Cognitive impairment in first-episode mania: a systematic review of the evidence in the acute and remission phases of the illness

There is evidence of cognitive impairment that persists in the remission phase of bipolar disorder; however, the extent of the deficits that occur from the first onset of the disorder remains unclear. This is the first systematic review on cognitive functioning in the early stages of bipolar I disorder. The aim of the study was to identify the patterns and degree of cognitive impairment that exists from first-episode mania. Three electronic databases (MEDLINE, PsycINFO and PubMed) were systematically searched for studies published from January 1980 to June 2014. Eligible studies were separated into two groups: acute and remission. The Newcastle-Ottawa quality assessment scale was utilised to measure the quality of the included studies. A total of seven studies (three acute and four remission), including 230 first-episode mania and 345 healthy control participants, were eligible for the review. The studies in the acute phase only examined aspects of executive functioning, with impairments identified in cognitive flexibility, though not in response inhibition and verbal fluency relative to healthy controls. The most consistent finding during the remission phase was a deficit in working memory, whereas in the other domains, the findings were equivocal. Non-verbal memory and verbal fluency were not impacted in remission from first-episode mania. In conclusion, deficits are present in some but not all areas of cognitive functioning during the early stages of bipolar I disorder. Further research is warranted to understand the longitudinal trajectory of change from first-episode mania.

An examination of the influence of maternal depression trajectories on child cognitive development and adolescent psychotic experiences

 This thesis investigated trajectories of maternal depression over time, and their influence on offspring's cognitive development in childhood and subsequent risk of psychotic experiences in early adolescence. Offspring’s IQ was also examined as a potential mediator of the relationship between maternal depression and offspring’s risk of psychotic experiences.

The relationship between personality traits and psychotic like experiences in a large non-clinical adolescent sample

Objective: The relationship between personality and psychosis is well established. It has been suggested that this relationship may be partly accounted for by higher levels of depression in individuals with certain personality traits. We explored whether the link between personality and psychotic symptoms is already apparent in adolescence, and if this association would still hold when depression was controlled for. Method: 654 secondary school students were surveyed via self-report questionnaires measuring the Five-Factor model of personality (NEO-FFI), depression (CES-D) and psychotic-like experiences (CAPE). Results: Positive associations were found between Neuroticism and all CAPE-subscales except Magical Thinking, which was in turn associated with all other personality traits when at high levels. Agreeableness was negatively associated with all CAPE-subscales, while Openness to Experience was only positively associated with Persecutory Ideas and Magical Thinking. After controlling for depression, many of the significant associations remained. Conclusion: Our findings suggest that the chance of having psychotic like experiences is more likely for adolescents with certain personality traits. These associations are not fully explained by depression, especially when psychotic experiences are at higher levels. Future research is needed to investigate if these personality traits might put a person at risk for the development of full-blown psychosis.

A single-blind, randomised controlled trial on the effects of lithium and quetiapine monotherapy on the trajectory of cognitive functioning in first episode mania: A 12-month follow-up study

BACKGROUND: Cognitive deficits have been reported during the early stages of bipolar disorder; however, the role of medication on such deficits remains unclear. The aim of this study was to compare the effects of lithium and quetiapine monotherapy on cognitive performance in people following first episode mania. METHODS: The design was a single-blind, randomised controlled trial on a cohort of 61 participants following first episode mania. Participants received either lithium or quetiapine monotherapy as maintenance treatment over a 12-month follow-up period. The groups were compared on performance outcomes using an extensive cognitive assessment battery conducted at baseline, month 3 and month 12 follow-up time-points. RESULTS: There was a significant interaction between group and time in phonemic fluency at the 3-month and 12-month endpoints, reflecting greater improvements in performance in lithium-treated participants relative to quetiapine-treated participants. After controlling for multiple comparisons, there were no other significant interactions between group and time for other measures of cognition. CONCLUSION: Although the effects of lithium and quetiapine treatment were similar for most cognitive domains, the findings imply that early initiation of lithium treatment may benefit the trajectory of cognition, specifically verbal fluency in young people with bipolar disorder. Given that cognition is a major symptomatic domain of bipolar disorder and has substantive effects on general functioning, the ability to influence the trajectory of cognitive change is of considerable clinical importance.

The trajectory of cognitive functioning following first episode mania: a 12-month follow-up study

OBJECTIVES: Cognitive deficits are apparent in the early stages of bipolar disorder; however, the timing and trajectory of cognitive functioning following a first episode of mania remains unclear. The aim of this study was to assess the trajectory of cognitive functioning in people following a first episode of mania over a 12-month period, relative to healthy controls. METHOD: The cohort included 61 participants who had recently stabilised from a first treated manic episode, and 21 demographically similar healthy controls. These groups were compared on changes observed over time using an extensive cognitive battery, over a 12-month follow-up period. RESULTS: A significant group by time interaction was observed in one measure of processing speed (Trail Making Test - part A,) and immediate verbal memory (Rey Auditory Verbal Learning Test - trial 1), with an improved performance in people following a first episode of mania relative to healthy controls. On the contrary, there was a significant group by time interaction observed on another processing speed task pertaining to focussed reaction time (Go/No-Go, missed go responses), with first episode of mania participants performing significantly slower in comparison with healthy controls. Furthermore, a significant group by time interaction was observed in inhibitory effortful control (Stroop effect), in which healthy controls showed an improvement over time relative to first episode of mania participants. There were no other significant interactions of group by time related to other measures of cognition over the 12-month period. CONCLUSION: Our findings revealed cognitive change in processing speed, immediate memory and one measure of executive functioning over a 12-month period in first episode of mania participants relative to healthy controls. There was no evidence of change over time for all other cognitive domains. Further studies focussed on the at-risk period, subgroup analysis, and the effects of medication on the cognitive trajectory following first episode of mania are needed.

Atypical features and treatment choices in bipolar disorders: a result of the National Bipolar Mania Pathway Survey in China.

In this study, we examined the point prevalence rate of atypical features in bipolar disorder, and estimated the potential impact of these features on treatment practices in China. Using the atypical features criteria of the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-IV), we documented the atypical symptoms in 3 906 consecutive participants with bipolar disorder enrolled at 26 psychiatric services across China. We further assessed the association between atypical features and the treatment approaches, including the prescription of antidepressants. The overall point prevalence rate of atypical features was 9.1% among patients with various bipolar disorder subtypes. When the definition was broadened to include atypical features B, the overall rate increased to 11.8%. Interestingly, among patients with the mixed state and remission subtypes, there was a significant difference in the rates of antidepressant medication usage between patients who met and those who did not meet the criteria for atypical features B. These findings indicate a trend of using antidepressants for these two types of patients with atypical features. Further, for both mixed state and remission patients, treatment approaches were related to atypical features B. Our findings provide evidence to assist clinicians to readily recognize atypical features in bipolar subtypes and can propose treatments based on these diagnoses.

Epigenetic predictors of psychotic symptoms in adolescence

 This thesis focused on the role of epigenetic processes in the development of psychotic symptoms during adolescence. The findings suggest that exposure to influenza and/or diabetes/glycosuria during gestation may predispose an individual to the later development of psychotic symptoms via altered expression of specific genes involved in early brain development.

Herb-drug interactions: a literature review

Herbs are often administered in combination with therapeutic drugs, raising the potential of herb-drug interactions. An extensive review of the literature identified reported herb-drug interactions with clinical significance, many of which are from case reports and limited clinical observations.
Cases have been published reporting enhanced anticoagulation and bleeding when patients on long-term warfarin therapy also took Salvia miltiorrhiza (danshen). Allium sativum (garlic) decreased the area under the plasma concentration-time curve (AUC) and maximum plasma concentration of saquinavir, but not ritonavir and paracetamol (acetaminophen), in volunteers. A. sativum increased the clotting time and international normalised ratio of warfarin and caused hypoglycaemia when taken with chlorpropamide. Ginkgo biloba (ginkgo) caused bleeding when combined with warfarin or aspirin (acetylsalicylic acid), raised blood pressure when combined with a thiazide diuretic and even caused coma when combined with trazodone in patients. Panax ginseng (ginseng) reduced the blood concentrations of alcohol (ethanol) and warfarin, and induced mania when used concomitantly with phenelzine, but ginseng increased the efficacy of influenza vaccination. Scutellaria baicalensis (huangqin) ameliorated irinotecan-induced gastrointestinal toxicity in cancer patients.
Piper methysticum (kava) increased the 'off' periods in patients with parkinsonism taking levodopa and induced a semicomatose state when given concomitantly with alprazolam. Kava enhanced the hypnotic effect of alcohol in mice, but this was not observed in humans. Silybum marianum (milk thistle) decreased the trough concentrations of indinavir in humans. Piperine from black (Piper nigrum Linn) and long (P. longum Linn) peppers increased the AUC of phenytoin, propranolol and theophylline in healthy volunteers and plasma concentrations of rifamipicin (rifampin) in patients with pulmonary tuberculosis. Eleutheroccus senticosus (Siberian ginseng) increased the serum concentration of digoxin, but did not alter the pharmacokinetics of dextromethorphan and alprazolam in humans. Hypericum perforatum (hypericum; St John's wort) decreased the blood concentrations of ciclosporin (cyclosporin), midazolam, tacrolimus, amitriptyline, digoxin, indinavir, warfarin, phenprocoumon and theophylline, but did not alter the pharmacokinetics of carbamazepine, pravastatin, mycophenolate mofetil and dextromethorphan. Cases have been reported where decreased ciclosporin concentrations led to organ rejection. Hypericum also caused breakthrough bleeding and unplanned pregnancies when used concomitantly with oral contraceptives. It also caused serotonin syndrome when used in combination with selective serotonin reuptake inhibitors (e.g. sertraline and paroxetine).
In conclusion, interactions between herbal medicines and prescribed drugs can occur and may lead to serious clinical consequences. There are other theoretical interactions indicated by preclinical data. Both pharmacokinetic and/or pharmacodynamic mechanisms have been considered to play a role in these interactions, although the underlying mechanisms for the altered drug effects and/or concentrations by concomitant herbal medicines are yet to be determined. The clinical importance of herb-drug interactions depends on many factors associated with the particular herb, drug and patient. Herbs should be appropriately labeled to alert consumers to potential interactions when concomitantly used with drugs, and to recommend a consultation with their general practitioners and other medical carers.