Affective lability as a prospective predictor of subsequent bipolar disorder diagnosis: a systematic review

Objectives The early pathogenesis and precursors of Bipolar Disorder (BD) are poorly understood. There is some cross-sectional and retrospective evidence of affective lability as a predictor of BD, but this is subject to recall biases. The present review synthesises the prospective evidence examining affective lability and the subsequent development of BD at follow-up. Methods The authors performed a systematic search of PubMed, PsycInfo and Embase (1960–June 2020) and conducted hand searches to identify studies assessing affective lability (according to a conceptually-inclusive definition) at baseline assessment in individuals without a BD diagnosis, and a longitudinal follow-up assessment of bipolar (spectrum) disorders. Results are reported according to the PRISMA guidelines, and the synthesis without meta-analysis (SWiM) reporting guidelines were used to strengthen the narrative synthesis. The Newcastle–Ottawa Scale was used to assess risk of bias (ROB). Results 11 articles describing 10 studies were included. Being identified as having affective lability at baseline was associated with an increased rate of bipolar diagnoses at follow-up; this association was statistically significant in six of eight studies assessing BD type I/II at follow-up and in all four studies assessing for bipolar spectrum disorder (BSD) criteria. Most studies received a ‘fair’ or ‘poor’ ROB grade. Conclusions Despite a paucity of studies, an overall association between prospectively-identified affective lability and a later diagnosis of BD or BSD is apparent with relative consistency between studies. This association and further longitudinal studies could inform future clinical screening of those who may be at risk of BD, with the potential to improve diagnostic accuracy and facilitate early intervention.

Prevalence and psychiatric comorbidities of night-eating behavior in obese bariatric patients: preliminary evidence for a connection between night-eating and bipolar spectrum disorders

Purpose The co-occurrence of obesity, eating and mood disorders has been frequently reported in clinical and epidemiological settings. This study aimed to explore the prevalence of night-eating obese patients referred for bariatric surgery and to identify associated psychopathology and psychiatric comorbidity. Methods The sample was composed of 121 obese patients consecutively enrolled between November 2010 and May 2012 during psychiatric evaluations for bariatric intervention. Clinical features and psychiatric diagnoses were collected. Night-eating was investigated through the administration of the Night-eating Questionnaires (NEQ) and was defined as the presence of self-reported evening hyperphagia and/or nocturnal ingestions. Binge-eating and purging behaviors and general psychopathology were respectively assessed using the Bulimic Investigatory Test, Edinburgh and the Symptom Checklist-90-Revised. Results Night-eating was reported by twenty subjects (16.5%). Patients with night-eating behavior were significantly more frequently diagnosed with bipolar spectrum disorders and with comorbid eating and mood disorders in comparison with other patients. Night-eating patients showed significantly more binging/purging behaviors and greater severity of somatization, obsessive–compulsive symptoms, phobic anxiety, psychoticism and sleep disorders. Patients with bipolar disorder type 1 or 2 scored significantly higher than those without mood disorders at NEQ total score, mood/sleep and nocturnal ingestions subscales, but also scored significantly higher than other patients with mood disorders at the latter subscale. Conclusion Patients with evening hyperphagia and/or nocturnal ingestions should be carefully evaluated to detect possible bipolar spectrum disorders and other eating disorders. Prompt management of these conditions should be provided before bariatric interventions. Level of evidence V, cross-sectional descriptive study.

Lower circulating neuron-specific enolase concentrations in adults and adolescents with severe mental illness

Background Both neurodegenerative and neurodevelopmental abnormalities have been suggested to be part of the etiopathology of severe mental illness (SMI). Neuron-specific enolase (NSE), mainly located in the neuronal cytoplasm, may indicate the process as it is upregulated after neuronal injury while a switch from non-neuronal enolase to NSE occurs during neuronal maturation. Methods We included 1132 adult patients with SMI [schizophrenia (SZ) or bipolar spectrum disorders], 903 adult healthy controls (HC), 32 adolescent patients with SMI and 67 adolescent HC. Plasma NSE concentrations were measured by enzyme immunoassay. For 842 adults and 85 adolescents, we used total grey matter volume (TGMV) based on T1-weighted magnetic resonance images processed in FreeSurfer v6.0. We explored NSE case-control differences in adults and adolescents separately. To investigate whether putative case-control differences in NSE were TGMV-dependent we controlled for TGMV. Results We found significantly lower NSE concentrations in both adult (p < 0.001) and adolescent patients with SMI (p = 0.007) compared to HC. The results remained significant after controlling for TGMV. Among adults, both patients with SZ spectrum (p < 0.001) and bipolar spectrum disorders (p = 0.005) had lower NSE than HC. In both patient subgroups, lower NSE levels were associated with increased symptom severity. Among adults (p < 0.001) and adolescents (p = 0.040), females had lower NSE concentrations than males. Conclusion We found lower NSE concentrations in adult and adolescent patients with SMI compared to HC. The results suggest the lack of progressive neuronal injury, and may reflect abnormal neuronal maturation. This provides further support of a neurodevelopmental rather than a neurodegenerative mechanism in SMI.

Psychological therapy for mood instability within bipolar spectrum disorder: a randomised, controlled feasibility trial of a dialectical behaviour therapy-informed approach (the ThrIVe-B programme)

Background A subgroup of those with bipolar spectrum disorders experience ongoing mood fluctuations outside of full episodes. We conducted a randomised, controlled feasibility study of a Dialectical Behavioural Therapy-informed approach for bipolar mood fluctuations (Therapy for Inter-episode mood Variability in Bipolar [ThrIVe-B]). Our study aimed to examine the feasibility and acceptability of a future definitive trial evaluating the clinical and cost effectiveness of the ThrIVe-B programme. Participants were required to meet diagnostic criteria for a bipolar spectrum disorder and report frequent mood swings outside of acute episodes. They were randomised to treatment as usual (control arm) or the ThrIVe-B intervention plus treatment as usual (intervention arm). Follow-up points were at 3, 6, 9 and 15 months after baseline, with 9 months as the primary end point. To evaluate feasibility and acceptability we examined recruitment and retention rates, completion rates for study measures, adverse events and feedback from participants on their experience of study participation and therapy. Results Of the target 48 participants, 43 were recruited (22 in the intervention arm; 21 in the control arm), with a recruitment rate of 3.9 participants per month. At 9 months 74% of participants engaged in research follow-up assessment, exceeding the pre-specified criterion of 60%. There were no serious concerns about the safety of the research procedures or the intervention. On one of the four candidate primary outcome measures, the 95% CI for the between-group mean difference score excluded the null effect and included the minimal clinically important difference, favouring the intervention arm, whilst on no measure was there evidence of deterioration in the intervention arm relative to the control arm. Attendance of the intervention (50% attending at least half of the mandatory sessions) was below the pre-specified continuation criterion of 60%, and qualitative feedback from participants indicated areas that may have hampered or facilitated engagement. Conclusions It is broadly feasible to conduct a trial of this design within the population of people with frequent bipolar mood swings. Changes should be made to the therapy to increase uptake, such as simplifying content and considering individual rather than group delivery. Trial registration ISRCTN: ISRCTN54234300. Registered 14th July 2017, http://www.isrctn.com/ISRCTN54234300