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Biomedical subjects

Guy M Goodwin

Publications and source records attributed to Guy M Goodwin.

At least 19 recordsLinked to original sources
PubMed2006

What is a mood stabilizer?

The concept of mood stability is attractive to both patients and clinicians alike, and hence the term 'mood stabilizer' has widespread currency. However, its worldwide acceptance and use in clinical practice is at odds with the absence of official recognition by regulatory authorities. The ideal mood stabilizer is said to have efficacy in the treatment of acute manic and depressive episodes, and also be effective in the prevention of recurrences. However, in reality, few drugs with perhaps the exception of lithium, come close to this gold standard; yet many agents aspire to the title, and some have arguably achieved it prematurely. It is, therefore, important to reconsider the definition of a mood stabilizer and critically review which agents, if any, satisfy the necessary eligibility requirements by reference to reasonable criteria and comparator data. The term mood stabilizer is an important label. It needs to be applied judiciously because it confers clinical credibility and qualifies long-term use in maintenance and prophylaxis. It is also important with respect to developing guidelines for treatment and the further development of novel agents. Most importantly, however, it is a term that is innately appealing because of what it promises: for this reason alone it should encompass only those agents that can deliver.

Affect↗
PubMed2006

5HT(3) antagonism abolishes the emotion potentiated startle effect in humans.

RATIONALE: The serotonergic system has been implicated in emotional processing in animals and humans. Although the contribution of different receptor subtypes has been hypothesised, there have been few direct tests of this in human subjects. OBJECTIVES: The current study aimed to explore the involvement of the serotonin type 3 (5HT3) receptor subtype in a battery of emotional processing tasks previously found to be sensitive to SSRI administration. MATERIALS AND METHODS: Healthy volunteers were randomised to receive the 5HT3 antagonist, ondansetron (12 mg, oral), or placebo in a double blind between groups design. Emotional processing was assessed using three tasks: affective modulation of the startle reflex, emotional categorisation and memory and facial expression recognition. Subjective state ratings, blood pressure and pulse were also collected before and after ondansetron and placebo. RESULTS: Ondansetron was well tolerated and did not affect subjective measures of mood, anxiety or well-being in these healthy volunteers. However, the emotion potentiated effect was abolished in the volunteers receiving ondansetron. Facial expression recognition and emotional memory were not significantly affected. CONCLUSIONS: These results suggest an involvement of 5HT3 receptors in certain aspects of fear processing in humans. These effects are consistent with anxiolytic actions of 5HT3 antagonism in animal models and suggest that the 5HT3 receptor may play a role in the effects of serotonergic manipulations on fear and anxiety.

Adult↗
PubMed2006

Antidepressant drug treatment modifies the neural processing of nonconscious threat cues.

BACKGROUND: The amygdala is believed to play a key role in processing emotionally salient, threat-relevant, events that require further online processing by cortical regions. Emotional disorders such as depression and anxiety have been associated with hyperactivity of the amygdala, but it is unknown whether antidepressant treatment directly affects amygdala responses to emotionally significant information. METHODS: The current study assessed the effects of 7 days administration of the selective serotonin reuptake inhibitor (SSRI), citalopram, on amygdala responses to masked presentations of fearful and happy facial expressions in never-depressed volunteers using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging. A double-blind, between-groups design was used with volunteers randomized to 20 mg/day citalopram versus placebo. RESULTS: Volunteers receiving citalopram showed decreased amygdala responses to masked presentations of threat compared with those receiving placebo. Citalopram also reduced responses within the hippocampus and medial prefrontal cortex (mPFC) specifically during the fear-relevant stimuli. These neural differences were accompanied by decreased recognition of fearful facial expressions assessed after the scan. By contrast, there was no effect of citalopram on the neural or behavioral response to the happy facial expressions. CONCLUSIONS: These results suggest a direct effect of serotonin potentiation on amygdala response to threat-relevant stimuli in humans. Such effects may be important in the therapeutic actions of antidepressants in depression and anxiety.

Adolescent↗
PubMed2006

Suicide trends in discharged patients with mood disorders: associations with selective serotonin uptake inhibitors and comorbid substance misuse.

We determined the rates of suicide in two consecutive time intervals of low and high selective serotonin reuptake inhibitor (SSRI) prescribing for men and women with mood disorders, who were at relatively high risk of suicide, in a discharged hospitalized sample. High quality Swedish national registers were cross-linked to estimate rates of suicide. The results were stratified by three age-bands, and rates of comorbid substance misuse were explored. These were compared with general population suicide rates. There were 1606 suicides in discharged patients with mood disorders. Suicide rates decreased for all women during 1989-94 and 1995-2000 [odds ratio (OR) = 0.74, 95% confidence interval (CI) = 0.64-0.85] and a trend was found towards lower rates in men (OR = 0.89, 95% CI = 0.78-1.02). Approximately 90% of suicides occurred in those aged over 40 years; thus, the inpatient sample lacked the power to discriminate clear effects in the younger age groups. There was no increase or decrease in the rates of substance use disorders in patients who committed suicide. There were 20 851 suicides in the general population during 1989-2000. Suicide rates were lower at all ages for men and women in the general population in the interval of high SSRI prescribing. We conclude that there is no evidence from this study of an increase in suicide rates following the introduction of SSRIs in the general population or in a high-risk inpatient sample.

Adolescent↗
PubMed2006

Aromatase inhibitors and bipolar mood disorder: a case report.

OBJECTIVE: To report a case in which the aromatase inhibitor letrozole produced irritable mood elevation followed by depression in a woman with a history of postpartum depression. METHODS: A 60-year-old Caucasian woman who had a severe depressive episode after the birth of her only child, 32 years earlier, was treated successively with anastrozole and letrozole following a mastectomy, radiotherapy and chemotherapy. RESULTS: Mrs X was prescribed anastrozole for about 6 weeks. During this time she experienced labile mood, increased activity, tremulousness and difficulty sleeping. These symptoms disappeared after stopping the anastrozole. On letrozole, she developed an acute irritable activated mood elevation, which then subsided into a prolonged major depression after withdrawal of letrozole. These effects occurred during co-prescription of amitriptyline at a low dose for urinary frequency. CONCLUSIONS: The present case suggests caution may be warranted when employing aromatase inhibitors, especially in women with a past history of postpartum affective disorder or bipolar disorder. As with postpartum mania, the primary mechanism of the effect may be acute reduction in circulating oestrogen levels.

Aggression↗
PubMed2006

Long-term prophylaxis in bipolar disorder.

Bipolar disorder is a major cause of disability, and the prevention of relapse is a key management goal. Pharmacological interventions, effectively delivered through enhanced clinical care, are central to long-term management. This article summarises the available evidence for a range of pharmacological options, and provides guidance on common issues in clinical management in line with current practice guidelines. The use of medications for long-term prophylaxis should be considered in all patients meeting criteria for bipolar I disorder. Increasing high-quality evidence from randomised trials informs management decisions relating to both novel agents, such as lamotrigine and olanzapine, and longer-established therapies, such as lithium and valproate, in monotherapy. Medications taken long-term in bipolar disorder differ in the extent to which they protect against manic and depressive relapse. Consequently, the emerging challenge is to understand how combination treatments can enhance efficacy and effectiveness based on data from controlled trials rather than random polypharmacy. Clinical care can be enhanced with effective education about the illness, and the use of strategies to improve treatment adherence and the recognition and management of stressors or prodromal symptoms. Where available, a range of specific psychological interventions can be effective as an adjunct to medication. When discontinuation of prophylaxis is necessary, gradual tapering of dose over weeks or months is recommended.

Age Factors↗
PubMed2006

Depression and associated physical diseases and symptoms.

Depression can occur in association with virtually all the other psychiatric and physical diagnoses. Physical illness increases the risk of developing severe depressive illness. There are two broadly different mechanisms. The most obvious has a psychological or cognitive mechanism. Thus, the illness may provide the life event or chronic difficulty that triggers a depressive episode in a vulnerable individual. Secondly, more specific associations appear to exist between depression and particular physical disorders. These may turn out to be of particular etiological interest. The best examples are probably stroke and cardiovascular disease. Finally, major depression, but especially minor depression, dysthymia, and depressive symptoms merge with other manifestations of human distress with which patients present to their doctors. Such somatic presentations test the conventional distinction between physical and mental disorder and are a perennial source of controversy.

Depressive Disorder↗
PubMed2005

Low-dose tryptophan depletion in recovered depressed patients induces changes in cognitive processing without depressive symptoms.

BACKGROUND: Acute tryptophan depletion can induce a transient reappearance of depressive symptoms in recovered depressed patients. The neurochemical mechanism is thought to be impairment of brain serotonin neurotransmission, but the neuropsychologic mechanisms underlying the effect are unclear. METHODS: To assess whether low-dose tryptophan depletion can tease out the psychological mechanisms sensitive to substrate depletion in vulnerable subjects without inducing mood changes, a between-subjects randomized design was used. Recovered depressed patients (n = 24) and healthy volunteers (n = 24) were administered while fasting either a tryptophan-free or a control mixture, containing 31.2 and 33.2 g of amino acids, respectively. Objective and subjective ratings of mood were made before and 5 hours after ingestion; at the latter time point, cognitive and emotional processing were also assessed. RESULTS: Low-dose tryptophan depletion did not affect mood. Significant changes in emotional and cognitive processing occurred in the recovered depressed group, however, and to a lesser extent in the healthy volunteers. The profile of effects seen in the recovered patients suggested a return of the impairments seen in acute depression. CONCLUSIONS: Our data suggest that low-dose tryptophan depletion permits investigation of the cognitive correlates of acute reductions in brain serotonin in populations vulnerable to depression and in healthy volunteers, without causing depressive symptoms.

Adult↗
PubMed2005

Sustained attention-deficit confirmed in euthymic bipolar disorder but not in first-degree relatives of bipolar patients or euthymic unipolar depression.

BACKGROUND: Cognitive dysfunction persists in the euthymic phase of bipolar disorder and may provide a marker of underlying neuropathology and disease vulnerability. This study aimed to replicate a deficit in sustained attention in euthymic bipolar patients and investigate sustained attention in first-degree relatives of bipolar probands and in remitted patients with major depressive disorder. METHODS: The rapid visual information processing (RVIP) task was used to measure sustained attention in 15 euthymic patients with bipolar disorder and 15 control subjects in experiment 1 and in 27 first-degree relatives of bipolar probands, 15 remitted patients with major depressive disorder, and 46 control subjects in experiment 2. RESULTS: Sustained attention deficit was confirmed in the euthymic bipolar patients in experiment 1, but the deficit was not statistically significant in remitted major depressed patients or in the relatives of bipolar probands. CONCLUSIONS: A deficit of sustained attention is not present in patients with recurrent major depression tested during remission nor is it discriminable in the first-degree relatives of bipolar probands. Thus, the confirmed abnormality in euthymic bipolar patients may be acquired as a consequence of bipolar illness. However, future studies of relatives will require larger sample sizes to exclude or utilize small genetic effects.

Adult↗
PubMed2005

The burden on informal caregivers of people with bipolar disorder.

Caregivers of people with bipolar disorder may experience a different quality of burden than is seen with other illnesses. A better understanding of their concerns is necessary to improve the training of professionals working with this population. Conceptualizing caregiver burden in a conventional medical framework may not focus enough on issues important to caregivers, or on cultural and social issues. Perceptions of caregivers about bipolar disorder have important effects on levels of burden experienced. It is important to distinguish between caregivers' experience of this subjective burden and objective burden as externally appraised. Caregivers' previous experiences of health services may influence their beliefs about the illness. Caregiver burden is associated with depression, which affects patient recovery by adding stress to the living environment. The objective burden on caregivers of patients with bipolar disorder is significantly higher than for those with unipolar depression. Caregivers of bipolar patients have high levels of expressed emotion, including critical, hostile, or over-involved attitudes. Several measures have been developed to assess the care burden of patients with depressive disorders, but may be inappropriate for patients with bipolar disorder because of its cyclical nature and the stresses arising from manic and hypomanic episodes. Inter-episode symptoms pose another potential of burden in patients with bipolar disorder. Subsyndromal depressive symptoms are common in this phase of the illness, resulting in severe and widespread impairment of function. Despite the importance of assessing caregiver burden in bipolar disorder, relevant literature is scarce. The specific effects of mania and inter-episode symptoms have not been adequately addressed, and there is a lack of existing measures to assess burden adequately, causing uncertainty regarding how best to structure family interventions to optimally alleviate burden. The relatively few studies into caregiver burden in bipolar disorder may largely reflect experiences in the US Veterans Affairs health service, but the findings may be limited in their generalizability. Nevertheless, available data suggest that caregiver burden is high and largely neglected in bipolar disorder. Clinically effective, well-targeted and practically viable interventions are needed. However, services cannot be enhanced on a rational basis without an improved understanding and capacity to measure and target caregiver burden the impact of any change in services be evaluated.

Affect↗
PubMed2005

Sleep-related functioning in euthymic patients with bipolar disorder, patients with insomnia, and subjects without sleep problems.

OBJECTIVE: The authors investigated sleep-related functioning in euthymic patients with bipolar disorder. METHOD: Euthymic patients with bipolar disorder (N=20), patients with insomnia (N=20), and subjects with good sleep (N=20) were compared on data from interviews and questionnaires and on findings from eight consecutive days and nights of sleep diary keeping (subjective sleep estimate) and actigraphy (objective sleep estimate). RESULTS: Seventy percent of the euthymic patients with bipolar disorder exhibited a clinically significant sleep disturbance. Compared with the other groups, the bipolar disorder group exhibited impaired sleep efficiency, higher levels of anxiety and fear about poor sleep, lower daytime activity levels, and a tendency to misperceive sleep. The bipolar disorder group held a level of dysfunctional beliefs about sleep that was comparable to that in the insomnia group and significantly higher than that in the good sleeper group. CONCLUSIONS: Insomnia is a significant problem among euthymic patients with bipolar disorder. Components of cognitive behavior therapy for insomnia, especially stimulus control and cognitive therapy, may be a helpful adjunct to treatment for patients with bipolar disorder.

Adaptation, Psychological↗
PubMed2005

Impairment of executive function but not memory in first-degree relatives of patients with bipolar I disorder and in euthymic patients with unipolar depression.

OBJECTIVE: The authors' goal was to characterize cognitive flexibility and verbal learning in relatives of patients with bipolar disorder and in euthymic patients with recurrent major depression. METHOD: The intradimensional/extradimensional shift task and California Verbal Learning Test were administered to 27 first-degree relatives of probands with bipolar I disorder, 15 euthymic outpatients with recurrent unipolar depression, and 47 healthy comparison subjects. RESULTS: The relatives of patients with bipolar I disorder and the euthymic patients with unipolar depression were more likely to fail the intradimensional/extradimensional shift task than the healthy comparison subjects. The impairments at the extradimensional shift stage were pronounced. Verbal learning, delayed recall, and recognition were unimpaired in all groups. CONCLUSIONS: Attentional set shifting may represent an endophenotype in mood disorder, related to underlying vulnerability rather than the actual disease phenotype.

Adolescent↗
PubMed2005

Enhanced early morning salivary cortisol in neuroticism.

OBJECTIVE: Neuroticism is a predisposing factor for major depression. The increase in salivary cortisol that follows waking provides a reliable measure of adrenocortical activity, and this response is increased in recovered depressed patients. This study compared waking cortisol levels in healthy subjects with high and low levels of neuroticism without a previous history of depression. METHOD: Salivary cortisol levels were measured upon waking and at 15-minute intervals for the next hour in volunteers selected to have high (>19/23) or low (<4/23) neuroticism based on the Eysenck Personality Inventory. RESULTS: Subjects with high neuroticism showed significantly greater levels of salivary cortisol 30 minutes after waking, which were maintained for the next half hour. CONCLUSIONS: Abnormalities in waking cortisol are associated with neuroticism in a way similar to those seen in major depression. Elevated waking cortisol may represent a vulnerability marker for mood disorder.

Biomarkers↗
PubMed2005

Lamotrigine in the treatment of bipolar disorder.

Lamotrigine is a novel anticonvulsant agent that has recently been introduced as a long-term treatment in bipolar disorder. Its role in the treatment of epilepsy is based on its actions to decrease ion channel conductance and antagonise glutamatergic function. Therefore, it has a mode of action unlike other agents used on a long-term basis in mood disorders. The evidence for efficacy is stronger for the prevention of depressive, rather than manic, episodes. The pivotal trials are in bipolar I disorder, but there is interest in its actions in patients with bipolar II and spectrum conditions. Its efficacy in other psychiatric conditions remains to be properly established. It is well tolerated and, with careful prescribing, the incidence of rash occurs no more than with placebo; however this is still a concern. Although usually well tolerated, headache, insomnia and drowsiness are probably the most common side effects.

Bipolar Disorder↗
PubMed2004

State- and trait-related deficits in sustained attention in bipolar disorder.

Investigation of neuropsychological functioning in bipolar disorder provides a potential link from the prominent cognitive symptoms of the disorder to the underlying neural mechanisms. Continuous performance measures of sustained attention have yielded consistent findings in bipolar disorder patients. There are impairments that appear to be both state- and trait-related. Impaired target detection may represent one of the most sensitive markers of illness course in bipolardisorder. It is unrelated to residual mood symptomatology and medication status, and is present in patients with good functional recovery. The impairment in target detection is exacerbated in the manic state, and is accompanied by an increased rate of false responding. Sustained attention deficit is present early in the course of the disorder, but becomes more pronounced with repeated episodes. This cognitive profile, of an early-onset, state-modulated, trait marker, is distinct from the profile of attentional disruption seen in schizophrenia or unipolar depression. The state- and trait-related impairments may be differentially associated with the ascending dopamine and noradrenaline projections.

Attention↗
PubMed2004

Developing the BALANCE trail--the role of the pilot study and start-up phase.

OBJECTIVES: The initial design of the BALANCE (Bipolar Affective disorder: Lithium / ANtiConvulsant Comparative Evaluation) Trial of maintenance treatment for bipolar disorder was based on the experience of previous trials in bipolar disorder and psychiatry and on the methods developed for large randomized trials in other areas of medicine. This report describes the adaptations to the initial design and trial procedures following the initial phases of the study. The rationale for the trial and full protocol have been published elsewhere. METHODS: A pilot study and start-up phase were used to check the tolerability of the interventions, refine the trial design and develop trial procedures that are acceptable to both clinicians and patients. RESULTS: Changes to the procedures included: the dropping of masking of allocated treatment from clinicians and participants; introduction of the use of postal delivery to supply medication; and dispensing with the proposed schedule of regular follow up appointments. In addition, support was made available to participating psychiatrists who often had limited experience of participating in randomized trials. CONCLUSIONS: Pilot studies and start-up phases are essential to refine clinical trial design and allow development of procedures that are both methodologically rigorous and flexible and robust enough to promote recruitment and follow up. BALANCE is now actively recruiting in the UK and USA.

Anticonvulsants↗
PubMed2004

Normalization of enhanced fear recognition by acute SSRI treatment in subjects with a previous history of depression.

OBJECTIVE: The present study aimed to 1) assess facial expression recognition in subjects with a previous history of major depressive disorder relative to subjects with no history of depression and 2) characterize the effects of acute citalopram infusion on recognition performance for both groups. METHOD: Unmedicated euthymic women with a history of major depression and matched comparison subjects with no history of depression were given a facial expression recognition task following intravenous infusion of saline or citalopram (10 mg) in a double-blind, between-group design. RESULTS: Following saline infusion, subjects with a previous history of depression showed a selectively greater recognition of fear relative to the subjects with no history of depression. The abnormal fear processing observed in the subjects with a previous history of depression was normalized following citalopram infusion, an effect that was opposite to that seen with the subjects with no history of depression. CONCLUSIONS: These results suggest that increased recognition of fear is a trait vulnerability marker for depression and that this is normalized following a single dose of citalopram.

Acute Disease↗