The effects of electro-convulsive therapy on the speed of information processing in major depression

BACKGROUND: This study investigates whether cognitive impairment is evident in inpatients diagnosed with Major Depression (MD) following electro-convulsive therapy (ECT), and if so, whether it is independent from depressive symptomatology. METHODS: Speed of information processing was measured using the inspection time (IT) task. IT was compared between twelve inpatients diagnosed with MD receiving ECT and twelve age-, gender-, verbal IQ-, and depression and anxiety severity matched control inpatients diagnosed with MD not receiving ECT, over four testing sessions (prior to ECT, following one ECT session, following the completion of an ECT block, and 4 to 6 weeks after the ECT block (follow-up)). RESULTS: The mean IT score for the inpatients diagnosed with MD who received ECT slowed significantly from the first ECT to immediately after the ECT block, and was significantly faster at follow-up. The mean IT score of the inpatients diagnosed with MD not receiving ECT gradually but significantly became faster over the entire equivalent time period. LIMITATIONS: Small sample sizes. CONCLUSIONS: ECT temporarily slows information processing speed in MD patients, independent of depression symptomatology.     

Validity of an operational definition for neurotic unipolar major depression

After we reviewed the literature to identify the clinical and phenomenologic correlates of neurotic depression, we constructed a 6-item operational definition to distinguish neurotic unipolar major depressive disorder from non-neurotic major depression. The neurotic depressives were characterized by a low rate of abnormal dexamethasone suppression test (DST) results and a strong family history of alcoholism. Neurotic depressives improved less than non-neurotic depressives during the index hospitalization, and were more frequently rehospitalized during a 6-month prospective follow-up. Neurotic subtyping was significantly negatively associated with DSM-III melancholia. Neurotic classification remained significantly associated with the above validating variables after melancholic status was held constant, whereas melancholic subtyping did not predict DST results, familial alcoholism rates, or outcome when neurotic status was controlled.     

A processing speed deficit in dyslexic adults? Evidence from a peg-moving task

Developmental dyslexia is diagnosed when literacy skills are not commensurate with a person's general cognitive ability and education. While the most common difficulty found in dyslexia is poor phonological processing, many dyslexics are reported to be clumsy, with poor handwriting, suggesting that there may be a motor deficit in dyslexia. To establish whether the motor difficulties described in dyslexic children persist into adulthood, we tested 18 dyslexic adults and 22 control participants on Annett's peg-moving task. The dyslexic participants performed significantly slower than control adults on the peg-moving task with their dominant hands (p = 0.004). Furthermore, response times (RTs) during tasks testing component literacy skills correlated with peg-moving ability in the dominant hand in the entire group (orthographic r = 0.448, p = 0.005; phonological r = 0.383, p = 0.025). These results indicate that a motor speed deficit in dyslexia may not be simply a sign of developmental delay, but may persist into adulthood. Furthermore, motor speed may be related to the speed at which literacy information is processed.     

Minor physical anomalies in non-familial unipolar recurrent major depression

BACKGROUND: The prevalence of minor physical anomalies (MPAs) was evaluated in patients with unipolar recurrent major depression to get indirect data on the possible role of aberrant neurodevelopment in the aetiology of major depression. One published study [Lohr et al., Am. J. Geriatr. Psychiatry 5 (1997) 318] on the MPA prevalence in unipolar depression, evaluated by the recently widely criticized Waldrop-scale, reports on a significantly higher MPA rate among patients. METHODS: A scale developed by Méhes [Prog. Clin. Biol. Res. 163 (1985) 45] was used to detect the presence or absence of 57 MPAs in 30 patients with major depression and in 30 matched controls. RESULTS: The depressive sample did not differ significantly from the control group (P=0.200). By comparing each MPA individually we could not find any significant differences between the depressive and the control sample. LIMITATIONS: Patients and control subjects had a negative family history in connection with affective disorders; a high-risk population should give significant positive results. CONCLUSIONS: The results do not support the role of an 'early neurodevelopmental origin' in unipolar depression.     

Alcoholism in antisocial and nonantisocial men with unipolar major depression

Men with primary and secondary unipolar major depression were divided into those with and without antisocial personality (ASP). The ASP depressives had a higher rate of alcoholism than the nonASP depressives, and among the nonASP depressives, those with drug abuse had a higher rate of alcoholism than those without drug abuse.The course of depression appeared to be related to the presence of nonaffective psychopathology. Depressed men with additional nonaffective disorders had fewer, but larger episodes than depressed men without, and depressed men with alcoholism had a higher risk of suicide.Our results confirm the close association of alcoholism and ASP and highlight the importance of recognizing nonaffective syndromes in the depressed patient.     

Distinguishing early and late onset non-melancholic unipolar depression

AIM: We seek to determine whether unipolar non-melancholic major depression commencing early in life has a differing clinical picture, and whether it may have differing determinants. METHODS: We study a sample of such patients, comparing those with depression onset in their first 25 years against residual subjects, matching exactly by sex and controlling for age. RESULTS: There were no differences in current depression severity. Despite early onset subjects having a distinctly younger current mean age, they had a lifetime pattern of both greater depression chronicity and disability, and judged themselves as less likely to have benefited from any antidepressant medication or psychotherapy. 'Phenotypically' early onset subjects did not differ in terms of 'depressive' symptoms, but were distinguished by a greater irritability, which we interpret as reflecting a temperament dimension influencing symptom expression. Multivariate analyses indicated that the clinical pattern in those with an early onset was distinguished by more evident irritability and anxiety, that there was a distinct familial contribution to early onset depression, that its forerunners were an early personality style of behavioural inhibition or shyness, and that they were more likely to use alcohol and illicit drugs. CONCLUSIONS: While early onset unipolar depression is unlikely to be a pure depressive 'type', it may well be that certain familial temperament characteristics lead to an early onset of depression marked by irritability, a process that invokes a spectrum disorder concept linking temperament style and the depressive manifestations. Early onset depression is indicative of a poor prognosis, both in terms of response to interventions and in regard to chronicity and disability.     

Venlafaxine monotherapy in women with bipolar II and unipolar major depression

BACKGROUND: Women with bipolar (BP) disorder have more depressive episodes and drug-induced manic switches compared to men. Current guidelines suggest treating BP type I and type II major depressive episode (MDE) with both a mood-stabilizer and antidepressant. In a post hoc analysis, we examined the safety and efficacy of venlafaxine monotherapy in women with BP II MDE. METHODS: 15 women with BP II MDE (mean+/-SD age: 37+/-12 years) were compared to 17 women with unipolar (UP) MDE (41+/-12 years). Patients were randomized to double-blind treatment with once versus twice daily venlafaxine up to 225 mg for 6 weeks. Efficacy was measured using the HAM-D(21), MADRS and CGI scales. Drug-induced manic switch episodes characterized by agitation, irritability, euphoria or mood lability were assessed at each visit. RESULTS: No episodes of drug-induced hypomania or rapid cycling were observed during 6 weeks of venlafaxine monotherapy. Similar efficacy was observed in BP and UP depressed women (p=ns). LIMITATIONS: This study was retrospective in nature and limited in patient number. Only BP II women were included in this study, and it is possible that efficacy and the manic switch rate might have differed if BP I women were included. CONCLUSION: Short-term venlafaxine monotherapy may be a safe and effective antidepressant treatment in women with BP II MDE.     

Cerebrospinal fluid interleukin (IL)-6 in unipolar major depression

BACKGROUND: Previous studies have suggested that regulation of the proinflammatory cytokine interleukin (IL)-6 is abnormal in patients with major depression. This study was undertaken to determine whether IL-6 concentrations in cerebrospinal fluid (CSF) differ between depressed patients and healthy control subjects. METHODS: Lumbar puncture with a standardized procedure was performed on 18 drug-free patients meeting DSM-IV criteria for unipolar major depression and 26 age- and sex-matched healthy volunteers. CSF was assayed for IL-6 using a quantitative 'sandwich' enzyme immunoassay technique. RESULTS: Mean+/-S.D. CSF IL-6 levels did not differ between depressed (2.2+/-1.0 pg/ml) and healthy control (2.4+/-1.9 pg/ml) subjects. LIMITATIONS: This study had adequate power (0.8) to detect a large (d=0.88) effect size at alpha = 0.05. Although sample sizes were comparable to or larger than those of previous CSF studies, it is possible that a less robust difference between depressed and healthy subjects was not detected. CONCLUSIONS: These findings fail to support speculation that immune activation may be causally involved in the pathogenesis of depression.     

Association between symptomatic profile and remission following antidepressant treatment in unipolar major depression

Background

To evaluate, in patients affected by an acute major depressive episode, what predictive value certain baseline psychopathological characteristics have with regard to expected therapeutic remission following biological antidepressant treatment (pharmacological/electroconvulsive; non-psychological).

Methods

Six predefined psychopathological characteristics in acute major depressive episode were evaluated using a logistic regression model through a protocolised antidepressant treatment to assess their predictive value with regard to expected remission rate.

Results

The final study sample consisted of 129 subjects affected by an acute major depressive episode. From the baseline evaluation of the anguish/restlessness, reduced emotional reactivity, reduced attention, reduced motor response, feeling of worthlessness, and mood characteristics items, it was possible to correctly classify 88.1% of the sample as remitter/non-remitter with sensitivity of 0.77 and specificity of 0.96. Addition of the 17-item HRSD baseline variable to the regression model increased the capacity for correct classification of the baseline sample by only 0.09%.

Limitations

Protocolised antidepressant treatment was used. The results of this study may not be generalisable to pharmacological treatments not included in this protocol.

Conclusions

The results of this study suggest that certain baseline psychopathological characteristics (and perhaps other clinical variables too) of the acute major depressive episode may be of great use in establishing patient subgroups according to expected clinical remission to the administration of biological antidepressant treatment. This could have considerable consequences for individualised therapeutic decision-making and for future researches (clinical trials included).     

Spatial processing of facial emotion in patients with unipolar depression: a longitudinal study

BACKGROUND: In this study, a face-in-the-crowd task was applied to examine the spatial detection of facial emotion as a function of depression and comorbid anxiety in the course of a psychotherapeutic inpatient treatment. METHODS: Patients with unipolar depression (n=22) and normal controls (n=22) were tested twice, about 7 weeks apart, on a face-in-the-crowd task using displays of schematic faces. Half the patients were suffering from a comorbid anxiety disorder. RESULTS: From test 1 to test 2, depressivity, frequency of negative thoughts, and worrying of patients improved significantly. At both sessions, depressed patients, irrespective of the presence of comorbid anxiety disorders, showed no performance differences in the detection of negative faces compared to controls. However, depressed patients with but not those without comorbid anxiety disorders were slower in responding to positive faces than controls. Both patient groups were slower in responding to the neutral faces' condition than controls. CONCLUSIONS: Our data indicate a spatial processing deficit for positive facial expression in depressives with a comorbid anxiety disorder. This impairment, which appears to persist during remission, might be due to deficits in effortful visual search processes.     

Nightmares, suicide attempts, and melancholic features in patients with unipolar major depression

OBJECTIVES: Recently, there has been a growing interest in the relationship between sleep disturbances and suicidality in major depression. Sleep disturbances are one of the 'modifiable risks' for suicide in major depression. The present study examines whether there is a relationship among nightmares, suicide attempts, and melancholic features in unipolar major depressed patients. METHODS: One hundred (49 males and 51 females) depressed patients with melancholic features and 49 (23 males and 26 females) patients without melancholic features were included in the study. All patients were classified as those who attempted suicide at least once during current depressive episode and as those who never attempted. RESULTS: Melancholic attempters had higher rates of nightmares, middle, and terminal insomnia than melancholic non-attempters. There was no significant difference between non-melancholic patients with and without suicidal attempts in terms of the frequency of all types of insomnia and nightmares. Limitations: This study does not have polysomnographic records for sleep variables. CONCLUSIONS: Feeling worse in the morning than later in the day may be related to the intervening dream content and affect and predict suicidal tendency. Melancholia may be associated with increased risk of suicide attempts due to repetitive and frightening dreams.     

Effects of an antidepressant on neural correlates of emotional processing in patients with major depression

We measured brain activation in patients with major depressive disorder when exposed to emotional pictures before and after antidepressant treatment. The participants included 18 first-episode unmedicated patients with current major depressive disorder and 18 age- and gender-matched control subjects. All subjects performed an emotional task during functional magnetic resonance imaging scanning at baseline and after 8 weeks of fluoxetine treatment. Unmedicated depressed patients showed lower accuracy rates (0.53 ± 0.26) than did subjects in the control group (0.71 ± 0.18) while viewing positive pictures. During exposure to positive stimuli, decreased activations were seen in the right insula (BA13) and left anterior cingulate cortex (BA32) in patients after antidepressant treatment. After antidepressant treatment, patients exhibited greater activation in the right middle frontal gyrus (BA8,9) in response to negative stimuli. Our results suggest that the prefrontal cortex, anterior cingulate cortex and insula may play key roles as biological markers for treatment response and as predictors of therapeutic success.     

The familial relation of personality disorders (DSM-II-R) to unipolar major depression.

Four hundred and fifty directly interviewed relatives of probands with non-psychotic unipolar major depression and 320 directly interviewed relatives of controls were compared by the prevalences of personality disorders (P.D.) as defined by DSM-III-R, in relation to presence or absence of the relatives' affective disorder. Overall, there was only a trend for an increased risk for P.D. in relatives of depressed patients. However, P.D. and unipolar major depression co-occurred more frequently in relatives than expected by chance. It is suggested that this association is mainly due to non-familial factors. Compared with other P.D., the relationship of borderline P.D. to major depression was not substantially stronger.     

Urinary steroid metabolites and 11beta-hydroxysteroid dehydrogenase activity in patients with unipolar recurrent major depression

BACKGROUND: The aim of the present study was to obtain comprehensive information on steroid metabolism in depressed patients. METHODS: 24-h urinary steroids were measured by gas chromatography in patients with unipolar recurrent major depression (URMD) compared to controls, and an index of relative activity of the 11beta-hydroxysteroid dehydrogenase (11beta-HSD) enzyme was calculated. RESULTS: The levels of etiocholanolone (E) (p < 0.05), beta-cortolone (beta-CL) (p < 0.01) were significantly decreased, while levels of allo-tetrahydrocorticosterone (aTHB) (p < 0.05) and cortisol (F) (p < 0.01) were elevated in depressed women. The levels of dehydroepiandrosterone (DHEA) (p < 0.01), tetrahydrocorticosterone (THB) (p < 0.01), beta-CL (p < 0.01), and aTHB (p < 0.05) were found significantly decreased in depressed men. The index of 11beta-HSD activity (p < 0.01) was significantly decreased in patients in both sexes. LIMITATIONS: The sample is limited to only urine samples of patient with URMD; the correlation between the severity of depression and F and DHEA was not analyzed. CONCLUSION: Our investigations confirmed that URMD associated with altered steroid metabolism, which shows gender differences, pointing to the different stress sensibility of women. These differences may be the cause as well as the consequence of the major depression (MD).     

Memory deficit in clinical depression: processing resources and the structure of materials

Resource theory predicts that the relative memory deficit shown by depressed patients should be greater with unstructured than structured material. Previous data using semantic categories word lists supports this, but lists approximating to text have produced the opposite result. Both types of structure were studied in this experiment. The prediction from resource theory was found to hold only when comparing medium and high levels of structure, and to hold more clearly for word lists approximating to text than for semantic categories lists. When word lists of low and medium levels of structure were compared, depressed patients showed relatively greater deficit with the more structured material. Ways in which this could be accommodated in a revised version of resource theory are discussed.     

Evidence demonstrating role of microRNAs in the etiopathology of major depression

Major depression is a debilitating disease. Despite a tremendous amount of research, the molecular mechanisms associated with the etiopathology of major depression are not clearly understood. Several lines of evidence indicate that depression is associated with altered neuronal and structural plasticity and neurogenesis. MicroRNAs are a newly discovered prominent class of gene expression regulators that have critical roles in neural development, are needed for survival and optimal health of postmitotic neurons, and regulate synaptic functions, particularly by regulating protein synthesis in dendritic spines. In addition, microRNAs (miRNAs) regulate both embryonic and adult neurogenesis. Given that miRNAs are involved in neural plasticity and neurogenesis, the concept that miRNAs may play an important role in psychiatric illnesses, including major depression, is rapidly advancing. Emerging evidence demonstrates that the expression of miRNAs is altered during stress, in the brain of behaviorally depressed animals, and in human postmortem brain of depressed subjects. In this review article, the possibility that dysregulation of miRNAs and/or altered miRNA response may contribute to the etiology and pathophysiology of depressive disorder is discussed.