Schizotypy represents an index of psychosis-proneness in the general population, often associated with childhood trauma exposure. Both schizotypy and childhood trauma are linked to structural brain alterations, and it is possible that trauma exposure moderates the extent of brain morphological differences associated with schizotypy.

We addressed this question using data from a total of 1182 healthy adults (age range: 18–65 years old, 647 females/535 males), pooled from nine sites worldwide, contributing to the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Schizotypy working group. All participants completed both the Schizotypal Personality Questionnaire Brief version (SPQ-B), and the Childhood Trauma Questionnaire (CTQ), and underwent a 3D T1-weighted brain MRI scan from which regional indices of subcortical gray matter volume and cortical thickness were determined.

A series of multiple linear regressions revealed that differences in cortical thickness in four regions-of-interest were significantly associated with interactions between schizotypy and trauma; subsequent moderation analyses indicated that increasing levels of schizotypy were associated with thicker left caudal anterior cingulate gyrus, right middle temporal gyrus and insula, and thinner left caudal middle frontal gyrus, in people exposed to higher (but not low or average) levels of childhood trauma. This was found in the context of morphological changes directly associated with increasing levels of schizotypy or increasing levels of childhood trauma exposure.

These results suggest that alterations in brain regions critical for higher cognitive and integrative processes that are associated with schizotypy may be enhanced in individuals exposed to high levels of trauma.

Lithium is viewed as the first-line long-term treatment for prevention of relapse in people with bipolar disorder.

This study examined factors associated with the likelihood of maintaining serum lithium levels within the recommended range and explored whether the monitoring interval could be extended in some cases.

We included 46 555 lithium rest requests in 3371 individuals over 7 years from three UK centres. Using lithium results in four categories (<0.4 mmol/L; 0.40–0.79 mmol/L; 0.80–0.99 mmol/L; ≥1.0 mmol/L), we determined the proportion of instances where lithium results remained stable or switched category on subsequent testing, considering the effects of age, duration of lithium therapy and testing history.

For tests within the recommended range (0.40–0.99 mmol/L categories), 84.5% of subsequent tests remained within this range. Overall, 3 monthly testing was associated with 90% of lithium results remaining within range, compared with 85% at 6 monthly intervals. In cases where the lithium level in the previous 12 months was on target (0.40–0.79 mmol/L; British National Formulary/National Institute for Health and Care Excellence criteria), 90% remained within the target range at 6 months. Neither age nor duration of lithium therapy had any significant effect on lithium level stability. Levels within the 0.80–0.99 mmol/L category were linked to a higher probability of moving to the ≥1.0 mmol/L category (10%) compared with those in the 0.4–0.79 mmol/L group (2%), irrespective of testing frequency.

We propose that for those who achieve 12 months of lithium tests within the 0.40–0.79 mmol/L range, the interval between tests could increase to 6 months, irrespective of age. Where lithium levels are 0.80–0.99 mmol/L, the test interval should remain at 3 months. This could reduce lithium test numbers by 15% and costs by ~$0.4 m p.a.

Lithium was first found to have an acute antimanic effect in 1948 with further corroboration in the early 1950s. It took some time for lithium to become the standard treatment for relapse prevention in bipolar affective disorder. In this study, our aims were to examine the factors associated wtih the likelihood of maintaining lithium levels within the recommended therapeutic range and to look at the stability of lithium levels between blood tests. We examined this relation using clinical laboratory serum lithium test requesting data collected from three large UK centres, where the approach to managing patients with bipolar disorder and ordering lithium testing varied.

46,555 lithium rest requests in 3,371 individuals over 7 years were included from three UK centres. Using lithium results in four categories (<0.4 mmol/L; 0.40–0.79 mmol/L; 0.80–0.99 mmol/L; ≥1.0 mmol/L), we determined the proportion of instances where, on subsequent testing, lithium results remained in the same category or switched category. We then examined the association between testing interval and proportion remaining within target, and the effect of age, duration of lithium therapy and testing history.

For tests within the recommended range (0.40–0.99 mmol/L categories), 84.5% of subsequent tests remained within this range. Overall 3-monthly testing was associated with 90% of lithium results remaining within range compared with 85% at 6-monthly intervals. At all test intervals, lithium test result history in the previous 12-months was associated with the proportion of next test results on target (BNF/NICE criteria), with 90% remaining within range target after 6-months if all tests in the previous 12-months were on target. Age/duration of lithium therapy had no significant effect on lithium level stability. Levels within the 0.80–0.99 mmol/L category were linked to a higher probability of moving to the ≥1.0 mmol/L category (10%) than those in the 0.40–0.79 mmolL group (2%), irrespective of testing frequency. Thus prior history in relation to stability of lithium level in the previous 12 months is a predictor of future stability of lithium level.

We propose that, for those who achieve 12-months of lithium tests within the 0.40–0.79mmol/L range, it would be reasonable to increase the interval between tests to 6 months, irrespective of age, freeing up resource to focus on those less concordant with their lithium monitoring. Where lithium level is 0.80–0.99mmol/L test interval should remain at 3 months. This could reduce lithium test numbers by 15% and costs by ~$0.4 m p.a.

This study examined lithium results and requesting patterns over a 6-year period, and compared these to guidance.

Bipolar disorder is the 4th most common mental health condition, affecting ~1% of UK adults. Lithium is an effective treatment for prevention of relapse and hospital admission, and is recommended by NICE as a first-line treatment.

We have previously shown in other areas that laboratory testing patterns are highly variable with sub-optimal conformity to guidance.

Lithium requests received by Clinical Biochemistry Departments at the University Hospitals of North Midlands, Salford Royal Foundation Trust and Pennine Acute Hospitals from 2012–2018 were extracted from Laboratory Information and Management Systems (46,555 requests; 3,371 individuals). We categorised by request source, lithium concentration and re-test intervals.

Many lithium results were outside the NICE therapeutic window (0.6–0.99mmol/L); 49.3% were below the window and 6.1% were above the window (median [Li]:0.61mmol/L). A small percentage were found at the extremes (3.2% at <0.1mmol/L, 1.0% at >1.4mmol/L). Findings were comparable across all sites.

For requesting interval, there was a distinct peak at 12 weeks, consistent with guidance for those stabilised on lithium therapy. There was no peak evident at 6 months, as recommended for those <65 years old on unchanging therapy. There was a peak at 0–7 days, reflecting those requiring closer monitoring (e.g. treatment initiation or results suggesting toxicity).

However, 77.6% of tests were requested outside expected testing frequencies.

We showed: (a) lithium levels are often maintained at the lower end of the NICE recommended therapeutic range (and the BNF range: 0.4-1.0mmol/L); (b) patterns of lithium results and testing frequency are comparable across three sites with differing models of care; (c) re-test intervals demonstrate a noticeable peak at the recommended 3-monthly interval, but not at 6-monthly intervals; (d) Many tests were repeated outside these expected frequencies (contrary to NICE guidance).