patients reached stability, defined by the absence of recurrences.Patients very much or much improved were 72.5% at 12months; while 12.5% discontinued memantine or were lost to follow-up.Conclusions: The results confirm our previous observations and strongly suggest that memantine, as augmenting agent, was associated with a clinically substantial antimanic and sustained mood-stabilizing effect, with excellent safety and tolerability profile.

Suicide Intent Scale in the prediction of suicide

J. Stefansson, P. Nordström, J. Jokinen — 2012-01-01

Abstract: Objective: To assess the predictive value of the Suicide Intent Scale in patients with high suicide risk. The secondary aim was to assess if the use of the factors of the Suicide Intent Scale may offer a better predictive value in suicide risk detection. Finally a shorter version of the scale was created after an item analysis.Method: Eighty-one suicide attempters were assessed with the Beck's Suicide Intent Scale (SIS). All patients were followed up for cause of death. Receiver-operating characteristic (ROC) curves and tables were created to establish the optimal cut-off values for SIS and SIS factors to predict suicide.Results: Seven patients committed suicide during a mean follow up of 9.5years. The major finding was that mean SIS scores distinguished between suicides and survivors. The positive predictive value was 16.7% and the Area Under Curve (AUC) was 0.74. Only the planning subscale reached statistical significance. Four items were used to test a shorter version of the SIS in the suicide prediction. The positive predictive value was 19% and the AUC was 0.82.Conclusions: The Suicide Intent Scale is a valuable tool in clinical suicide risk assessment, a shorter version of the scale may offer a better predictive value.

A prospective cohort study of lesion location and its relation to post-stroke depression among Chinese patients

2012-01-01

Abstract: Background: Post-stroke depression (PSD) is a common consequence of stroke that negatively interferes with the rehabilitation outcome in patients. It remains unclear what relationship exists between the site and size of brain infarcts and the development of PSD and the risk factors for PSD. We conducted a MRI-based cohort study to examine the radiological correlations for PSD in Chinese patients with ischemic stroke.Methods: Our study included 163 patients with acute ischemic stroke. The diagnosis of PSD was made with World Health Organization Composite International Diagnostic Interview (WHO-CIDI), which is based on Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) during a follow-up exam at 3-month post stroke. The demographic, clinical, and detailed radiological variables (e.g., lesion location, and degree of white matter lesions) were also examined.Results: The univariate analyses suggested that the frequency of multiple acute infarcts, the total number and volume of acute infarcts were higher in the PSD group than those in the non-PSD group. In particular, PSD patients showed higher rates of infarcts in cortical–subcortical area of the frontal and temporal lobe as well as in internal capsule (including genu, anterior and posterior limb). The multivariate analysis suggested that independent radiological risk factors for PSD may include the presence of multiple acute infarcts, the infarct affecting either side of posterior limb of internal capsule, genu of internal capsule, and cortical–subcortical areas in the temporal lobe.Conclusion: Our study on ischemic stroke patients suggested that certain neuroanatomical factors (i.e., lesions at posterior limb and genu of internal capsule and cortical–subcortical area of the temporal lobe, as well as the presence of multiple acute infarcts) may correlate with the PSD development.

Long-term treatment with supraphysiological doses of thyroid hormone in affective disorders — effects on bone mineral density

2012-01-01

Abstract: Background: To investigate the long-term effects of supraphysiological, TSH suppressive doses of levothyroxine (TSDL) on bone mineral density (BMD) in patients with affective disorders during an average treatment duration of 69months.Methods: In 22 patients, BMD of the spine (lumbar vertebrae L1–4) and femur (femoral neck) was measured by dual energy X-ray absorptiometry (DXA). Forty (40) measurements from the prior study and 48 new follow-up measurements were included. BMD was expressed as Z-scores as a population standard reference. We used a linear mixed model to investigate the duration of TSDL as an explanatory factor for change in BMD compared to an age and gender matched reference population.Results: We found no significant differences in bone loss between the study and the reference population. The estimated non-significant decrease in Z-score compared to the reference population found was: a) lumbar spine (L1–4): −0.00069/month (p=0.9759) b) neck region of femur: −0.01405/month (p=0.4436). We did not find the factors age, thyroxine-dose or postmenopausal state as predictors for a decline in BMD.Limitations: Small sample size, no bone density assessment prior to treatment with TSDL, no patient control group with mood disorders who did not receive TSDL, variable bone density follow-up intervals.Conclusion: This study did not demonstrate evidence that long-term treatment of affectively ill patients with TSDL accelerates loss of BMD compared to an age- and gender-matched reference population.

A randomized, single-blind, comparison of duloxetine with bupropion in the treatment of SSRI-resistant major depression

G. Rosso, S. Rigardetto, F. Bogetto, G. Maina — 2012-01-01

Abstract: Introduction: For patients who continue to experience depressive symptoms despite an adequate antidepressant SSRI trial, across-class switch is considered one of the best treatment options. The goal of the present work was to compare in terms of efficacy two different dual-action compounds, duloxetine and bupropion, in patients who failed to respond in two consecutive antidepressant trials with SSRIs.Methods: The patients were allocated randomly to duloxetine (120mg daily) or bupropion extended release (300mg daily). The intended medication period was 6weeks. The primary measure of efficacy was depressive symptoms severity.Results: A total of 49 participants were randomly assigned to duloxetine 120mg (n=27) or bupropion 300mg (n=22). The ITT efficacy patient sample consisted of 46 patients. Relatively high response and remission rates in treatment groups were found: from 60 to 70% of patients responded to treatment, and approximately 30 to 40% were in remission by the endpoint (week 6). No statistically significant difference emerged between the two groups at any post-baseline assessment, neither on mean scores of rating scales nor on qualitative efficacy measures.Limits: Limitations of the study are the lack of a placebo arm, difficult to include owing to ethical reasons, and the relatively small size of the sample.Conclusions: These preliminary results seem to support the hypothesis that in patients unresponsive to SSRIs the administration of antidepressants with different mechanisms of action is an effective switching strategy. Further studies are needed in light of the challenge posed by resistant depression.

Molecular cytogenetic interphase analysis of Phosphoinositide-specific Phospholipase C β1 gene in paraffin-embedded brain samples of major depression patients

Vincenza Rita Lo Vasco, Patrizia Polonia — 2012-01-01

Abstract: Mood disorders represent a major medical need, as their chronic treatments are not effective in all patients. Literature data suggested that phosphoinositides (PI) signal transduction pathway and related molecules such as the Phosphoinositide-specific Phospholipase C (PI-PLC) enzymes, might be involved in the pathophysiology of mood disorders, including major depression. By using interphase fluorescent in situ hybridization methodology, we analyzed PLCB1 gene, which codifies for the PI-PLC β1 enzyme, in paraffin embedded samples of orbito-frontal cortex of 15 patients affected with major depression and in 15 normal controls. No deletions of PLCB1 were identified with the methodology used, which allows to exclude wide gene deletions. The results, the technical aspects of the FISH methodology, and its limitations are discussed.

Increased plasma VEGF levels in major depressive or manic episodes in patients with mood disorders

Bun-Hee Lee, Yong-Ku Kim — 2012-01-01

Abstract: Background: The neurotrophic hypothesis suggests that mood disorders are associated with dysfunction of neuronal networks under the influence of neurotrophic factors. Vascular endothelial growth factor (VEGF) is a neurotrophic factor as well as an angiogenic cytokine.Methods: We examined plasma VEGF levels in 35 unipolar patients who were diagnosed with current major depressive disorder (MDD), 35 bipolar patients who were diagnosed with bipolar I disorder, manic episode (BM), and 60 healthy controls. The severity of depressive or manic symptoms was measured using the Hamilton Depression Rating Scale (HDRS) or the Young Mania rating scale (YMRS), respectively.Results: Plasma VEGF levels were 163.28±135.33pg/mL in MDD patients, 199.82±182.59pg/mL in BM patients, and 110.05±109.57pg/mL in healthy controls. Both MDD and BM patients had significantly higher VEGF levels than healthy controls when controlling for BMI as a covariate (p=0.010). Patients' VEGF levels were not correlated with either HDRS or YMRS scores.Limitations: We assessed plasma VEGF levels at one time point, and we did not determine the source of VEGF in our samples.Conclusions: Plasma VEGF levels were elevated in patients with acute episodes of major depressive disorder and bipolar disorder. Such an alteration of VEGF in acute episode, mood disorders may be associated with a neuroprotective role for VEGF.

Protein levels of β-catenin and activation state of glycogen synthase kinase-3β in major depression. A study with postmortem prefrontal cortex

2012-01-01

Abstract: Background: The Wnt/GSK3β signaling pathway was implicated in mood disorders. Beta-catenin is a protein targeted by this signaling axis. We aimed to examine whether there is an abnormality in this signaling axis in major depression.Methods: Postmortem brains from 20 depressed and 20 non-depressed subjects were used. In both groups, suicide and non-suicide were included in equal number. Protein levels of β-catenin, tGSK3β and ser9-pGSK3β were determined in prefrontal cortex.Results: ANOVA yielded significant variations between groups in β-catenin (F3,36=19.5; p<0.001) and pGSK3β protein (F3,36=14.3; p<0.001) and in tGSK3β-to-pGSK3β ratio (F3,36=10.9; p<0.001). Fisher tests showed decrease in both groups of MDD and MDD with suicide (MDD+S) for β-catenin (p<0.001) and pGSK3β levels (p<0.001) respectively. The tGSK3β-to-pGSK3β ratio was increased in MDD and MDD+S subjects (p<0.001). A negative correlation was observed between β-catenin levels and the activation state of the GSK3β (r2=0.358; p<0.005).Limitations: The sample was small and only a fraction of s9-pGSK3β, albeit significant, was used and; the mood state at the time of death was unknown.Conclusions: The study observed a dysregulation of Wnt/GSK3β signaling associated with a lifetime of major depression. The study may have relevance in further development of drugs based on GSK3β inhibition.

Stressful life events and the serotonin transporter gene (5-HTT) in recurrent clinical depression

2012-01-01

Abstract: Background: An interaction between recent stressful life events (SLEs) and a serotonin transporter promoter polymorphism (5-HTTLPR) in depression has been inconsistently reported. Some of this variability may be due to a previous focus on sub-clinical depression, inclusion of individuals at the lower or upper ends of the age-span, or assumptions concerning the degree of dominance of the low expressing allele. Therefore, a large sample of patients with recurrent clinically diagnosed depression and controls screened for absence of depression was utilised to examine the moderating effect of each 5-HTTLPR genetic model on the association between SLEs and severe depressive episodes.Method: A sample of 1236 recurrent unipolar depression cases and 598 age-matched, never psychiatrically ill controls completed the List of Threatening Experiences Questionnaire to assess the number of SLEs experienced in the 6months prior to the most severe depressive episode (cases) or interview (controls). DNA extracted from blood or cheek swabs was genotyped for the short (s) and long (l) alleles of 5-HTTLPR.Results: A greater number of SLEs were reported by cases than controls and this held across all genotypic groups. There was no main effect of 5-HTTLPR on depression and no evidence of interaction between total SLEs and any of the 5-HTTLPR genetic models. The results were the same for men and women.Limitations: Utilisation of retrospective self-reported SLEs may have reduced the accuracy of the findings and the cross-sectional design prevents causal inference.Conclusions: This study failed to find evidence of gene–environment interplay in recurrent clinical depression.

The railway suicide death of a famous German football player: Impact on the subsequent frequency of railway suicide acts in Germany

Karl-Heinz Ladwig, Sabine Kunrath, Karoline Lukaschek, Jens Baumert — 2012-01-01

Abstract: Background: The railway suicide of Robert Enke, an internationally respected German football goal keeper, sent shockwaves throughout the world of football. We analyzed its impact on the frequency of subsequent railway suicide acts (RS).Methods: Two analytic approaches were performed applying German Railway Event database Safety (EDS) data: first, an inter-year approach comparing the incidence of RS during a predefined “index period” with identical time windows in 2006 to 2008; second, an intra-year approach comparing the number of RS 28days before and after the incidence. To analyze a possible “compensatory deficit”, the number of RS in the subsequent first quarter of 2010 was compared with the identical time windows in the preceding three years. Incidence ratios with 95% confidence intervals were estimated by Poisson regression. Findings were controlled for temperature.Findings: Compared to the preceding three years, the incidence ratio (IR) of the number of RS in the index period increased by 1.81 (1.48–2.21; p<0.001), leading to an overall percentage change of 81% (48–121%; p<0.001). Comparing the number of suicides 28days before and after the incidence revealed an even more pronounced increase of IR (2.2; 1.6–3.0). No modifications of these associations were observed by daytime, by location of the suicide and fatality. No compensatory deficit occurred in the post-acute period.Interpretation: The substantial increase of RS in the aftermath of the footballer's suicide death brought about copycat behavior in an unforeseen amount, even though the media reporting was largely sensitive and preventive measures were taken.