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Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Mixed bipolar states are not infrequent and may be extremely difficult to treat. Lithium, anticonvulsants including valproate and carbamazepine, and antipsychotics such as olanzapine, ziprasidone, and aripiprazole have been reported to be at least partially effective in controlled clinical trials, but many patients do not respond to pharmacological approaches. Electroconvulsive therapy has been tested to be efficacious for the treatment of both manic and depressive episodes, but much less evidence is available with regards to mixed states. The aim of the review was to report the available evidence for the use of electroconvulsive therapy in mixed bipolar states.
A systematic review of the literature on treatment of mixed states, focused on electroconvulsive therapy, was made, beginning in August 1992 and ending in March 2007. The key words were “electroconvulsive therapy” and “mixed bipolar”.
Only three studies met the required quality criteria and were included. This literature suggests that ECT is an effective, safe, and probably underutilized treatment of mixed states. Recent technical developments have made ECT more friendly, tolerable, and safe. Potential alternatives, such as vagus nerve stimulation, deep brain stimulation, or transcranial stimulation, are still far to be proved as effective as ECT.
Maria Reinares, Bipolar Disorders Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona,
Eduard Vieta, Bipolar Disorders Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona,
Antoni Benabarre, Bipolar Disorders Program, Institute of Neuroscience, Hospital Clinic, University of Barcelona,
Andreas Marneros, Department of Psychiatry and Psychotherapy, Martin Luther University, Halle-Wittenberg
The term “schizoaffective psychosis” was first introduced by Kasanin (1933) when he described a group of patients with good premorbid functioning who developed acute psychoses with a mixture of psychotic and affective symptoms, but fully recovered after a few months. While Kasanin is credited with introducing the term, it is defined differently now. Schizoaffective disorder is a complex illness whose definition has changed significantly over time. Despite the continued attempts to better define and classify schizoaffective disorder, much controversy and conflicting results remain. Unfortunately, schizoaffective disorders have been poorly investigated. Kahlbaum (1863) is usually considered the first psychiatrist in modern times to describe schizoaffective disorders as a separate group (Angst and Marneros, 2001). As Tsuang and Simpson (1984) reported, empirical findings are often contradictory and have at times supported the idea that schizoaffective disorder is (a) a variant of schizophrenia; (b) a variant of affective disorder; (c) a different and heterogeneous diagnostic group.
Regarding classification systems, in DSM-II schizoaffective disorder was included in the group of schizophrenic disorders, although some studies with controversial results were published (Procci, 1976; Harrow, 1984). While in DSM-III schizoaffective disorders had only the state of a remnant category, in DSM-III-R schizoaffective disorders were extended to a “true” entity with specific diagnostic criteria (Jäger et al., 2004).
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