Effects of Chronic Mild Stress in Female Bax Inhibitor-1-Gene Knockout Mice

OBJECTIVE: The anti-apoptotic protein Bax inhibitor-1 (BI-1) is a regulator of apoptosis linked to endoplasmic reticulum (ER) stress, and BI-1-/- mice exhibit increased sensitivity to tissue damage. The purpose of this study was to investigate the role of BI-1 in the pathogenesis of chronic mild stress (CMS)-induced depression-like behaviors in BI-1-/- mice. METHODS: We delivered CMS for 2 or 6 weeks in BI-1-knockout and wild-type mice. Control groups of BI-1-knockout and wild-type mice were left undisturbed. The measured parameters were sucrose consumption at weeks 1, 2, 3, 4, 5, and 6, spontaneous locomotion, and a forced swimming test (FST) at weeks 2 and 6. RESULTS: Significant decreases in sucrose consumption and increases in immobility time in the FST were observed in both stress groups compared with the non-stress groups. Interestingly, at week 2, but not at week 6, BI-1-/--stress mice showed less sucrose intake and greater immobility time than did BI-1+/+-stress mice. CONCLUSION: These results suggest that BI-1 may play role in protecting against the depressogenic effects of CMS in the short term, but not in the long term. Further study is required to deepen understanding of the role of BI-1 in protecting against depression.

How Can We Differentiate Schizoaffective Disorder from Mood Disorder with Psychotic Feature? / 대한정신분열병학회지

Difficulties surrounding the classification of mixed psychotic and mood symptoms continue to plague psychiatric nosology. Since schizoaffective disorder was first defined in the literature, it has raised a considerable controversy regarding its clinical distinction from schizophrenia and mood disorder, especially mood disorder with psychotic feature. Recently, it seems that more people are diagnosed as mood disorder with psychotic feature rather than schizoaffective disorder when they are showing concurrent psychotic and mood symptoms. This may be due to unwillingness to make severe diagnosis at first and aggressive trend to expand the diagnostic criteria for bipolar disorder. Over-diagnosis of mood disorder with psychotic feature would expose the patients to unnecessary mood stabilizer. Therefore, it is critical to make exact diagnosis based on current diagnostic criteria and other relevant study findings. We conducted in-depth review into diagnostic criteria of DSM and ICD-10 for schizoaffective disorder and mood disorder with psychotic feature and other related studies comparing clinical features between the two disorders. As a result, important points helpful in differentiating the two disorders are highlighted and future suggestions are described.

How Can We Differentiate Schizoaffective Disorder from Mood Disorder with Psychotic Feature? / 대한정신분열병학회지

Difficulties surrounding the classification of mixed psychotic and mood symptoms continue to plague psychiatric nosology. Since schizoaffective disorder was first defined in the literature, it has raised a considerable controversy regarding its clinical distinction from schizophrenia and mood disorder, especially mood disorder with psychotic feature. Recently, it seems that more people are diagnosed as mood disorder with psychotic feature rather than schizoaffective disorder when they are showing concurrent psychotic and mood symptoms. This may be due to unwillingness to make severe diagnosis at first and aggressive trend to expand the diagnostic criteria for bipolar disorder. Over-diagnosis of mood disorder with psychotic feature would expose the patients to unnecessary mood stabilizer. Therefore, it is critical to make exact diagnosis based on current diagnostic criteria and other relevant study findings. We conducted in-depth review into diagnostic criteria of DSM and ICD-10 for schizoaffective disorder and mood disorder with psychotic feature and other related studies comparing clinical features between the two disorders. As a result, important points helpful in differentiating the two disorders are highlighted and future suggestions are described.

Effects of Aripiprazole and Haloperidol on Fos-like Immunoreactivity in the Prefrontal Cortex and Amygdala

OBJECTIVE: Aripiprazole, a dopamine system stabilizer, shows efficacy against both negative symptoms and positive symptoms in patients with schizophrenia. The aim of this study was to investigate the effects of aripiprazole and haloperidol on c-FOS expression in rat brain. METHODS: Aripiprazole (1, 10 and 30 mg/kg, i.p.) and haloperidol (0.1 and 1 mg/kg, i.p.) were administered to adult Male Sprague-Dawley rats. After 2 h of drug or vehicle administration, the rats were killed and their brains were removed and perfused with fixative, then cut into 40 microm slices on a freezing microtome. Brain regions of interest were the medial prefrontal cortex (mPFC), the nucleus accumbens core and shell (NAC-C and NAC-S), the hippocampus (CA1, CA3 and DG), the central amygdala (Ce), the basolateral amygdala (BL) and the temporal cortex (Tc). Immunohistochemistry was performed to label cell bodies containing c-FOS. RESULTS: The administration of aripiprazole at all doses (1, 10 or 30 mg/kg) resulted in greater Fos-like immunoreactivity (FLI) in the investigated brain areas, as compared to the vehicle. Comparable increases in FLI were demonstrated in the NAC-C and NAC-S in response to both aripiprazole and haloperidol treatment. The administration of haloperidol (0.1 or 1 mg/kg) also resulted in greater FLI in the investigated brain areas, except the mPFC, where no changes were observed. In the Ce and BL, a significant increase in Fos-positive neurons was observed only with 0.1 mg/kg of haloperidol. CONCLUSION: Both aripiprazole and haloperidol increased FLI in limbic areas, which are considered important targets of antipsychotic drugs. The differential action of aripiprazole on FLI in the amygdala and mPFC as compared to haloperidol may be a good way to differentiate atypical from typical antipsychotics.

Amisulpride and Haloperidol-Induced c-Fos Expression in the Rat Brain / 대한정신약물학회지

OBJECTIVE: Amisulpride, a D2/D3 dopamine receptor blocker, shows efficacy against both negative symptoms in a low dose range and positive symptoms in a high dose range. The aim of the study was to investigate the effects of amisulpride and haloperidol on the c-Fos expression in rat brain. METHODS: Amisulpride (0.5, 5 and 50 mg/kg, ip) and haloperidol (0.1 and 1 mg/kg, ip) were administered to adult male Sprague-Dawley rats. Two hours after drugs or vehicle administration, rats were killed and their brains were perfused with fixative. The brains were cut at 40 microm on a freezing microtome. Brain regions of interest were medial prefrontal cortex (mPFC), nucleus accumbens core and shell, hippocampus (CA1, CA3 and dentate gyrus), central amygdala nucleus, basolateral amygdala nucleus and temporal cortex. To label cell bodies containing c-Fos, immunohistochemistry was performed. RESULTS: The administration of amisulpride in all doses (0.5, 5 and 50 mg/kg) demonstrated greater c-Fos expressions in all of the investigated brain areas, compared to the vehicle. Interestingly, low doses (0.5 mg/kg) of amisulpride showed greater c-Fos expression in the mPFC than high dose of amisulpride (50 mg/kg). The administration of haloperidol (0.1 and 1 mg/kg) also demonstrated greater c-Fos expressions in all of the investigated brain areas except mPFC, compared to the vehicle. CONCLUSION: Both amisulpride and haloperidol increased c-Fos expressions in limbic areas which are considered as the sites of antipsychotic effects. The findings that lower doses of amisulpride increased greater c-Fos expressions in the mPFC, may explain the beneficial effects of low dose of amisulpride on the negative or depressive symptoms in patients with schizophrenia.

Complete Heart Block due to Lithium Toxicity / 대한정신약물학회지

Lithium treatment has been associated with a wide range of cardiac complications. We observed a 53-year-old female patient who presented with complete heart block due to lithium toxicity. The patient had been diagnosed as schizoaffective disorder and had been taking a stable dose of lithium, 1,500 mg/day since January 2007. Recently, she begun a strict diet and experienced muscle weakness and lethargy a few days later. While receiving fluid therapy, she lost her consciousness and was transferred to an emergency medical center. An electrocardiogram revealed that she had complete heart block, so a temporary pacemaker was inserted immediately. After 4 days of intensive care, her heartbeat recovered spontaneously and the temporary pacemaker was removed. On the 11th day, she had sufficiently recovered and could ambulate by herself. Lithium levels were measured at 5.22 mEq/L and 0.66 mEq/L on the 1st and 4th day of treatment, respectively. This case illustrates the importance of educating patients and their relatives about the possible lithium toxicity caused by a strict diet.

Complete Heart Block due to Lithium Toxicity / 대한정신약물학회지

Lithium treatment has been associated with a wide range of cardiac complications. We observed a 53-year-old female patient who presented with complete heart block due to lithium toxicity. The patient had been diagnosed as schizoaffective disorder and had been taking a stable dose of lithium, 1,500 mg/day since January 2007. Recently, she begun a strict diet and experienced muscle weakness and lethargy a few days later. While receiving fluid therapy, she lost her consciousness and was transferred to an emergency medical center. An electrocardiogram revealed that she had complete heart block, so a temporary pacemaker was inserted immediately. After 4 days of intensive care, her heartbeat recovered spontaneously and the temporary pacemaker was removed. On the 11th day, she had sufficiently recovered and could ambulate by herself. Lithium levels were measured at 5.22 mEq/L and 0.66 mEq/L on the 1st and 4th day of treatment, respectively. This case illustrates the importance of educating patients and their relatives about the possible lithium toxicity caused by a strict diet.