Relationship between age at onset and magnetic resonance image-defined hyperintensities in mood disorders

OBJECTIVES: To examine in patients with mood disorders the relationship of age at onset with the location and degree of MRI-defined brain hyperintensities. METHOD: Fifty-two patients diagnosed as having mood disorders and 14 controls participated in the study. Brain MR images were analyzed according to semiquantitative ratings for the anatomical distribution and severity of T2-weighted hyperintensities. We compared these hyperintensities among the three age- and sex-matched groups of late-onset mood disorder patients (LOM), early-onset mood disorder patients (EOM), and controls. The time since the onset of disorder was significantly longer in the EOM than in the LOM group. We also conducted linear multiple regression analysis using the severity of hyperintensities as dependent variable to determine whether the clinical features correlate with vascular pathology. RESULTS: As for deep white matter hyperintensity (DWMH), LOM exhibited higher ratings than EOM; as for brain areas, significant between-group differences were detected in the bilateral frontal areas and in the left parieto-occipital area. No significant difference was observed between EOM and controls. As for periventricular hyperintensity, there was no difference among the three groups. We obtained a significant regression model to predict DWMH ratings; age, number of ECTs, and LOM were selected as significant variables. CONCLUSION: The present study suggests that the time since the onset of disorder does not affect the development of white matter lesions, but that white matter lesions are associated with late-onset mood disorders. The frontal areas and the left parieto-occipital area would be important for the development of late-onset mood disorders.     

Gender differences in rates of depression among undergraduates: measurement matters

Two studies tested for gender differences in rates of depression among undergraduates using three conceptualizations of depression (mood, syndrome, disorder). The first sample consisted of 325 non-referred undergraduate students, who completed pencil-and-paper measures of depressed mood, depressive syndrome and a depressive disorder analogue. The second sample consisted of 894 undergraduate students seeking counselling services, who participated in clinical intake interviews assessing depressed mood and depressive disorder. Results of analyses provide no evidence of gender differences in rates of depressed mood in either samples or of depressive syndrome in the non-referred sample. However, in both samples, gender differences in rates of depressive disorder were found, with male students more likely than female students to be depressed.     

Diagnosing major depressive disorder IX: are patients who deny low mood a distinct subgroup?

A dysphoric mood is not required for the diagnosis of DSM-IV major depressive disorder. Individuals who deny depression, sadness, or feeling blue may nonetheless be diagnosed with major depressive disorder if they have lost interest or pleasure in all, or almost all, of their usual activities, and experienced at least four other symptoms of depression. The underlying assumption is that depressed patients without low mood are no different than depressed patients who report dysphoric mood. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services project, we examined the validity of this assumption. We compared the demographic, family history, and clinical characteristics of patients who met the DSM-IV criteria for a current major depressive episode who did (N = 839) and did not (N = 63) report low mood. Patients without depressed mood were significantly younger, and their current episodes were briefer, less severe, and associated with less suicidality and less psychosocial impairment. The results thus do not support DSM-IV's implicit assumption of no difference between depressed patients who do and do not report low mood. The alternative ways this might be addressed in future editions of the DSM are discussed.     

Frontal lobe syndrome reassessed: comparison of patients with lateral or medial frontal brain damage

Examination of mood and behaviour changes after frontal damage may contribute to understanding the functional role of distinct prefrontal areas in depression and anxiety. Depression and anxiety disorders, symptoms, and behaviour were compared in eight patients with single lateral and eight patients with single medial frontal lesions matched for age, sex, race, education, socioeconomic status, side, and aetiology of lesion 2 weeks and 3 months after brain injury. DSM IV major depressive and generalised anxiety disorders were more frequent in patients with lateral compared with medial lesions at 2 weeks but not at 3 months. At 3 months, however, patients with lateral damage showed greater severity of depressive symptoms, and greater impairment in both activities of daily living and social functioning. At initial evaluation depressed mood and slowness were more frequent, whereas at 3 months slowness, lack of energy, and social unease were more frequent in the lateral than the medial group. Patients with lateral lesions showed greater reduction of emotion and motivation (apathy) during both examinations. Medial frontal injury may fail to produce emotional dysregulation or may inhibit experience of mood changes, anxiety, or apathy. Lateral prefrontal damage may disrupt mood regulation and drive while leaving intact the ability to experience (negative) emotions.     

Attentional disturbances in patients with unipolar psychotic depression: a selective and sustained attention study

Psychotic depression is a clinical subtype of major depressive disorder in the recent editions of the psychiatric diagnostic systems ICD-10 (1992) and DSM-IV (1994). Recent evidence suggests that psychotic depressed patients are more impaired on neuropsychologic tests measuring attention as compared to nonpsychotic depressed patients. However, information on this issue between psychotic and nonpsychotic depression is limited. It has become clear that attention is not a single concept; thus we studied both selective and sustained attention using the theoretic model of automatic and controlled information processing. Thirty-two patients with major depressive disorder, 16 psychotics and 16 nonpsychotics, were investigated and compared with 20 patients with schizophrenic disorder and 20 healthy volunteers who comprised the control groups, using Ruff's 2 and 7 selective attention tests. Compared to the healthy controls, both depressed groups were impaired; however, the psychotic depressed group was more severely impaired on both measures. Attentional performance speed and accuracy scores, on both effortless and effortful conditions, were significantly lower in the psychotic depressed group than in the nonpsychotic depressed group. No significant differences were found on attentional performance between the psychotic depressed patients and those with schizophrenic disorder. Attention deficits are thus more prominent in psychotic than in nonpsychotic depression. Furthermore, taking attention as a criterion, psychotic depression, although of mood congruent subtype, lies closer to schizophrenia than to nonpsychotic depression.     

Is apathy in late-life depressive illness related to age-at-onset, cognitive function or vascular risk?

BACKGROUND: Apathy has been shown to be an important feature of degenerative, vascular or traumatic brain disorder. Its presence is associated with high depression scores, higher age, low performance on frontal tasks, and more severe deep white matter hyperintensities. In late-life depression, lack of interest or motivation are often more prominent than depressed mood, especially in the late-onset type. It was hypothesized that in a heterogeneous sample of elderly depressed patients, apathy is associated with late-onset type of depression, cognitive dysfunction or vascular risk factors. METHOD: The Apathy Evaluation Scale (AES) was administered to twenty-nine elderly (> or = 60 years) inpatients with a DSM-IV major depression or dysthymic disorder. The severity of the depression was measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and cognitive function with the Mini-mental State Examination (MMSE). The presence of vascular risk factors was traced in the patient's medical records. RESULTS: Apathy was found in 86% of the patients. The AES-score was correlated with the negative symptom score, but not with total MADRS or MMSE-score. No difference in AES-score between early-onset depressed (n = 16) and late-onset depressed (n = 13) patients was found, and between patients with or without vascular risk. CONCLUSION: Apathy is a main feature of moderate to severe depressive illness in elderly patients and related to the negative symptoms of the disorder. Further studies should include less severely depressed patients and investigate the relation between depression severity and apathy.     

Anatomic location and laterality of MRI signal hyperintensities in late-life depression

OBJECTIVES: Evidence is mounting linking cerebrovascular disease with the development of major depression in the elderly. Lesions in both white and gray matter have been associated with geriatric depression. In addition, the literature on poststroke depression suggests that left-sided lesions are associated with depression. We sought to examine the severity and location of white- and gray-matter lesions in a group of elderly depressives and nondepressed control subjects. METHOD: 115 depressed patients (69 with late onset, 46 with early onset) and 37 controls, all over age 45, received magnetic resonance imaging (MRI). Semiquantitative severity ratings and quantitative measurements of number and size of MRI hyperintensities were obtained, and groups were compared using Cochran-Mantel-Haenszel (CMH) analyses and repeated-measures analyses of covariance adjusting for age. RESULTS: Late-onset depressed patients had more severe hyperintensity ratings in deep white matter than early-onset patients and controls. Late- and early-onset patients had more severe subcortical gray-matter hyperintensities (particularly in the putamen) compared with controls. Left-sided white-matter lesions were significantly associated with older age of depression onset, whereas right-anterior white matter and left-subcortical lesions (particularly in the putamen) were associated with melancholia in the depressed group. CONCLUSION: These findings extend previous reports of an association between cerebrovascular disease and depression, as well as recent studies showing lateralized lesion involvement in geriatric depression. Such vascular pathology may disrupt neural pathways involved in affective processing and the maintenance of a normal mood and psychomotor state.     

The homocysteine hypothesis of depression

High levels of homocysteine are associated with cerebrovascular disease, monoamine neurotransmitters, and depression of mood. A plausible hypothesis for these associations is that high homocysteine levels cause cerebral vascular disease and neurotransmitter deficiency, which cause depression of mood. The homocysteine depression hypothesis, if true, would mandate inclusions of imaging studies for cerebrovascular disease and measures of homocysteine, folate, and B12 and B6 vitamins in the clinical evaluation of older depressed patients. Longitudinal studies and clinical trials should be designed to challenge the hypothesis.     

Are depressive symptoms nonspecific in patients with acute stroke?

OBJECTIVE: Some investigators have suggested that major depression might be overdiagnosed in stroke patients because of changes in appetite, sleep, or sexual interest caused by their medical illness; others have suggested that depression may be underdiagnosed in stroke patients who deny symptoms of depression because of anosognosia, neglect, or aprosody. The authors' goal was to determine how frequently depressive symptoms occur in acute stroke patients with and without depressed mood to estimate how often diagnostic errors of inclusion or exclusion may be made. METHOD: They examined the rate of autonomic and psychological symptoms of depression in 205 patients who were consecutively hospitalized for acute stroke. Eighty-five (41%) of these patients had depressed mood, and 120 (59%) had no mood disturbance. Forty-six (54%) of the 85 patients with depressed mood (22% of all patients) were assigned the DSM-III diagnosis of major depression. RESULTS: The 120 patients without mood disturbance had a mean of one autonomic symptom, but the 85 patients with depressed mood had a mean of almost four. Tightening the diagnostic criteria to account for one more nonspecific autonomic symptom decreased the number of patients with major depression by only three; adding two more criteria decreased the number by only five. Thus, the rate of DSM-III major depression was 1% higher than the rate with one extra nonspecific autonomic symptom and 2% higher than the rate with two extra criteria. Conversely, loosening diagnostic criteria to account for denial of depressive illness increased the rate of major depression by only 5%. CONCLUSIONS: Both autonomic and psychological depressive symptoms are strongly associated with depressed mood in acute stroke patients.     

Depressed mood and major depressive disorder in two ethnic groups

This study examines the relation of depressive mood, measured using the Center for Epidemiologic Studies Depression scale, with major depression, assessed using the Diagnostic Interview Schedule. Data are from 1244 Mexican American and 1149 non-Hispanic white randomly-selected community residents. Major depression is strongly related to depressed mood, irrespective of the persistence or content of mood, with some components of depressed mood (negative affect and somatic disturbance) more strongly associated with major depression than other components (lack of positive affect and interpersonal problems). Low socioeconomic status and social isolation contribute to depressed mood independent of major depression. Low education is associated with persistent depressed mood. Mexican Americans report more overall depressive mood than non-Hispanic whites, but there is no ethnic difference in major depression or in the mood symptoms most strongly related to major depression. Mexican Americans report more persistent symptoms than non-Hispanic whites in every content category. Ethnic differences in education appear to account for ethnic differences in all components of depressed mood except lack of positive affect, which may be attributable to language differences.     

Antidepressants in the medically ill: prediction of benefits

Although depression secondary to medical illness occurs frequently, little is known about its response to conventional antidepressant therapy. In this retrospective study of 50 patients, the authors assessed the charted therapeutic effect of antidepressants and sought to define pretreatment features associated with good outcome. Half (9/18) of the patients with a previous history of depression improved while only 22% (7/32) of the patients without a previous history of depression showed improvement in mood. Those patients meeting DSM-III criteria for major depressive disorder were no more likely to benefit from antidepressants than were patients meeting criteria for adjustment disorder with depressed mood. The authors conclude that previous history of depression should be considered when assessing risks and benefits for antidepressants for medically ill patients with depressive syndromes.     

Depression and major depressive disorder in patients with Parkinson's disease

The prevalence of depression in Parkinson's disease (PD) varies greatly. In this study, we investigated major depressive disorder (MDD) and depressive symptoms without MDD in patients with PD. The psychopathological characteristics of depressive symptoms were assessed by a psychiatric interview. A total of 105 Japanese patients with PD without dementia were included. The Japanese version of the Beck Depression Inventory‐II (BDI‐II) with a cutoff score of 13/14 was used to screen for depression. Using a structured interview, a comprehensive psychiatric evaluation of patients with BDI‐II scores >13 (high BDI patients) was completed using the criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM)‐IV‐TR. Forty patients (38%) had a BDI‐II >13, but 29 did not show any depressed mood. Five cases met the criteria for MDD (three current, two past) and one patient was diagnosed with minor depressive disorder. A slight depressed mood that was associated with worrying about PD was seen in 6 of 34 patients without any depressive disorder and fluctuated with aggravation of PD symptoms in two of these patients. For the diagnosis of MDD, the number of positive items from the DSM‐IV‐TR definition of MDD is most important and useful for differentiating MDD and non‐MDD. The low‐prevalence rate of MDD in our patient population suggests that PD may be a psychological stressor for MDD, but does not necessarily induce MDD. © 2009 Movement Disorder Society     

The use of diet and dietary components in the study of factors controlling affect in humans: a review.

Although one of the first biological treatments of a major psychiatric disorder was the dietary treatment of pellagra, the use of diet and dietary components in the study of psychopathology has not aroused much interest. This article reviews three areas in which the dietary approach has provided interesting information. The tryptophan depletion strategy uses a mixture of amino acids devoid of tryptophan to lower brain tryptophan in order to study the symptoms that can be elicited. One effect of tryptophan depletion is a lowering of mood, the magnitude of which seems to depend on the baseline state of the subject. Therefore, recovered depressed patients often undergo an acute relapse, while normal subjects show more moderate changes of mood. Totally euthymic subjects show no lowering of mood, but subjects with high normal depression scale scores or subjects with a family history of depression show a moderate lowering of mood. These data indicate that low serotonin levels alone cannot cause depression. However, serotonin does have a direct effect on mood, and low levels of serotonin contribute to the etiology of depression in some depressed patients. Folic acid deficiency causes a lowering of brain serotonin in rats, and of cerebrospinal fluid 5-hydroxyindoleacetic acid in humans. There is a high incidence of folate deficiency in depression, and there are indications in the literature that some depressed patients who are folate deficient respond to folate administration. Folate deficiency is known to lower levels of S-adenosylmethionine, and S-adenosylmethionine is an antidepressant that raises brain serotonin levels. These data suggest that low levels of serotonin in some depressed patients may be a secondary consequence of low levels of S-adenosylmethionine. They also suggest that the dietary intake and psychopharmacological action of methionine, the precursor of S-adenosylmethionine, should be studied in patients with depression. Normal meals have definite effects on mood and performance in humans. The composition of the meal, in terms of protein and carbohydrate content, can influence these behaviors. Because protein and carbohydrate meals can influence brain serotonin in rats, these effects in humans have usually been interpreted in terms of altered serotonin functioning. However, the current balance of evidence is against the involvement of serotonin in the acute effects of protein and carbohydrate meals in humans. The underlying mechanisms involved are unknown, but there are a variety of possibilities.(ABSTRACT TRUNCATED AT 400 WORDS)     

Depressive disorders among somatizing patients in primary health care

Unrecognized, untreated and undertreated depressive disorders incur inordinate human and economic costs, despite the availability of an exclusive array of clinical interventions. The aim of this study was to identify cases of masked depression in primary health care, employing a two-stage design. In the first stage, involving a study of 442 patients, the prevalence of recognized depression was 1.8%. In the second step, 62 patients from stage 1 were investigated further because of their high score on somatization tendency. In total, 41 of the 62 patients were found to have a mood disorder according to DSM-III-R, i.e. a major depressive disorder or dysthymia. Two patients were found to have already had a diagnosis of major depression assigned to them in stage 1, but they were joined by 13 more patients. A further 26 patients were found to be suffering from dysthymia, nine had adjustment disorders with depressed mood, and 12 patients showed no signs of depressed mood. For the group suffering from a current episode of major depression or dysthymia, the prevalence rate increased to 11.7% in the initial total population after stage 2. The diagnostic category with the highest rate of depressed patients was ‘musculoskeletal diseases’. Patients with masked depression had higher scores for alexithymia and psychasthenia than depressed patients who were directly diagnosed.     

Lamotrigine Monotherapy Improves Depressive Symptoms in Epilepsy: A Double-Blind Comparison with Valproate

Depressive symptoms are highly prevalent in patients with epilepsy. The antiepileptic drug lamotrigine has been shown to be an effective treatment for the depressive phase of bipolar disorder and to enhance mood and well-being in epilepsy patients. The effects of lamotrigine monotherapy on depressive symptoms in epilepsy have not been evaluated to date in a controlled clinical trial. A recently completed double-blind epilepsy trial comparing the effects of lamotrigine monotherapy and valproate monotherapy on weight change incorporated a battery of standard mood assessments. Mean screening Beck Depression Inventory scores showed that both lamotrigine and valproate groups suffered from mild depression at baseline. Lamotrigine monotherapy was reliably associated with earlier and larger improvements than valproate in mood assessed with the Beck Depression Inventory, the Cornell Dysthymia Rating Scale, and the Profile of Mood States. Considered in the context of other data showing lamotrigine's antidepressant efficacy in bipolar depression, these results suggest that lamotrigine improves mood in mildly depressed patients with epilepsy. Lamotrigine may be particularly useful in treating epilepsy patients with comorbid depression, the most common psychiatric illness in epilepsy.     

Previous mood state predicts response and switch rates in patients with bipolar depression

OBJECTIVE: The treatment of bipolar depression is a significant clinical problem that remains understudied. The role for antidepressant (AD) agents vs. mood stabilizers has been particularly problematic to ascertain. METHOD: Detailed life charting data from 42 patients with 67 depressive episodes were reviewed. Response rates and rates of switch into mania were compared based on the preceding mood state and on whether an AD or mood stabilizing (MS) agent was added following onset of depression. RESULTS: Patients who became depressed following a period of euthymia were more likely to respond to treatment (62.5%) than patients who became depressed following a period of mania or hypomania (27.9%). The ratio of response to switch for previously euthymic patients was particularly favorable. CONCLUSION: Mood state prior to onset of depression in bipolar disorder appears to be an important clinical variable that may guide both choice of treatment administered and expectation of outcome to treatment.     

Sustained unemployment in psychiatric outpatients with bipolar depression compared to major depressive disorder with comorbid borderline personality disorder

Zimmerman M, Martinez JH, Young D, Chelminski I, Dalrymple K. Sustained unemployment in psychiatric outpatients with bipolar depression compared to major depressive disorder with comorbid borderline personality disorder. Bipolar Disord 2012: 14: 856–862. © 2012 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd. Objectives: The morbidity associated with bipolar disorder is, in part, responsible for repeated calls for improved detection and recognition. No such clinical commentary exists for improved detection of borderline personality disorder in depressed patients. Clinical experience suggests that borderline personality disorder is as disabling as bipolar disorder; however, no studies have directly compared the two disorders. For this reason we undertook the current analysis from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project comparing unemployment and disability rates in patients with bipolar disorder and borderline personality disorder. Methods: Patients were interviewed with semi‐structured interviews. We compared three non‐overlapping groups of depressed patients: (i) 181 patients with DSM–IV major depressive disorder and borderline personality disorder, (ii) 1068 patients with major depressive disorder without borderline personality disorder, and (iii) 84 patients with bipolar depression without borderline personality disorder. Results: Compared to depressed patients without borderline personality disorder, depressed patients with borderline personality disorder were significantly more likely to have been persistently unemployed. A similar difference was found between patients with bipolar depression and major depressive disorder without borderline personality disorder. No differences were found between patients with bipolar depression and depression with borderline personality disorder. Conclusions: Both bipolar disorder and borderline personality disorder were associated with impaired occupational functioning and thus carry a significant public health burden. Efforts to improve detection of borderline personality disorder in depressed patients might be as important as the recognition of bipolar disorder.     

Low plasma gamma-aminobutyric acid levels in male patients with depression.

Plasma levels of gamma-aminobutyric acid (GABA) were significantly lower in males with primary unipolar major depressive disorder than in healthy controls. Although the difference in means between control and symptomatic depressed patient groups was small, the distribution of plasma GABA in the depressed patients was markedly different from controls. Forty percent of depressed patients had plasma GABA levels below those of controls. Plasma GABA levels correlated positively with duration of illness, and negatively with age at onset of the mood disorder and the total Endogenomorphic Symptom Score on the Hamilton Rating Scale. Plasma GABA levels may be a biochemical marker of vulnerability to depression, as opposed to a consequence of the illness. A low GABA condition in depression fits and complements the prevailing biogenic amine hypotheses of depression.     

Prolactin response to fenfluramine administration in patients with unipolar and bipolar depression and healthy controls

The hormonal response to the serotonin releasing agent/uptake inhibitor fenfluramine has been used as an indicator of central serotonin system function. The serotonergic system plays an important role in the etiology and pathogenesis of mood disorders. We compared the prolactin response to fenfluramine administration in unipolar depressed patients (major depressive disorder), depressed patients with bipolar disorder, and healthy controls. We found a trend towards a blunted prolactin response in depressed patients compared to healthy controls, after controlling for sex, family history, family history-by-gender interaction, and baseline levels. There was no significant difference between unipolar and bipolar patients in the baseline prolactin levels or the response to the fenfluramine administration. We also found a negative correlation between aggression and impulsivity scores and prolactin responses in subgroup with unipolar but not bipolar depression. Female patients with unipolar depression who had first-degree relatives with unipolar depression and normal controls had significantly higher prolactin responses than female patients with unipolar depression who did not have first-degree relatives with unipolar depression. The lack of difference in the response to fenfluramine administration between unipolar and bipolar depressed patients may indicate that overall serotonergic function in unipolar and bipolar depressed patients is similarly impaired.