ANNOTATION (Paula Zimbrean)

The Findings: The study reports the incidence of patients receiving renal replacement therapy (RRT) for lithium-induced nephropathy (LiN) as resulted from the analysis of the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA). There were 0.14 cases per million population per year (95% CI, 0.06–0.22) in 1992–1996 and 0.78 (0.67–0.90) in 2007–2011. As a proportion of all incident RRT patients, LiN increased from 0.19% in 1992–1996 to 0.70% in 2007–2011. LiN patients were more likely than other patients to be women, to be white, to smoke and to have a higher body mass index, but were of similar age and less likely to have undergone renal biopsy.

Strengths and Weaknesses: This is an epidemiological study assessing a relatively rare but important disorder for psychiatrists, LiN. Diagnostic bias is possible with any registry data. There are several possible confounding variables: the nephrologist awareness of irreversible LiN may have increased over time, patients with bipolar disorder might have been referred more often for RRT after developing LiN, patients with bipolar disorder may be receiving better medical care, and the patterns of prescribing lithium might have changed over time. Existing data did not allow for determining the number of patients with ESRD associated with LiN who are not recorded in ANZDATA, because they do not receive RRT.

Relevance: Lithium is a unique psychiatric medication whose use has been limited by its side effects, among which LiN is one of the most severe. Information about incidence of this complication allows better appreciation of the risk/benefit ratio when considering prescribing Li.

ANNOTATION (Paula Zimbrean)

The Finding: The study investigated the brain functional connectivity in patients with end stage renal disease ESRD) on hemodialysis (HD). Forty-two connections between every two regions of interests (ROIs) were significantly different (all P<0.05, Bonferroni corrected) in ESRD patients compared with controls and were defined as connectivity of interests (COIs) for further analysis. Among these COIs, 39 (92.9%) connections, either negative or positive, were weaker in ESRD patients than in the controls and only 3 positive ones were stronger in patients. Among the 39 connections weaker in ESRD patients, 24 COIs (61.5 %, 24/39) including 13 positive and 11 negative connections, were related to the frontal lobe regions. Fifteen weaker COIs of ESRD patients were not related to frontal lobe regions, which were mainly between the insula, partial lobes, temporal lobes and basal ganglia. The Z-scores of 29 COIs were associated with alterations in DST scores; 19 COIs related with frontal lobes were correlated with SAS scores; 8 COIs were correlated with SDT scores; 4 COIs related with LTT scores; one connection was correlated with NCT-A. No correlations were found between COIs and SDS scores.

Strengths and Weaknesses: The strengths of the study consist in having a control group, a comprehensive neuropsychiatric battery of tests, and extensive fMRI imaging.
The description of the study in the article is somewhat vague, as the authors call it a retrospective study. However, this appears to be a cross-sectional study with the study group consisting of 71 HD patients currently inpatient, and a control group of 43 age- and gender-matched healthy subjects recruited from the community. A battery of neuropsychiatric tests was administered: number connection test type A (NCT-A), digit symbol test (DST), line-tracing test (LTT), the serial-dotting test (SDT), the self-rating anxiety scale (SAS), and self-rating depression scale (SDS). All subjects underwent fMRI evaluation of the brain including 3D T1 weighted anatomical images for spatial normalization and Axial T2-FLAIR.
Limitations: The high number of COIs found impacts the statistical power to find significant correlations between COIs and specific clinical presentations. The inpatient status of the study group may introduce a potential bias of patients having severe ESRD or other medical comorbidities which may impact the brain connectivity.

Relevance: This study suggests that cognitive and mood disturbances present in ESRD may be related to specific brain connectivity patterns for patients with ESRD. This supports the view that psychiatric problems in ESRD have a biological basis that can be explored, and are not merely an expression of adaptation to medical illness.

ANNOTATION (Paula Zimbrean)

The Finding: The overall incidence of depression was 44% (95% CI: −0.137-0.027). The patients with higher serum VD levels at baseline tended to have fewer depressive symptoms. Administration of vitamin D improved serum vitamin D levels, but did not impact the depressive symptoms.

Strengths and Limitations: The main strength of this study consists in the prospective character, high number of subjects: 484 dialysis patients (382 hemodialysis [HD] cases and 102 peritoneal dialysis [PD] cases), aged 18–60 years), and significant time for follow up (one year). The limitations of the paper consist in lack of control group, relatively low dose of vitamin D used (0.5 μg/day 1,25-Dihydroxyvitamin D orally), and questionable cut-off value for Beck Depression Inventory at 16.

Relevance: This study adds to the existing literature related to the significance of vitamin D serum levels in depression. The results suggest that repletion of vitamin D alone does not impact depression in this population.