Cognitive Effects of Combined Amisulpride and Quetiapine Treatment in Patients With Refractory Schizophrenia: A Naturalistic, Prospective Study.

BACKGROUND: Regarding the treatment of patients with resistant schizophrenia, different options exit, although they are supported by limited evidence. In this study, antipsychotic polypharmacy, comprising 1200 mg of amisulpride and 600 mg of quetiapine, was used. Clinical change evaluation was performed using neurocognitive evaluations. STUDY QUESTION: The use of amisulpride and quetiapine will imply a clinical improvement in patients affected by schizophrenia, which will be specially reflected in a cognitive improvement. STUDY DESIGN: Naturalistic and prospective study. Twenty-six patients were applied and assessed by a battery of neurocognitive evaluations since the pretreatment baseline until 6-month treatment. The patients had no biological response to medication, high social maladjustment, and a long clinical history of the disease. Kane and Brenner criteria for treatment-resistant schizophrenia were applied to choose the subjects. MEASURES AND OUTCOMES: The cognitive improvement will imply a significant betterment, from the pretreatment baseline until 6-month treatment, in the following cognitive tests: Stroop Test, WAIS Coding Subtest, and Comprehensive Trail Making Test (CTMT). An improvement in the Calgary Depression Scale, Simpson-Angus Scale, and Visual Analogue Scale (EVA) will also be observed. This scales were been used during the baseline, 3 months after, and then, 6 months. RESULTS: Subjects, after 6-month treatment with amisulpride and quetiapine, did show statistically significant differences in the assessed areas: WAIS Coding Subtest (P < 0.001), CTMT A and B (CTMT A P < 0.034; CTMT B P < 0.000), and Stroop Tests: Word (P < 0.001), Word-Color (P < 0.007), and Interference (P < 0.039). Furthermore, they showed a statistically significant difference in the Calgary Depression Scale (P < 0.002), Simpson-Angus Scale (P < 0.019), and EVA (P < 0.001). CONCLUSIONS: The results of this report show a cognitive and clinical improvement in refractory patients after the administration of amisulpride and quetiapine.

Life cycle and suicidal behavior among women.

It is nowadays accepted that, independently of methodological issues, women commit fewer suicides than men but make more frequent attempts. Yet, female suicidal risk varies greatly along the lifetime and is linked to the most significant moments in it. A wide analysis of the existing literature was performed to provide a narrative description on the evolution of female suicidal rates from childhood to old age, considering the milestones in their life history. A detailed analysis of gender differences in suicidal behavior is key to establish preventive measures and priorities. More specific studies are needed to adapt future interventions on female suicide.

Lack of association between testosterone and suicide attempts.

OBJECTIVE: To determine whether testosterone levels differ in male suicide attempters versus healthy controls and to explore the associations between testosterone levels and time of blood collection, and between testosterone levels and characteristics of suicide attempts. METHOD: A sample of 112 male suicide attempters was studied. Thirty-seven male blood donors were recruited as controls. RESULTS: The mean testosterone levels were 5.1 ± 2.9 ng/ml in male attempters and 4.6 ± 1.6 ng/ml in controls. Group differences in testosterone levels were not significant when we studied the interaction with time of extraction (F = 0.37; d.f. = 2; p = 0.70) or when matched by age and time of extraction (t = -0.74; d.f. = 26; p = 0.47). When partial correlations were performed correcting for the effect of time of extraction, significant partial correlations were found in testosterone levels with history of aggressive behavior and lethality of the attempt. CONCLUSIONS: When circadian variation and age were considered, we found no support for the putative role of testosterone as a biological marker of suicidal behavior. Further research should consider: (1) testosterone and neurosteroids; (2) serial determinations with a minimal time gap between the attempt and the blood extraction; (3) controls within the same time periods, and (4) other variables that may affect testosterone levels, such as body mass index, physical activity and sleep disturbances.

Suicide attempts among women during low estradiol/low progesterone states.

The relationship between the menstrual cycle and risk for suicidal behaviors is not clear. The aim of this study is to determine whether perimenstrual phases in fertile women are associated with acute risk for suicide attempt and explore whether risk is elevated during low estradiol/low progesterone states. Women (N=431) recruited within 24h of a suicide attempt were assessed for psychopathology, suicidal behavior and LH, FSH, estradiol and progesterone blood levels. Among fertile women (N=281/431), suicide attempts were more likely to occur during menses (26%, 72/281 observed vs. 15%, 43/281 expected attempts; p<0.001). Compared to women whose attempts occurred during other phases, women who attempted suicide during low estradiol/low progesterone states (menstrual phase, amenorrhea and menopause) reported severe suicide intent, a measure that may be predictive of eventual suicide death. Suicide attempts among women are more likely when estrogen and progesterone levels are low and attempts made under these conditions are associated with greater severity. Low gonadal hormone levels may constitute a key factor in the neurobiological basis of suicidal behavior among women, suggesting a novel, testable hypothesis regarding the underpinnings of suicidal acts.

Nucleotide variation in central nervous system genes among male suicide attempters.

Despite marked morbidity and mortality associated with suicidal behavior, accurate identification of individuals at risk remains elusive. The goal of this study is to identify a model based on single nucleotide polymorphisms (SNPs) that discriminates between suicide attempters and non-attempters using data mining strategies. We examined functional SNPs (n = 840) of 312 brain function and development genes using data mining techniques. Two hundred seventy-seven male psychiatric patients aged 18 years or older were recruited at a University hospital psychiatric emergency room or psychiatric short stay unit. The main outcome measure was history of suicide attempts. Three SNPs of three genes (rs10944288, HTR1E; hCV8953491, GABRP; and rs707216, ACTN2) correctly classified 67% of male suicide attempters and non-attempters (0.50 sensitivity, 0.82 specificity, positive likelihood ratio = 2.80, negative likelihood ratio = 1.64). The OR for the combined three SNPs was 4.60 (95% CI: 1.31-16.10). The model's accuracy suggests that in the future similar methodologies may generate simple genetic tests with diagnostic utility in identification of suicide attempters. This strategy may uncover new pathophysiological pathways regarding the neurobiology of suicidal acts.

Low serum cholesterol may be associated with suicide attempt history.

OBJECTIVE: This case-control study used both healthy blood donors and psychiatric inpatients as controls and controlled for gender, age, low body mass index, alcohol and nicotine use, and aggressive and impulsive behaviors to examine the association between low serum cholesterol levels and suicide attempts. METHOD: At a Spanish general hospital, the recruitment included 417 patients with suicide attempt history (138 men and 279 women), 155 psychiatric inpatient controls without suicide history (68 men and 87 women), and 358 healthy controls (220 men and 138 women). All participants were aged 18 years or older. To study the association between low serum cholesterol levels (fasting < 160 mg/dL) and suicide attempts, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in univariate analyses. Logistic regression models adjusted ORs for confounding variables in male, female, and total samples. The study was conducted from January 1996 to December 1997. RESULTS: The ORs in the total sample (for psychiatric and healthy controls respectively) were 1.8 (95% CI = 1.2 to 2.9, p = .007) and 1.9 (95% CI = 1.4 to 2.6, p < .001) for the univariate analyses, and 1.6 (95% CI = 0.95 to 2.6, p = .08) and 1.6 (95% CI = 1.0 to 2.4, p = .04) after variable adjustment. In women, the adjusted OR was 1.8 (95% CI = 0.90 to 3.5, p = .09) for psychiatric controls. In men, the adjusted OR was 2.0 (95% CI = 0.99 to 4.1, p = .05) for healthy controls. All ORs were in the hypothesized direction but some subsamples appeared too small to reach significance. CONCLUSION: This study, somewhat limited by the small sample size, suggests that low cholesterol may be associated with suicide attempts. Low cholesterol level in suicide attempts may be more important from a pathophysiologic than from a diagnostic point of view.

Dysregulation of emotional response in current and abstinent heroin users: negative heightening and positive blunting.

OBJECTIVE: Evidence suggests that abstinent opioid users have abnormal emotional response to natural reinforcing stimuli, but little is known about the emotional response of subjects currently using heroin. Abnormal emotional experience could underlie poor sensitivity to negative events related to heroin use and reduced ability to consider alternative reinforcers to help overcome addiction. In this paper, we will assess the subjective response of current and abstinent heroin users exposed to emotionally competent positive and negative stimuli. MATERIALS AND METHODS: We administered the "Clinical Instrument for Emotional Response Evaluation" (including neutral, pleasant, and unpleasant images from the International Affective Picture System) to 22 current opioid users enrolled in a clinical trial using controlled prescribed heroin and 41 abstinent opioid users enrolled in residential treatment. The dependent variable was their subjective response to the images measured with the Self-Assessment Manikin, a scale designed to rate the International Affective Picture System (IAPS) images in the three dimensions of emotion: valence, arousal, and dominance. We compared these ratings with IAPS normative values for healthy participants. RESULTS: Significant group x emotional condition interactions were found in the arousal dimension. Post-hoc tests showed that compared to healthy participants, both current and abstinent heroin users had greater emotional response to neutral images and lower response to pleasant images. Furthermore, current opioid users had higher emotional response to unpleasant images when compared to healthy participants and lower response to pleasant images when compared to abstinent users. CONCLUSIONS: Current opioid users have abnormal emotional experience, characterized by heightened response to unpleasant stimuli and blunted response to pleasant stimuli.

Low plasma cholesterol levels in suicidal males: a gender- and body mass index-matched case-control study of suicide attempters and nonattempters.

Findings from animal and human studies suggest an association between low cholesterol levels and suicidal behaviors. The purpose of this case-control study was to test whether cholesterol levels in suicide attempters are lower than in controls without suicide attempt history matched by gender, age, and body mass index (BMI). Suicide attempters (n=177: 68 men and 109 women) and controls (177 blood donors) were assessed. Serum cholesterol levels were significantly lower in suicide attempters than in controls. After gender stratification, the difference remained significant in men, but not in women.

Association between obsessive-compulsive disorder and a variable number of tandem repeats polymorphism in intron 2 of the serotonin transporter gene.

BACKGROUND: Pharmacological studies indicate a dysregulation of the serotonergic system in obsessive-compulsive disorder (OCD). A variable number tandem repeats (VNTR) polymorphism with three alleles (Stin2.9, Stin2.10, Stin2.12) has been described in intron 2 of the serotonin transporter (5-HTT) gene. This polymorphism has been associated with unipolar depression, bipolar disorder, schizophrenia, and anxiety disorders including OCD. METHODS: The association between OCD and the polymorphism is examined in 97 OCD patients, 578 psychiatric controls and 406 healthy controls, all Spanish Caucasians. RESULTS: Genotype frequencies for the polymorphism were significantly different in OCD patients, psychiatric patients and controls. There was a significant excess of 12/12 and 12/10 genotypes in OCD patients compared to psychiatric patients and controls. CONCLUSIONS: Our results indicate a possible association between the Stin2.12 allele of the VNTR polymorphism and OCD.

Premenstrual symptoms and luteal suicide attempts.

OBJECTIVE: If premenstrual symptoms (PMS) are temporally and specifically associated with suicidal attempts, suicide attempts in women with PMS should occur more frequently in the luteal phase. METHOD: In a general hospital, 125 fertile female suicide attempters (and 83 blood donors as controls) with regular menstrual cycles were prospectively studied. A retrospective DSM-IV diagnosis of Premenstrual Dysphoric Disorder (PMDD) was made. RESULTS: Attempts during the luteal phase were not more frequent in females with PMDD (34%,23/68) than in those without PMDD (35%, 20/57). The sample had enough power to detect medium and large effect sizes. As expected, there was a significantly higher frequency of PMDD in suicide attempters than in the controls (54% vs 6%; Fisher's exact test, p < or = 0.001). CONCLUSION: This study was limited by the use of retrospective PMDD diagnosis but suggests that PMDD may not be associated with suicidal acts during the luteal phase,when PMS are present.

Association between the menses and suicide attempts: a replication study.

OBJECTIVE: In our prior (first) study, suicide attempts were associated with the menses. The main hypothesis of this replication (second) study is that the proportion of suicide attempters during the menses is significantly higher than the expected probability in the general population. METHODS: Using the same methodology and setting, this replication naturalistic study included 120 fertile female suicide attempters with regular menstrual cycles during a 1-year period in the emergency room of a general hospital in Madrid, Spain, serving a catchment area of 500,000 people. RESULTS: The significant increase in probability of attempting suicide during the menses for the first study was 1.61; for the second study, 1.72; and for both studies combined, 1.68 (95% confidence interval, 1.27-2.09). Thus, using the combined results, the probability of attempting suicide during the menses was 1.68 times higher than the overall probability of attempting suicide for any fertile women. In the catchment area, the population rate of fertile women arriving at the hospital after a suicide attempt was 166 per 100,000. The probability for women during the menses arriving at the hospital after a suicide attempt was significantly higher, 279 per 100,000 (1.68 x 166 per 100,000). The 95% confidence interval was 211 to 347 per 100,000. CONCLUSIONS: Despite inherent limitations, this naturalistic study replicates a small but significant increase of suicide attempts during the menses.

A pilot study on a gene-hormone interaction in female suicide attempts.

This one-year naturalistic study included all suicide attempters in a catchment area. In the first published set of analyses, an association between menses and suicide attempts was replicated. According to the polymorphism of the serotonin transporter promoter area, the subjects can be classified as S individuals (s/s or s/l) or L individuals (l/l). In the second published set of analyses, L females appeared protected from suicide attempts since they were underrepresented among female (and not male) attempters. This new, unpublished third set of analyses tested for an interaction between the same polymorphism and low hormonal activity (during menses and menopause). In fertile female attempters, the proportion of L women in the menses (41%, 7/17) was significantly higher than expected in the population (15.5 %) and almost significantly higher than in S female attempters (22%,19/87). L females were also overrepresented in postmenopausal attempters. Despite sample size limitations, this gene-hormone interaction needs to be further investigated in female suicide attempters.