Cortisol in mood disorders

Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis has been well-described in mood disorders. Hypercortisolaemia, which has been attributed to a breakdown in glucocorticoid-receptor-mediated negative feedback mechanisms within the HPA axis, may be central to the pathogenesis of both the depressive symptoms and the cognitive deficits, which characterise severe mood disorders. Strategies to normalise glucocorticoid receptor (GR) function, and thus restore HPA functional integrity, have been the focus of recent research. Preliminary preclinical and clinical studies report encouraging results which suggest that lowering circulating cortisol levels, by up-regulating GRs, may have therapeutic efficacy in terms of improvements in depressive symptoms and cognitive functioning.     

The association of perimenopausal mood disorders with other reproductive-related disorders

Data regarding the increased incidence of psychiatric illness during midlife in women are still conflicting. However, there is a growing consensus that certain groups of women may in fact be at higher risk for mood symptoms and psychiatric disorders during the perimenopausal transition. Mood symptoms during the perimenopause may be related to mood disorders during other periods of hormonal fluctuation throughout a woman's reproductive lifecycle. Elucidating these associations may advance the understanding of mood disorders during the perimenopausal transition. The epidemiology and treatment of perimenopausal mood symptoms compared with the epidemiology and treatment of mood disorders during the late luteal phase of the menstrual cycle, pregnancy, and postpartum. Common risk factors associated with mood disorders during these periods of hormonal changes or instability include poor lifestyle habits, a history of hormonally related mood disorders, stress and negative life events, ethnicity, and comorbidity. Reproductive-related mood disorders also are subject to an improvement in symptoms in response to treatment with selective serotonin reuptake inhibitors. As the morbidity associated with mood disorders during midlife may be quite significant, and as life expectancy continues to increase, recognition, prevention, and treatment of perimenopausal affective illness is becoming increasingly essential.     

Temperamental emotionality in preschoolers and parental mood disorders

A number of models developed in the adult psychopathology literature (i.e., L. A. Clark & D. Watson, 1991) have asserted that low levels of positive emotionality (PE) are predisposing factors or precursors for depression and represent a form of temperamental risk for depression. Further support for this claim would derive from evidence linking low PE to known indicators of risk for depression. The authors examined the association between temperamental emotionality in young children and parental mood disorders. One hundred unselected preschool-aged children completed a battery of emotion-eliciting tasks tapping aspects of PE, negative emotionality (NE), and behavioral inhibition (BI). Parental psychopathology was assessed with semistructured diagnostic interviews. Low PE in children was associated with maternal, but not paternal, mood disorder. The low PE-maternal depression link was relatively specific, as there were few associations between low PE and other forms of parental psychopathology or between NE and BI and parental mood disorders.     

Neural circuits underlying the pathophysiology of mood disorders

Although mood disorders constitute leading causes of disability, until recently little was known about their pathogenesis. The delineation of anatomical networks that support emotional behavior (mainly derived from animal studies) and the development of neuroimaging technologies that allow in vivo characterization of anatomy, physiology, and neurochemistry in human subjects with mood disorders have enabled significant advances towards elucidating the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD). In this review, we integrate insights from human and animal studies, which collectively suggest that MDD and BD involve dysfunction within an extended network including the medial prefrontal cortex and anatomically-related limbic, striatal, thalamic and basal forebrain structures.     

Effects of daily stress on negative mood

This article examines the influence of daily stressors on mental health in a community sample. Ss were 166 married couples who completed diaries each day for 6 weeks. In pooled within-person analyses, daily stressors explained up to 20% of the variance in mood. Interpersonal conflicts were by far the most distressing events. Furthermore, when stressors occurred on a series of days, emotional habituation occurred by the second day for almost all events except interpersonal conflicts. Contrary to certain theoretical accounts, multiple stressors on the same day did not exacerbate one another's effects: rather an emotional plateau occurred. Finally on days following a stressful event, mood was better than it would have been if the stressor had not happened. These results reveal the complex emotional effects of daily stressors, and in particular they suggest that future investigations should focus primarily on interpersonal conflicts.     

A model of hippocampal neurogenesis in memory and mood disorders

The mounting evidence for neurogenesis in the adult hippocampus has fundamentally challenged the traditional view of brain development. The intense search for clues as to the functional significance of the new neurons has uncovered a surprising connection between neurogenesis and depression. In animal models of depression, neurogenesis is reduced, whereas many treatments for depression promote neurogenesis. We speculate on why the hippocampus, traditionally viewed as a memory structure, might be involved in mood disorders, and what specific role the new neurons might have in the pathogenesis of and recovery from depression. The proposed role of neurogenesis in contextual-memory formation predicts a specific pattern of cognitive deficits in depression and has important implications for treatment of this highly prevalent and debilitating disorder.     

Reliability of DSM-IV anxiety and mood disorders: implications for the classification of emotional disorders

The reliability of current and lifetime Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) anxiety and mood disorders was examined in 362 outpatients who underwent 2 independent administrations of the Anxiety Disorders Interview Schedule for DSM-IV: Lifetime version (ADIS-IV-L). Good to excellent reliability was obtained for the majority of DSM-IV categories. For many disorders, a common source of unreliability was disagreements on whether constituent symptoms were sufficient in number, severity, or duration to meet. DSM-IV diagnostic criteria. These analyses also highlighted potential boundary problems for some disorders (e.g., generalized anxiety disorder and major depressive disorder). Analyses of ADIS-IV-L clinical ratings (0-8 scales) indicated favorable interrater agreement for the dimensional features of DSM-IV anxiety and mood disorders. The findings are discussed in regard to their implications for the classification of emotional disorders.     

Acceptability and suppression of negative emotion in anxiety and mood disorders

The present study investigated perceived acceptability and suppression of negative emotion in participants with anxiety and mood disorders. Sixty participants with these disorders and 30 control participants watched an emotion-provoking film and completed self-report measures of their experience and regulation of emotions. The film elicited similar increases in negative emotion for clinical and nonclinical participants; however, clinical participants judged their resulting emotions as less acceptable and suppressed their emotions to a greater extent. The higher level of suppression in the clinical group was attributable to females in the clinical group suppressing their emotions more than females in the nonclinical group. For all participants, high levels of suppression were associated with increased negative emotion during the film and during a postfilm recovery period. Further analyses showed that appraising emotions as unacceptable mediated the relationship between negative emotion intensity and use of suppression in the clinical group. This study extends the literature on emotion regulation to a clinical sample and suggests that judging emotions as unacceptable and suppressing emotions may be important aspects of the phenomenology of emotional disorders.     

Beyond monoamines: glutamatergic function in mood disorders

The monoamine theory has implicated abnormalities in serotonin and norepinephrine in the pathophysiology of major depression and bipolar illness and contributed greatly to our understanding of mood disorders and their treatment. Nevertheless, some limitations of this model still exist that require researchers and clinicians to seek further explanation and develop novel interventions that reach beyond the confines of the monoaminergic systems. Recent studies have provided strong evidence that glutamate and other amino acid neurotransmitters are involved in the pathophysiology and treatment of mood disorders. Studies employing in vivo magnetic resonance spectroscopy have revealed altered cortical glutamate levels in depressed subjects. Consistent with a model of excessive glutamate-induced excitation in mood disorders, several antiglutamatergic agents, such as riluzole and lamotrigine, have demonstrated potential antidepressant efficacy. Glial cell abnormalities commonly associated with mood disorders may at least partly account for the impairment in glutamate action since glial cells play a primary role in synaptic glutamate removal. A hypothetical model of altered glutamatergic function in mood disorders is proposed in conjunction with potential antidepressant mechanisms of antiglutamatergic agents. Further studies elucidating the role of the glutamatergic system in the pathophysiology of mood and anxiety disorders and studies exploring the efficacy and mechanism of action of antiglutamatergic agents in these disorders, are likely to provide new targets for the development of novel antidepressant agents.     

The subgenual anterior cingulate cortex in mood disorders

The anterior cingulate cortex (ACC) ventral to the genu of the corpus callosum has been implicated in the modulation of emotional behavior on the basis of neuroimaging studies in humans and lesion analyses in experimental animals. In a combined positron emission tomography/magnetic resonance imaging study of mood disorders, we demonstrated that the mean gray matter volume of this "subgenual" ACC (sgACC) cortex is abnormally reduced in subjects with major depressive disorder (MDD) and bipolar disorder, irrespective of mood state. Neuropathological assessments of sgACC tissue acquired postmortem from subjects with MDD or bipolar disorder confirmed the decrement in gray matter volume, and revealed that this abnormality was associated with a reduction in glia, with no equivalent loss of neurons. In positron emission tomography studies, the metabolic activity was elevated in this region in the depressed relative to the remitted phases of the same MDD subjects, and effective antidepressant treatment was associated with a reduction in sgACC activity. Other laboratories replicated and extended these findings, and the clinical importance of this treatment effect was underscored by a study showing that deep brain stimulation of the sgACC ameliorates depressive symptoms in treatment-resistant MDD. This article discusses the functional significance of these findings within the context of the preclinical literature that implicates the putative homologue of this region in the regulation of emotional behavior and stress response. In experimental animals, this region participates in an extended "visceromotor network" of structures that modulates autonomic/neuroendocrine responses and neurotransmitter transmission during the neural processing of reward, fear, and stress. These data thus hold important implications for the development of neural models of depression that can account for the abnormal motivational, neuroendocrine, autonomic, and emotional manifestations evident in human mood disorders.     

Postpartum mood disorders: Results of an online survey

Purpose: Postpartum mood disorders (PMDs), the distressing mental and emotional symptoms experienced by women after childbirth, are just now receiving the attention they warrant. Given the serious and sometimes life‐threatening nature of PMDs, we used a qualitative research design to examine more closely the nature of symptoms experienced and the effective strategies women used to cope with PMD. Participants: The respondents were 252 members of PMD and breast‐feeding (La Leche League) support groups throughout the United States. Method: Participants responded anonymously to open‐ended questions in an online survey. The data were reviewed by the research team to determine common themes and prevailing issues. Results: Participants reported myriad different symptoms and used a host of various strategies to alleviate problematic thoughts, feelings, and behaviours following childbirth. Postpartum symptoms affected participants’ plans to have future children. For some women, symptoms became more intense during subsequent births. Despite the problematic nature of PMD, more than half of the participants reported receiving little or no information from healthcare providers about PMDs. Implications for counsellors and other healthcare providers are discussed in detail.     

Glutamate-hypothalamic-pituitary-adrenal axis interactions: implications for mood and anxiety disorders

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a pathologic feature of certain mood and anxiety disorders that results in the increased production and secretion of corticotropin-releasing factor. There is increasing preclinical evidence that glutamate, an excitatory amino acid, plays an important role in the regulation of the HPA axis. Activation of glutamatergic projections to limbic structures such as the amygdala and brainstem structures such as the nucleus tractus solitarius is implicated in the stress response. There are laboratory and clinical suggestions that glutamatergic N-methyl-D-aspartate (NMDA) receptor antagonists function as antidepressants, and that chronic antidepressant treatments have a significant impact on NMDA receptor function. Clinical investigations of glutamate antagonists in patients with mood and anxiety disorders are in their infancy, with a few reports suggesting the presence of mood-elevating properties. Ultimately, HPA axis modulators, serotonin-enhancing agents, and glutamate antagonists might serve to increase neurotropic factors in key brain regions for affective and anxiety regulation, providing a putative final common pathway.     

Examination stress and changes in mood and health related behaviours

Abstract

The present exploratory study evaluated the effect of stress (an examination period) on changes in mood and health related behaviours. 83 medical students completed measures of mood and health related bchaviours at baseline and four weeks later either during their examinations period (the stress condition) or after a comparative control period (the control condition). All subjects also completed ratings of stress mediating variables: social support, perceived control and coping style at baseline. The results showed deterioration in mood in terms of increases in depression and anxiety and changes in health related behaviours in terms of increased numbers of subjects who identified thcmsehes as smokers, and dcmascs in alcohol consumption, exercise and food intake in subjects in the stress condition. The results also suggest that social support moderated the effects of the examination stress and was related to greater decreases in smoking, decrcases in alcohol craving and increases in eating behaviour. In addition, an avoidance coping style (problem avoidance, wishful thinking) was related to greater decreases in eating behaviour. 'Ihe nsults an discussed in the context of the stress/illness link and the role of behavioural change.     

Childhood-onset multiple sclerosis and mood disorders: a case study.

Multiple Sclerosis (MS) is rare in children. Little research exists regarding emotional and behavioral disorders in childhood-onset MS, despite the occurrence of such problems in adults with MS. This paper describes the cognitive and behavioral characteristics of a boy diagnosed with MS at age 9 and mood disorder at age 10. He displayed no cognitive or behavioral problems prior to the onset of physical symptoms of MS. Three years after diagnosis, this child showed persistent problems with speed of processing, visual-motor skills, and parent and teacher-reported executive functioning. In addition, he had difficulties with emotional lability, behavioral disinhibition, depression, and social interaction. As with adults, children with MS may be at increased risk for mood disorder compared to their peers. Mood disorders in children with MS are likely to be multiply determined, although the specific causal mechanisms are unknown.     

Post traumatic stress disorders

A clinical overview of the Post-Traumatic Stress Disorders (PTSD) is presented emphasizing altered qualities of experience and behavior. A schema of human psychological responses to stressful life events is reviewed as an introduction to the extensive development of concepts of pathological stress response syndromes: Post-Traumatic Stress Disorders; post-traumatic stress disorder, chronic type; delayed Post-Traumatic Stress Disorder. An illustrative case history is presented. The potential development of PTSD in individuals experiencing less than overwhelming stressors is conceptualized.     

Co-occurrence of personality disorders with mood, anxiety, and substance use disorders in a young adult population

The purpose of this study was to determine the co-occurrence of DSM- III-R personality disorders (PDs) with mood, anxiety, and substance use disorders in a young adult population. The members of the Northern Finland 1966 Birth Cohort Project, living in the city of Oulu with an age of 31 years (N = 1,609) were invited to participate in a two-phase field study. The SCID I and II were used as diagnostic instruments. One hundred and seventy-seven out of 321 interviewed subjects met the criteria for mood, anxiety, or substance use disorders. Altogether 72 (41%) of the subjects with an Axis I disorder met the criteria for at least one PD. The weighted co-occurrence rate of any PD varied from 28% for mood disorders to 47% for anxiety disorders. PDs, especially those in Cluster C, are highly associated with Axis I psychiatric disorders in population.