Why Don't You Try Harder? An Investigation of Effort Production in Major Depression

Depression is mainly characterized as an emotional disorder, associated with reduced approach behavior. It remains unclear whether the difficulty in energising behavior relates to abnormal emotional states or to a flattened response to potential rewards, as suggested by several neuroimaging studies. Here, we aimed to demonstrate a specific incentive motivation deficit in major depression, independent of patients' emotional state. We employed a behavioral paradigm designed to measure physical effort in response to both emotional modulation and incentive motivation. Patients did exert more effort following emotionally arousing pictures (whether positive or negative) but not for higher monetary incentives, contrary to healthy controls. These results show that emotional and motivational sources of effort production are dissociable in pathological conditions. In addition, patients' ratings of perceived effort increased for high incentives, whereas controls' ratings were decreased. Thus, depressed patients objectively behave as if they do not want to gain larger rewards, but subjectively feel that they try harder. We suggest that incentive motivation impairment is a core deficit of major depression, which may render everyday tasks abnormally effortful for patients.     

Serotonin transporter gene,childhood emotional abuse and cognitive vulnerability to depression

Meta‐analyses evaluating the association between the serotonin transporter polymorphism (5‐HTTLPR) with neuroticism and depression diagnosis as phenotypes have been inconclusive. We examined a gene–environment interaction on a cognitive vulnerability marker of depression, cognitive reactivity (CR) to sad mood. A total of 250 university students of European ancestry were genotyped for the 5‐HTTLPR, including SNP rs25531, a polymorphism of the long allele. Association analysis was performed for neuroticism, CR and depression diagnosis (using a self‐report measure). As an environmental pathogen, self‐reported history of childhood emotional abuse was measured because of its strong relationship with depression. Participants with the homozygous low expressing genotype had high CR if they had experienced childhood emotional maltreatment but low CR if they did not have such experience. This interaction was strongest on the Rumination subscale of the CR measure. The interaction was not significant with neuroticism or depression diagnosis as outcome measures. Our results show that 5‐HTTLPR is related to cognitive vulnerability to depression. Our findings provide evidence for a differential susceptibility genotype rather than a vulnerability genotype, possibly because of the relatively low levels of abuse in our sample. The selection of phenotype and environmental contributor is pivotal in investigating gene–environment interactions in psychiatric disorders.     

Mitochondrial Dysfunction and Psychiatric Disorders

Mitochondrial oxidative phosphorylation is the major ATP-producing pathway, which supplies more than 95% of the total energy requirement in the cells. Damage to the mitochondrial electron transport chain has been suggested to be an important factor in the pathogenesis of a range of psychiatric disorders. Tissues with high energy demands, such as the brain, contain a large number of mitochondria, being therefore more susceptible to reduction of the aerobic metabolism. Mitochondrial dysfunction results from alterations in biochemical cascade and the damage to the mitochondrial electron transport chain has been suggested to be an important factor in the pathogenesis of a range of neuropsychiatric disorders, such as bipolar disorder, depression and schizophrenia. Bipolar disorder is a prevalent psychiatric disorder characterized by alternating episodes of mania and depression. Recent studies have demonstrated that important enzymes involved in brain energy are altered in bipolar disorder patients and after amphetamine administration, an animal model of mania. Depressive disorders, including major depression, are serious and disabling. However, the exact pathophysiology of depression is not clearly understood. Several works have demonstrated that metabolism is impaired in some animal models of depression, induced by chronic stress, especially the activities of the complexes of mitochondrial respiratory chain. Schizophrenia is a devastating mental disorder characterized by disturbed thoughts and perception, alongside cognitive and emotional decline associated with a severe reduction in occupational and social functioning, and in coping abilities. Alterations of mitochondrial oxidative phosphorylation in schizophrenia have been reported in several brain regions and also in platelets. Abnormal mitochondrial morphology, size and density have all been reported in the brains of schizophrenic individuals. Considering that several studies link energy impairment to neuronal death, neurodegeneration and disease, this review article discusses energy impairment as a mechanism underlying the pathophysiology of some psychiatric disorders, like bipolar disorder, depression and schizophrenia.     

Childhood Maltreatment in Extremely Obese Male and Female Bariatric Surgery Candidates**

Objective: To examine rates of self‐reported childhood maltreatment in extremely obese bariatric surgery candidates and to explore associations with sex, eating disorder features, and psychological functioning. Research Methods and Procedures: Three hundred forty (58 men and 282 women) extremely obese consecutive candidates for gastric bypass surgery completed a questionnaire battery. The Childhood Trauma Questionnaire was given to assess childhood maltreatment. Results: Overall, 69% of patients self‐reported childhood maltreatment: 46% reported emotional abuse, 29% reported physical abuse, 32% reported sexual abuse, 49% reported emotional neglect, and 32% reported physical neglect. Except for higher rates of emotional abuse reported by women, different forms of maltreatment did not differ significantly by sex. Different forms of maltreatment were generally not associated with binge eating, current BMI, or eating disorder features. At the Bonferonni‐corrected significance level, emotional abuse was associated with higher eating concerns and body dissatisfaction, and emotional neglect was associated with higher eating concerns. In terms of psychological functioning, at the Bonferonni‐corrected level, emotional abuse and emotional neglect were associated with higher depression and lower self‐esteem, and physical abuse was associated with higher depression. Discussion: Extremely obese bariatric surgery candidates reported rates of maltreatment comparable with those reported by clinical groups and roughly two to three times higher than normative community samples. Reported experiences of maltreatment differed little by sex and were generally not significantly associated with current BMI, binge eating, or eating disorder features. In contrast, maltreatment—notably emotional abuse and neglect—were significantly associated with higher depression and lower self‐esteem.     

Plasma and erythrocyte membrane long chain polyunsaturated fatty acids in endogenous depression

Patients suffering from endogenous depression had significantly greater proportions of long chain polyunsaturated fatty acids (LCP), docosahexaenoic acid (22:6ω3) and eicosapentaenoic acid (20:5ω3), and a reduced proportion of linoleic acid (18:2ω6) in their plasma choline phosphoglycerides (CPG) compared with age-sex-matched healthy controls. Patients suffering from reactive depression or from other psychiatric disorders did not differ significantly from matched controls. Changes in the fatty acid composition of the major erythrocyte membrane phospholipids were in the same direction but were less marked. The importance and possible reasons for the elevated LCP in endogenous depression are discussed.     

Muscarinic supersensitivity of anterior pituitary ACTH and B-endorphin release in major depressive illness

Subjects with major depressive illness had greater increases in plasma concentrations of ACTH and B-endorphin immunoreactivity in response to central muscarinic stimulation by physostigmine, than did normal control subjects, or psychiatric control subjects without major depressive illness. These findings provide further evidence for muscarinic receptor supersensitivity in depression and may implicate an abnormality of peptide physiology in the pathogenesis of depression.     

Convergent and Divergent Functional Connectivity Patterns in Schizophrenia and Depression

Major depression and schizophrenia are two of the most serious psychiatric disorders and share similar behavioral symptoms. Whether these similar behavioral symptoms underlie any convergent psychiatric pathological mechanisms is not yet clear. To address this issue, this study sought to investigate the whole-brain resting-state functional magnetic resonance imaging (MRI) of major depression and schizophrenia by using multivariate pattern analysis. Thirty-two schizophrenic patients, 19 major depressive disorder patients and 38 healthy controls underwent resting-state functional MRI scanning. A support vector machine in conjunction with intrinsic discriminant analysis was used to solve the multi-classification problem, resulting in a correct classification rate of 80.9% via leave-one-out cross-validation. The depression and schizophrenia groups both showed altered functional connections associated with the medial prefrontal cortex, anterior cingulate cortex, thalamus, hippocampus, and cerebellum. However, the prefrontal cortex, amygdala, and temporal poles were found to be affected differently by major depression and schizophrenia. Our preliminary study suggests that altered connections within or across the default mode network and the cerebellum may account for the common behavioral symptoms between major depression and schizophrenia. In addition, connections associated with the prefrontal cortex and the affective network showed promise as biomarkers for discriminating between the two disorders.     

Reliable change in depression during behavioral weight loss treatment among women with major depression

Objective: Although behavioral weight loss interventions generally have been shown to improve depressive symptoms, little is known as to whether some people with major depressive disorder experience worsening of depression during a weight loss intervention. Design and Methods: Rates and predictors of change in depression symptoms among 148 obese women with major depressive disorder who participated in a trial comparing depression treatment plus behavioral weight loss treatment (Behavioral Activation; BA) to behavioral weight loss treatment alone (Lifestyle Intervention; LI) were examined. A statistically reliable change in depression was calculated as ≥9 points on the Beck Depression Inventory in this sample. Results: At 6 months, 73% of participants in BA and 54% of participants in LI showed reliable improvement in depression symptoms and 1.5% of participants in BA and 1.3% of participants in LI showed reliable worsening in depression symptoms. Rates of reliable change were similar at 12 months. Participants who experienced reliable improvement in depression lost significantly more weight than those who did not in both conditions. In the LI condition, baseline psychiatric variables and change in physical activity during treatment were also related to reliable improvement in depression. Conclusion: No evidence for an iatrogenic effect of behavioral weight loss treatment on depressive symptoms among obese women with major depressive disorder was detected; rather, behavioral weight loss treatment appears to be associated with significant concurrent improvement in depression. Even greater rates of reliable improvement were observed when depression treatment was added to weight loss treatment.     

Effects of depression on physical health and mortality in the elderly. Longitudinal results of the LASA research

This longitudinal study examines the physical health consequences of depression among 3107 older persons (55-85 years). Major depression was defined according to DSM-III criteria in a psychiatric interview. Minor depression was defined by a Center for Epidemiologic Studies Depression score > or = 16. Health consequences were assessed by 3-year change in self-reported functional status, 3-year change in performance on objective tests, and risk of death over 4.5 years. At baseline, 12.8% of the older persons had minor depression and 2.0% major depression. Minor depression was associated with a significantly greater decline in functional status and performance and, only in men but not in women, with an increased risk of death. Major depression also increases decline in functional status and the risk of death (irrespective of sex), but was not associated with decline in physical performance. These results show that late-life depression has strong unfavorable physical health consequences. The consequences of minor depression are comparable with those of major depression.     

非人灵长类动物模型睡眠研究在神经精神疾病的早期诊断和药效评价中的作用

清醒-睡眠的周期性调节需要众多单胺类神经递质(5-HT、NE、DA等)、乙酰胆碱等兴奋性神经递质以及GABA等抑制性神经递质的参与。这些递质系统的异常不仅会导致睡眠周期紊乱,还与一系列的精神性和神经退行性疾病相关。睡眠异常被认为是抑郁症、帕金森氏病等神经系统疾病发生的早期预警信号。相比起低等哺乳动物,非人灵长类动物的睡眠与人类的睡眠具有更好的可比性。近来,利用非人灵长类动物来建立神经精神疾病模型的研究已取得明显进展。在建模的同时监测动物的睡眠状况,有助于我们进一步了解睡眠在这些疾病早期诊断和发展过程中的作用,为疾病的早期诊断、治疗和药效评价提供更好的客观依据。     

Stimulating personality: Ethical criteria for deep brain stimulation in psychiatric patients and for enhancement purposes

Within the recent development of brain-machine-interfaces deep brain stimulation (DBS) has become one of the most promising approaches for neuromodulation. After its introduction more than 20 years ago, it has in clinical routine become a successful tool for treating neurological disorders like Parkinson's disease, essential tremor and dystonia. Recent evidence also demonstrates efficacy in improving emotional and cognitive processing in obsessive-compulsive disorder and major depression, thus allowing new treatment options for treatment refractory psychiatric diseases, and even indicating future potential to enhance functioning in healthy subjects. We demonstrate here that DBS is neither intrinsically unethical for psychiatric indications nor for enhancement purposes. To gain normative orientation, the concept of “personality” is not useful – even if a naturalistic notion is employed. As an alternative, the common and widely accepted bioethical criteria of beneficence, non-maleficence, and autonomy allow a clinically applicable, highly differentiated context- and case-sensitive approach. Based on these criteria, an ethical analysis of empirical evidence from both DBS in movement disorders and DBS in psychiatric disease reveals that wide-spread use of DBS for psychiatric indications is currently not legitimated and that the basis for enhancement purposes is even more questionable. Nevertheless, both applications might serve as ethically legitimate, promising purposes in the future.     

Counselling in a general practice setting: controlled study of health visitor intervention in treatment of postnatal depression.

OBJECTIVE--To determine whether counselling by health visitors is helpful in managing postnatal depression. DESIGN--Controlled, random order trial. SETTING--Health centres in Edinburgh and Livingston. PATIENTS--Sixty women identified as depressed by screening at six weeks post partum and by psychiatric interview at about 13 weeks post partum. Five women did not wish to participate, and a further five did not complete the trial. Age, social and obstetric factors, and diagnosis were similar in women who completed the trial and those who withdrew. INTERVENTION--Eight weekly counselling visits by health visitors who had been given a short training in counselling for postnatal depression. END POINT--Reduction of depression. MEASUREMENTS and main results--Standardised psychiatric interviews and a 10 point self report scale were used to identify depression before and after intervention. The psychiatrist was not told to which group women were allocated. After three months 18 (69%) of the 26 women in the treatment group had fully recovered compared with nine (38%) of the 24 in the control group. The difference between the groups was thus 32% (95% confidence interval 5 to 58). CONCLUSIONS--Counselling by health visitors is valuable in managing non-psychotic postnatal depression.     

Genetic and epigenetic factors associated with depression: An updated overview

Depression is a complex psychiatric disturbance involving many environmental, genetic, and epigenetic factors. Until now, genetic, and non-genetic studies are still on the way to understanding the complex mechanism of this disease, and there are still many questions that have not yet been answered. Depression includes a large spectrum of heterogeneous symptoms correlated to the deficit of a range of psychological, cognitive, and emotional processes, and it affects various age groups. It is classified into several types according to the severity of symptoms, time of occurrence, and time. Following the World Health Organization (WHO), depression attacks near 350 million persons globally. Several factors overlap in causing depression, including genetic and epigenetic factors, environmental conditions, various stresses, lack of some nutrients to which people are exposed, and excessive stress and abuse in childhood. This study included conducting surveys on depression and new treatment trends based on epigenetic factors associated with the occurrence of the disease. Epigenetic factors provide a completely novel dimension to therapeutic approaches as most diseases are not monogenic, and it is likely that the environment has a significant contribution. Epigenetic inheritance is included in many mental and psychiatric disorders such as depression. In general, epigenetic modifications could be summarized in 3 major points: DNA methylation, histone modification, and non-mediated regulation of RNA (ncRNA). This study also describes some genes associated with one of the depressive disorders using bioinformatics tools and gene bank and had the genes: SLC6A4, COMT, TPH2, FKBP5, MDD1, HTR2A, and MDD2. As in this study, the awareness of Saudi society about depression and its genetic and non-genetic causes was estimated. The results showed that an encouraging percentage of more than half of the research sample possessed correct information about this disorder.     

Emotion Processing in Parkinson’s Disease: A Three-Level Study on Recognition,Representation, and Regulation

Background

Parkinson’s disease (PD) is characterised by well-known motor symptoms, whereas the presence of cognitive non-motor symptoms, such as emotional disturbances, is still underestimated. One of the major problems in studying emotion deficits in PD is an atomising approach that does not take into account different levels of emotion elaboration. Our study addressed the question of whether people with PD exhibit difficulties in one or more specific dimensions of emotion processing, investigating three different levels of analyses, that is, recognition, representation, and regulation.

Methodology

Thirty-two consecutive medicated patients with PD and 25 healthy controls were enrolled in the study. Participants performed a three-level analysis assessment of emotional processing using quantitative standardised emotional tasks: the Ekman 60-Faces for emotion recognition, the full 36-item version of the Reading the Mind in the Eyes (RME) for emotion representation, and the 20-item Toronto Alexithymia Scale (TAS-20) for emotion regulation.

Principal Findings

Regarding emotion recognition, patients obtained significantly worse scores than controls in the total score of Ekman 60-Faces but not in any other basic emotions. For emotion representation, patients obtained significantly worse scores than controls in the RME experimental score but no in the RME gender control task. Finally, on emotion regulation, PD and controls did not perform differently at TAS-20 and no specific differences were found on TAS-20 subscales. The PD impairments on emotion recognition and representation do not correlate with dopamine therapy, disease severity, or with the duration of illness. These results are independent from other cognitive processes, such as global cognitive status and executive function, or from psychiatric status, such as depression, anxiety or apathy.

Conclusions

These results may contribute to better understanding of the emotional problems that are often seen in patients with PD and the measures used to test these problems, in particular on the use of different versions of the RME task.     

Genetic biomarkers of depression

Depression is a term that has been used to describe a variety of ailments, ranging from minor to incapacitating. Clinically significant depression, termed as major depression, is a serious condition characterized not only by depressed mood but also by a cluster of somatic, cognitive, and motivational symptoms. Significant research efforts are aimed to understand the neurobiological as well as psychiatric disorders, and the evaluation of treatment of these disorders is still based solely on the assessment of symptoms. In order to identify the biological markers for depression, we have focused on gathering information on different factors responsible for depression including stress, genetic variations, neurotransmitters, and cytokines and chemokines previously suggested to be involved in the pathophysiology of depression. The present review illustrates the potential of biomarker profiling for psychiatric disorders, when conducted in large collections. The review highlighted the biomarker signatures for depression, warranting further investigation.     

Depression and other psychiatric morbidity in carers of elderly people living at home.

OBJECTIVE--To describe the mental health of a community sample of carers of elderly people with dementia, depression, or physical disability and to compare that with the mental health of other adults living in the household and of those living alone. DESIGN--Assessment of psychiatric morbidity and physical disability with standardised questionnaire in randomly selected enumeration districts; subjects were interviewed at home. SETTING--London Borough of Islington. SUBJECTS--700 people aged > or = 65 and other coresidents. MAIN OUTCOME MEASURE--Depression measured with standardised interview. RESULTS--The prevalence of depression was not significantly higher in carers overall (15%) than in coresidents (11%). Being a woman carer was a significant predictor of psychiatric illness. Depression was more common in the carers of people with a psychiatric disorder than in coresidents (24% v 11%, P < 0.05) and in those living alone (19%). Depression was most common (47%) in women carers of people with dementia. CONCLUSION--The increase in psychiatric morbidity reported in carers of people with psychiatric disorders may reflect the lack of a confiding relationship.     

Neuropeptide Y in Frontal Cortex Is Not Altered in Major Depression

Abstract: Previously, we reported a modest but significant reduction in the concentration of neuropeptide Y in frontal cortices from victims of suicide relative to age-matched natural or accidental death control subjects. The reduction in neuropeptide Y appeared to be greatest in a subgroup of victims of suicide for which there was indirect evidence of histories of depression. We pursued these initial findings in the present study by measuring neuropeptide Y concentrations in frontal cortices from natural or accidental death control subjects and from suicide victims in whom a firm diagnosis of major depression was established by psychiatric autopsy. Because several subjects with major depression had a comorbid diagnosis of alcoholism, a group of victims of suicide that had an Axis I diagnosis of alcohol dependence was also studied. No significant differences in neuropeptide Y concentrations were observed between control subjects and victims of suicide with major depression or victims of suicide with alcohol dependence. These findings do not support a role for neuropeptide Y in major depression.     

Corticotropin-releasing hormone: from endocrinology to psychobiology

Corticotropin-releasing hormone (CRH) is a brain neuropeptide which coordinates the endocrine, autonomic and behavioral responses to stress. We review the abnormal response to exogenous CRH in various psychiatric syndromes, including major depression and anorexia nervosa. We also contrast pituitary responses to CRH in patients with depression versus Cushing's disease. We hypothesize that CRH may play a role in the pathogenesis of various psychiatric syndromes which are characterized during their course by the symptom of depression.     

Psychiatric consequences of road traffic accidents.

OBJECTIVE--To determine the psychiatric consequences of being a road traffic accident victim. DESIGN--Follow up study of road accident victims for up to one year. SETTING--Emergency department of the John Radcliffe Hospital, Oxford. SUBJECTS--188 consecutive road accident victims aged 18-70 with multiple injuries (motorcycle or car) or whiplash neck injury, who had not been unconscious for more than 15 minutes, and who lived in the catchment area. MAIN OUTCOME MEASURES--Present state examination "caseness"; post-traumatic stress disorder and travel anxiety; effects on driving and on being a passenger. RESULTS--Acute, moderately severe emotional distress was common. Almost one fifth of subjects, however, suffered from an acute stress syndrome characterised by mood disturbance and horrific memories of the accident. Anxiety and depression usually improved over the 12 months, though one tenth of patients had mood disorders at one year. In addition, specific post-traumatic symptoms were common. Post-traumatic stress disorder occurred during follow up in one tenth of patients, and phobic travel anxiety as a driver or passenger was more common and frequently disabling. Emotional disorder was associated with having pre-accident psychological or social problems and, in patients with multiple injuries, continuing medical complications. Post-traumatic syndromes were not associated with a neurotic predisposition but were strongly associated with horrific memories of the accident. They did not occur in subjects who had been briefly unconscious and were amnesic for the accident. Mental state at three months was highly predictive of mental state at one year. CONCLUSIONS--Psychiatric symptoms and disorder are frequent after major and less severe road accident injury. Post-traumatic symptoms are common and disabling. Early information and advice might reduce psychological distress and travel anxiety and contribute to road safety and assessing "nervous shock."     

Preventive Psychiatry: The Psychiatric Team as Consultant to the Public Health Nurse

Various forms of collaboration between the disciplines of public health and psychiatry are briefly reviewed and the 25-year-old mental health program of the Vancouver Health Department is described. The public health nurse has prime responsibility in all children with emotional disorders. She is supported by a psychiatric team which provides active treatment and educational and consultative help for the nurse and the school. During the year 1963, six social workers had 2357 contacts with nurses and school personnel but only 1049 treatment interviews. Of 401 children referred to the psychiatric team, 138 received active clinic treatment, 141 remained under supervision by the public health nurse, and 122 were referred elsewhere. In addition, 1330 children were identified as “mental hygiene cases” in the caseload of the 170 public health nurses in the community. By close co-ordination, the public health nurse and the psychiatric team can enhance each other''s contributions to community mental health.