Lack of genetic association between the phospholipase A2 gene and bipolar mood disorder in a European multicentre case-control study.

The possible association between phospholipase A2 gene and bipolar mood disorder was examined in 557 bipolar patients and 725 controls (all personally interviewed), recruited from seven countries (Belgium, Bulgaria, Croatia, Germany, Greece, Italy, and UK). The frequencies of the eight alleles that were identified did not differ between patients and control individuals in the whole population, while the power to detect an association based on our sample was relatively high. Some differences were noted among the various ethnic groups, but no significant trends existed, suggesting that population stratification by country may not be responsible for a type II error. On the basis of these results, mutations of the phospholipase A2 gene, at least in the region close to the polymorphism examined between exons 1 and 2, are not involved in the pathogenesis of bipolar mood disorder.

Co-occurrence of disturbed sleep and appetite loss differentiates between unipolar and bipolar depressive episodes.

The aim of this study was to examine whether the co-occurrence of disturbed sleep and appetite loss, two commonly encountered somatic symptoms of depression, can differentiate the clinical expression of depressive episodes between bipolar (BP) and unipolar patients (UP). Forty BP and 40 UP outpatients were interviewed through the Schedules for the Clinical Assessment in Neuropsychiatry (SCAN) and the presence of sleep disturbance and appetite loss during their most severe depressive episode was determined. Other variables studied were patients' gender and age, clinical characteristics related to the course of the disease (age at onset, duration of illness, and number and frequency of depressive and manic episodes), severity of the worst major depressive episode, and presence or absence of certain associated symptoms during that episode (loss of energy, low interest, feelings of guilt and/or self-reproach, impaired concentration, suicidal ideation, and agitation or retardation). Appetite loss was found to be more frequently present in UP (78%) than BP patients (55%, P<.05). No significant difference in the occurrence of sleep disturbance was found between the two groups. Among BP patients, appetite loss was present in 73% of those with sleep disturbance vs. 33% of those without (P<.02), while no such difference in co-occurrence of sleep disturbance and appetite loss was noticed among UP patients (74% vs. 85%, respectively, n.s.); this finding did not seem to be related to differences in severity of depression among UP and BP patients. Furthermore, those BP patients with co-occurrence of the two somatic symptoms complained also of loss of energy and low interest more often than those without (P<.01 and P<.05, respectively). No similar differences were observed among UP patients. The results of the present study suggest that the pathophysiological mechanisms underlying depressive episodes may differ between BP and UP affective disorder, and that those BP patients with simultaneous occurrence of sleep disturbance and appetite loss can be considered to belong to a particular nosologic subgroup with potential therapeutic and prognostic implications.

Changes in central serotonergic function as a correlate of duration of illness in paranoid schizophrenia.

There is evidence that the duration of untreated psychosis may affect both the course and outcome of treatment in schizophrenic patients. In the present study, we used neuroendocrine probes to test the hypothesis that untreated psychosis may induce time-dependent changes in central serotonergic and dopaminergic neurotransmission. Prolactin responses to the administration of clomipramine (i.v.) and haloperidol (i.m.) were measured in healthy control subjects and in 16 never-treated male patients with DSM-IV diagnoses of schizophreniform or schizophrenic disorders of paranoid subtype, both before and after 5 weeks of treatment with haloperidol. In the drug-free state, schizophrenic patients exhibited significantly increased prolactin responses to clomipramine administration compared with both the healthy control subjects and the schizophreniform patients. Maximum prolactin responses to clomipramine in the total group of patients were positively correlated with the duration of psychotic illness and negatively correlated with changes in Positive and Negative Syndrome Scale (PANSS) total, negative symptoms and general psychopathology scores after 5 weeks of treatment with haloperidol. Prolactin responses to haloperidol challenge in the drug-free state were lower in the schizophreniform group than in the control and the schizophrenic groups, but the differences did not reach statistical significance. The results provide evidence that the persistence of psychotic psychopathology induces secondary neuroadaptive effects, which seem to involve changes in central serotonergic function.