Specific alterations in plasma proteins during depressed, manic, and euthymic states of bipolar disorder

Bipolar disorder (BD) is a common psychiatric mood disorder affecting more than 1-2% of the general population of different European countries. Unfortunately, there is no objective laboratory-based test to aid BD diagnosis or monitor its progression, and little is known about the molecular basis of BD. Here, we performed a comparative proteomic study to identify differentially expressed plasma proteins in various BD mood states (depressed BD, manic BD, and euthymic BD) relative to healthy controls. A total of 10 euthymic BD, 20 depressed BD, 15 manic BD, and 20 demographically matched healthy control subjects were recruited. Seven high-abundance proteins were immunodepleted in plasma samples from the 4 experimental groups, which were then subjected to proteome-wide expression profiling by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandem mass spectrometry. Proteomic results were validated by immunoblotting and bioinformatically analyzed using MetaCore. From a total of 32 proteins identified with 1.5-fold changes in expression compared with healthy controls, 16 proteins were perturbed in BD independent of mood state, while 16 proteins were specifically associated with particular BD mood states. Two mood-independent differential proteins, apolipoprotein (Apo) A1 and Apo L1, suggest that BD pathophysiology may be associated with early perturbations in lipid metabolism. Moreover, down-regulation of one mood-dependent protein, carbonic anhydrase 1 (CA-1), suggests it may be involved in the pathophysiology of depressive episodes in BD. Thus, BD pathophysiology may be associated with early perturbations in lipid metabolism that are independent of mood state, while CA-1 may be involved in the pathophysiology of depressive episodes.

Clinical significance of lifetime panic disorder in the course of bipolar disorder type I

Objectives: The aim of the study was to analyze the impact of lifetime panic disorder (PD) diagnosis in a sample of patients with bipolar disorder type I (BPI), evaluating clinical and demographic variables. Methods: Ninety-five outpatients from the Bipolar Disorder Research Program at the Institute of Psychiatry of the University of Sao Paulo Medical School were enrolled. Twenty-seven BPI patients with PD were compared to 68 BPI patients without any anxiety disorders regarding clinical and demographic variables. Results: Compared to BPI patients without any anxiety disorders, patients with BPI + PD presented significantly higher number of mood episodes (18.9 +/- 13.8 vs 8.5 +/- 7.8; P < .001), depressive episodes (10.8 +/- 8.2 vs 4.6 +/- 4,8; P = .001), and manic episodes (7.4 +/- 7.3 vs 3.6 +/- 3.6; P = .008). Patients with BPI + PD had more frequently a depressive episode as their first one compared to BPI patients without anxiety disorders (94.1% vs 57.5%; P = .011). Patients with BPI + PD had more comorbidity with lifetime diagnosis of drug abuse or dependence (33.3% vs 8.8%; P = .010) and eating disorders (29.6% vs 6.0%; P = .004). Conclusions: The higher number of mood episodes in general presented by patients with BPI + PD when compared with BPI patients without any anxiety disorders, along with the higher frequencies of drug misuse and eating disorders, indicates that PD comorbidity is associated with a poorer Course and outcome of BPI. The higher frequency of depression as the onset mood episode and the higher number of manic episodes in the group with PD may have important treatment implications and should be further investigated. (C) 2009 Elsevier Inc. All rights reserved.

Plasma cortisol in first episode drug-naive mania: Differential levels in euphoric versus irritable mood

Background: Dysregulation of HPA axis has been widely described in subjects with bipolar disorder (BD), including changes in cortisol levels during mood episodes and euthymia. However, most of the studies were done with medicated BD patients with variable length of illness, which was shown to interfere on peripheral cortisol levels. Therefore, the present study aims to evaluate plasma cortisol levels in drug-naive BD subjects during the first manic episode, as well as investigate the relationship between plasma cortisol levels and manic symptomatology. Methods: Twenty-six drug-naive patients were enrolled meeting criteria for a first manic episode in bipolar I disorder. Severity of mania was assessed using the Young Mania Rating Scale (YMRS). The control group included 27 healthy subjects matched by age and gender. Cortisol was quantified using a direct radioimmunoassay. Results: Plasma cortisol levels were decreased during first manic episode compared to healthy controls. Higher cortisol levels were positively associated with the presence of irritability (dysphoria), while elated mania showed lower cortisol levels compared to controls. Limitation: Data including larger samples are lacking. Conclusion: Higher cortisol in dysphoric mania compared to predominantly elated/euphoric mania may indicate a clinical and neurobiological polymorphic phenomenon, potentially involving a higher biological sensitivity to stress in the presence of irritable mood. The present findings highlight the importance to add a dimensional approach to the traditional categorical diagnosis for future neurobiological studies in BD. (C) 2011 Elsevier B.V. All rights reserved.

Structuring depressive discourse: A descriptive narrative process

This study aimed to evaluate the importance of a descriptive narrative process of the significance involved in a depressive phenomenon. The research population consisted of 324 adult and adolescent patients of both genders, located in the central area of the city of Paraiba, for clinical and psychological health care. For surveyed patients, suffering and or psychological pain were the most common complaints. A sample of 159 patients was taken, including male and female adolescents and adults. Data were collected through a narrative interview. Shutz' procedure was used for information analysis. The obtained data offered the opportunity to review concepts, discuss life history and listen to narrative positioning episodes of manifested depression. The narratives were considered to be a determinant factor to consider inherent conflicts.

Clinical and sociodemographic factors in a sample of older subjects experiencing depressive symptoms

Objectives This study aims to determine the frequency of clinically significant depressive symptoms (CSDS) in a community sample of older Brazilians and to examine their relationship with sociodemographic factors, cognitive and functional impairment (CFI), and medical illness. Methods A total of 1145 subjects aged 60?years or older living in the City of Ribeirao Preto, State of Sao Paulo, Brazil, were interviewed. The following instruments were used: a 10-item scale for screening of depressive symptoms in older people, the mini mental state examination, the Fuld Object Memory Evaluation, the Informant Questionnaire on Cognitive Decline in the Elderly, the Bayer Activities of Daily Living Scale, and a sociodemographic and clinical questionnaire. Results The frequency of CSDS was 15.7%. Logistic regression analysis indicated that being previously depressed, having CFI, having lower level of education, using psychotropics, and not engaging in physical exercise were related to CSDS. On the other hand, being a woman, older, medically ill, employed, or married was not associated with CSDS. Conclusions Consistent with previous reports, lower education, lack of physical activity, and CFI were significantly associated with higher frequencies of CSDS. Further investigations are necessary to clarify the occurrence of depression and possible modifiable factors in developing countries such as Brazil. Copyright (C) 2011 John Wiley & Sons, Ltd.

Demographic and clinical predictors of depressive symptoms among incarcerated women

Abstract Background Imprisonment may lead to the development of mental illness, especially depression. This study examines the clinical and sociodemographic profiles of imprisoned women, identifies indicative signs of depression, and relates these indicators to other variables. Methods This study took the form of descriptive exploratory research with a psychometric evaluation. A total of 100 of 300 women in a female penitentiary were interviewed. A questionnaire with sociodemographic, clinical and penal situation information was used, along with the Beck Depression Inventory. The authors performed bivariate and multivariate analysis regarding depression. Results In all, 82 women presented signs of depression (light = 33, mild = 29 and severe = 20). Comorbidities, lack of religious practice, absence of visitors and presence of eating disorders were risk factors for depression (P = 0.03, 0.03, 0.02, 0.04, and 0.01). Being older was a protection factor against severe depression; for women over 30, the risk of depression was multiplied by 0.12. The rate of depression among women prisoners was high. Conclusions Comorbidities, the lack of religious practice, not having visitors and eating disorders are significant risk factors for depression, while age is a protective factor, among incarcerated women.

Differences between first episode schizophrenia and schizoaffective disorder

Background The diagnostic and clinical overlap between schizophrenia and schizoaffective disorder is an important nosological issue in psychiatry that is yet to be resolved. The aim of this study was to compare the clinical and functional characteristics of an epidemiological treated cohort of first episode patients with an 18-month discharge diagnosis of schizophrenia (FES) or schizoaffective disorder (FESA). Methods This study was part of the larger First Episode Psychosis Outcome Study (FEPOS) which involved a medical file audit study of all 786 patients treated at the Early Psychosis Prevention and Intervention Centre between 1998 and 2000. Of this cohort, 283 patients had an 18-month discharge diagnosis of FES and 64 had a diagnosis of FESA. DSM-IV diagnoses and clinical and functional ratings were derived and validated by two consultant psychiatrists. Results Compared to FES patients, those with FESA were significantly more likely to have a later age of onset (p=.004), longer prodrome (p=.020), and a longer duration of untreated psychosis (p<.001). At service entry, FESA patients presented with a higher illness severity (p=.020), largely due to the presence of more severe manic symptoms (p<.001). FESA patients also had a greater number of subsequent inpatient admissions (p=.017), had more severe depressive symptoms (p=.011), and higher levels of functioning at discharge. Discussion The findings support the notion that these might be considered two discernable disorders; however, further research is required to ascertain the ways and extent to which these disorders are discriminable at presentation and over time.

Beyond words: Sensory properties of depressive thoughts

Verbal thoughts (such as negative cognitions) and sensory phenomena (such as visual mental imagery) are usually conceptualised as distinct mental experiences. The present study examined to what extent depressive thoughts are accompanied by sensory experiences and how this is associated with symptom severity, insight of illness and quality of life. A large sample of mildly to moderately depressed patients (N = 356) was recruited from multiple sources and asked about sensory properties of their depressive thoughts in an online study. Diagnostic status and symptom severity were established over a telephone interview with trained raters. Sensory properties of negative thoughts were reported by 56.5% of the sample (i.e., sensation in at least one sensory modality). The highest prevalence was seen for bodily (39.6%) followed by auditory (30.6%) and visual (27.2%) sensations. Patients reporting sensory properties of thoughts showed more severe psychopathological symptoms than those who did not. The degree of perceptuality was marginally associated with quality of life. The findings support the notion that depressive thoughts are not only verbal but commonly accompanied by sensory experiences. The perceptuality of depressive thoughts and the resulting sense of authenticity may contribute to the emotional impact and pervasiveness of such thoughts, making them difficult to dismiss for their holder.

Stimulant medication and psychotic symptoms in offspring of parents with mental illness

BACKGROUND: Stimulants, such as methylphenidate, are among the most commonly used medications in children and adolescents. Psychotic symptoms have been reported as rare adverse reactions to stimulants but have not been systematically inquired about in most previous studies. Family history of mental illness may increase the vulnerability to drug-induced psychotic symptoms. We examined the association between stimulant use and psychotic symptoms in sons and daughters of parents with major mood and psychotic disorders. METHODS: We assessed psychotic symptoms, psychotic-like experiences, and basic symptoms in 141 children and youth (mean ± SD age: 11.8 ± 4.0 years; range: 6–21 years), who had 1 or both parents with major depressive disorder, bipolar disorder, or schizophrenia, and of whom 24 (17.0%) had taken stimulant medication. RESULTS: Psychotic symptoms were present in 62.5% of youth who had taken stimulants compared with 27.4% of participants who had never taken stimulants. The association between stimulant use and psychotic experiences remained significant after adjustment for potential confounders (odds ratio: 4.41; 95% confidence interval: 1.82–10.69; P = .001) and was driven by hallucinations occurring during the use of stimulant medication. A temporal relationship between use of stimulants and psychotic symptoms was supported by an association between current stimulant use and current psychotic symptoms and co-occurrence in cases that were assessed on and off stimulants. CONCLUSIONS: Psychotic symptoms should be monitored during the use of stimulants in children and adolescents. Family history of mood and psychotic disorders may need to be taken into account when considering the prescription of stimulants.

Prospective longitudinal voxel-based morphometry study of major depressive disorder in young individuals at high familial risk

BACKGROUND Previous neuroimaging studies indicate abnormalities in cortico-limbic circuitry in mood disorder. Here we employ prospective longitudinal voxel-based morphometry to examine the trajectory of these abnormalities during early stages of illness development. METHOD Unaffected individuals (16-25 years) at high and low familial risk of mood disorder underwent structural brain imaging on two occasions 2 years apart. Further clinical assessment was conducted 2 years after the second scan (time 3). Clinical outcome data at time 3 was used to categorize individuals: (i) healthy controls ('low risk', n = 48); (ii) high-risk individuals who remained well (HR well, n = 53); and (iii) high-risk individuals who developed a major depressive disorder (HR MDD, n = 30). Groups were compared using longitudinal voxel-based morphometry. We also examined whether progress to illness was associated with changes in other potential risk markers (personality traits, symptoms scores and baseline measures of childhood trauma), and whether any changes in brain structure could be indexed using these measures. RESULTS Significant decreases in right amygdala grey matter were found in HR MDD v. controls (p = 0.001) and v. HR well (p = 0.005). This structural change was not related to measures of childhood trauma, symptom severity or measures of sub-diagnostic anxiety, neuroticism or extraversion, although cross-sectionally these measures significantly differentiated the groups at baseline. CONCLUSIONS These longitudinal findings implicate structural amygdala changes in the neurobiology of mood disorder. They also provide a potential biomarker for risk stratification capturing additional information beyond clinically ascertained measures.

Medical conditions and depressive, anxiety, and somatic symptoms in older adults with and without generalized anxiety disorder

OBJECTIVE: The objective of this study was to examine medical illness and anxiety, depressive, and somatic symptoms in older medical patients with generalized anxiety disorder (GAD). METHOD: A case-control study was designed and conducted in the University of California, San Diego (UCSD) Geriatrics Clinics. A total of fifty-four older medical patients with GAD and 54 matched controls participated. MEASUREMENTS: The measurements used for this study include: Brief Symptom Inventory-18, Mini International Neuropsychiatric Interview, and the Anxiety Disorders Interview Schedule. RESULTS: Older medical patients with GAD reported higher levels of somatic symptoms, anxiety, and depression than other older adults, as well as higher rates of diabetes and gastrointestinal conditions. In a multivariate model that included somatic symptoms, medical conditions, and depressive and anxiety symptoms, anxiety symptoms were the only significant predictors of GAD. CONCLUSION: These results suggest first, that older medical patients with GAD do not primarily express distress as somatic symptoms; second, that anxiety symptoms in geriatric patients should not be discounted as a byproduct of medical illness or depression; and third, that older adults with diabetes and gastrointestinal conditions may benefit from screening for anxiety.

Comorbid Migraine in Major Depressive Disorder Suggests a Subgroup Related to Bipolar Disorder

Aims: Previous small-scale studies suggest presence of migraine in major depressive disorder (MDD) is associated with specific clinical characteristics that may overlap with those of bipolar disorder. We aimed to compare a broad range of characteristics in participants who have MDD with and without migraine, and to explore possible similarities between those characteristics associated with the presence of migraine in MDD and those in bipolar disorder in a large UK sample. Methods: Lifetime and episodic clinical characteristics and affective temperaments in DSM-IV MDD with (n=134) and without (n=218) migraine were compared. Characteristics associated with the presence of migraine were then compared with a sample of participants with DSM-IV bipolar disorder (n=407). All participants were recruited into the Bipolar Disorder Research Network (www.bdrn.org). Results: The presence of migraine in MDD was associated with female gender (76.9% vs 56.9%, p<0.001), younger age of onset (23 vs 27 years, p=0.002), history of attempted suicide (38.3% vs 22.7%, p=0.002), and more panic/agoraphobia symptomatology (6 vs 4, p<0.001). Female gender (OR=2.44, p=0.006) and younger age of onset (OR=0.97, p=0.013) remained significant in a multivariate model. These clinical characteristics were not significantly different to those of our participants with bipolar disorder. Conclusions: The presence of migraine in MDD delineates a subgroup of individuals with a more severe illness course. The clinical presentation of this subgroup more closely resembles that of bipolar disorder than that of MDD without migraine. The presence of migraine in major depression may be a marker of a specific subgroup that could be useful in future research.

Autistic and Schizotypal Traits and Global Functioning in Bipolar I Disorder

Objective: To determine the expression of autistic and positive schizotypal traits in a large sample of adults with bipolar I disorder (BD-I), and the effect of co-occurring autistic and positive schizotypal traits on global functioning in BD-I. Method: Autistic and positive schizotypal traits were self-assessed in 797 individuals with BD-I recruited by the Bipolar Disorder Research Network. Differences in global functioning (rated using the Global Assessment Scale) during lifetime worst depressive and manic episodes (GASD and GASM respectively) were calculated in groups with high/low autistic and positive schizotypal traits. Regression analyses assessed the interactive effect of autistic and positive schizotypal traits on global functioning. Results: 47.2% (CI=43.7-50.7%) showed clinically significant levels of autistic traits, and 23.22% (95% CI=20.29-26.14) showed clinically significant levels of positive schizotypal traits. In the worst episode of mania, the high autistic, high positive schizotypal group had better global functioning compared to the other groups. Individual differences analyses showed that high levels of co-occurring traits were associated with better global functioning in both mood states. Limitations: Autistic and schizotypal traits were assessed using self-rated questionnaires. Conclusions: Expression of autistic and schizotypal traits in adults with BD-I is prevalent, and may be important to predict illness aetiology, prognosis, and diagnostic practices in this population. Future work should focus on replicating these findings in independent samples, and on the biological and/or psychosocial mechanisms underlying better global functioning in those who have high levels of both autistic and positive schizotypal traits.

Autistic and Schizotypal Traits and Global Functioning in Bipolar Disorder

Background and Aims To determine the expression of autistic and positive schizotypal traits in a large sample of adults with bipolar disorder (BD), and the effect of co-occurring autistic and positive schizotypal traits on global functioning in BD. Methods Autistic and positive schizotypal traits were assessed in 797 individuals with BD recruited by the Bipolar Disorder Research Network (BDRN), using the Autism-Spectrum Quotient and Kings Schizotypy Questionnaire (KSQ), respectively. Differences in global functioning (rated using the Global Assessment Scale) during lifetime worst depressive and manic episodes (GASD and GASM respectively) were calculated in groups with high/low autistic and positive schizotypal traits. Regression analyses assessed the interactive effect of autistic and positive schizotypal traits on global functioning. Results 47.2% (CI = 43.7–50.7%) showed clinically significant levels of autistic traits. Mean of sample on the KSQ-Positive scale was 11.98 (95% CI: 11.33–12.62). In the worst episode of mania, the high autistic, high positive schizotypal group had better global functioning than the low autistic, low positive schizotypal group (mean difference = 3.72, p = 0.004). High levels of co-occurring traits were associated with better global functioning in both mood states in individuals with a history of psychosis (GASM: p < 0.001; GASD: p = 0.055). Conclusions Expression of autistic and schizotypal traits in adults with BD is prevalent, and may be important to predict course of illness, prognosis, and in devising individualised therapies. Future work should focus on replicating these findings in independent samples, and on the biological and/or psychosocial mechanisms underlying better global functioning in those who have high levels of both autistic and positive schizotypal traits.

Self-report depressive symptoms do not directly predict suicidality in nonclinical individuals: Contributions toward a more psychosocial approach to suicide risk

Although suicidality is associated with mental illness in general and depression in particular, many depressed individuals do not attempt suicide and some individuals who attempt to or do die by suicide do not present depressive symptoms. This article aims to contribute to a more psychosocial approach to understanding suicide risk in nonclinical populations. In advocating a psychosocial perspective rather than a depression-focused approach, this article presents four diverse studies that demonstrate sampling and measurement invariance in findings across different populations and specific measures. Study 1 tests the mediation effects of 2 interpersonal variables, thwarted belongingness and perceived burdensomeness, in the association between depressive symptoms and recent suicidality. Studies 2 and 3 evaluate the contribution of hopelessness and psychache, beyond depressive symptoms, to suicidality. Study 4 tests the contribution of life events behind depressive symptoms, and other relevant sociodemographic and clinical variables, to the estimation of “future suicidality.” Overall, results demonstrate that depressive symptoms do not directly predict suicidality in nonclinical individuals, but that other psychosocial variables mediate the association between depressive symptoms and suicidality or predict suicidality when statistically controlling for depressive symptoms. The article contributes to understanding some of the nonpsychopathological factors that potentially link depressive symptoms to suicide risk and that might themselves contribute to suicidality, even when controlling for depressive symptoms.