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.

Microcytic Anaemia as Susceptibility Factors in Bipolar Spectrum Disorders: Review of the Literature, Replication Survey, and Co-Segregation within Families

Background: Potential interactions between mood disorders and microcytic anaemias have been suggested by case reports, surveys of haematological parameters in psychiatric populations, and surveys of psychiatric morbidity in thalassaemic carriers. Objectives: a) To review published studies. b) To study the prevalence of microcytic anaemia in a sample of Sardinian outpatients with recurrent mood disorders. c) To check whether mood disorders and microcytic anaemia co-segregate within families. Methods: We extracted data on blood count and serum iron concentrations from the records of patients admitted between January 1st, 2001 and December 31st, 2016, to our clinic for mood disorders. Moreover, we studied siblings of subjects with both major mood disorders (according to Research Diagnostic Criteria) and heterozygous thalassaemia (according to Mean Corpuscular Volume, serum iron, and haemoglobin A2 concentrations). Siblings affected with a major mood disorder were examined for haematological concordance with the proband (reduced MCV and/or increased HbA2 in case of heterozygous β-thalassaemia, or presence of gene deletions in case of α-thalassaemia). Results: Microcytic anaemia was highly prevalent (81/337 = 24.0%) among outpatients with mood disorders. Starting from 30 probands with heterozygous ß-thalassaemia, concordance for reduced MCV and/or increased HbA2 was found in 78% (35/45) of affected siblings. Starting from 3 probands with heterozygous α-thalassaemia, only one of the 5 affected siblings carried four α-globin functional genes. Conclusion: Based on the review of the literature, the high prevalence of microcytic anaemia in outpatients, and the concordance between affected siblings, we can conclude that a role of heterozygous thalassaemias is highly probable. Future studies are required to establish the relevance of heterozygous thalassaemias and evaluate the magnitude of the effect, possibly using a molecular diagnosis also in the case of heterozygous β-thalassaemia.

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.

Flexible Applications of Family-Based Therapy for Youth with Bipolar Spectrum Disorders

Bipolar spectrum disorders (BPSD) affect approximately 3.9% of youth and are associated with meaningful impairments across social, academic, and family domains. Early psychosocial treatment, in conjunction with psychotropic intervention, can ameliorate the negative impact of symptoms by equipping youth and their families with knowledge and skills to promote understanding and management of the disorder, leading to improved short- and long-term outcomes. Family-focused treatment for adolescents (FFT-A), family-focused cognitive behavioral therapy (CFF-CBT), and psychoeducational psychotherapy (PEP) represent a well-established class of manual-based interventions that have been found to improve mood symptoms and family functioning through the use of family psychoeducation and skill building. We detail and discuss the core components of these interventions, with a specific focus on how treatment components can be successfully adapted and delivered to ensure an individualized approach for optimal care. Flexibility is further illustrated by a depiction of ways in which PEP has been adapted to meet practical needs of families and clinicians while maintaining fidelity to the intervention.

An Exploratory Study of Emotional Dysregulation Dimensions in Youth With Attention Deficit Hyperactivity Disorder and/or Bipolar Spectrum Disorders

Emotional dysregulation (ED) is currently the most frequently used term to describe children with an impaired regulation of emotional states. Recent research studies speculate whether ED may be a neurodevelopmental disorder itself, a shared risk factor, or a common key feature of several psychiatric disorders, including, among others, attention deficit hyperactivity disorder (ADHD), and bipolar spectrum disorders (BSD). The association between ADHD and ED is one of the main reasons of misconceptions in the definition of boundaries between ADHD and BSD, leading to the frequent misdiagnosis of ADHD as BSD. Since ED is a multidimensional concept, a novel instrument—the Reactivity, Intensity, Polarity and Stability (RIPoSt) scale—was recently developed to assess the different dimensions of ED, which could help in detecting specific ED profiles in clinical youths. Our study included 154 patients, aged 13.8 ± 2.3 years, diagnosed with either ADHD, BSD, or comorbid condition, and a school-based sample of 40 healthy control (HC) adolescents, aged 12.5 ± 1.2 years. The RIPoSt scale and the Child Behavior Checklist were administered to both groups. Our results indicate that affective instability and negative emotionality subscales, as well as negative emotional dysregulation, are higher in BSD, both pure and comorbid with ADHD, while emotional impulsivity is higher in the comorbid condition and similar in the ADHD and BSD alone group; all clinical groups scored higher than HC. Conversely, positive emotionality is similar among clinical groups and within them and HC. Our findings also support the validity of the RIPoSt questionnaire, since the instrument proved to have good-to-excellent internal consistency, and strongly significant positive correlations were found with the CBCL-Dysregulation Profile, which is a commonly used, indirect measure of ED. Hence, the five subscales of the RIPoSt can be reliably used as an effective tool to study the emotional dysregulation in different clinical conditions, to help disentangle the complex relationship between ADHD and juvenile BSD and to provide clinicians with crucial evidence for better diagnostic characterization and therapeutic indications.

Emotional awareness, affective dysregulation, and bipolar spectrum psychopathology: A multilevel path analysis

Affective dysregulation is present in those with subsyndromal symptoms of hypomania and mania and prospectively predicts the development of bipolar spectrum disorders. A crucial, understudied area related to the experience and regulation of emotion in this population is emotional awareness – emotional clarity (Clarity) and attention to emotion (Attention). We examined whether scores on the Hypomanic Personality Scale (HPS) were associated with deficits in emotional awareness and b) whether these deficits were associated with heightened intensity and instability of negative (NA) and positive affect (PA). Young adults (n=233), oversampled for HPS scores completed self-reports and 14 days of experience sampling assessing high and low arousal NA and PA. HPS scores were associated with low Clarity and unassociated with Attention. High HPS scores were associated with greater high and low arousal NA intensity and instability only for those at low and mean levels of Attention. In contrast, there was a significant indirect association between HPS scores and intensity of high and low arousal NA and PA, as well as instability of high arousal NA, through low clarity. Results highlighted that individual differences exist in the extent to which facets of emotional awareness differentially link scores on the HPS to emotional outcomes.

Use of antipsychotics in Denmark 1997–2018: a nation-wide drug utilisation study with focus on off-label use and associated diagnoses

Aims Antipsychotics are primarily labelled for the treatment of severe mental illness and have documented clinical utility in certain neurological disorders or palliative care. However, off-label use of antipsychotics is common and increasing, and prior studies on antipsychotic utilisation have not specifically assessed users in neurology, palliative care or general practice. We aimed to explore diagnoses associated with antipsychotic use, treatment patterns and characteristics of users without diagnoses relevant to antipsychotic treatment. Methods Population-based study identifiying all users of antipsychotics in Denmark (pop 5.7 mio.) 1997–2018 in the Danish National Prescription Register (DNPR). Possible indications for antipsychotic therapy were evaluated using in- and outpatient contacts from the DNPR. Users were divided hierarchically into six groups: severe mental disorders (schizophrenia, bipolar-spectrum disorders), chronic mental disorders (dementias, mental retardation, autism), other mental disorders (depression-spectrum, anxiety and personality disorders, etc.), selected neurological diseases, cancer and antipsychotic users without any of these diagnoses. This last group was characterised regarding demographics, antipsychotic use, health care utilisation and likely antipsychotic treatment initiator in 2018. Results Altogether, 630 307 antipsychotic users were identified, of whom 127 649 had filled prescriptions during 2018. Users without diagnoses relevant to antipsychotic treatment comprised of the largest group (37%), followed by schizophrenia and bipolar-spectrum disorders (34%), other mental disorders (15%), dementia, autism and mental retardation (11%), cancer (2.2%) and neurological diagnoses (2.0%). Of 37 478 incident users in 2018, 39% had no diagnosis relevant to antipsychotic treatment, 7.9% had major depression, 7.7% neurotic/stress-related disorders and 7.5% dementia. Quetiapine was most commonly used, both overall (51%) and among users without diagnoses relevant to antipsychotic treatment (58%). Of 14 474 incident users in 2018 without diagnoses relevant to antipsychotic treatment, treatment was most likely initiated by a general practitioner (65%), with only 17% seeing a psychiatrist during the following year. As many as 18% of patients with adjustment disorders and 14% of those without relevant diagnoses for antipsychotic use, remained on antipsychotic treatment 5 years after their first prescription. Conclusions Over one-third of antipsychotic users in Denmark did not have psychiatric, neurological or cancer diagnoses as possible indications for antipsychotic therapy. Many antipsychotics are initiated or prescribed in general practice, and a concerningly large subgroup without documented diagnoses relevant for antipsychotics continued to receive them. Rational prescribing, adequate side effect monitoring and further research into reasons for the observed antipsychotic use patterns and their risk–benefit ratio are needed.