Heterozygosity for neuronal ceroid lipofuscinosis predisposes to bipolar disorder

Objective: Bipolar disorder is a heritable chronic mental disorder that causes psychosocial impairment through depressive/manic episodes. Familial transmission of bipolar disorder does not follow simple Mendelian patterns of inheritance. The aim of this study was to describe a large family with 12 members affected by bipolar disorder. Whole-exome sequencing was performed for eight members, three of whom were diagnosed with bipolar disorder, and another reported as "borderline." Methods: Whole-exome sequencing data allowed us to select variants that the affected members had in common, including and excluding the "borderline" individual with moderate anxiety and obsessive-compulsive traits. Results: The results favored designating certain genes as predispositional to bipolar disorder: a heterozygous missense variant in CLN6 resulted in a "borderline" phenotype that, if combined with a heterozygous missense variant in ZNF92, is responsible for the more severe bipolar disorder phenotype. Both rare missense changes are predicted to disrupt protein function. Conclusions: Loss of both alleles in CLN6 causes neuronal ceroid lipofuscinosis, a severe progressive childhood neurological disorder. Our results indicate that heterozygous CLN6 carriers, previously reported as healthy, may be susceptible to bipolar disorder later in life if associated with additional variants in ZNF92.

Heterozygosity for neuronal ceroid lipofuscinosis predisposes to bipolar disorder.

OBJECTIVE: Bipolar disorder is a heritable chronic mental disorder that causes psychosocial impairment through depressive/manic episodes. Familial transmission of bipolar disorder does not follow simple Mendelian patterns of inheritance. The aim of this study was to describe a large family with 12 members affected by bipolar disorder. Whole-exome sequencing was performed for eight members, three of whom were diagnosed with bipolar disorder, and another reported as "borderline." METHODS: Whole-exome sequencing data allowed us to select variants that the affected members had in common, including and excluding the "borderline" individual with moderate anxiety and obsessive-compulsive traits. RESULTS: The results favored designating certain genes as predispositional to bipolar disorder: a heterozygous missense variant in CLN6 resulted in a "borderline" phenotype that, if combined with a heterozygous missense variant in ZNF92, is responsible for the more severe bipolar disorder phenotype. Both rare missense changes are predicted to disrupt protein function. CONCLUSIONS: Loss of both alleles in CLN6 causes neuronal ceroid lipofuscinosis, a severe progressive childhood neurological disorder. Our results indicate that heterozygous CLN6 carriers, previously reported as healthy, may be susceptible to bipolar disorder later in life if associated with additional variants in ZNF92.

Pharmacotherapeutic strategies for treating binge eating disorder. Evidence from clinical trials and implications for clinical practice.

INTRODUCTION: Binge eating disorder (BED) is the most common eating disorder and was newly recognized in 2013 in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). BED is frequently associated with obesity and the metabolic syndrome, as well as with other psychiatric diseases, such as mood (49%), anxiety (41%), and substance use (22%) disorders. BED is highly prevalent and carries a high burden of mental and physical illness and disability. However, BED is frequently under-recognized and under-treated. AREAS COVERED: This paper reviews the main pharmacological treatments for BED and provides an expert opinion based on the available evidence and on the authors' clinical experience with patients affected by BED. EXPERT OPINION: Several medications have proven to be effective for the treatment of BED, including Lisdexamfetamine (LDX), topiramate as well as anti-anxiety and antidepressant medications. To date, LDX is the only FDA approved medication for BED. Consequently, as a general rule, the use of an FDA approved medication should always be preferred. However, when in the presence of concomitant psychiatric conditions such as anxiety or depression, other medications that have proven efficacy in those comorbid conditions can be used and may contextually provide a benefit for BED.