Biological risk factors in late life depression.

A number of biological risk factors have been tentatively identified for unipolar and bipolar disorder in the elderly. The list includes genetic factors as well as medical illness in general and vascular disease in particular. Most of these risk factors have been identified on the basis of cross sectional studies rather than longitudinal studies. There is a need for long term epidemiologic and prevention studies (in the case of modifiable risk factors). The modifiable risk factors include medical illness in general and vascular disease in particular. An example is the use of antidepressants following stroke to prevent the onset of depression. Of particular interest is the role of vascular risk factors and MRI changes suggesting subtle cerebrovascular disease in the development of depression and bipolar disorder in late life. The changes have been established using both clinical samples and in the case of depression in cross sectional epidemiologic samples. The location of these cerebrovascular changes has contributed to our understanding of the regions of the brain implicated in the pathophysiology of depression. Further longitudinal and preventive studies are needed to conclusively demonstrate these as biological risk factors.     

Psychosocial risk factors to major depression after childbirth

BACKGROUND: Risk factors to postnatal depression (PND) have generally been identified in well-defined homogenous samples of primiparous women. There is a need for studies to assess risk factors in a heterogeneous sample of women. AIM: This study is aimed to identify psychosocial risk factors to postnatal depression. METHOD: Subjects underwent a baseline assessment within 2 days of childbirth and completed postal questionnaires at 6, 12, 18 and 24 weeks postpartum. Postnatal depression was defined as scoring above 12 on the Edinburgh Postnatal Depression Scale on two occasions and meeting criteria for major depression using the Structured Clinical Interview for DSM-III-R. RESULTS: Four hundred and twenty-five women with a mean age of 26.9 years participated in the study. Forty-two women were considered to be cases of postnatal depression. A significantly increased risk for postnatal depression was associated with (a) being 16 years old or younger, (b) a past history of psychiatric illness, (c) experiencing one or more life events, (d) marital dissatisfaction, (e) experiencing unsatisfactory social support, (f) a vulnerable personality and (g) having a baby of the nondesired sex. CONCLUSION: This study confirmed that psychosocial risk factors, predominantly in the areas of social support and personality style, are closely associated with postnatal depression.     

Shaming experiences and the association between adolescent depression and psychosocial risk factors

OBJECTIVE: To investigate whether psychosocial risk factors such as parental separation, parental unemployment and experiences of sexual abuse are associated with adolescent depression, and whether shaming experiences (defined as experiences of being degraded, or ridiculed by others) may account for such an association. METHOD: A total of 5048 Swedish adolescents answered the Survey of Adolescent Life in Vestmanland 2004 (SALVe-2004) during classhours. The survey included questions about depressive symptoms, parental separation, parental unemployment and experiences of sexual abuse. RESULTS: The psychosocial risk factors studied were all associated with depression, but several of these associations became non-significant when a factor for shaming experiences was entered into the models. The explained variance for depression furthermore increased from approximately 4-7% to 17-20% when shame was included. CONCLUSION: Shaming experiences may mediate part of the association between psychosocial risk factors and depression. These findings may have important implications for the understanding of psychotherapeutic treatment of the effects of risk factors in depressed patients.     

Hypnosis in treating symptoms and risk factors of major depression

This article summarizes aspects of effective psychotherapy for major depression and describes how hypnosis can further enhance therapeutic effectiveness. Hypnosis is helpful in reducing common symptoms of major depression such as agitation and rumination and thereby may decrease a client' sense of helplessness and hopelessness. Hypnosis is also effective in facilitating the learning of new skills, a core component of all empirically supported treatments for major depression. The acquisition of such skills has also been shown to not only reduce depression, but also the likelihood of relapses, thus simultaneously addressing issues of risk factors and prevention.     

Cortisol activity and cognitive changes in psychotic major depression

OBJECTIVE: The theory that psychotic major depression is a distinct syndrome is supported by reports of statistically significant differences between psychotic and nonpsychotic major depression in presenting features, biological measures, familial transmission, course and outcome, and response to treatment. This study examined differences in performance on a verbal memory test and in cortisol levels between patients with psychotic and nonpsychotic major depression and healthy volunteers. METHOD: Ten patients with psychotic major depression, 17 patients with nonpsychotic major depression, and 10 healthy volunteers were administered the Wallach Memory Recognition Test and had blood drawn at half-hour intervals over the course of an afternoon to assay cortisol levels. RESULTS: Subjects with psychotic major depression had a higher rate of errors of commission on the verbal memory test (incorrectly identified distracters as targets) than did subjects with nonpsychotic major depression or healthy volunteers; errors of omission were similar among the three groups. Subjects with psychotic major depression had higher cortisol levels throughout the afternoon than subjects with nonpsychotic major depression or healthy volunteers. This effect became even more pronounced later in the afternoon. CONCLUSIONS: Psychotic major depression is endocrinologically different from nonpsychotic major depression and produces cognitive changes distinct from those seen in nonpsychotic major depression.     

Detecting psychotic major depression using psychiatric rating scales

OBJECTIVE: The aim of this study was to assess whether individual or clusters of psychiatric symptoms can differentiate patients with psychotic major depression (PMD) from those with nonpsychotic depression (NPMD). METHOD: Data were pooled from two studies investigating patients with moderate depression. A total of 129 subjects were studied. Patients in Sample 1 were unmedicated, while the majority of the patients in Sample 2 were taking psychotropic medications. Baseline rating scales were obtained for all subjects, including the Hamilton depression rating scale and the brief psychiatric rating scale (BPRS). We used discriminant function analyses, logistic regression, and ROC analyses to determine the patterns in symptoms that differentiated the groups. RESULTS: Psychotic patients were adequately differentiated by the unusual thought content (UTC) item of the BPRS. Even mild UTC endorsement was an indicator of PMD. Furthermore, results suggest that the positive symptom subscale of the BPRS was even better at differentiating PMD from NMPD patients. Sensitivity and specificity for this scale were 84% and 99%, respectively. CONCLUSION: Psychotic major depression is often undiagnosed and poorly treated. One reason for this trend is the failure of physicians to inquire in a more detailed manner about positive symptoms in patients with primary mood symptoms. Although physicians are not likely to have the time to conduct an entire BPRS during an evaluation, our results suggest that a few key symptoms, if assessed directly, may aid the psychiatrist to more effectively diagnose and subsequently treat their depressed patients.     

Early childhood and adolescent risk factors for psychotic depression in a general population birth cohort sample

Background and purpose

In the group of severe mental disorders, psychotic depression (PD) is essentially under-researched. Knowledge about the risk factors is scarce and this applies especially to early risk factors. Our aim was to study early childhood and adolescent risk factors of PD in a representative birth cohort sample with a follow-up of up to 50 years.

Methods

The study was carried out using the Northern Finland Birth Cohort 1966 (NFBC 1966). We used non-psychotic depression (NPD) (n = 746), schizophrenia (SZ) (n = 195), psychotic bipolar disorder (PBD) (n = 27), other psychoses (PNOS) (n = 136) and healthy controls (HC) (n = 8200) as comparison groups for PD (n = 58). We analysed several potential early risk factors from time of birth until the age of 16 years.

Results

The main finding was that parents’ psychiatric illness [HR 3.59 (1.84–7.04)] was a risk factor and a high sports grade in school was a protective factor [HR 0.29 (0.11–0.73)] for PD also after adjusting for covariates in the multivariate Cox regression model. Parental psychotic illness was an especially strong risk factor for PD. The PD subjects had a parent with psychiatric illness significantly more often (p < 0.05) than NPD subjects. Differences between PD and other disorder groups were otherwise small.

Conclusions

A low sports grade in school may be a risk factor for PD. Psychiatric illnesses, especially psychoses, are common in the parents of PD subjects. A surprisingly low number of statistically significant risk factors may have resulted from the size of the PD sample and the underlying heterogeneity of the etiology of PD.

     

Depressive symptoms as relative and attributable risk factors for first-onset major depression.

Using longitudinal data from a community study of 9900 adults drawn from four sites in the United States and interviewed twice, 1 year apart, we investigated the predictors of first-onset major depression. Using odds ratios to estimate relative risk, we found that persons with depressive symptoms, compared with those without such symptoms, were 4.4 times more likely and persons with dysthymia were 5.5 times more likely to develop a first-onset major depression during a 1-year period. The lifetime prevalence rate for depressive symptoms was 24%. The attributable risk is a compound epidemiologic measure that reflects both the relative risk associated with depressive symptoms (4.4) and the prevalence of exposure to that risk (24%). It is a useful measure to document the burden of a risk to the community, and it was determined to be greater than 50%. Thus, more than 50% of cases of first-onset major depression are associated with prior depressive symptoms. The high prevalence of depressive symptoms in the community and their strong association with first-onset major depression make them important from a public health perspective. Because depressive symptoms are often unrecognized and untreated in clinical practice, we conclude that their identification and the development of effective treatments could have implications for the prevention of major depression.     

Current and emerging somatic treatment strategies in psychotic major depression

Psychotic major depressive disorder (MDD) is a mood disorder characterized by severe affective and neurovegetative symptoms together with the presence of delusions and/or hallucinations. It is a common disorder seen in a quarter of consecutively admitted depressed patients and is often associated with severe symptomatology, increased suicide risk, poor acute response to antidepressants and poor acute and long-term treatment outcome. It is possible that poor response in psychotic depression is caused by the fact that we have yet to identify the most efficacious treatment protocol for psychotic MDD. Multiple studies have shown that modifications in the treatment paradigm may increase treatment efficacy in psychotic MDD. It has been generally accepted that, during the acute treatment phase, antidepressant-antipsychotic drug combination therapy is more effective than either treatment alone, although this strategy has recently been challenged. The question of the optimal duration of pharmacotherapy in order to prevent relapse and improve long-term (i.e., 5-year) outcome is a focus of current investigation. This article will review currently recommended treatment strategies for the acute, continuation and maintenance phases of therapy. In particular, it will address the role of newer-generation antidepressants, the role of second-generation antipsychotics, the use of mood stabilizers and indications for electroconvulsive therapy. Other possible treatment strategies such as transcranial magnetic stimulation, vagus nerve stimulation, deep-brain stimulation and glucocorticoid receptor antagonists will be discussed. Current recommendations for the prevention of relapse and improvement of long-term outcome will be reviewed.     

Cortisol circadian rhythm alterations in psychotic major depression.

BACKGROUND: Increased hypothalamic-pituitary-adrenal axis activity is well described in psychotic depression with an emphasis on 24-hour, urinary free cortisol levels or dexamethasone suppression tests. There are limited data on cortisol levels during specific times of the day. METHODS: Patients with depression with (PMD) and without (NPMD) psychosis and healthy control subjects were studied using rating scales of depression and psychosis and measures of HPA activity, including overnight cortisol and adrenocorticotropin levels. We used analysis of variance to determine group differences and regression analyses to assess contributions of specific measures to cortisol levels. RESULTS: PMDs had higher cortisol during the evening hours than did NPMDs or control subjects, who did not differ from one another. Regression analyses suggest that depression and the combination of depressive and psychotic symptoms were important contributors to variance in evening cortisol. CONCLUSIONS: PMD is associated with increased cortisol levels during the quiescent hours. Enhanced cortisol activity, particularly a higher nadir, was related to depression severity and the interaction of depressive and psychotic symptoms. This increase suggests a defect in the action of the circadian timing system and HPA axis, creating a hormonal milieu similarly seen in early Cushing's syndrome and potentially an (im)balance of mineralocorticoid and glucocorticoid receptor activity.     

Current issues in the classification of psychotic major depression

Depression is one of the most common mental disorders worldwide. There are a number of depression subtypes, and there has been much debate about how to most accurately capture and organize the features and subtypes of major depression. We review the current state of categorizing unipolar major depression with psychotic features (psychotic major depression, PMD), including clinical, biological, and treatment aspects of the disorder. We then propose some improvements to the current unipolar major depression categorization system. Finally, we identify important issues in need of further research to help elucidate the subtype of unipolar PMD.     

Anorexia nervosa and major depression: shared genetic and environmental risk factors

OBJECTIVE: The authors sought to derive heritability estimates for anorexia nervosa and to explore the etiology of the comorbid relationship between anorexia nervosa and major depression. METHOD: They applied bivariate structural equation modeling to a broad definition of anorexia nervosa and lifetime major depression as assessed in a population-based sample of 2,163 female twins. RESULTS: Anorexia nervosa was estimated to have a heritability of 58% (95% confidence interval=33%-84%). The authors were unable to completely rule out a contribution of shared environment. The comorbidity between anorexia nervosa and major depression is likely due to genetic factors that influence the risk for both disorders. CONCLUSIONS: Although the study was limited by the small number of affected twins, the results suggest that genetic factors significantly influence the risk for anorexia nervosa and substantially contribute to the observed comorbidity between anorexia nervosa and major depression.     

Identification of proteomic signatures associated with depression and psychotic depression in post-mortem brains from major depression patients

Major depressive disorder (MDD) is a leading cause of disability worldwide and results tragically in the loss of almost one million lives in Western societies every year. This is due to poor understanding of the disease pathophysiology and lack of empirical medical tests for accurate diagnosis or for guiding antidepressant treatment strategies. Here, we have used shotgun proteomics in the analysis of post-mortem dorsolateral prefrontal cortex brain tissue from 24 MDD patients and 12 matched controls. Brain proteomes were pre-fractionated by gel electrophoresis and further analyzed by shotgun data-independent label-free liquid chromatography-mass spectrometry. This led to identification of distinct proteome fingerprints between MDD and control subjects. Some of these differences were validated by Western blot or selected reaction monitoring mass spectrometry. This included proteins associated with energy metabolism and synaptic function and we also found changes in the histidine triad nucleotide-binding protein 1 (HINT1), which has been implicated recently in regulation of mood and behavior. We also found differential proteome profiles in MDD with (n=11) and without (n=12) psychosis. Interestingly, the psychosis fingerprint showed a marked overlap to changes seen in the brain proteome of schizophrenia patients. These findings suggest that it may be possible to contribute to the disease understanding by distinguishing different subtypes of MDD based on distinct brain proteomic profiles.     

Biogenic amine metabolites in delusional (psychotic) depression and melancholia subtypes of major depression

1. 1. The levels of the urinary main metabolites of norepinephrine 3-methoxy-4-hydroxyphenylglycol (MHPG), of dopamine homovanillic acid (HVA) and of serotonin 5-hydroxyindoleacetic acid (5-HIAA) were measured in 84 patients with major depressive disorder, 34 delusional and 50 nondelusional. Melancholia subtype was also defined (N=62).

2. 2. MHPG was significantly higher in the delusional depressed group (p=0.023). Female patients with delusional major depression also had significantly higher HVA excretion than female patients with non delusional major depression (p=0.036). 5-HIAA excretion was similar in the two patient subgroups.

3. 3. No significant differences in the three monoamine metabolites were found between the melancholic and nonmelancholic depressed patients.

Biological and psychosocial environmental risk factors influence symptom severity and psychiatric comorbidity in children with ADHD

Attention-deficit/hyperactivity disorder (ADHD) is a genetically as well as environmentally determined disorder with a high rate of psychiatric comorbidity. In this study, non-genetic biological and psychosocial risk factors for ADHD symptom severity and comorbid disorders were assessed in 275 children with ADHD, aged 5–13 years, mean age 9.7 (SD 1.9). Pre-/perinatal biological and lifetime psychosocial risk factors as well as data on parental ADHD were obtained. A different pattern of risk factors emerged for inattentive and hyperactive-impulsive ADHD symptoms. Inattentive symptoms were strongly influenced by psychosocial risk factors, whereas for hyperactive-impulsive symptoms, predominantly biological risk factors emerged. Hyperactive-impulsive symptoms also were a strong risk factor for comorbid oppositional defiant (ODD) and conduct disorder (CD). Smoking during pregnancy was a risk factor for comorbid CD but not ODD and further differential risk factors were observed for ODD and CD. Comorbid anxiety disorder (AnxD) was not related to ADHD symptoms and additional biological and psychosocial risk factors were observed. This study adds to the body of evidence that non-genetic biological and psychosocial risk factors have an impact on ADHD symptom severity and differentially influence comorbid disorders in ADHD. The findings are relevant to the prevention and treatment of ADHD with or without comorbid disorders.