Does relapse cause illness progression in first-episode psychosis? A review.

BACKGROUND: It is widely believed that relapse in first-episode psychosis (FEP) causes illness progression, with previous reviews suggesting that treatment non-response develops in one in six patients who relapse. This belief contributes to the primary treatment goal in FEP being relapse-prevention, often in favor of other recovery-oriented goals. However, previous reviews primarily reported on naturalistic studies in chronic schizophrenia and predated multiple major studies with higher-quality designs. METHODS: We conducted a narrative review of studies of any design that examine the impact of relapse on medication response and other symptomatic and functional outcomes in FEP. RESULTS: We identified eight relevant studies, five of these published since the last major review on this topic. Observational studies show a clear association between relapses and worse response to medication, but poorly control for confounding. Three higher-quality studies (two randomized) generally do not find worse symptomatic or functional outcomes among medication reduction/discontinuation arms compared to maintenance controls, despite significantly higher initial rates of relapse. CONCLUSION: While the social and psychological consequences of a relapse should not be dismissed, clinicians should demand high-quality evidence about the risks of relapse on long-term outcomes. The conventional notion that relapse leads to treatment non-response or worse long-term outcomes is generally not supported by the highest quality studies. These findings can help clinicians and patients weigh the risks and benefits of competing treatment strategies in FEP.

Vitamin B12 Supplementation in Psychiatric Practice.

PURPOSE OF REVIEW: Vitamin B12 (B12, cobalamin) deficiency has been associated with neuropsychiatric symptoms, suggesting a role for B12 supplementation both as a treatment for psychiatric symptoms due to B12 deficiency and as an augmentation strategy for pharmacological treatments of psychiatric disorders. This critical review discusses the major causes of B12 deficiency, the range of psychiatric and non-psychiatric manifestations of B12 deficiency, the indications for testing B12 levels, and the evidence for B12 supplementation for major psychiatric disorders. RECENT FINDINGS: We find that high-quality evidence shows no benefit to routine B12 supplementation for mild depressive symptoms or to prevent depression. There is very limited evidence on the role of B12 supplementation to augment antidepressants. No high-quality evidence to date suggests a role for routine B12 supplementation in any other major psychiatric disorder. No formal guidelines indicate when clinicians should test B12 levels for common psychiatric symptoms, in the absence of major risk factors for deficiency or cardinal symptoms of deficiency. No robust evidence currently supports routine B12 supplementation for major psychiatric disorders. However, psychiatrists should be aware of the important risk factors for B12 deficiency and should be able to identify symptoms of B12 deficiency, which requires prompt testing, medical workup, and treatment. Testing for B12 deficiency should be considered for atypical or severe psychiatric presentations.

Inappropriate study inclusion in meta-analysis of sham-controlled rTMS for treatment-resistant depression.

Dr. Vida and colleagues have published an important meta-analysis on a critical topic in psychiatry: the efficacy of double-blind, sham-controlled rTMS in treatment-resistant depression (TRD) [1]. The primary reported finding was a significant effect of rTMS on remission and response (RR 2.25 and 2.78 respectively) compared to sham rTMS. A close evaluation of the studies included in this meta-analysis raises concerns about the accuracy of these findings.

Intellectual Functioning in Offspring of Parents with Bipolar Disorder: A Review of the Literature.

Impaired intellectual functioning is an important risk factor for the emergence of severe mental illness. Unlike many other forms of mental disorder however, the association between bipolar disorder and intellectual deficits is unclear. In this narrative review, we examine the current evidence on intellectual functioning in children and adolescents at risk for developing bipolar disorder. The results are based on 18 independent, peer-reviewed publications from 1980 to 2017 that met criteria for this study. The findings yielded no consistent evidence of lower or higher intellectual quotient (IQ) in offspring of parents diagnosed with bipolar disorder. Some tentative evidence was found for lower performance IQ in offspring of bipolar parents as compared to controls. It is recommended that future research examine variability in intellectual functioning and potential moderators. These findings demonstrate the need to examine how intellectual functioning unfolds across development given the potential role of IQ as a marker of vulnerability or resilience in youth at high risk for affective disorders.

The genetics of early-onset bipolar disorder: A systematic review.

BACKGROUND: Early-onset bipolar disorder has been associated with a significantly worse prognosis than late-onset BD and has been hypothesized to be a genetically homogenous subset of BD. A sizeable number of studies have investigated early-onset BD through linkage-analyses, candidate-gene association studies, genome-wide association studies (GWAS), and analyses of copy number variants (CNVs), but this literature has not yet been reviewed. METHODS: A systematic review was conducted using the PubMed database on articles published online before January 15, 2015 and after 1990. Separate searches were made for linkage studies, candidate gene-association studies, GWAS, and studies on CNVs. RESULTS: Seventy-three studies were included in our review. There is a lack of robust positive findings on the genetics of early-onset BD in any major molecular genetics method. LIMITATIONS: Early-onset populations were quite small in some studies. Variance in study methods hindered efforts to interpret results or conduct meta-analysis. CONCLUSIONS: The field is still at an early phase for research on early-onset BD. The largely null findings mirror the results of most genetics research on BD. Although most studies were underpowered, the null findings could mean that early-onset BD may not be as genetically homogenous as has been hypothesized or even that early-onset BD does not differ genetically from adult-onset BD. Nevertheless, clinically the probabilistic developmental risk trajectories associated with early-onset that may not be primarily genetically determined continued to warrant scrutiny. Future research should dramatically expand sample sizes, use atheoretical research methods like GWAS, and standardize methods.