• ALS
• frontotemporal dementia
• psychiatry
• psychology

The clinical phenotype of behavioural variant frontotemporal dementia (bvFTD) is characterised by neuropsychiatric symptoms, including loss of empathy, compulsive behaviour, behavioural disinhibition and apathy. An expansion of a hexanucleotide (GGGGCC) repeat in the chromosome 9 open reading frame 72 gene (c9orf72^RE) is the most common genetic cause of bvFTD. Neurobiological and behavioural changes have been evidenced in carriers of c9orf72^RE, decades before the estimated onset of symptoms. Recently, Gossink and colleagues investigated the hypothesis that the c9orf72^RE genotype phenotypically could encompass a neuropsychiatric hypervulnerability, emerging during early childhood. They used clinical case-record data and performed semistructured biographical interviews with spouses, first-degree relatives and patients with bvFTD with (N=20) and without (N=23) c9orf72^RE. The results revealed limited empathic behaviour early in life and increased rates of compulsive personality traits in c9orf72^RE carriers.1

Notably, the c9orf72^RE does not only cause bvFTD but may also result in amyotrophic lateral sclerosis (ALS), in which it is more frequently associated with neuropsychiatric symptoms, compared with non-c9orf72^RE ALS variants. In addition, socioemotional deficits consistent with empathic impairment have been reported in c9orf72^RE-carriers with only very mild cognitive and/or functional impairments.2 Also, increased hazard ratios for psychiatric disorders have been reported in kindreds of c9orf72^RE carriers.3 These combined findings give rise to the hypothesis that, compared with the general population, the prevalence of psychopathological characteristics is increased in c9orf72^RE carriers who do not (yet) fulfil the clinical …