We report the first genome-wide association study in 1000 bipolar I patients and 1000 controls, with a replication of the top hits in another 409 cases and 1000 controls in the Han Chinese ...population. Four regions with most strongly associated single-nucleotide polymorphisms (SNPs) were detected, of which three were not found in previous GWA studies in the Caucasian populations. Among them, SNPs close to specificity protein 8 (SP8) and ST8 α-N-acetyl- neuraminide α-2,8-sialyltransferase (ST8SIA2) are associated with Bipolar I, with P-values of 4.87 × 10(-7) (rs2709736) and 6.05 × 10(-6) (rs8040009), respectively. We have also identified SNPs in potassium channel tetramerization domain containing 12 gene (KCTD12) (rs2073831, P=9.74 × 10(-6)) and in CACNB2 (Calcium channel, voltage-dependent, β-2 subunit) gene (rs11013860, P=5.15 × 10(-5)), One SNP nearby the rs1938526 SNP of ANK3 gene and another SNP nearby the SNP rs11720452 in chromosome 3 reported in previous GWA studies also showed suggestive association in this study (P=6.55 × 10(-5) and P=1.48 × 10(-5), respectively). This may suggest that there are common and population-specific susceptibility genes for bipolar I disorder.
Objectives:
Serotonin (5‐hydroxytryptamine, 5‐HT) was implicated in the pathophysiology of manic‐depressive illness as early as 1958. Although extensive evidence has accumulated since then to support ...5‐HT's role in depression, relatively fewer studies examined its role in mania. The purpose of this paper was to review and summarize the current state of knowledge on the role of 5‐HT in mania and its treatment. Methods: We systemically reviewed clinical studies of 1) 5‐HT function in mania and 2) 5‐HT in the mechanism of action of mood stabilizers, including lithium and anticonvulsants. Results: Review showed that cerebrospinal fluid, postmortem, platelet, neuroendocrine challenge, and tryptophan depletion studies provided some evidence to support the hypothesis that a 5‐HT deficit is involved in mania and that enhancement of 5‐HT neurotransmission exerts a mood‐stabilizing effect. Conclusions: There is some evidence from clinical studies for the contribution of 5‐HT in mania and in the mechanism of action of mood stabilizers. However, it is very likely that other neurotransmitters also play important roles. Future directions for research include 1) in vivo study of 5‐HT receptor subtypes using positron emission tomography, 2) investigation of the interaction between 5‐HT and other neurotransmitter systems, and 3) determination of the relationships between diagnostic subtypes of mania and 5‐HT function and other neurotransmitter systems.
Over the past twenty years, several lines of evidence from preclinical and clinical studies has accumulated suggesting that a GABA deficit may be involved in mood disorders, particularly in ...depression, and that increasing GABAergic neurotransmission may exert an antidepressant effect and perhaps a mood stabilizing effect. Given that GABA has an inhibitory effect on biogenic amine neurotransmitters such as norepinephrine and serotonin and this inhibition may be involved in local circuits and interneurons, it has been suggested that the hypothesis of a GABA deficit in mood disorders does not compete with but complements the well-established hypotheses of alterations in noradrenergic and serotonergic function in mood disorders. In this paper, we systematically reviewed the results from preclinical and clinical studies of GABA function in the pathophysiology of mood disorders and in the mechanism of action of mood stabilizers, antidepressants and electroconvulsive therapy. We also discussed the unifying theory of the neurochemistry of mood disorders, which integrates the GABA hypothesis into the biogenic amine hypotheses, and indicated future directions for research.
This study’s objective was to evaluate the effect of an assertiveness training program on nursing and medical students’ assertiveness, self-esteem, and interpersonal communication satisfaction. Using ...a longitudinal research design, 69 participants whose scores on the Assertive Scale were ⩽50% (i.e., low assertiveness) and who were willing to participate were included and assigned to an experimental group (33 subjects) or comparison group (36 participants; participants were matched with the experimental group by grade and sex). Participants in the experimental group received eight 2-h sessions of assertiveness training once a week. Data were collected before and after training and again one month after the end of the training using the Rotter’s Internal versus External Control of Reinforcement Scale, Sex Role Inventory, Assertive Scale, Esteem Scale, and Interpersonal Communication Satisfaction Inventory. The generalized estimated equation (GEE) method was used for statistical analysis. The assertiveness and self-esteem of the experimental group were significantly improved in nursing and medical students after assertiveness training, although interpersonal communication satisfaction of the experimental group was not significantly improved after the training program.
Objective: In DSM-IV, winter seasonal affective disorder (SAD) is classified as a seasonal pattern of recurrent major depressive episodes in winter with full remission of symptoms in summer. However, ...other groups with “winter depression” have been identified, including patients with incomplete summer remission (ISR) and subsyndromal SAD (sub-SAD, winter depressive symptoms that do not meet criteria for major depression). In this study, we compare the clinical characteristics of these three seasonal groups and their response to light therapy.
Method: 558 patients assessed at a specialized SAD Clinic were diagnosed using DSM-III-R or DSM-IV criteria. Clinical information was recorded using a checklist at index assessment. A subset of patients (
N=192) were treated with an open, 2 week trial of light therapy using a 10 000 lux fluorescent light box for 30 min per day in the early morning. Patients were assessed before and after treatment with the 29 item modified Hamilton Depression Rating Scale and clinical response was defined as greater than 50% improvement in scores.
Results: The rates of some melancholic symptoms, anxiety, panic, suicidal ideation, and family history of mood disorder were lowest in the sub-SAD group. The clinical response rates to light therapy were highest in the sub-SAD group (
N=32, 78%), intermediate in the SAD group (
N=113, 66%), and lowest in the ISR group (
N=47, 51%).
Limitations: This was a retrospective study of patients seen in a specialty clinic, although information was obtained in a standardized format. The light therapy trial had an open design so that placebo response could not be determined.
Conclusions: There are differences in both the patterns of clinical symptoms and the response to light therapy in these three groups with winter depression. These results are consistent with a dual vulnerability hypothesis that considers these groups to result from interaction of separate factors for seasonality and depression.
Recent case reports suggest that some patients with seasonal affective disorder (SAD) may become suicidal after initial treatment with light therapy. This retrospective study sought to determine the ...effects of light therapy on suicidal ideation in patients with SAD.
The cases of 191 depressed patients with SAD by DSM-III-R or DSM-IV criteria treated with an open trial of morning light therapy using cool white fluorescent light boxes (2500 lux for 2 hours per day or 10,000 lux for 30 minutes per day) for 2 weeks were retrospectively analyzed. Patients had been rated before and after treatment with the expanded Hamilton Depression Rating Scale (SIGH-SAD).
Sixty-seven percent of patients were rated as clinical responders to light therapy. There was significant improvement in the SIGH-SAD suicide item score, with 45% of patients showing a reduction in score. Only 6 patients (3%) had slight worsening of suicide scores. No patients attempted suicide or discontinued light therapy because of emergent suicidality.
Light therapy relieves suicidal ideation in patients with SAD consistent with overall clinical improvement. Emergence of suicidal ideas or behaviors is very uncommon with light therapy.
OBJECTIVE: Although dopaminergic hyperactivity has been implicated in mania, the precise location in the brain of the abnormality is unclear. This study assessed presynaptic dopamine function in ...neuroleptic- and mood-stabilizer-naive nonpsychotic first-episode manic patients before and after treatment with divalproex sodium by measuring 18F6-fluoro-l-dopa (18FDOPA) uptake in the striatum with positron emission tomography (PET). METHOD: Thirteen patients with DSM-IV bipolar I disorder, manic episode, and 13 healthy comparison subjects underwent 18FDOPA PET scans. Ten of the 13 patients had repeat PET scans 2-6 weeks after beginning treatment with divalproex sodium monotherapy. 18FDOPA uptake rate constants (Ki values) in the striatum were calculated by using graphical analysis with activity from the occipital cortex as the input function. RESULTS: No significant differences in 18FDOPA uptake rate constants in the striatum were found between the manic patients and the comparison subjects. After treatment with divalproex sodium, 18FDOPA rate constants were significantly reduced in the patients and were lower in the patients than in the comparison subjects. CONCLUSIONS: Although presynaptic dopamine function as reflected by 18FDOPA uptake is not altered in mania, presynaptic dopamine function in manic patients was lower after treatment with divalproex sodium.
Several studies have shown that olanzapine is effective in weight restoration and maintenance for patients with anorexia nervosa (AN). However, major depression is a very common comorbid psychiatric ...disorder associated with AN. Additional antidepressant therapy may be required for treating anorexic patients with major depression. The authors present a case of AN associated with major depression, who responded well to the combination treatment of olanzapine and mirtazapine. A 27-year-old Taiwanese woman was admitted because of severe weight loss, poor nutrition, amenorrhea, major depression, and starvation complications including hematological dyscrasis, electrolytes and endocrine imbalance, and sinus bradycardia. In additional to nutritional and medical treatments, the patient was given olanzapine 10 mg/day and mirtazapine 30 mg/day. She took the combined medications for six months. Meanwhile she received cognitive behavior therapy and family therapy. With these treatments, the patient's depression was in remission, her body weight was increased from 24 to 38 kg, and her body mass index was increased from 9.8 to 15.5. Our case suggests that the combined treatment of olanzapine and mirtazapine can be used in the treatment of AN associated with major depression.
Background: There is increasing evidence that an activation of the immune–inflammatory system is involved in the pathophysiology of depressive disorders. The purposes of this study were to (1) ...compare immune–inflammatory markers in patients with seasonal affective disorder (SAD) with those in matched normal controls; and (2) examine the effects of light therapy on the immune–inflammatory markers in patients with SAD.
Methods: Plasma concentrations of interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R) and soluble IL-2 receptor (sIL-2R) were measured in 15 patients with SAD and 15 age- and sex-matched normal controls. Of the 15 patients, 14 had repeated blood sampling for these variables following 2 weeks of light therapy.
Results: We found that patients with SAD had significantly increased IL-6 levels compared to normal controls (
P<0.0005). There was a trend toward increased sIL-2R in patients with SAD (
P=0.09). There was no significant difference in sIL-6R level between the two diagnostic groups (
P=0.18), but the product term (IL-6×sIL-6R) was significantly higher in patients with SAD than that in normal control controls (
P<0.0003). Furthermore, all 14 patients who completed the study improved with 2 weeks of light therapy and nine of them (64%) had 50% reduction in score of the Hamilton Depression Rating Scale–SAD version post-treatment compared to baseline. However, the initially increased immune markers in SAD patients were not significantly altered by the therapeutic light therapy.
Limitations: This study was limited to a small sample size and other immune inflammatory markers should be measured for further evidence of immune activation in seasonal depression.
Conclusions: Our results of increased IL-6, IL-6×sIL-6R, and sIL-2R in patients with SAD suggest an activation of the immune–inflammatory system in winter depression, which is not altered by 2 weeks of successful light therapy.
Bupropion is an antidepressant that is structurally related to amphetamines and enhances dopamine neurotransmission through inhibiting neuronal dopamine re-uptake. Bupropion-related psychosis has ...been recognized in several papers, but these reports of bupropion-related psychosis almost all involve immediate release (IR) formulation. We present a case of acute psychosis following sustained release bupropion (SR) overdose. A 23-year-old male was admitted because of major depression and a suicidal attempt by ingesting 28 tablets of 150 mg bupropion SR and 14 tablets of 7.5 mg midazolam. He developed paranoid delusions 12 h after the bupropion SR overdose. The paranoid symptoms remitted on the third day of his admission. Our case of acute psychosis following bupropion SR overdose indicates the importance of being aware of the rare complication in patients receiving bupropion SR treatment.
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