Albert Michael

Emotional bias and inhibitory control processes in mania and depression

BACKGROUND Despite markedly different clinical presentations, few studies have reported differences in neuropsychological functioning between mania and depression. The disinhibited behaviour characteristic of mania and evidence that subgenual prefrontal cortex is differentially activated in mania and depression both suggest that dissociable deficits will emerge on tasks that require inhibitory control and are subserved by ventromedial prefrontal cortex. METHODS Manic patients and controls undertook computerized neuropsychological tests of memory and planning ability. In addition, manic and depressed patients were directly compared with controls on a novel affective shifting task that requires inhibitory control over different components of cognitive and emotional processing. RESULTS Manic patients were impaired on tests of memory and planning. Importantly, affective shifting performance of manic patients differed from that of depressed patients. Manic patients were impaired in their ability to inhibit behavioural responses and focus attention, but depressed patients were impaired in their ability to shift the focus of attention. Depressed patients exhibited an affective bias for negative stimuli, and we believe this to be the first demonstration of an affective bias for positive stimuli in manic patients. CONCLUSIONS Observed impairments on tests of memory and planning suggest a global pathology for mania consistent with previous profiles for this disorder and similar to established profiles for depression. The results on the affective shifting task demonstrate the presence of mood-congruent bias and dissociable components of inhibitory control in mania and depression. Against a background of memory and planning impairments in the two groups, these findings are consistent with a role for the ventromedial prefrontal cortex in mediating mood-cognition relationships.

Early Detection and Differential Diagnosis of Alzheimer’s Disease and Depression with Neuropsychological Tasks

The development of novel treatments for Alzheimer’s disease (AD), aimed at ameliorating symptoms and modifying disease processes, increases the need for early diagnosis. Neuropsychological deficits such as poor episodic memory are a consistent feature of early-in-the-course AD, but they overlap with the cognitive impairments in other disorders such as depression, making differential diagnosis difficult. Computerised and traditional tests of memory, attention and executive function were given to four subject groups: mild AD (n = 26); questionable dementia (QD; n = 43); major depression (n = 37) and healthy controls (n = 39). A visuo-spatial associative learning test accurately distinguished AD from depressed/control subjects and revealed an apparent sub-group of QD patients who performed like AD patients. QD patients’ performance correlated with the degree of subsequent global cognitive decline. Elements of contextual and cued recall may account for the task’s sensitivity and specificity for AD.

Cognitive impairment in remission in bipolar affective disorder.

BACKGROUND Although the traditional view of bipolar affective disorder is that the majority of patients have full remission between episodes, recent evidence suggests that residual cognitive deficits are present. The aim of this study was to determine whether memory and executive deficits were present in a well-defined clinically remitted group of patients. METHODS This was a case-control study of bipolar patients in remission (N = 18). Subjects had to fulfil stringent clinical criteria for inclusion into the study and had to have been in remission for at least 4 months. Subjects also had no history of substance dependence. The cognitive battery examined memory and executive function. RESULTS Patients in excellent clinical remission and who reported good social adaptation showed imipairment on tests of visuospatial recognition memory. Accuracy on four tests of executive function was not impaired in patients in remission compared with controls, although response latency on these executive tests was still impaired. CONCLUSIONS As our group and others have shown, patients with mania and unipolar depression show generalized impairment on tests of memory and executive function. In comparison, this study has demonstrated that patients in remission show a relatively specific impairment in memory with recovery of accuracy measures on executive function task. The increased response latency on the executive tasks suggests a possible small residual impairment. These findings suggest that in netIroanatomical terms, more posterior cortical function (temporal lobe) has not improved but there is at least some recovery of frontal lobe function in remission.

Altered salivary dehydroepiandrosterone levels in major depression in adults

BACKGROUND The authors sought to examine whether levels of dehydroepiandrosterone are abnormal in depression. METHODS Three groups of subjects aged 20-64 were studied: 44 major depressives, 35 subjects with partially or completely remitted depression, matched as far as possible for age and drug treatment, and 41 normal control subjects. Dehydroepiandrosterone and cortisol in saliva were determined from specimens taken at 8:00 AM and 8:00 PM on 4 days. RESULTS The mean age of the three groups did not differ. Dehydroepiandrosterone was lowered at 8:00 AM and 8:00 PM compared with control subjects. Values for the remitted group were intermediate. Dehydroepiandrosterone levels at 8:00 AM correlated negatively with severity of depression and were not related to drug treatment or smoking, but decreased with age (as expected). Cortisol was elevated in depression in the evening. The molar cortisol/dehydroepiandrosterone ratio also differentiated those with depression from the control group. CONCLUSIONS Lowered dehydroepiandrosterone levels are an additional state abnormality in adult depression. Adrenal steroid changes are thus not limited to cortisol. Because dehydroepiandrosterone may antagonize some effects of cortisol and may have mood improving properties, these findings may have significant implications for the pathophysiology of depression.

Abnormal neural response to feedback on planning and guessing tasks in patients with unipolar depression

BACKGROUND It has been suggested that patients with unipolar depression show abnormal responses to negative feedback in the performance of cognitive tasks. Positron emission tomography (PET) has previously identified blood flow abnormalities in depressed patients during cognitive performance. We have also used PET to identify regions where there is differential neural response to performance feedback in normal volunteers. In this study we aimed to test the hypothesis that blood flow in these regions, the medial caudate and ventromedial prefrontal cortex, would be abnormal in depressed patients. METHODS Six patients with unipolar depression and six matched controls were scanned using PET while performing cognitive tasks in the presence and absence of feedback. RESULTS Compared with controls, depressed patients failed to show significant activation in the medial caudate and ventromedial orbitofrontal cortex. Blood flow was lower and a differential response, observed in normals, under different task and feedback conditions was not seen in the patients. DISCUSSION The findings suggest that the behavioural response to feedback in depressed patients is associated with an abnormal neural response within the medial caudate and ventromedial orbitofrontal cortex, regions implicated in reward mechanisms. We argue that the observed abnormalities may depend on a combination of psychological factors, with both cognitive and emotive components.

Approach and avoidance learning in patients with major depression and healthy controls: relation to anhedonia

BACKGROUND Central to understanding of the behavioural consequences of depression has been the theory that the disorder is accompanied by an increased sensitivity to negative compared with positive reinforcement (negative bias), whereas other theorists have emphasized a global reduction in sensitivity to reinforcement in depression (blunting). METHOD In this study, we used a probabilistic selection task that was designed to examine independently rates of learning to predict both positive and negative reinforcement. Twenty-three depressed out-patients and 23 healthy controls from the local population participated in the study. RESULTS No evidence for a negative bias was observed on the task, either during acquisition of the task or during generalization of the learned information. Depressed patients responded slower on the task than controls but showed a similar modulation of reaction times (RTs) as controls following reinforcement. Evidence for blunting was observed on the training phase, as reflected in reduced trial-by-trial adjustment during this phase. However, this effect was related specifically to the severity of anhedonia, as measured by the Snaith-Hamilton Pleasure Scale (SHAPS), and was independent of overall depression severity. CONCLUSIONS We argue that the observation of a negative bias or blunting in a group of depressed patients may be dependent on the neuropsychological task and the symptoms of the patients tested. Our results provide insight into how these theories might be further tested.

Sexual dysfunction in depression

Sexual dysfunction is a well‐known symptom of depression. However, it has received little, if any, attention from clinicians and researchers. A review of published literature suggests that sexual dysfunction occurs in the majority of depressed patients. It has a major impact on the quality of life of the patients. The pathophysiology of sexual dysfunction in depression involves a complex interplay of various neurotransmitters and hormones. Clinicians need to be more proactive in enquiring about sexual dysfunction in depressed patients. More information is needed about the nature, prevalence and pathophysiology of sexual dysfunction in depression. Copyright

A rare coding variant within the wolframin gene in bipolar and unipolar affective disorder cases.

A recent report has shown that Wolfram syndrome carriers (heterozygotes) are 26-fold more likely to require psychiatric hospitalization compared with non-carriers, and that Wolfram syndrome heterozygotes may constitute approximately 25% of individuals hospitalized with depression and suicide attempts. We analyzed a His611Arg polymorphism of the wolframin gene by the polymerase chain reaction (PCR) and HhaI restriction digestion, in 158 bipolar I and 163 unipolar major affective disorder cases, and 316 controls. Statistical analyses of allele or genotype frequencies do not support a major role for wolframin in affective disorder. HhaI restriction digestion and sequencing of PCR products from four affective disorder cases showed a heterozygous Ala559Thr change. The Ala559Thr variant was not detectable in 382 controls tested. Thus, the rare wolframin 559Thr allele deserves consideration as a risk allele for affective disorder.

No association of an insertion/deletion polymorphism in the angiotensin I converting enzyme gene with bipolar or unipolar affective disorders.

A recent Japanese study on the angiotensin I converting enzyme gene (ACE) insertion/deletion polymorphism reported that both the D allele (P < 0.02) and the DD genotype (P < 0.002) were significantly more frequent in affective disorder cases than in controls [Arinami et al., 1996: Biol Psychiatry 40:1122-1127]. A replication study was performed by using 157 bipolar I affective disorder cases, 169 major depressive disorder cases, and 313 controls. No significant association with this polymorphism was found in either disorder or in a combined affective disorder group. These results do not support the ACE gene having a major role in the etiology of either bipolar or unipolar affective disorders. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:733-735, 2000.

Emotion modulates cognitive flexibility in patients with major depression.

BACKGROUND Depression is associated with alterations of emotional and cognitive processing, and executive control in particular. Previous research has shown that depressed patients are impaired in their ability to shift attention from one emotional category to another, but whether this shifting deficit is more evident on emotional relative to non-emotional cognitive control tasks remains unclear. METHOD The performance of patients with major depressive disorder and matched healthy control participants was compared on neutral and emotional variants of a dynamic cognitive control task that requires participants to shift attention and response from one category to another. RESULTS Relative to controls, depressed patients were impaired on both tasks, particularly in terms of performance accuracy. In the neutral go/no-go task, the ability of depressed patients to flexibly shift attention and response from one class of neutral stimuli to the other was unimpaired. This contrasted with findings for the emotional go/no-go task, where responding was slower specifically on blocks of trials that required participants to shift attention and response from one emotional category to the other. CONCLUSIONS The present data indicate that any depression-related difficulties with cognitive flexibility and control may be particularly evident on matched tasks that require processing of relevant emotional, rather than simply neutral, stimuli. The implications of these findings for our developing understanding of cognitive and emotional control processes in depression are discussed.