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Biomedical subjects

Gin S Malhi

Publications and source records attributed to Gin S Malhi.

At least 19 recordsLinked to original sources
PubMed2006

A sham-controlled trial of the efficacy and safety of twice-daily rTMS in major depression.

BACKGROUND: Studies of repetitive transcranial magnetic stimulation (rTMS) in depression have mostly involved once-daily treatment, with positive but modest clinical results. This study tested the efficacy and safety of twice-daily rTMS over 2 weeks. METHOD: Thirty-eight depressed subjects enrolled in a double-blind, sham-controlled trial of twice-daily rTMS (left prefrontal cortex, 10 Hz, 110% intensity, 1500 stimuli per session) over 2 weeks. Mood and neuropsychological functioning were assessed weekly by blind raters, using the Montgomery-Asberg Depression Rating Scale (MADRS) as the primary outcome measure, plus the Hamilton Rating Scale for Depression (HRSD) and self-report measures. After the blind period, 22 subjects continued with once-daily rTMS to receive a total of 6 weeks of active rTMS. RESULTS: Subjects were moderately treatment resistant. Active treatment resulted in significantly greater improvement than sham over the 2-week blind period on one outcome measure only (MADRS p<0.05). Subjects showed further improvement over the 6 weeks of active rTMS. Neuropsychological test scores did not change significantly. CONCLUSIONS: rTMS given twice daily was effective and safe, with no adverse neuropsychological effects.

Adult↗
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

Reduced activation to implicit affect induction in euthymic bipolar patients: an fMRI study.

OBJECTIVE: To examine whether euthymic bipolar patients engage similar or contrasting brain regions as healthy subjects when responding to implicit affect induction. METHODS: The study examined 10 euthymic patients with bipolar I disorder, and 10 age- and gender-matched healthy subjects using event-related functional magnetic resonance imaging (fMRI) while subjects engaged in a modified word-based memory task designed to implicitly evoke negative, positive or no affective change. The activation paradigm involved nominating whether a target word was contained within a previously presented word list using specified response keys. RESULTS: The fMRI task produced significantly greater activation in healthy subjects as compared to patients in response to both negative and positive affect in the anterior and posterior cingulate, medial prefrontal cortex, middle frontal and right parahippocampal gyri. Only negative affect produced significantly greater activation in the postcentral gyrus, inferior parietal lobule, thalamus and putamen and only positive affect achieved the same in the precentral, superior temporal and lingual gyri, precuneus, cuneus, caudate, pons, midbrain and cerebellum. There were no brain regions in which responses were greater in patients as compared to healthy subjects. There were no statistically significant differences between the groups with respect to speed or accuracy. CONCLUSIONS: Diminished prefrontal, cingulate, limbic and subcortical neural activity in euthymic bipolar patients as compared to healthy subjects is suggestive of emotional compromise that is independent of cognitive and executive functioning. This finding is of clinical importance and has implications both for the diagnosis and treatment of bipolar disorder. Future studies should aim to replicate these findings and examine the development of bipolar disorder, investigating in particular the effects of medication.

Adult↗
PubMed2006

The management of bipolar disorder in general practice.

General practitioners have a key role in managing patients with bipolar disorder, a condition which affects at least one in 200 Australians each year and is the sixth leading cause of disability in the population. Although diagnosis and treatment of the illness is complex, effective treatment can lead to good outcomes for many patients. GPs can contribute significantly to early recognition of bipolar disorder, avoiding the long delays in accurate diagnosis that have been reported. As in other complex recurrent or persistent illnesses, GPs are well placed to coordinate multidisciplinary "shared care" with specialists and other health care professionals. GPs also provide continuing general medical care for patients with bipolar disorder, and are in a unique position to understand patients' life circumstances and to monitor their progress over time. The last decade has seen many advances in medication for bipolar disorder, including the introduction of new therapies and the refinement of treatment protocols using older medications. There has also been increasing recognition of the contribution of psychological therapies to symptom relief, relapse prevention, optimal function, and quality of life.

Antidepressive Agents↗
PubMed2006

Diagnosing bipolar disorder: how can we do it better?

Accurate diagnosis of bipolar disorder is essential for effective treatment. The diagnosis of bipolar disorder is particularly complex, resulting in lengthy delays between first presentation and initiation of appropriate therapy. Inappropriate therapy destabilises the course and outcome of the disease. Although the defining features of bipolar disorder are manic or hypomanic episodes, patients typically present for treatment of depression and commonly deny symptoms of mood elevation. A correct diagnosis can easily be masked by comorbidities, personality issues and complex phenomenology. A diagnosis of bipolar disorder can be assisted by: asking about symptoms of mania or hypomania in every patient presenting with symptoms of depression. recognising mixed states in which manic and depressive symptoms occur simultaneously. identifying the features of bipolar depression that distinguish it from unipolar depression. There is a risk of over-diagnosis of bipolar disorder among patients who are histrionic, show abnormal illness behaviour and/or have issues of secondary gain.

Age of Onset↗
PubMed2006

Do bullied children become anxious and depressed adults?: A cross-sectional investigation of the correlates of bullying and anxious depression.

There is little empirical research examining the historical and clinical correlates of exposure to childhood bullying in adult clinical subjects. Using structured clinical assessments, the authors studied a group of adult males and females presenting to an outpatient depression clinic, to examine the childhood risk factors and the distinguishing comorbid features associated with those reporting exposure to bullying. Just over a quarter of both men and women reported having experienced bullying that was severe and traumatic. More of these subjects also reported several other well studied childhood risk factors. Childhood correlates that were particularly relevant for exposure to bullying were parental overcontrol, illness or disability, and the tendency to have an inhibited temperament early in life. The experience of childhood bullying was strongly related to high levels of comorbid anxiety, both in terms of greater levels of state anxiety and a higher prevalence of both social phobia and agoraphobia. Independent of other childhood risk factors, exposure to bullying was especially predictive of subjects' higher levels of general state anxiety and the tendency to express anxious arousal externally when under stress. These results are compatible with both cross-sectional and prospective studies of child and adolescent samples, and highlight the potential etiological significance of early peer victimization experiences for a percentage of adults suffering from depression with comorbid anxiety.

Adult↗
PubMed2006

Why am I depressed?: An investigation of whether patients' beliefs about depression concur with their diagnostic subtype.

We investigated whether patients' beliefs about the causes of their depression concurred with their diagnostic subtype. Depressed patients (N = 196) attending a tertiary referral clinic completed a questionnaire regarding putative biological and nonbiological causes of their depression. Subtyping diagnoses of melancholic or nonmelancholic depression were made. Patients with nonmelancholic depression were more likely to attribute nonbiological factors as the cause of their depression than those with melancholic depression, whereas patients with melancholic depression were no more likely to attribute biological factors as the cause of their depression. Patients can distinguish differing causes of depression. The implications of the findings for the current classificatory systems of depression are discussed.

Adolescent↗
PubMed2006

Emerging drugs for bipolar disorder.

Bipolar disorder is a relatively common condition characterised by recurrent episodes of mania and depression, and associated with high levels of morbidity and mortality. Although there have been substantial advances in the pharmacotherapeutics of this condition over the last 10-15 years, the benefits have been predominantly in terms of tolerability and safety, with no new treatments being demonstrated to be more effective than lithium--the prototype mood stabiliser. This article reviews current and emerging medications for bipolar disorder. Most of the emerging treatments in pharmaceutical industry developmental programmes are new or modified anticonvulsants or atypical antipsychotics. A number of possible future directions and challenges for the field are discussed. The treatment of bipolar disorder is unlikely to advance substantially until the causative pathogenetic molecular processes are elucidated.

Bipolar Disorder↗
PubMed2006

Cognitive compromise in bipolar disorder with chronic cannabis use: cause or consequence?

This article briefly reviews the neuropsychological deficits associated with bipolar disorder and examines how substance abuse, in particular chronic cannabis use, may contribute to these. The focus of the article is cannabis, owing to its popularity in patients with bipolar disorder, although many studies focus on its use in conjunction with other substances. The findings are contextualized within bipolar disorder, examining functional outcome.

Bipolar Disorder↗
PubMed2006

A randomized controlled trial of cognitive therapy for bipolar disorder: focus on long-term change.

BACKGROUND: This study reports the outcome of a randomized controlled trial of cognitive therapy (CT) for bipolar disorder. The treatment protocol differed from other published forms of CT for bipolar disorder through the addition of emotive techniques. METHOD: Fifty-two patients with DSM-IV bipolar I or II disorder were randomly allocated to a 6-month trial of either CT or treatment as usual, with both treatment groups also receiving mood stabilizers. Outcome measures included relapse rates, dysfunctional attitudes, psychosocial functioning, hopelessness, self-control, and medication adherence. Patients were assessed during treatment by independent raters blind to the patients' group status. RESULTS: At posttreatment, patients allocated to CT had experienced less severe depression scores (Beck Depression Inventory and Montgomery-Asberg Depression Rating Scale) and less dysfunctional attitudes. After controlling for the presence of major depressive episode at baseline, there was a statistical trend toward a greater time to depressive relapse (p=.06) for the CT group. At 12-month follow-up, the CT group showed a trend toward lower Young Mania Rating Scale scores and improved behavioral self-control. The Clinical Global Impressions-Improvement scale, comparing the 18 months prior to treatment to the severity of illness status at follow-up, showed a substantial difference between groups in favor of CT. CONCLUSION: Our findings corroborate previous bipolar disorder research in demonstrating the value of CT, particularly immediately post-treatment, and indicate some continuation (albeit diminishing) of benefits in the succeeding 12 months. These findings suggest that psychological booster sessions may be crucial for maintaining the beneficial effects of cognitive therapy.

Adult↗
PubMed2005

To combine or not to combine? A literature review of antidepressant combination therapy.

OBJECTIVE: Treatment resistant depression is a common clinical problem and a major public health concern. The use of antidepressant combinations to overcome treatment resistance, while somewhat controversial, is a popular strategy in practice. This paper reviews published trials on combination antidepressants with a view to inform clinical practice. METHOD: A systematic but selective review of the published literature was conducted using EMBASE, PSYCHLIT and MEDLINE with relevant search terms. RESULTS: A number of trials suggesting efficacy of combination antidepressants were found. These are incorporated into a number of treatment guidelines for the management of treatment refractory depression. Clinicians should be cautious regarding pharmacokinetic and pharmacodynamic interactions, including the serotonin syndrome, however combination strategies are an effective option. CONCLUSIONS: Many antidepressants can be usefully combined especially if they engage separate mechanisms of action. Clinically, antidepressant combinations provide a useful resort in otherwise treatment resistant individuals. However, much further research is needed to determine relative efficacy and determine long term outcome.

Antidepressive Agents↗
PubMed2005

Relationship between self-reported childhood behavioral inhibition and lifetime anxiety disorders in a clinical sample.

To examine the association between an early inhibited temperament and lifetime anxiety disorders, we studied a sample of patients with major depression who were not selected on the basis of comorbid axis I anxiety disorders. One-hundred eighty-nine adults (range = 17-68 years) referred to a tertiary depression unit underwent structured diagnostic interviews for depression and anxiety and completed two self-report measures of behavioral inhibition, the retrospective measure of behavioural inhibition (RMBI) [Gladstone and Parker, 2005] and the adult measure of behavioural inhibition (AMBI) [Gladstone and Parker, 2005]. Patients' scores were classified into "low," "moderate," or "high" inhibition. While groups did not differ in terms of depression severity, there were differences across groups in clinically diagnosed nonmelancholic status and age of onset of first episode. Those reporting a high degree of childhood inhibition were significantly more likely to qualify for a diagnosis of social phobia, and this association was independent of their scores on the AMBI. Findings are discussed in light of the existing risk-factor literature and support the hypothesis that an early inhibited temperament may be a significant precursor to later anxiety, especially social anxiety disorder.

Adolescent↗
PubMed2005

'Bipolar missed states': the diagnosis and clinical salience of bipolar mixed states.

OBJECTIVE: To explore diagnostic and treatment issues concerning bipolar mixed states. METHOD: Bipolar mixed states are described and concerns about diagnostic and treatment difficulties are summarized and discussed. RESULT: Mixed states can present with equal admixtures of depressive or manic symptoms, or more commonly one component predominates. There is fair consensus, although little data, regarding the management of manic mixed states. However depressive mixed states are far more complex both in terms of recognition and management. People suffering from mixed states characteristically present with complaints of depression. CONCLUSIONS: The boundaries between depressive mixed states and agitated depression are vague, yet carry substantial therapeutic implications. Bipolar mixed states are often difficult to treat, and tend to take much longer to settle than either pure mania or depression. Furthermore there is data that treatment with antidepressants can worsen the course of mixed states. Hence missed diagnoses can potentially have negative clinical implications. Therefore in this paper the clinical presentation, diagnosis and therapy of mixed states is reviewed with a view to improving management.

Affect↗
PubMed2005

Anatomical MRI abnormalities in bipolar disorder: do they exist and do they progress?

AIM: Morphometric brain imaging studies have revealed regional brain abnormalities in patients with bipolar disorder, which may play a role in illness pathophysiology. It is not known whether such changes are of neurodevelopmental, neurodegenerative, or combined origin. We reviewed the anatomical brain imaging literature in bipolar disorder, in an attempt to determine whether there is evidence to suggest that such abnormalities are progressive. METHOD: Literature searches were conducted using MEDLINE for the period from 1966 to June 2004, using specific key words; bipolar disorder and the names of the individual brain structures. Papers were selected according to their salience in relation to whether reported changes are progressive. RESULTS: Available findings suggest reduced grey matter in prefrontal brain regions such as anterior cingulate and subgenual prefrontal cortex, and abnormalities in amygdala size in adult and paediatric bipolar patients. White matter hyperintensities, which are non-specific abnormalities, are also common in bipolar patients. Bipolar patients may lose more brain grey matter by ageing. There is also evidence for impaired myelination of the corpus callosum in bipolar disorder. Lithium may reverse or prevent grey matter prefrontal cortex abnormalities in bipolar patients by its neuroprotective effects. CONCLUSIONS: Both early developmental and later neurodegenerative processes may play a role in the pathophysiology of bipolar disorder. Findings from anatomical brain imaging studies implicate key regions involved in mood regulation. The evidence for the progressive nature of this illness is tentative, as no follow-up study with bipolar patients has been reported to this date.

Amygdala↗
PubMed2005

Obsessive-compulsive behaviour: a disorder of decision-making.

OBJECTIVE: Compulsive individuals are habitually indecisive, and indecision reaches its pathological apex in obsessive-compulsive disorder (OCD). With the increasing interest in the neurobiology of decision-making, it may be useful to conceptualize OCD as a disorder of decision-making. METHOD: A selective review of the neurobiological studies of the decision-making process was performed, and the convergence with the understanding of the neurobiology of OCD examined. RESULTS: The dorsolateral, orbitofrontal and anterior cingulate cortices are engaged in multiregion neural subsystems that interact with each other to retain information online, manipulate options, make choices and maintain goals. These interact with the limbic regions, especially the amygdala, in relation to history of reward and emotional valence relating to a choice, and the basal ganglia for behavioural execution. Abnormalities in these regions also characterize OCD and related disorders, therefore leading to problems in making some decisions that are affect-laden by nature or association. CONCLUSION: Conceptualizing OCD as a disorder of decision-making leads to new approaches for its investigation, and novel strategies for both physical and behavioural-cognitive treatments.

Affect↗
PubMed2005

When euthymia is just not good enough: the neuropsychology of bipolar disorder.

Bipolar disorder (BD) is a debilitating psychiatric illness that is uniquely characterized by switching between psychopathologically contrasting phases of mania and depression, often with intervening periods of euthymia. However, these periods of apparent clinical recovery (euthymia) are marked by subtle social, occupational, and cognitive impairments, profiled by recent neuropsychological investigations. Determining the cognitive changes across these three phases may help differentiate the disruptions that are mood state-dependent from those associated with underlying pathology. This article therefore critically reviews the reported neuropsychological impairments in BD and the methodological limitations facing such research. Integration of the available evidence, principally from the field of neuropsychology, when synthesized, implicates the prefrontal cortex in the etiopathogenesis of BD and posits cortical-subcortical-limbic disruption in recovered euthymic patients that manifests as cognitive dysfunction.

Bipolar Disorder↗
PubMed2005

Executive functioning and theory of mind in euthymic bipolar disorder.

OBJECTIVES: To examine the nature of executive deficits in euthymic patients with bipolar disorder (BD). METHODS: Fifteen euthymic BD patients and 13 controls were administered a battery of executive tasks including verbal fluency, Stroop, Theory of Mind (ToM) tests and selected subtests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). Self-report and clinician ratings of mood and social and occupational functioning were also obtained. RESULTS: There were no significant differences between BD patients and controls on the primary measures of the following executive tasks: verbal fluency, attentional set-shifting, problem solving or planning. On secondary measures of speed, BD patients were slower to complete the first trial of the Stroop task (p = 0.001). Patients with BD committed more errors across all secondary measures. Patients performed poorly when compared with controls on tests of verbal ToM (p = 0.02), and although they performed non-verbal ToM tasks at a level comparable to controls (p = 0.60), they were slower to initiate a response (p = 0.006). ToM was not significantly correlated with any measure of social and occupational functioning; however it correlated with the achievement scores of the CANTAB Stockings of Cambridge task (Pearson's r = 0.68, p < 0.01). CONCLUSIONS: Deficits found in euthymic bipolar patients suggest fronto-subcortical pathway dysfunction. This is consistent with other neuropsychological and neuroimaging research that points to a trait deficit in BD. Further investigation is necessary perhaps using more real-world tests.

Adult↗