It appears that variations in the CLOCK gene do not play a major role in the development of schizophrenia, bipolar disorder, or major depressive disorder (MDD), conclude Japanese investigators.

Clock genes not only regulate circadian rhythms but also have an influence on dopamine neural transmission, and it is thought that abnormalities in both of these systems are associated with schizophrenia, bipolar disorder, and MDD. Furthermore, there is evidence that CLOCK is linked to these conditions.

To investigate further, Taro Kishi, from Fujita Health University School of Medicine in Aichi, and colleagues genotyped 733 schizophrenia patients, 149 bipolar disorder patients, 324 MDD patients, and 795 healthy controls for the six tagging single nucleotide polymorphisms (SNPs) in CLOCK.

There were no overall associations between the tag SNPs and schizophrenia, bipolar disorder, or MDD. Exploration of gender differences revealed an association between one SNP and schizophrenia in women, although this did not survive Bonferroni correction.

The researchers also report in the European Archives of Psychiatry and Clinical Neuroscience that that there were no gender associations between any of the studied SNPs and MDD or bipolar disorder.

They suggest: “CLOCK may not play a major role in the pathophysiology of schizophrenia, bipolar disorder, and MDD in the Japanese population. However, it will be important to replicate and confirm these findings in other independent studies using larger samples.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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Bipolar disorder patients who have a first affective episode with psychotic symptoms and a history of mania have a semantic verbal fluency deficit that occurs in spite of generally preserved function, say UK scientists.

Bipolar disorder patients have memory, attention, and executive function deficits that persist during euthymia. While such deficits are correlated with the number of prior affective episodes, they have also been demonstrated in first-episode patients.

To examine the extent to which such deficits represent “core” bipolar disorder characteristics, Eugenia Kravariti, from King’s College London, and colleagues administered, among other tests, a neuropsychological battery to 35 bipolar disorder patients with a first affective episode showing psychotic symptoms and a positive history of mania and 274 community controls.

In addition, a subanalysis was performed between the patients and 105 controls matched for current IQ (”good” versus “poor”) and IQ trajectory (”stable,” “declined,” and “improved”).

There were no differences between patients and either groups of controls in terms of gender, education, or National Adult Reading Test IQ, whereas there were significant differences in age and ethnicity.

The results, published in the journal Bipolar Disorders, show that there was evidence of a suggested deficit in patients compared with controls on the Rey Auditory Verbal Learning Test Trial 6, and a significant deficit in patients compared with controls in semantic fluency.

Only the latter deficit was detectable in patents compared with IQ-matched controls. Compared with the overall control group, semantic fluency had a medium effect size, and a small-to-medium effect size compared with IQ-matched controls. There were no other significant deficits.

Further analysis demonstrated that antipsychotic medication had a small and nonsignificant negative correlation with semantic fluency, at average scores of 34.78 in medicated cases versus 45.00 in two non-medicated patients.

The team writes: “In summary, our results point to a moderate, isolated impairment in semantic verbal fluency in patients with a first affective episode with psychotic symptoms and a positive history of mania.

“This pattern contrasts sharply with the widespread neuropsychological dysfunction seen in the early phases of schizophrenia.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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