The dopamine D3 receptor gene (DRD3) is a meaningful candidate gene because it unifies the dopamine and the limbic hypotheses for schizophrenia. We tested for an allelic association between schizophrenia and the DRD3 Mscl alleles, hypothesising heterogeneity between childhood/early adolescence-onset schizophrenia (CO-SZ) and adult-onset schizophrenia (A-SZ).

The frequencies of the DRD3 alleles were compared between 70 DSM-III-R schizophrenics (35 CO-SZ and 35 A-SZ) and 79 controls.

Compared with the controls, the subsample of A-SZ, but not CO-SZ, showed an over-proportion (P = 0.025) of allele 1. The association was not found in the total sample, combining the two subsamples.

Consistently with former studies, our data suggest an aetiological heterogeneity between CO-SZ and A-SZ and a possible specificity of the excess of allele 1 to the familial form of schizophrenia and to schizophrenia with a better outcome.

There are many reports of adolescents with periodic episodes each followed by complete remission within 2 weeks, but the nosology and long-term prognosis of such cases have not been elucidated.

A prospective follow-up study on 11 cases (nine girls and two boys) meeting predetermined criteria is reported.

The first several episodes were found to meet ICD–10 symptomatic criteria for recurrent depressive disorder in all cases, and, except for two cases, showed psychotic features. The episodes were linked to one phase of the menstrual cycle in only two of six girls with regular menses. There were no recurrences while on lithium in eight of nine cases. Of eight patients followed up 5–14 years after the first onset, three had been well, three had become bipolar and two were still suffering from brief depressive episodes.

Recurrent brief episodes in adolescence tend to show a near-monthly rhythm and psychotic features. Most of them appear to be manifestations of affective illness and may be treated and prevented as such.

Bipolar disorder is a highly heritable polygenic disorder. Recent enrichment analyses suggest that there may be true risk variants for bipolar disorder in the expression quantitative trait loci (eQTL) in the brain.

We sought to assess the impact of eQTL variants on bipolar disorder risk by combining data from both bipolar disorder genome-wide association studies (GWAS) and brain eQTL.

To detect single nucleotide polymorphisms (SNPs) that influence expression levels of genes associated with bipolar disorder, we jointly analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls) and a genome-wide brain (cortical) eQTL (193 healthy controls) using a Bayesian statistical method, with independent follow-up replications. The identified risk SNP was then further tested for association with hippocampal volume (n = 5775) and cognitive performance (n = 342) among healthy individuals.

Integrative analysis revealed a significant association between a brain eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes factor = 5.48; bipolar disorder P = 5.85×10–5). Follow-up studies across multiple independent samples confirmed the association of the risk SNP (rs6088662) with gene expression and bipolar disorder susceptibility (P = 3.54×10–8). Further exploratory analysis revealed that rs6088662 is also associated with hippocampal volume and cognitive performance in healthy individuals.

Our findings suggest that 20q11.22 is likely a risk region for bipolar disorder; they also highlight the informative value of integrating functional annotation of genetic variants for gene expression in advancing our understanding of the biological basis underlying complex disorders, such as bipolar disorder.

Medicine is rapidly becoming molecular medicine, and little escapes the grasp of modern genetics. Most disorders associated with learning disability have at least a genetic component influencing their expression; in many disorders, disturbances of genetic mechanisms play a pivotal role.

Dynamic mutations, imprinting mechanisms and gene-dosage effects are explained with reference to genetic disorders that lead to learning disability.

A review of recent important studies in the genetics of learning disability.

A host of new genetic connections to conditions associated with learning disability have been made.

A basic understanding of these genetic connections is important for all learning disability psychiatrists if they are to follow the rapid changes – already beginning to influence our practice – that hold immense promise for the future.