Comparison of brain N-acetylaspartate levels and serum brain-derived neurotrophic factor (BDNF) levels between patients with first-episode schizophrenia psychosis and healthy controls

Background

N-acetylaspartate (NAA) levels and serum brain-derived neurotrophic factor (BDNF) levels in patients with first-episode schizophrenia psychosis and age- and sex-matched healthy control subjects were investigated. In addition, plasma levels of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were compared between the two groups.

Method

Eighteen patients (nine males, nine females; age range: 13-52 years) were enrolled in the study, and 18 volunteers (nine males, nine females; age range: 15-49 years) with no current or past psychiatric history were also studied by magnetic resonance spectroscopy (MRS) as sex- and age-matched controls.

Results

Levels of NAA/Cr in the left basal ganglia (p = 0.0065) and parieto-occipital lobe (p = 0.00498), but not in the frontal lobe, were significantly lower in patients with first-episode schizophrenia psychosis than in control subjects. No difference was observed between the serum BDNF levels of patients with first-episode schizophrenia psychosis and control subjects. In regard to the plasma levels of catecholamine metabolites, plasma MHPG, but not HVA, was significantly lower in the patients with first-episode psychosis than in control subjects. In addition, a significantly positive correlation was observed between the levels of NAA/Cr of the left basal ganglia and plasma MHPG in all subjects.

Conclusion

These results suggest that brain NAA levels in the left basal ganglia and plasma MHPG levels were significantly reduced at the first episode of schizophrenia psychosis, indicating that neurodegeneration via noradrenergic neurons might be associated with the initial progression of the disease.     

Functional outcomes in first-episode patients with bipolar disorder: a prospective study from the Systematic Treatment Optimization Program for Early Mania project

Background

Bipolar disorder causes substantial psychosocial morbidity, as it frequently affects independent living, vocational, and social activities. However, there is a relative dearth of research on functional outcomes and their predictors in first-episode manic patients from prospective studies early in the course of bipolar disorder.

Methods

The Systematic Treatment Optimization Program for Early Mania (STOP-EM) project recruited 53 patients who recently experienced their first episode of mania with or without psychosis. Multidimensional Scale of Independent Functioning (MSIF) was used as the main measure of functional outcome. Of the 53 patients recruited, 35 completed the 6-month follow-up assessment.

Results

At entry, 62.3% of patients had met criteria for full remission of mood symptoms. Despite this, the mean baseline MSIF score was 4.5 points; 62.3% of the patients had at least moderate disability. A significant improvement in functioning was noted at 6 months relative to entry as indicated by the reduction in mean MSIF scores from 4.5 to 2.6 (t = 4.1, df = 34, P < .001). The proportion of patients with at least moderate disability was reduced from 62.3% to 25.7% at 6 months. Remission of depressive symptoms at 6 months was associated with better functioning (P < .01). In a regression model, only depressive symptoms were significantly correlated with the MSIF global functional scores at 6 months. Even subsyndromal depressive symptoms were significantly correlated with disability (r = 0.3, P < .05).

Conclusion

The findings highlight the deleterious impact of depressive symptoms on functional recovery after a first manic episode even when they are subsyndromal. Considered together, these results emphasize the importance of an aggressive treatment of subsyndromal depressive symptoms for functional recovery.     

Temporal relationship of first-episode non-affective psychosis with cannabis use: A clinical verification of an epidemiological hypothesis

Background

We analyzed the association of age at onset of psychosis treatment (AOPT) with having a history of cannabis use in patients with a first episode of non-affective psychosis. We also investigated the impact on the AOPT of exposure to cannabis in adolescence, compared with young adulthood, and of the additional exposure to cocaine.

Method

We recruited 112 consecutive patients (66 men and 46 women; age range, 18-57 years) with a first psychotic episode. The composite international diagnostic interview (CIDI) was used to assess drug use and to define the age at onset of heaviest use (AOHU) of a drug, defined as the age when drug was used the most for each patient. The effect of cannabis and cocaine AOHU on AOPT was explored through Kruskal-Wallis and Mann-Whitney tests, and logistic regression. Sex-adjusted cumulative hazard curves and Cox regression models were used to compare the AOPT of patients with and without a history of cannabis use, or associated cocaine use.

Results

We found that the AOPT was significantly associated with the use of cannabis, independently of sex, use of cocaine, tobacco smoking or excessive alcohol consumption. There was a dose-response relationship between cannabis AOHU and AOPT: the earlier the AOHU the earlier the AOPT. Hazard curves showed that patients with a history of cannabis use had a higher hazard of having a first-episode psychosis than the rest of the patients (sex-adjusted log-rank χ² = 23.43, df = 1, p < 0.001). Their respective median AOPT (25th, 75th percentiles) were 23.5 (21, 28) and 33.5 years (27, 45) (for log-transformed AOPT, t = 5.6, df = 110, p < 0.001). The sex-adjusted hazard ratio of psychosis onset comparing both groups was 2.66 (95% CI, 1.74-4.05).

Conclusions

Our results are in favor of a catalytic role for cannabis use in the onset of psychosis.     

Hippocampus abnormalities in at risk mental states for psychosis? A cross-sectional high resolution region of interest magnetic resonance imaging study

Background

Hippocampal volume (HV) reduction is well documented in schizophrenia. However, it is still unclear whether this change is a pre-existing vulnerability factor, a sign of disease progression, a consequence of environmental factors, such as drug use, antipsychotic medication, or malnutrition. The timing of HV changes is not well established, but a lack of macrostructural hippocampal brain abnormalities before disease onset would rather support a neuroprogressive illness model.

Aim

To investigate the timing of HV changes in emerging psychosis.

Methods

A cross-sectional MRI study of manually traced HVs in 37 individuals with an At Risk Mental State (ARMS) for psychosis, 23 individuals with First-Episode Psychosis (FEP), and 22 Healthy Controls (HC) was performed. We compared left and right HVs corrected for whole brain volume across groups using analysis of covariance (ANCOVA) with gender as a covariate. Sixteen of 37 ARMS individuals developed a psychotic disorder during follow up (ARMS-T). The mean duration of follow up in ARMS was 25.1 months.

Results

The overall ANCOVA model comparing left HVs across FEP, ARMS and HC indicated a significant general group effect (p < .05) with largest volumes in ARMS and smallest in FEP. ARMS-T subjects had significantly larger left HVs compared to FE but no HV differences compared to HC (p < 0.05). Over all groups, we found an asymmetry between the left and right mean HVs and a strong effect of sex.

Discussion

The present study suggests that macrostructural hippocampal abnormalities probably occur in the context of the first psychotic breakdown.     

A longitudinal study of obsessive-compulsive disorder in individuals at ultra-high risk for psychosis

Background

We evaluated whether (1) a diagnosis of obsessive-compulsive disorder (OCD) at baseline, or (2) the persistence, remission or emergence of de novo OCD at follow-up, were associated with the development of different psychotic disorders in a cohort of individuals at ultra-high risk (UHR) for psychosis.

Methods

Patients were assessed for OCD at baseline and after a mean of 7.4 years follow-up and classified into: (i) Non-OCD group - patients without OCD both at baseline and follow-up (n = 269; 86.2%), (ii) Incident OCD group - patients without OCD at baseline but with OCD at follow-up (n = 17; 5.4%), (iii) Remitting OCD group - patients with OCD at baseline but without OCD at follow-up (n = 20; 6.4%), (iv) Persistent OCD group - patients with OCD both at baseline and at follow-up (n = 6; 1.9%). Rates of different DSM-IV psychotic disorders at follow-up were compared across these groups.

Results

Patients who displayed remitting OCD were not related to the development of any DSM-IV psychotic disorder. A diagnosis of incident OCD was associated with greater rates of psychotic disorders at follow-up, particularly mood disorders with psychotic features and psychotic disorders not otherwise specified (PDNOS), and greater baseline severity of general psychopathology, alogia, and avolition-apathy. Two of the six patients (40%) with persistent OCD developed schizophrenia, while only 12.5%, 5.0%, and 9.7% of incident, remitting, and non-OCD groups, respectively, exhibited the same condition at follow-up. Rates of antipsychotic use in the previous two years were not significantly different between the groups.

Conclusions

Our findings suggest that, in a cohort of individuals at UHR for psychosis, remission of OCD does not increase the risk of psychosis, while de novo OCD was associated with development of mood disorders with psychotic features and PDNOS.     

A pilot study of antipsychotic prescribing decisions for acutely-Ill hospitalized patients

Background

Evidence on antipsychotic prescribing decisions is limited. This pilot study quantified factors considered in choosing an antipsychotic and evaluated the influence of metabolic status on treatment decisions.

Methods

Prescribing decisions by 4 psychiatrists were examined based on 80 adult patients initiated on antipsychotic medication diagnosed with schizophrenia, schizoaffective disorder or bipolar disorder by DSM-IV criteria, who were admitted to an acute inpatient psychiatric program of an urban Veterans Affairs Medical Center. The primary analysis examined the association between antipsychotic treatment choice and predictions of symptom control and metabolic risk. Secondary analyses included comparison of the chosen and next best treatments in predicted symptom control and metabolic risk, the frequency of reasons cited for drug choice, and the association between treatment choice and patients' baseline metabolic parameters. Mean differences and odds-ratios (OR) with 95% confidence intervals were used to compare relationships between treatment choice, ratings of risk and metabolic data.

Results

Antipsychotic choice correlated significantly with ratings of predicted symptom control (OR = .92, p = 0.02) and metabolic risk (OR = .88, p = 0.01). Mean differences between the chosen and next best drugs were significant but small in predicted symptom control (F = 2.81, df = 3, 76; p < 0.05) compared with larger differences in anticipated metabolic risk (F = 14.80, df = 3, 76; p = 0.0001). Nevertheless, among 24 identified reasons influencing drug selection, anticipated metabolic risk of chosen antipsychotics was cited less often than efficacy measures. In contrast to psychiatrists' expectations of metabolic risk with selected treatments, we found that patients' actual baseline BMI, fasting glucose, blood pressure, and Framingham risk levels did not necessarily predict antipsychotic treatment choice independent of other factors.

Conclusion

In the context of an acute psychiatric hospitalization, pilot data suggest that predictions of symptom control and metabolic risk correlated significantly with antipsychotic choice, but study psychiatrists were willing to assume relative degrees of metabolic risk in favor of effective symptom control. However, prescribing decisions were influenced by numerous patient and treatment factors. These findings support the potential utility of the ATCQ questionnaire in quantifying antipsychotic prescribing decisions. Further validation studies of the ATCQ questionnaire could enhance translation of research findings and application of treatment guidelines.     

Thrombogenic potential of whole blood is higher in patients with acute coronary syndrome than in patients with stable coronary diseases

Introduction

Although thrombogenic potential of blood may play an important role for the onset of acute coronary syndrome (ACS), there is no established way to evaluate it by single parameter. We compared the thrombogenic potential of whole blood between patients with ACS and those with stable coronary diseases using single comprehensive parameter.

Materials and Methods

Consecutive patients with ACS (n = 146) and those with stable coronary heart diseases (control, n = 92) were prospectively examined. Thrombogenic potential of whole blood was evaluated by blood vulnerability index measured by Micro-Channel Array Flow Analyzer (MC-FAN).

Results

Blood vulnerability index was higher in ACS than in control patients (5099 ± 2278 vs. 2071 ± 389, p < 0.0001), higher in acute MI than in unstable angina patients (5693 ± 2146 vs. 3524 ± 1841, p < 0.0001), and higher in ACS patients with initial TIMI 0/1 flow grade than in those with TIMI 2/3 flow grade (6061 ± 1936 vs. 2560 ± 1301, p < 0.0001). Furthermore, blood vulnerability index decreased from acute to chronic stage in acute MI patients. Multivariate logistic regression analysis revealed that high blood vulnerability index, high LDL cholesterol, high CRP, no use of aspirin, and no use of β-blocker were the independent contributors for the onset of ACS.

Conclusion

High thrombogenic potential of whole blood evaluated by blood vulnerability index was significantly associated with ACS and was reduced from acute to chronic stage in acute MI.

Condensed Abstract

Thrombogenic potential of whole blood was evaluated by blood vulnerability index measured comprehensively by Micro-Channel Array Flow Analyzer (MC-FAN) in consecutive patients with ACS (n = 146) or stable coronary diseases (control, n = 92) prospectively. Blood vulnerability index was significantly higher in ACS patients, especially in acute MI and poor initial TIMI flow grade patients, compared with control patients; and blood vulnerability index was reduced from acute to chronic stage in acute MI patients.     

Inflammation in psychotic disorders: a population-based study

We investigated inflammatory markers in psychotic disorders and their association with metabolic comorbidity, antipsychotic medication, smoking, alcohol use, physical condition, and mood. From the population-based Finnish Health 2000 study, we identified all persons with schizophrenia (n = 45), other nonaffective psychosis (ONAP) (n = 57), affective psychosis (n = 37) and chose controls matched by age, sex, and region of residence. We found that persons with schizophrenia had significantly higher sIL-2Rα, IL-1RA and C-reactive protein (CRP), persons with ONAP significantly higher IL-1RA and CRP and persons with affective psychosis almost significantly higher TNF-α compared to their matched controls. Current antipsychotic use was associated with elevated IL-1RA and CRP. After taking metabolic and lifestyle-related variables that associated with inflammatory markers into account, only antipsychotic medication remained associated with elevated IL-1RA and TNF-α which are markers related to the activation of innate immune system. CRP was influenced by both antipsychotic medication and nonaffective psychosis. sIL-2Rα, a marker of T-cell activation, was associated with depressive symptoms, schizophrenia, and affective psychosis. We conclude that in persons with psychotic disorders, activation of mononuclear phagocyte system was mostly related to metabolic comorbidity and antipsychotic medication use, whereas T-cell activation had a more direct relationship with both psychotic disorders and depressive symptoms.     

Relationship of “prodromal” symptoms with severity and type of psychopathology in the active phase of schizophrenia

Background

Both retrospective and prospective studies have identified a broad spectrum of “prodromal” symptoms, but their relationship to those of frank psychosis remains largely unexplored.

Method

In 73 successive hospitalized patients with schizophrenia in the first or second psychotic episode and with duration of illness 3 years or less from the onset of psychosis, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, Axis I diagnoses were made. In addition, within the first 5 days from the psychotic episode's onset, symptom severity was assessed with the Positive and Negative Syndrome Scale (PANSS).

Results

Stepwise regression analyses showed that 8 prodromal symptoms carried an increased risk for high total PANSS and the components of the PANSS scores, independently of sex; 1 symptom was associated with mild psychopathology. However, the categories of negative- and positive-disorganization prodromal symptoms were not associated with the corresponding PANSS components. Similar findings were observed in the nonparanoid patients, whereas in the paranoid, only 2 nonspecific symptoms were associated with high PANSS psychopathology. In addition, there were significant associations between number of prodromal symptoms and total PANSS and the subscales positive and general scores in the patients with the nonparanoid subtypes, but there were not such associations in those with the paranoid.

Conclusions

Several prodromal symptoms, as well as the number of symptoms, are associated with the severity of the psychopathology of frank psychosis. In the nonparanoid subtypes there is a continuance in the transition from the prepsychotic to the psychotic stage, whereas in the paranoid, the transition appears to be disrupted.     

Trouble psychotique révélant une épilepsie associée à une tumeur dysembryoplasique neuroépithétliale de l’hippocampe gauche

Introduction

Psychotic symptoms are a rare but well-known complication of epilepsy. The prevalence is estimated between 4 and 9%.

Patient

We report a case of a 40-year-old patient, unrecognized epileptic, who presented an acute psychotic syndrome which seemed to be of functional origin, the EEG performed during the episode, and the cerebral CT scan being normal. Nevertheless, the clinical presentation, especially the sudden ending of delusions, led to further investigations. Careful history taking and repeated EEG recordings allowed the diagnosis of partial epilepsy that had begun 17 years earlier and symptomatic of a dysembryoplastic tumour of the left hippocampus revealed by MRI.

Discussion and conclusion

Search for an epileptic origin of an acute psychotic syndrome must always be undertaken by systematic EEG. The possibility of a symptomatic temporal tumor must not be overlooked.     

Fibrinogen and D-dimer analysis of chronic subdural hematomas and computed tomography findings: a prospective study

Objective

We investigated the relationship between fibrinolytic factors and computed tomography (CT) findings in patients with chronic subdural hematomas (CSDHs).

Methods

Thirty-one patients with CSDHs were divided on the basis of CT findings into heterogeneous and homogeneous groups. A sample from the subdural hematoma was obtained at surgery to measure the concentrations of fibrinogen and D-dimer.

Results

The mean level of fibrinogen in the heterogeneous group, including the layering (n = 4) and mixed (n = 10) type, was 88.2 ± 121.2 mg/dL, whereas in the homogeneous group, including high density (n = 2), isodensity (n = 9), and low density (n = 6) types, it was <25 mg/dL. The concentration of fibrinogen was significantly higher in the heterogeneous group than in the homogeneous group (p = 0.006). The mean level of D-dimer in the heterogeneous group was 35,407.9 ± 16,325.5 μg/L, whereas for the homogeneous group it was 1476.4 ± 2091.4 μg/L. The concentration of D-dimer was significantly higher in the heterogeneous group than in the homogeneous group (p < 0.001).

Conclusions

The layering and mixed types of CSDH exhibited higher concentrations of fibrinogen and D-dimer in subdural hematoma than the homogeneous types. These fibrinolytic factors appear to be associated with evolution in CSDHs with heterogeneous density.     

Anticoagulation therapy with combined low dose aspirin and warfarin following mechanical heart valve replacement

Introduction

This study was designed to evaluate safety and efficacy of combined low dose aspirin and warfarin therapy following mechanical heart valve replacement.

Methods

A total of 1 496 patients (686 males, mean age 35 ± 8.5 years) undergoing mechanical heart valvular replacement were randomly divided into study (warfarin plus 75-100 mg aspirin) or control (warfarin only) group. International normalized ratio (INR) and prothrombin time was maintained at 1.8-2.5 and 1.5-2.0 times of the normal value, respectively. Thromboembolic events and major bleedings were registered during follow up.

Results

Patients were followed up for 24 ± 9 months. The average dose of warfarin in the study and control group was 2.92 ± 0.87 mg and 2.89 ± 0.79 mg, respectively (p > 0.05). The overall thromboembolic events in study group were lower than in control group (2.1% vs. 3.6%, p = 0.044). No statistically significant differences were found in hemorrhage events (3.5% vs. 3.7%, p > 0.05) or mortality (0.3% vs 0.4%, p > 0.05) between the two groups.

Conclusions

Following mechanical valve replacement, combined low dose aspirin and warfarin therapy was associated with a greater reduction in thromboembolism events than warfarin therapy alone. This combined treatment was not associated with an increase in the rate of major bleeding or mortality.     

Effect of initial ziprasidone dose on treatment outcome of korean patients with acute manic or mixed episodes

Objective

We investigated the efficacy and tolerability of ziprasidone combined with divalproex to determine the relationship between the initial dose of ziprasidone and the treatment effect among Korean patients with acute bipolar manic or mixed disorders.

Methods

This study was a 6-week, open-label, prospective investigation of Korean patients with an acute manic or mixed episode of bipolar disorder. Sixty-five patients were recruited. The patients were categorized based on the initial dose of ziprasidone as follows: low (20-79 mg/day) and standard (80 mg/day). Ziprasidone was given in combination with divalproex in flexible doses, according to the clinical response and tolerability.

Results

The response and remission rates were significantly higher in the standard-dose group than the low-dose group. The combination of ziprasidone and divalproex was well-tolerated and adverse events were mostly mild with no statistically significant increase in body weight.

Conclusion

The results of this study showed that a standard starting dose of ziprasidone in combination with divalproex for bipolar disorder is more effective than a low starting dose.     

Cerebrovascular reactivity over time-course - From major depressive episode to remission

Introduction

Depression is a prospective risk factor for stroke. Little is known, however, about the pathophysiologic links leading to this association. Cerebrovascular reactivity (CVR) reflects the compensatory dilatory capacity of cerebral arterioles to a dilatory stimulus and is an important mechanism to provide constant cerebral blood flow. In the absence of major arterial stenosis, an impaired CVR has been associated with a higher risk of stroke. We hypothesized that CVR might be continuously reduced in patients with major depression even after successful remission thus contributing to the association between depression and stroke.

Materials and methods

We investigated CVR in a group of patients (N = 29) in the acute episode of depressive illness and after 21 months under euthymic condition. A healthy control group (N = 33) was investigated at comparable time intervals. All patients and controls were otherwise healthy. CVR was investigated by calculating the increase in cerebral blood flow velocity after stimulation with acetazolamide. Blood flow velocities were measured by transcranial doppler ultrasound.

Results

A group of acutely depressed patients presented a significantly reduced CVR compared to controls. On follow-up 21 months later after treatment and remission, CVR in the patient group had significantly improved, whereas CVR in the control group remained unchanged. Confounding factors had no significant influence.

Discussion

CVR is impaired during major depression. Since CVR seems to improve after treatment of depression, the contribution to an increased stroke risk among depressive patients may be true for a subgroup only and needs to be further investigated.     

Dimensions underlying psychotic and manic symptomatology: Extending normal-range personality traits to schizophrenia and bipolar spectra

Objective

Covariance among psychiatric disorders can be accounted for by higher-order internalizing, externalizing, and psychosis dimensions, but placement of bipolar disorder within this framework has been inconsistent. Moreover, whether deviations in normal-range personality can explain psychosis and vulnerability to severe mood lability, as seen in schizophrenia and bipolar disorder, remains unclear.

Methods

Exploratory factor analysis of interviewer-rated clinical symptoms in patients with schizophrenia or bipolar disorder, their first-degree biological relatives, and nonpsychiatric controls (total N = 193), followed by examination of associations between symptom dimensions and self reports on personality questionnaires.

Results

Covariance in symptoms was accounted for by five factors: positive symptoms of psychosis, negative symptoms of psychosis, disorganization, mania, and depression/anxiety. Schizophrenia and bipolar patients/relatives reported elevated negative emotionality and absorption and lower positive emotionality relative to controls. Personality did not differ between schizophrenia and bipolar patients/relatives, but there was a different pattern of associations between symptoms and personality in these groups.

Conclusions

Discrete dimensions reflecting psychotic, manic, and depressive symptoms emerge when a broad set of clinical symptoms is examined in a sample overrepresented by psychotic experiences and affective disturbances. Although normal-range personality traits index common phenotypes spanning schizophrenia and bipolar spectra, the same symptoms may carry different significance across disorders.     

Clinical characteristics influencing age at onset in psychotic disorders

Background

Age at onset of psychosis may carry clinical significance across psychotic disorders and appears to be associated with specific genetic abnormalities.

Methods

We used the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) to examine clinical characteristics contributing to age at onset variability in patients with schizophrenia (n = 80), schizoaffective disorder (n = 61), and bipolar disorder with psychotic features (n = 92).

Results

Age at onset did not differ across DSM-IV diagnostic groups. Multiple regression analyses revealed that comorbid lifetime cannabis, but not alcohol, abuse/dependence was associated with a statistically significant 3 years earlier age at onset of psychosis. Patients developed cannabis abuse/dependence an additional 3 years before psychosis. Patients with comorbid lifetime panic disorder also had a 4-year earlier age at onset of psychosis. The effects of panic disorder and cannabis abuse/dependence were independent of one another.

Conclusions

Early onset of psychosis, regardless of the specific DSM-IV diagnosis, is characterized by differential clinical features, notably a history of lifetime cannabis abuse/dependence. Panic disorder comorbidity is also associated with earlier age at onset of psychosis. Our findings indicate that examination of clinical and biological characteristics of patients with psychosis regardless of DSM-IV diagnosis can uncover relevant information.     

Reduced mismatch negativity predates the onset of psychosis

Background

Individuals with an “At Risk Mental State” have a 20-30% chance of developing a psychotic disorder within two years; however it is difficult to predict which individuals will become ill on the basis of their clinical symptoms alone. We examined whether mismatch negativity (MMN) could help to identify those who are particularly likely to make a transition to psychosis.

Method

41 cases meeting PACE criteria for the At Risk Mental State (ARMS) and 50 controls performed a duration-deviant passive auditory oddball task whilst their electroencephalogram was recorded. The amplitude of the MMN wave was compared between groups using linear regression. The ARMS subjects were then followed for 2 years to determine their clinical outcome.

Results

The MMN amplitude was significantly reduced in the ARMS group compared to controls. Of the at-risk subjects who completed followed up (n = 41), ten (24% of baseline sample) subsequently developed psychosis. The MMN amplitude in this subgroup was significantly smaller across all three recording sites (FZ, F3 and F4) than in the ARMS individuals who did not become psychotic. Conclusion: Among those with the ARMS, MMN amplitude reduction is associated with an increased likelihood of developing frank psychosis.     

Effects of haloperidol and risperidone on cerebrohemodynamics in drug-naive schizophrenic patients

Background

Use of antipsychotics may be associated with cerebrovascular adverse events in psychotic patients. In this study, the effects of haloperidol and risperidone on the cerebral hemodynamics and the possible relationships between antipsychotics and cerebrovascular risks tendency were evaluated by Transcranial Doppler ultrasonography (TCD).

Methods

Twenty drug-na?¨ve schizophrenic patients and 20 normal control subjects were included. The patients were divided into haloperidol- and risperidone-treated groups and received treatment for 8 weeks double-blindly. The subjects’ cerebral blood flow mean velocities (MV) and pulsatility index (PI) were measured weekly by TCD. The Positive and Negative Syndrome Scale for schizophrenia (PANSS) was used to assess the patients’ psychopathological symptoms.

Results

Increased MV and decreased PI were found significantly in drug-na?¨ve schizophrenic patients than normal subjects before treatment (p < 0.01). The decreased PI could be normalized after 8 weeks of antipsychotic treatment, while the increased MV could not. Treatment with haloperidol could significantly increase the PI than the treatment with risperidone (p < 0.01) throughout the treatment course. The PANSS scores of both groups were significantly improved (p < 0.05) at the endpoints of treatment.

Conclusions

Our findings indicate that haloperidol may affect the cerebral hemodynamics in drug-na?¨ve schizophrenics more prominently than that of risperidone via TCD monitoring.     

Early onset of antipsychotic response in the treatment of acutely agitated patients with psychotic disorders

OBJECTIVE: While the efficacy of antipsychotic medications for the treatment of psychosis is generally established, the speed of onset of antipsychotic action remains controversial. The objective of this study was to evaluate the early response (within the first 24 h) in psychosis with ziprasidone IM treatment, and to determine whether this early effect is distinct from a reduction in agitation symptoms. METHODS: In a 24-h, double-blind study, hospitalized patients with psychotic disorder and acute agitation were randomized to treatment with fixed doses of IM ziprasidone: 2 mg (N=38) or 20 mg (N=41). Efficacy assessments were based on the PANSS positive subscale and PANSS early psychosis factor score (conceptual disorganization, hallucinatory behavior, and unusual thought content) at 4 and 24 h. RESULTS: Ziprasidone IM demonstrated a significant dose-related effect (20 mg vs. 2 mg) on both the PANSS early psychosis factor score and the PANSS positive subscale at the first post-baseline time point (4 h), and at 24 h (all p<0.05). There was a significant direct effect of ziprasidone IM on early psychosis at 24 h (p<0.05), distinct from improvement in agitation symptoms. CONCLUSIONS: These findings suggest, in addition to an early reduction in acute agitation, ziprasidone IM may be associated with a more rapid improvement in psychotic symptoms than previously reported, thus lending further support to the emergent hypothesis of early psychosis improvement in antipsychotic treatment.     

Adjunctive antipsychotic treatment of adolescents with bipolar psychosis.

BACKGROUND: A combination of an antipsychotic medication and a mood stabilizer is often used for initial treatment of acute psychotic mania. However, the optimal duration of this adjunctive antipsychotic medication is unknown. METHOD: As part of a lithium efficacy study, acutely manic adolescents with psychotic features were given open combination treatment with lithium and an adjunctive antipsychotic medication. If the psychosis resolved, the antipsychotic medication dose was gradually tapered and discontinued after 4 weeks of therapeutic lithium levels. The subject was then given a trial of maintenance lithium monotherapy for up to 4 weeks. RESULTS: Significant improvement was seen in 64% of the sample with psychotic features after 4 weeks of combination treatment. However, few maintained their response after discontinuation of the antipsychotic medication. Successful discontinuation of antipsychotic medication in this sample was associated with first episode, shorter duration of psychosis, and the presence of thought disorder at baseline. CONCLUSIONS: Adjunctive antipsychotic medication needs to be maintained for longer than 4 weeks in the vast majority of adolescents with psychotic mania, even though the manic and psychotic symptoms have resolved and lithium treatment is maintained. Future studies to determine the optimal duration of adjunctive antipsychotic medication treatment are warranted.