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Many studies have indicated that the norepinephrine transporter (NET) may play an important role in the mechanisms underlying affective disorders. Thus, the genes of the NET (SLC6A2) are good candidates for research on bipolar disorder (BPD). This study examined whether the NET gene is a susceptibility factor for the BPD in Han Chinese. A promoter -182 T/C polymorphism (rs 2242446) and the exonic polymorphism 1287 G/A (rs 5569) of the NET gene were analysed using a polymerase chain reaction (PCR)-based method in 261 BPD patients and 245 unrelated, age- and gender-matched controls. Furthermore, to reduce the clinical heterogeneity, we also carried out analysis in clinical subgroups of bipolar patients defined according to type I and type II BPD, presence or absence of family history of major affective disorders and the age at onset of BPD. No significant difference was found between either bipolar patients or its more homogeneous subgroups and healthy controls in the genotype and allele frequencies for the investigated NET polymorphisms. Our results suggest that the investigated polymorphisms of NET are not major risk factors responsible for predisposition to BPD or its clinical subtypes in Han Chinese. However, replication studies with larger different ethnic samples are needed.

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Background:Much evidence supports the role of the serotonin transporter (SERT) in the pathophysiology and pharmacotherapy of major depressive disorder (MDD) and suicidal behaviors.Methods:In this study, we recruited 17 antidepressant-naïve patients with MDD and 17 age- and gender-matched healthy controls. SERT availability was measured in vivo with N,N-dimethyl-2-(2-amino-4-[18F]fluorophenylthio)benzylamine (4-[18F]-ADAM) positron emission tomography (PET) imaging. The 21-item Hamilton Depression Rating Scale (HDRS) and Beck Scale for Suicide Ideation were used to assess the severity of depression and the intent of suicide ideation prior to PET imaging. All subjects with MDD were in a current state of depression with HDRS scores ≧18. Subjects who attempted suicide within two weeks of the study onset were recruited in the depressed suicidal group (n = 8). Subjects with MDD who denied any prior suicide attempt were recruited into the depressed non-suicidal group (n = 9).Results:A significant reduction of SERT availability in the midbrain, thalamus, and striatum was noted in the MDD group relative to the control group (Bonferroni-adjusted p-value < 0.05). Moreover, this effect was more pronounced in the depressed suicidal group compared to the control group (Bonferroni-adjusted p-value < 0.01). Relative to both the depressed non-suicidal and control groups, the depressed suicidal group showed an increased prefrontal cortex (PFC)/midbrain SERT binding ratio (Bonferroni-adjusted p-value < 0.01).Conclusions:This study suggests an incongruent reduction of PFC SERT binding relative to the midbrain might discriminate between depressed suicide attempters and non-attempters in patients with MDD and may be involved in the pathophysiology of suicide behaviors.