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.     

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.     

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.     

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.     

Neuroreceptor imaging of stress and mood disorders

Techniques such as positron emission tomography and single photon emission computed tomography allow for the imaging of neurotransmitter receptors and transporters in the brain. These tools have been used to investigate serotonergic, dopaminergic, and opioidergic function in healthy subjects as well as in patients with major depressive disorder, bipolar disorder, and other mood disorders. Pharmacologic challenges, such as amphetamine challenge, and physiologic stressors, such as pain challenge, have been used to further examine the function of these neurotransmitter systems. Neuroimaging of patient populations before and after medication treatment may be useful to understand changes in neurotransmission that accompany disease remission. As new radiotracers with higher selectivity for the various receptors and transporters are developed, imaging techniques may provide new insights into the pathophysiology of mood disorders, leading to improved diagnosis and treatment.     

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.     

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.     

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.     

Perceptions of parental relationships in the eating disorders: the relevance of depressed mood

Recent studies have suggested that subtypes of eating-disordered persons differ in their perceptions of their family environments. This study used Benjamin's (1983) Structural Analysis of Social Behavior to examine how depressed mood influenced eating-disordered subjects' ratings of their parental relationships. The results indicated that when level of mood disturbance was statistically controlled, there were no significant differences in parent ratings among restricting anorexics, bulimic-anorexics, bulimics, and normal control subjects. The results are discussed in terms of the possible relations of mood, eating disorder, and perception of family relationships.     

A slow wave investigation of working memory biases in mood disorders

Mood-congruent working memory biases were examined in a delayed matching to sample paradigm using the slow wave (SW) event-related brain potential (ERP) component. Mood-congruent working memory biases, indexed by SW amplitudes, were demonstrated among individuals experiencing a major depressive episode (MDE) and nondepressed controls but not individuals with dysthymia. However, analyses of symptom severity demonstrated that those with dysthymia exhibited significantly less negative SW amplitudes with increasing depressive mood severity, whereas individuals with major depression demonstrated more negative SW amplitudes with increasing depressive mood severity. These results are discussed in the context of diagnostic specificity for cognitive biases associated with working memory of mood-disordered individuals.     

Transdiagnostic processes in emotional disorders and insomnia: results from a sample of adult outpatients with anxiety and mood disorders

Conceptual similarities between recent models of insomnia and emotional disorders suggest there may be common factors that underlie or maintain these difficulties. Maladaptive cognitive and behavioral processes similar to those described in connection with emotional disorders have been cited as key mechanisms in the maintenance of primary insomnia. Unfortunately, research on this potential overlap is lacking. The present study examined the relationship among anxiety sensitivity (AS), dysfunctional beliefs, fatigue, safety behaviors, and insomnia severity in 59 outpatients with anxiety and mood disorders. Key insomnia processes (dysfunctional beliefs, fatigue, safety behaviors) were all related to insomnia severity in the comorbid sample, although AS was not. However, as hypothesized, AS did moderate the relationship of both dysfunctional beliefs and fatigue with insomnia severity. The relationships between key insomnia processes and insomnia severity was strongest among individuals high in AS. Results support the hypothesis that common mechanisms are involved for insomnia and emotional disorders. AS might function as a mechanism for the maintenance of sleep disturbance in the context of anxiety and mood disorders, suggesting a promising avenue for future research.     

Rethinking the mood and anxiety disorders: a quantitative hierarchical model for DSM-V

The fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1994) groups disorders into diagnostic classes on the basis of the subjective criterion of "shared phenomenological features." There are now sufficient data to eliminate this rational system and replace it with an empirically based structure that reflects the actual similarities among disorders. The existing structural evidence establishes that the mood and anxiety disorders should be collapsed together into an overarching class of emotional disorders, which can be decomposed into 3 subclasses: the bipolar disorders (bipolar I, bipolar II, cyclothymia), the distress disorders (major depression, dysthymic disorder, generalized anxiety disorder, posttraumatic stress disorder), and the fear disorders (panic disorder, agoraphobia, social phobia, specific phobia). The optimal placement of other syndromes (e.g., obsessive-compulsive disorder) needs to be clarified in future research.     

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 social deviance: substance use disorders and the dimensions of psychopathy

High rates of comorbidity between psychopathy and substance use disorders (SUD) have long been recognized. However, the extent to which relationships between SUD and psychopathy extends beyond shared relationship with general antisociality remains undetermined. We examined zero-order and unique relationships between the elements of psychopathy and four categories of SUD; alcohol, cannabis, cocaine, and opioid dependence. The sample consisted of 399 European American and African American male county jail inmates. The relationship between psychopathy and SUD extended beyond general antisociality to core features of the psychopathic personality. Relationships were relatively stable across ethnicity but were more generalized across SUD categories for European American inmates. The relationship between SUD and impulsive and irresponsible behavior was most consistent across categories of SUD; relationships with other elements of psychopathy varied according to category of SUD.