Intrahippocampal injection of brain-derived neurotrophic factor increases anxiety-related, but not panic-related defensive responses: involvement of serotonin

Changes in brain-derived neurotrophic factor (BDNF)mediated signaling in the hippocampus have been implicated in the etiology of depression and in the mode of action of antidepressant drugs. There is also evidence from animal studies to suggest that BDNF-induced changes in the hippocampus may play a role in another stress-related pathology: anxiety. However, it is still unknown whether this neurotrophin plays a differential role in defensive responses associated with distinguished subtypes of anxiety disorders found in the clinic, such as generalized anxiety and panic disorder. In the present study, we investigated the effect of an acute BDNF injection into the rat dorsal hippocampus (DH) on inhibitory avoidance acquisition and escape expression measured in the elevated T-maze (ETM). We also assessed whether serotonergic neurotransmission may account for such effects. Intra-DH BDNF injection (200 pg) facilitated inhibitory avoidance in ETM. BDNF was equally anxiogenic in the light/dark transition test. Preadministration of the 5-HT1A receptor antagonist WAY-100635 fully counteracted the anxiogenic effect of BDNF in both tests. Intra-DH midazolam administration (10 nmol) impaired avoidance acquisition in ETM, suggesting an anxiolytic effect. Therefore, in the DH, facilitation of BDNF signaling seems to enhance 5-HT1A receptor-mediated neurotransmission to exert an anxiogenic effect associated with generalized anxiety. Behavioural Pharmacology 23:80-88 (C) 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Treatment-resistant depression increases health costs and resource utilization

Objective: Major Depressive Disorder (MDD) is a debilitating condition with a marked social impact. The impact of MDD and Treatment-Resistant Depression (TRD+) within the Brazilian health system is largely unknown. The goal of this study was to compare resource utilization and costs of care for treatment-resistant MDD relative to non-treatment-resistant depression (TRD-). Methods: We retrospectively analyzed the records of 212 patients who had been diagnosed with MDD according to the ICD-10 criteria. Specific criteria were used to identify patients with TRD+. Resource utilization was estimated, and the consumption of medication was annualized. We obtained information on medical visits, procedures, hospitalizations, emergency department visits and medication use related or not to MDD. Results: The sample consisted of 90 TRD+ and 122 TRD-patients. TRD+ patients used significantly more resources from the psychiatric service, but not from non-psychiatric clinics, compared to TRD-patients. Furthermore, TRD+ patients were significantly more likely to require hospitalizations. Overall, TRD+ patients imposed significantly higher (81.5%) annual costs compared to TRD-patients (R$ 5,520.85; US$ 3,075.34 vs. R$ 3,042.14; US$ 1,694.60). These findings demonstrate the burden of MDD, and especially of TRD+ patients, to the tertiary public health system. Our study should raise awareness of the impact of TRD+ and should be considered by policy makers when implementing public mental health initiatives.

Does ragging play a role in medical student depression - Cause or effect?

Background: Medical students experience a lot of stress what may contribute to symptoms of depression. In this study we set out to look at the environmental factors which may be contributing in one medical school in Brazil. Methods: We assessed depressive symptoms using Beck's Depression Inventory in 465 and 267 medical students in 2001 and 2006 respectively. We explored possible social and environmental causes using qualitative data. Results: Nearly 15% scored above the cut off for depression in both the samples. Males in the pre-clinical stage in 2006 showed an increase in depressive symptoms than males in the same cycle in 2001 (aOR = 7.36 [95% CI = 0.85-63.5] p = 0.07). Qualitative data confirmed that factors such as ragging and low social involvement were correlated with depressive symptoms in pre-clinical stage males. Limitations: The sample size was small both for quantitative and qualitative aspects of the study. Conclusions: It appears that ragging plays an important role in the genesis of depressive symptoms in medical students. (C) 2012 Elsevier B.V. All rights reserved.

Does anti-obsessional pharmacotherapy treat so-called comorbid depressive and anxiety states?

Background: Obsessive-compulsive disorder (OCD) is a chronic condition that normally presents high rates of psychiatric comorbidity. Depression, tic disorders and other anxiety disorders are among the most common comorbidities in OCD adult patients. There is evidence that the higher the number of psychiatric comorbidities, the worse the OCD treatment response. However, little is known about the impact of OCD treatment on the outcome of the psychiatric comorbidities usually present in OCD patients. The aim of this study was to investigate the impact of exclusive, conventional treatments for OCD on the outcome of additional psychiatric disorders of OCD patients, detected at baseline. Methods: Seventy-six patients with primary OCD admitted to the treatment protocols of the Obsessive-Compulsive Spectrum Disorders Program between July 2007 and December 2009 were evaluated at pre-treatment and after 12 months. Data were analyzed to verify possible associations between,OCD treatment response and the outcome of psychiatric comorbidities. Results: Results showed a significant association between OCD treatment response and improvement of major depression and dysthymia (p-value = 0.002), other anxiety disorders (generalized anxiety disorder, social phobia, specific phobia, posttraumatic stress disorder, panic disorder, agoraphobia and anxiety disorder not otherwise specified) (p-value = 0.054) and tic disorders (p-value = 0.043). Limitations: This is an open, non-blinded study, without rating scales for comorbid conditions. Further research is necessary focusing on the possible mechanisms by which OCD treatment could improve these specific disorders. Conclusions: Our results suggest that certain comorbid disorders may benefit from OCD-targeted treatment. (C) 2012 Elsevier B.V. All rights reserved.

Relations between Depression, Alcohol and Gender in the Metropolitan Region of Sao Paulo, Brazil

As part of the GENACIS project, this paper sought to assess the prevalence of depression in an urban sample in the city of Sao Paulo, Brazil, as well as the association between depression and alcohol abuse according to gender. To achieve this, an epidemiological survey was conducted using a stratified probability sample, including 2,083 adults. CIDI SF was used to identify depression. The Rao Scott test and multivariate logistic regression were used for statistical analysis. The response rate was 74.9%. Females (58.3%) under 40 years of age (52%) were predominant. The prevalence of depression was 28.3% for women and 12.7% for men. Most men declared being drinkers (61.1%) in the last year. Depression was associated with an alcohol drinking pattern, mostly binge drinking, in addition to the occurrence of problems derived from alcohol use. Most women declared being abstainers (69.5%). Depression was associated with cohabiting with spouses with alcohol-related problems. Results reveal that the association between depression and alcohol consumption is distinct between genders.

Validation of the Brazilian Portuguese version of the Beck Depression Inventory-II in a community sample

Background: The Beck Depression Inventory (BDI) is used worldwide for detecting depressive symptoms. This questionnaire has been revised (1996) to match the DSM-IV criteria for a major depressive episode. We assessed the reliability and the validity of the Brazilian Portuguese version of the BDI-II for non-clinical adults. Methods: The questionnaire was applied to 60 college students on two occasions. Afterwards, 182 community-dwelling adults completed the BDI-II, the Self-Report Questionnaire, and the K10 Scale. Trained psychiatrists performed face-to-face interviews with the respondents using the Structured Clinical Interview (SCID-I), the Montgomery-angstrom sberg Depression Scale, and the Hamilton Anxiety Scale. Descriptive analysis, signal detection analysis (Receiver Operating Characteristics), correlation analysis, and discriminant function analysis were performed to investigate the psychometric properties of the BDI-II. Results: The intraclass correlation coefficient of the BDI-II was 0.89, and the Cronbach's alpha coefficient of internal consistency was 0.93. Taking the SCID as the gold standard, the cut-off point of 10/11 was the best threshold for detecting depression, yielding a sensitivity of 70% and a specificity of 87%. The concurrent validity (a correlation of 0.63-0.93 with scales applied simultaneously) and the predictive ability of the severity level (over 65% correct classification) were acceptable. Conclusion: The BDI-II is reliable and valid for measuring depressive symptomatology among Portuguese-speaking Brazilian non-clinical populations.

Should Psychotherapy Consider Reincarnation?

There is increasing recognition of the need to take into account the cultural environment and belief systems of psychotherapy patients because these values reflect basic assumptions about man's nature and the cognitive references used to cope with psychological difficulties. Currently accepted psychotherapeutic approaches take no account of the belief in life after death held by most of the world's population. The World Values Survey (http://www.worldvaluessurvey.org) showed that there are large numbers of reincarnationists around the world, and whatever the reasons for believing in reincarnation, psychotherapeutic approaches should not ignore this significant group of people. Respect for patient opinions and subjective realities is a therapeutic need and an ethical duty, even though therapists may not share the same beliefs. Guidelines are suggested for professionals to develop collaborative models that help patients mobilize their intrinsic intelligence to find solutions to their complaints.

Treatment of Depression in Older Adults

Depression is the most frequent mental disorder in older people, often causing emotional distress and reduced quality of life. Despite its clinical significance, depression remains underdiagnosed and inadequately treated in older patients. Regarding prognosis, data suggest that almost 70% of patients, treated long enough and with appropriate doses, recover from an index episode of depression. Antidepressants are efficient for treating depressed outpatients with several comorbid physical diseases as well as hospitalized patients, with selective serotonin reuptake inhibitors being the antidepressants of choice for older patients. Available data can guide pharmacological treatment in both the acute and maintenance stages, but further research is required to guide clinical strategies when remission is not achieved. Approaches for the management of resistance to treatment are summarized, including optimization strategies, drug changes, algorithms, and combined and augmentation pharmacological treatments. Finally, additional therapeutic choices such as electroconvulsive therapy, transcranial magnetic stimulation, and integrated psychotherapy are presented.

Antenatal depression strongly predicts postnatal depression in primary health care

Objective: To estimate the association between antenatal and postnatal depression and to examine the role of socioeconomic conditions in the risk of postnatal depression. Methods: A prospective cohort study, conducted between May 2005 and January 2006, with 831 pregnant women recruited from primary care clinics in the public sector in the city of Sao Paulo, Brazil. The presence of antenatal and postnatal depression was measured with the Self Report Questionnaire (SRQ-20). Sociodemographic and socioeconomic characteristics and obstetric information were obtained through a questionnaire. Crude and adjusted risk ratios (RR), with 95% CI, were calculated using a Poisson regression. Results: The prevalence of postnatal depressive symptoms was 31.2% (95% CI: 27.8-34.8%). Among the 219 mothers who had depressive symptoms, nearly 50% had already shown depressive symptoms during pregnancy. Women who had antenatal depression were 2.4 times more likely to present with postnatal depression than were women who did not have such symptoms during pregnancy. In the multivariate analysis, higher scores for assets (RR: 0.76, 95% CI 0.61-0.96), higher education (RR: 0.75 95% CI 0.59-0.96), daily contact with neighbors (RR: 0.68, 95% CI 0.51-0.90) and antenatal depression (RR: 2.44, 95% CI 1.93-3.08) remained independently associated with postnatal depression. Conclusions: Antenatal and postnatal depression are highly prevalent in the primary care setting.

Are mental health problems and depression associated with bruxism in children?

Renner AC, da Silva AAM, Rodriguez JDM, Simoes VMF, Barbieri MA, Bettiol H, Thomaz EBAF, Saraiva MC. Are mental health problems and depression associated with bruxism in children? Community Dent Oral Epidemiol 2011. (C) 2011 John Wiley & Sons A/S Abstract Objectives: Previous studies have found an association between bruxism and emotional and behavioral problems in children, but reported data are inconsistent. The objective of this study was to estimate the prevalence of bruxism, and of its components clenching and grinding, and its associations with mental problems and depression. Methods: Data from two Brazilian birth cohorts were analyzed: one from 869 children in Ribeirao Preto RP (Sao Paulo), a more developed city, and the other from 805 children in Sao Luis SL (Maranhao). Current bruxism evaluated by means of a questionnaire applied to the parents/persons responsible for the children was defined when the habit of tooth clenching during daytime and/or tooth grinding at night still persisted until the time of the assessment. Additionally, the lifetime prevalence of clenching during daytime only and grinding at night only was also evaluated. Mental health problems were investigated using the Strength and Difficulties Questionnaire (SDQ) and depression using the Childrens Depression Inventory (CDI). Analyses were carried out for each city: with the SDQ subscales (emotional symptoms, conduct problems, peer problems, attention/hyperactivity disorder), with the total score (sum of the subscales), and with the CDI. These analyses were performed considering different response variables: bruxism, clenching only, and grinding only. The risks were estimated using a Poisson regression model. Statistical inferences were based on 95% confidence intervals (95% CI). Results: There was a high prevalence of current bruxism: 28.7% in RP and 30.0% in SL. The prevalence of clenching was 20.3% in RP and 18.8% in SL, and grinding was found in 35.7% of the children in RP and 39.1% in SL. Multivariable analysis showed a significant association of bruxism with emotional symptoms and total SDQ score in both cities. When analyzed separately, teeth clenching was associated with emotional symptoms, peer problems, and total SDQ score; grinding was significantly associated with emotional symptoms and total SDQ score in RP and SL. Female sex appeared as a protective factor for bruxism, and for clenching and grinding in RP. Furthermore, maternal employment outside the home and white skin color of children were associated with increased prevalence of teeth clenching in SL. Conclusions: Mental health problems were associated with bruxism, with teeth clenching only and grinding at night only. No association was detected between depression and bruxism, neither clenching nor grinding. But it is necessary to be cautious regarding the inferences from some of our results.

Profilo psicopatologico e qualità della vita in bambini e adolescenti narcolettici: studio caso-controllo

Scopo del nostro lavoro è stato descrivere ed inquadrare gli aspetti psico-comportamentali e la qualità di vita della narcolessia in età evolutiva. Metodi: Abbiamo pertanto disegnato uno studio caso-controllo comprendente 30 pazienti narcolettici, 39 epilettici, e 39 controlli sani, appaiati per sesso e età. Risultati: La nostra popolazione di bambini e adolescenti affetti da narcolessia mostra un aumento delle problematiche internalizzanti. I due gruppi patologici hanno in comune punteggi più elevati rispetto ai controlli per i disturbi d’ansia, le difficoltà attentive e di socializzazione, i disturbi oppositivo-provocatori. Ciò che distingue, invece, i pazienti narcolettici, sono gli aspetti di ritiro e depressione, la tendenza alla somatizzazione, i problemi del pensiero ed i disturbi affettivi. Fattori di rischio psicopatologici per i giovani narcolettici sono risultati essere l’esordio precoce, il ritardo diagnostico, il sonno notturno disturbato, la minor latenza di sonno all’addormentamento, un maggior numero di SOREMP all’MSLT. Dall’altro lato la terapia farmacologica, un maggior numero di sonnellini spontanei e la durata di malattia, sembrano influenzare positivamente l’evoluzione comportamentale. La salute psicosociale dei giovani narcolettici, inoltre, risulta essere peggiore rispetto ai controlli sani, mentre la salute fisica non mostra differenze. I problemi internalizzanti influenzano negativamente tutti gli ambiti della salute di questi ragazzi, mentre la durata di malattia sembra migliorare il funzionamento scolastico. Conclusioni: Il nostro lavoro conferma che i giovani narcolettici presentano un maggior rischio psicopatologico sia rispetto ai controlli sani sia rispetto un’altra patologia neurologica cronica. Se da un lato alcuni aspetti comportamentali possono essere giustificati come una reazione adattativa verso una patologia neurologica invalidante, dall’altro un quadro distimico caratterizzato da ritiro e lamentele somatiche, sembra essere tipico dei bambini ed adolescenti narcolettici.

Transgenic mice as a tool for depression research: examples from the endocannabinoid and the corticotropin-releasing hormone system

Major depression belongs to the most serious and widespread psychiatric disorders in today’s society. There is a great need for the delineation of the underlying molecular mechanisms as well as for the identification of novel targets for its treatment. In this thesis, transgenic mice of the endocannabinoid and the corticotropin-releasing hormone (CRH) system were investigated to determine the putative role of these systems for depression-like phenotypes in mice. In the first part of the thesis, we found that the endocannabinoid system was prominently involved in a brain region-specific and temporally controlled manner in acute as well as in chronic stress processing. Genetic deletion in combination with pharmacological intervention revealed the importance of a fully functional endocannabinoid system for efficient neuroendocrine and behavioral stress coping. Accordingly, cannabinoid type 1 (CB1) receptor-deficient mice displayed several depression-like symptoms and molecular alterations, including “behavioral despair”, stress hormone hypersecretion and decreased glucocorticoid receptor and brain-derived neurotrophic factor expression in the hippocampus. However, the endocannabinoid system was dispensable for the efficacy of currently used antidepressant drugs. To facilitate future endocannabinoid research, a transgenic mouse was generated, which overexpressed the CB1 receptor protein fused to a fluorescent protein. In the second part of the thesis, conditional brain region-specific CRH overexpressing mice were evaluated as a model for pathological chronic CRH hyperactivation. Mutant mice showed aberrant neuroendocrine and behavioral stress coping and hyperarousal due to CRH-induced activation of the noradrenergic system in the brain. Mutant mice appeared to share similarities with naturally occurring endogenous CRH activation in wild-type mice and were sensitive to acute pharmacological blockade of CRH receptor type 1 (CRH-R1). Thus, CRH overexpressing mice serve as an ideal in vivo tool to evaluate the efficacy of novel CRH-R1 antagonists. Together, these findings highlight the potential of transgenic mice for the understanding of certain endo-phenotypes (isolated symptoms) of depression and their molecular correlates.

Psychosocial correlates of rehabilitation from stroke: a longitudinal study

The general aim of this dissertation was to uncover the association between psychosocial factors and rehabilitation outcome after stroke. METHOD. A sample of patients with stroke (n=40) and their caregivers (n=36) were assessed at admission to and six months after discharge from rehabilitation hospital, using the following instruments: Structured Clinical Interview for DSM-IV, structured interview based on Diagnostic Criteria for Psychosomatic Research, Symptom Questionnaire, Psychosocial Index, Psychological Well-Being Scales, and Family Assessment Device. 40 subjects from the general population underwent the same psychological assessment. In addition, patients' functional status was measured using the Functional Independence Measure. RESULTS. Stroke survivors reported lower education and higher alcohol consumption than controls. No significant differences emerged between the two groups in the prevalence of psychiatric diagnoses or psychosomatic syndromes, however patients reported significantly higher levels of anxiety, depression, somatic symptoms, and lower autonomy than controls. Caregivers reported significantly higher scores in anxiety, depression, and somatic symptoms compared to normative data, while no impairments emerged in psychological well-being and family functioning. At six-month follow-up, in patients a significant decrease in smoking habit and an increase in DSM diagnoses were reported. Both stroke survivors and caregivers showed significant reductions in anxiety, with patients displaying also a decrease in somatic symptoms, an increase in stress and a deterioration in quality of life. Significant deteriorations in several aspects of family functioning was perceived only by patients. An association between patients' functional recovery in the cognitive domain and family behavior control emerged. For caregivers, family functioning significantly predicted hostility and somatic symptoms were associated with family affective involvement. CONCLUSIONS. These data highlight the utility in the Italian setting of the adoption of a psychosocial assessment and a family-systems approach in stroke rehabilitation, in order to development interventions properly targeted to the characteristics of patients and their family members.

Atypical depression and alcohol misuse are related to the cardiovascular risk in the general population

OBJECTIVE: The aims of the present study were to assess the associations between mood, anxiety and substance use disorders, including their subtypes, and the prevalence of cardiovascular risk factors (CVRFs). METHOD: Thorough physical investigations, biological measures and standardized interview techniques were used to assess 3716 subjects of an urban area, aged 35-66 years. RESULTS: Atypical depression was associated with increased prevalence of overweight, diabetes and the metabolic syndrome (OR = 1.5, 95% C.I. 1.1-2.0; OR = 2.0, 95% C.I. 1.1-3.5, OR = 1.6, 95% C.I. 1.0-2.4 respectively), whereas decreased prevalence of overweight was found in melancholic (OR = 0.7, 95% C.I. 0.6-0.9) and unspecified depression (OR = 0.8, 95% C.I. 0.7-1.0). Alcohol abuse was associated with diabetes (OR = 1.8, 95% C.I. 1.1-2.9) and dyslipidemia (OR = 1.3, 95% C.I. 1.0-1.8), alcohol dependence with dyslipidemia only (OR = 1.4, 95% C.I. 1.0-2.0). Almost all mental disorders were associated with a lifetime history of regular cigarette smoking, and atypical depression, alcohol misuse and drug dependence were associated with inactivity. CONCLUSION: To conclude results emphasize the need to subtype depression and to pay particular attention to the atypical subtype. Comorbid alcohol misuse may further increase the cardiovascular risk. Efforts to diminish smoking in subjects with mental disorders could be crucial measures to reduce their high incidence of cardiovascular disease.

Adolescent survivors of childhood cancer: are they vulnerable for psychological distress?

OBJECTIVES: We aimed to (i) evaluate psychological distress in adolescent survivors of childhood cancer and compare them to siblings and a norm population; (ii) compare the severity of distress of distressed survivors and siblings with that of psychotherapy patients; and (iii) determine risk factors for psychological distress in survivors. METHODS: We sent a questionnaire to all childhood cancer survivors aged <16 years when diagnosed, who had survived ≥5 years and were aged 16-19 years at the time of study. Our control groups were same-aged siblings, a norm population, and psychotherapy patients. Psychological distress was measured with the Brief Symptom Inventory-18 (BSI-18) assessing somatization, depression, anxiety, and a global severity index (GSI). Participants with a T-score ≥57 were defined as distressed. We used logistic regression to determine risk factors. RESULTS: We evaluated the BSI-18 in 407 survivors and 102 siblings. Fifty-two survivors (13%) and 11 siblings (11%) had scores above the distress threshold (T ≥ 57). Distressed survivors scored significantly higher in somatization (p = 0.027) and GSI (p = 0.016) than distressed siblings, and also scored higher in somatization (p ≤ 0.001) and anxiety (p = 0.002) than psychotherapy patients. In the multivariable regression, psychological distress was associated with female sex, self-reported late effects, and low perceived parental support. CONCLUSIONS: The majority of survivors did not report psychological distress. However, the severity of distress of distressed survivors exceeded that of distressed siblings and psychotherapy patients. Systematic psychological follow-up can help to identify survivors at risk and support them during the challenging period of adolescence. Copyright © 2013 John Wiley & Sons, Ltd.