Retinal function and preclinical risk traits in children and adolescents at genetic risk of schizophrenia and bipolar disorder.

BACKGROUND: The millions of children having a parent affected by a major psychiatric disorder may carry, as vulnerability indicators, electroretinographic (ERG) anomalies resembling those seen in adult patients. Our goal was to determine whether ERG anomalies in high-risk youths are related to clinical precursors of a later transition to illness such as the presence of childhood DSM-IV diagnoses, bouts of psychotic like experiences, lower global IQ and social functioning deterioration. METHODS: The 99 youths (53% males) aged 5-27 years had one parent affected by schizophrenia, bipolar disorder or major depressive disorder. They were assessed with a best-estimate DSM-IV diagnoses based on review of medical charts and a structured interview (K-SADS or SCID), global IQ (WISC-V and WAIS-IV), global functioning (GAF scale) and psychotic-like experiences using interviews and a review of medical records. The electroretinogram of rods and cones was recorded. RESULTS: Cone Vmax latency was longer in offspring having psychotic-like experiences, respective adjusted mean [SE] ms of 31.59 [0.27] and of 30.96 [0.14]; P = 0.018). The cone Vmax delayed latency was associated with a lower global IQ (R = -0.18; P = 0.045) and with deteriorated global functioning (GAF; R = -0.25; P = 0.008). In contrast, rods had decreased b-wave amplitude only in offspring with a non-psychotic non-affective DSM diagnoses, respective means [SE] µV of 170.18 [4.90] and of 184.01 [6.12]; P = 0.044). CONCLUSIONS: ERG may mark neurodevelopmental pathways leading to adult illness and have an effect on early pre-clinical traits, giving clues to clinicians for the surveillance of sibling differences in high-risk families.

Differences and similarities in the serotonergic diathesis for suicide attempts and mood disorders: a 22-year longitudinal gene-environment study.

To investigate similarities and differences in the serotonergic diathesis for mood disorders and suicide attempts, we conducted a study in a cohort followed longitudinally for 22 years. A total of 1255 members of this cohort, which is representative of the French-speaking population of Quebec, were investigated. Main outcome measures included (1) mood disorders (bipolar disorder and major depression) and suicide attempts by early adulthood; (2) odds ratios and probabilities associated with 143 single nucleotide polymorphisms in 11 serotonergic genes, acting directly or as moderators in gene-environment interactions with childhood sexual or childhood physical abuse (CPA), and in gene-gene interactions; (3) regression coefficients for putative endophenotypes for mood disorders (childhood anxiousness) and suicide attempts (childhood disruptiveness). Five genes showed significant adjusted effects (HTR2A, TPH1, HTR5A, SLC6A4 and HTR1A). Of these, HTR2A variation influenced both suicide attempts and mood disorders, although through different mechanisms. In suicide attempts, HTR2A variants (rs6561333, rs7997012 and rs1885884) were involved through interactions with histories of sexual and physical abuse whereas in mood disorders through one main effect (rs9316235). In terms of phenotype-specific contributions, TPH1 variation (rs10488683) was relevant only in the diathesis for suicide attempts. Three genes contributed exclusively to mood disorders, one through a main effect (HTR5A (rs1657268)) and two through gene-environment interactions with CPA (HTR1A (rs878567) and SLC6A4 (rs3794808)). Childhood anxiousness did not mediate the effects of HTR2A and HTR5A on mood disorders, nor did childhood disruptiveness mediate the effects of TPH1 on suicide attempts. Of the serotonergic genes implicated in mood disorders and suicidal behaviors, four exhibited phenotype-specific effects, suggesting that despite their high concordance and common genetic determinants, suicide attempts and mood disorders may also have partially independent etiological pathways. To identify where these pathways diverge, we need to understand the differential, phenotype-specific gene-environment interactions such as the ones observed in the present study, using suitably powered samples.

Clinical diagnoses in young offspring from eastern Québec multigenerational families densely affected by schizophrenia or bipolar disorder.

OBJECTIVE: The follow-up since 1989 of a large sample of multigenerational families of eastern Québec that are densely affected by schizophrenia (SZ) or bipolar disorder (BP) has permitted to look at the rates of DSM diagnoses in the young offspring of a SZ parent (HRSZ) and of a BP parent (HRBP) who had an extremely loaded family history. METHOD: The sample (average age of 17.5, SD 4.5) consisted of 54 high-risk offspring (HR) having one parent affected by a DSM-IV SZ or BP. The parents descended from 21 multigenerational families that constitute a quasi-total sample of such kindred in eastern Québec. The HRs were administered a lifetime best estimate DSM-IV diagnosis. RESULTS: We observed that the rates, the diversity of diagnoses, the high comorbidity, the severity and the age of onset of the clinical diagnoses tended to be similar with those already reported in the offspring of affected parents with a low familial loading. Although the sample size was small, HRSZ and HRBP also tended to show similarities in their clinical status. CONCLUSION: Overall, taking into account methodological limitations, the observation early in life of some shared characteristics among HRSZ and HRBP in terms of non-psychotic diagnosis may be congruent with the accumulating evidence that several phenotypic features are shared in adulthood by the two major psychoses.