Cannabidiol as an Adjunctive Treatment for Acute Bipolar Depression: A Pilot Study: Le cannabidiol comme traitement d'appoint de la dépression bipolaire aiguë : une étude pilote.

OBJECTIVE: The treatment of bipolar depression remains challenging due to the limited effective and safe therapeutic options available; thus, developing newer treatments that are effective and well tolerable is an urgent unmet need. The objective of the present trial was to test 150 to 300 mg/day of cannabidiol as an adjunctive treatment for bipolar depression. METHOD: A randomized, double-blind, placebo-controlled pilot study to assess the efficacy of adjunctive cannabidiol in bipolar depression was used. Efficacy parameters were changes in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to week 8. Secondary outcomes included response and remission rates, changes in anxiety and psychotic symptoms, and changes in functioning. Patients continued double-blind treatment until week 12 to monitor for adverse effects, laboratory analysis, and manic symptoms. Study registry: NCT03310593. RESULTS: A total of 35 participants were included. MADRS scores significantly decreased from baseline to the endpoint (placebo, -14.56; cannabidiol, -15.38), but there was no significant difference between the groups. Similarly, there were no other significant effects on the secondary outcomes. However, an exploratory analysis showed a significant effect of cannabidiol 300 mg/day in reducing MADRS scores from week 2 to week 8 (placebo, -6.64; cannabidiol, -13.72). There were no significant differences in the development of manic symptoms or any other adverse effects. CONCLUSION: Cannabidiol did not show significantly higher adverse effects than placebo. Despite the negative finding on the primary outcome, an exploratory analysis suggested that cannabidiol should be further studied in bipolar depression in higher doses of at least 300 mg/day and under research designs that could better control for high placebo response.

Differential biomarker signatures in unipolar and bipolar depression: A machine learning approach.

OBJECTIVE: This study used machine learning techniques combined with peripheral biomarker measurements to build signatures to help differentiating (1) patients with bipolar depression from patients with unipolar depression, and (2) patients with bipolar depression or unipolar depression from healthy controls. METHODS: We assessed serum levels of interleukin-2, interleukin-4, interleukin-6, interleukin-10, tumor necrosis factor-α, interferon-γ, interleukin-17A, brain-derived neurotrophic factor, lipid peroxidation and oxidative protein damage in 54 outpatients with bipolar depression, 54 outpatients with unipolar depression and 54 healthy controls, matched by sex and age. Depressive symptoms were assessed using the Hamilton Depression Rating Scale. Variable selection was performed with recursive feature elimination with a linear support vector machine kernel, and the leave-one-out cross-validation method was used to test and validate our model. RESULTS: Bipolar vs unipolar depression classification achieved an area under the receiver operating characteristics (ROC) curve (AUC) of 0.69, with 0.62 sensitivity and 0.66 specificity using three selected biomarkers (interleukin-4, thiobarbituric acid reactive substances and interleukin-10). For the comparison of bipolar depression vs healthy controls, the model retained five variables (interleukin-6, interleukin-4, thiobarbituric acid reactive substances, carbonyl and interleukin-17A), with an AUC of 0.70, 0.62 sensitivity and 0.7 specificity. Finally, unipolar depression vs healthy controls comparison retained seven variables (interleukin-6, Carbonyl, brain-derived neurotrophic factor, interleukin-10, interleukin-17A, interleukin-4 and tumor necrosis factor-α), with an AUC of 0.74, a sensitivity of 0.68 and 0.70 specificity. CONCLUSION: Our findings show the potential of machine learning models to aid in clinical practice, leading to more objective assessment. Future studies will examine the possibility of combining peripheral blood biomarker data with other biological data to develop more accurate signatures.

Postural changes in different stages of schizophrenia is associated with inflammation and pain: a cross-sectional observational study.

OBJECTIVES: To assess the relationship between posture and inflammatory response markers (C-reactive protein [CRP] and von Willebrand factor [vWF]) in schizophrenics. METHODS: Forty patients with stable schizophrenia were divided into early-stage (<10 years since first episode, n = 15) and late-stage (≥10 years since first episode, n = 25) groups. Both groups were compared to controls (n = 26). All participants underwent postural assessment by biophotogrammetry. Cases alone underwent blood collection. The significance level was set at 5%, and analyses were carried out in SPSS 18.0. RESULTS: In the early-stage group, 15 postural angles were significantly different from their reference ranges, whereas in the late-stage group, only seven angles were significantly different. In comparison with the control group, only six angles were significantly different. There was no difference in inflammation markers between the early- and late-stage groups. However, CRP levels were higher in cases with greater disease severity, and vWF was associated with forward head posture. Pain correlated with five postural angles, and late-stage patients reported more pain than early-stage cases. CONCLUSIONS: CRP was associated with disease severity, while vWF and pain were associated with forward head posture, hyperlordosis and scoliosis, suggesting an association between vascular inflammation and pain, with an influence on posture.

Impaired endoplasmic reticulum stress response in bipolar disorder: cellular evidence of illness progression.

Bipolar disorder (BD) is a severe chronic psychiatric disorder that has been associated with cellular dysfunctions related to mitochondria, neurotrophin levels, and oxidative stress. Evidence has shown that endoplasmic reticulum (ER) stress may be a common pathway of the cellular changes described in BD. In the present study we assessed unfolded protein response (UPR) and the effects of this cellular process on lymphocytes from patients with BD. We also evaluated whether the stage of chronicity of BD was associated with changes in UPR parameters. Cultured lymphocytes from 30 patients with BD and 32 age- and sex-matched controls were treated with tunicamycin, an ER stressor, for 12 or 24 h to measure levels of UPR-related proteins (GRP78, eIF2α-P, and CHOP) using flow cytometry, and for 48 h to analyse ER stress-induced cell death. In healthy controls but not in patients we found an increase in levels of GRP78, eIF2α-P, and CHOP after ER stress induction. In addition, tunicamycin-induced cell death was significantly higher in patients compared to controls. More importantly, early-stage patients did not differ from controls while the late-stage patients showed an impaired ER stress response. Thus, dysfunction in ER-related stress response may be associated with decreased cellular resilience in BD and illness progression.

Measurement methods of BDNF levels in major depression: a qualitative systematic review of clinical trials.

There is evidence that the brain-derived neurotrophic factor (BDNF) has implications for the pathophysiology of major depressive disorders (MDD). Measures of BDNF levels are highly dependent on the methodologies used and these vary among different studies. Therefore, the aim of this study was to carry out a descriptive analysis of the methodologies used to measure BDNF in clinical trials (CT) in patients with the diagnosis of major depression. We conducted a qualitative systematic review of CT that included samples of subjects diagnosed with major depression and evaluated the BDNF levels as an outcome. The search was performed on Pubmed, Scielo, Psychinfo and Lilacs. The selected articles were analyzed according to the CONSORT Statement and their methods of BDNF collection and analysis were described. Twenty-eight studies were included in the final analysis. Of those, 6 trials (21.4%) involved non-pharmacological interventions and only half had the MDD diagnosis based on structured interview. Trials used different methods to evaluate BDNF levels: most of them verified serum BDNF levels, 17 (60.7%) trials mentioned that measured BDNF levels in duplicate and 9 (32.1%) collected blood in fasting. A variety of methods for BDNF collection and analysis was used in the different studies, making it difficult to compare results. However, despite of the methodology, BDNF seems to increase after treatment for major depression.

Ketamine study: Protocol for naturalistic prospective multicenter study on subcutaneous ketamine infusion in depressed patients with active suicidal ideation.

Background: Psychiatric disorders are associated with more than 90% of reported suicide attempts worldwide, but few treatments have demonstrated a direct effect in reducing suicide risk. Ketamine, originally an anesthetic, has been shown anti-suicide effects in clinical trials designed to treat depression. However, changes at the biochemical level were assessed only in protocols of ketamine with very limited sample sizes, particularly when the subcutaneous route was considered. In addition, the inflammatory changes associated with ketamine effects and their correlation with response to treatment, dose-effect, and suicide risk warrant further investigation. Therefore, we aimed to assess whether ketamine results in better control of suicidal ideation and/or behavior in patients with depressive episodes and whether ketamine affects psychopathology and inflammatory biomarkers. Materials and methods: We report here the design of a naturalistic prospective multicenter study protocol of ketamine in depressive episodes carried out at Hospital de Clínicas de Porto Alegre (HCPA) and Hospital Moinhos de Vento (HMV). The study was planned to recruit adult patients with Major depressive disorder (MDD) or Bipolar disorder (BD) types 1 or 2, who are currently in a depressive episode and show symptoms of suicidal ideation and/or behavior according to the Columbia-Suicide Severity Rating Scale (C-SSRS) and have been prescribed ketamine by their assistant psychiatrist. Patients receive ketamine subcutaneously (SC) twice a week for 1 month, but the frequency can be changed or the dose decreased according to the assistant physician's decision. After the last ketamine session, patients are followed-up via telephone once a month for up to 6 months. The data will be analyzed using repeated measures statistics to evaluate the reduction in suicide risk as a primary outcome, as per C-SSRS. Discussion: We discuss the need for studies with longer follow-ups designed to measure a direct impact on suicide risk and that additional information about the safety and tolerability of ketamine in particular subset of patients such as those with depression and ideation suicide. In line, the mechanism behind the immunomodulatory effects of ketamine is still poorly understood. Trial registration: https://clinicaltrials.gov/, identifier NCT05249309.

Cognitive impairment in school-aged children with early trauma.

Exposure to traumatic events during childhood is often associated with the development of psychiatric disorders, cognitive impairment, and poor functioning in adulthood. However, few studies have examined cognitive function, including executive function, memory, and attention, in school-aged children with early trauma compared with age- and sex-matched controls. We recruited 30 medication-naive children between 5 and 12 years of age with a history of early severe trauma from a foster care home, along with 30 age- and sex-matched controls. Psychiatric diagnoses were based on Kiddie Schedule for Affective Disorders and Schizophrenia Epidemiologic Version (K-SADS-E) for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and were confirmed with a clinical interview. The neuropsychologic battery was tailored to assess broad cognitive domains such as learning/working memory, executive function, attention, verbal/premorbid intellectual functioning, and impulsivity. There was a higher prevalence of subsyndromal symptoms in children with a history of childhood trauma, although they rarely met all of the diagnostic criteria for a disorder. Moreover, lower estimated intellectual functioning scores were associated with subsyndromal symptoms in children with a history of trauma, and they performed more poorly on the Digits Span Test of the Wechsler Intelligence Scale for Children-III Edition, suggesting attention impairment. There is a high prevalence of subsyndromal symptoms in school-aged children with trauma and an attention impairment, which may contribute to a cumulative deficit early in cognitive development. These findings further support the need for early interventions that can prevent cognitive impairment when childhood trauma occurs.

Pharmacological treatment of bipolar depression: qualitative systematic review of double-blind randomized clinical trials.

Randomized clinical trial (RCT) is the best study design for treatment-related issues, yet these studies may present a number of biases and limitations. The objective of this study is to carry out a qualitative analysis of RCT methodology in the treatment of bipolar depression (BD). A systematic review covering the last 20 years was performed on PubMed selecting double-blind RCTs for BD. The identification items of the articles, their design, methodology, outcome and grant-related issues were all analyzed. Thirty articles were included, all of which had been published in journals with an impact factor >3. While almost half studies (46.7%) used less than 50 patients as a sample, 70% did not describe or did not perform sample size calculation. The Last Observation Carried Forward (LOCF) method was used in 2/3 of the articles and 53.4% of the studies had high sample losses (>20%). Almost half the items were sponsored by the pharmaceutical industry and 33.3% were sponsored by institutions or research foundations. Articles on the pharmacological treatment of BD have several limitations which hinder the extrapolation of the data to clinical practice. Methodological errors and biases are common and statistical simplifications compromise the consistency of the findings.

Symptom dimensional approach and BDNF in unmedicated obsessive-compulsive patients: an exploratory study.

UNLABELLED: IntroductionThe dimensional approach of the obsessive-compulsive symptoms may help to find more homogeneous groups of patients. The brain derived neurotrophic factor (BDNF) may help to identify neurobiological differences between obsessive-compulsive symptom dimensions. METHODS: We compared serum BDNF (pg/µg) levels of 25 unmedicated patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for obsessivecompulsive disorder (OCD) and 25 controls, using the Dimensional Yale-Brown Obsessive-Compulsive Scale, the Yale-Brown Obsessive-Compulsive Scale and the Beck's Anxiety and Depression Inventories. RESULTS: There were no sociodemographic differences between the groups. The standard error of mean serum BDNF levels were reduced in unmedicated OCD patients (0.47+0.038) when compared to healthy controls (0.75+0.060) (P<.001). The patients with the presence of sex/religion obsessive-compulsive symptoms (OCS) dimension (P=.002), with chronic course of OCS (P=.022) and the presence of lifetime major depression (P=.016) and social anxiety (P=.030) presented higher levels of BDNF than OCD patients without those features. The severity of aggression (P=.039) and sex/religion (P<.001) OCS dimension presented direct (moderate and strong, respectively) correlation with serum BDNF levels in this sample. Serum BDNF levels were decreased in OCD patients when compared to healthy controls.Discussion/ConclusionSexual and religious content of symptoms and aggression and sex/religion dimensions severity should be better explored, since these specific OCS dimensions could be based on neurocircuits diverse from those of the other OCS dimensions.

Validity of a short functioning test (FAST) in Brazilian outpatients with bipolar disorder.

OBJECTIVES: As the use of functioning outcomes is increasingly being advocated in multinational clinical trials and comparative studies, making available instruments with known validity and reliability in several languages is required. Here we present data on the Portuguese validation of the Functioning Assessment Short Test (FAST), which was explicitly designed to gauge functioning dimensions empirically linked to bipolar disorder. METHODS: One hundred patients with bipolar disorder and matched controls were assessed with the FAST, which was evaluated regarding discriminant, content and construct validity, concurrent validity with functioning instruments, internal consistency and test-retest reliability. RESULTS: The FAST displayed a five-factor structure very similar to its conceptualization, successfully discriminated patient and control groups, and correlated highly with other functioning measures; it also showed excellent test-retest reliability and internal consistency. CONCLUSIONS: The FAST is a measure with sufficient validity and reliability, with potential for the use in international clinical trials and comparative studies.

Sleep in bipolar patients.

BACKGROUND: Sleep disturbance has been described in bipolar disorder (BPD). Specific complaints may include frequent nighttime awakenings, poor quality of sleep, reduction in total sleep time, and nightmares. Most patients with BPD also report insomnia when in depression, but a significant percentage of patients report hypersomnia symptoms with prolonged nighttime sleep, difficulty in wakening, and excessive daytime sleepiness. OBJECTIVES: The present study aims to investigate whether bipolar patients with sleep disorders presented impairment in quality of life, disability, and global function. METHODS: One hundred ninety bipolar patients type-I diagnosed by application of Structured Clinician Interview for DSM-IV Disorders (SCID), were distributed in two groups based on absence or presence of sleep disorders. Quality of life, disability, and global dysfunction were evaluated using the Health Organization's Quality of Life instrument (WHOQOL-Brief), the Sheehan Disability Scale, and the Global Assessment of Functioning (GAF), respectively. RESULTS: Sleep complaints have negative influence on general quality of life, observed by decreased scores in WHOQOL and GAF domains and increased Sheehan scores, indicating the importance of maintenance of normal sleep in bipolar patients. CONCLUSION: Our results suggest that sleep complains impair quality of life and global function. Collectively, further studies are warranted to investigate the impairment of sleep disturbance on others neurotrophic factors and neurochemical pathways.

Proinflammatory and anti-inflammatory biomarkers in schizophrenia and influence of simvastatin on the interleukin-6.

The present study sought to assess biomarkers of inflammation in stable patients with schizophrenia (SZ) on clozapine therapy. We recruited 60 outpatients with SZ and 60 healthy controls, matched for sex and age. Compared with controls, patients had significantly increased concentrations of interleukin-6 and tumor necrosis factor-α. Interestingly, patients on simvastatin had lower interleukin-6 levels compared with patients not on simvastatin and controls. This study corroborated previous evidence for increased inflammatory biomarkers in SZ and detected a potential anti-inflammatory action of simvastatin in patients with a clinical diagnosis of SZ on clozapine therapy.

Effects of lithium and valproate on serum and hippocampal neurotrophin-3 levels in an animal model of mania.

It has been demonstrated that lithium (Li) and valproate (VPT), first line mood stabilizers, increase BDNF content in rat hippocampus and frontal cortex, which suggests that the regulation of neurotrophic factors might be associated with their pharmacological effects. In sight of the scarcity of studies with other neurotrophins, and the possible relevance of multiple neurotrophic signaling systems in bipolar disorder we investigated the effects of Li and VPT on NT-3 levels in rat serum and hippocampus, using an animal model of mania induced by amphetamine (AMPH). In the reversal model, adult male Wistar rats received AMPH or saline for 14 days, and between the 8th and 14th days, animals were treated with Li, VPT or saline. In the prevention model, rats were pretreated with Li, VPT or saline, and between the 8th and 14th days, the animals received AMPH or saline. Li increased serum and hippocampal NT-3 levels in all conditions, whereas VPT increased hippocampal NT-3 in the prevention model only. Li reversed AMPH changes in NT-3 in the reversal model, and VPT prevented AMPH changes in NT-3 in the prevention model. These results suggest that both Li and VPT modulate serum and central (hippocampal) NT-3 levels, and further support that the regulation of neurotrophic signaling systems may be related to the mechanisms of action of mood stabilizers.

Decreased serum neurotrophin 3 in chronically medicated schizophrenic males.

There is evidence that major psychiatric disorders such as schizophrenia (SZ) are associated with deregulation of synaptic plasticity with downstream alterations of neurotrophins. NT3 is an important neurotrophin in the central nervous system, and performs key biological functions, such as promoting the survival, differentiation, and plasticity of neurons. NT3 has a central role in the early neuronal development; enhancing the survival of dopaminergic neurons, suggesting possible involvement in the physiopathology of dopamine related neuropsychiatric disorders such as SZ. Variations in the NT3 gene increase the risk of SZ. Three groups of chronically medicated DSM-IV patients with SZ, on treatment with clozapine (n=12), haloperidol (n=12), risperidone (n=12) and 10 healthy controls had 5 ml blood samples collected by venipuncture. NT3 serum levels were assessed using sandwich-ELISA and were significantly lower in SZ patients (p<0.005) when compared to either controls. These findings suggest that the NT3 signaling system may play a role in the pathophysiology of SZ and might be related to the course of illness or to treatment variables. Longitudinal studies are warranted.

Elevated serum superoxide dismutase and thiobarbituric acid reactive substances in different phases of bipolar disorder and in schizophrenia.

UNLABELLED: There is an increasing body of evidence suggesting that oxidative stress may play a role in the pathophysiology of both schizophrenia (SZ) and bipolar disorder (BD). METHODS: We compared the antioxidant enzyme, serum superoxide dismutase (SOD) and the lipid peroxidation product, thiobarbituric acid reactive substances (TBARS) as assessed in depressed (N=21), manic (N=32) and euthymic (N=31) bipolar patients, and in chronically medicated patients with schizophrenia (N=97), all fulfilling DSM-IV diagnostic criteria, and a group of healthy controls (N=32). RESULTS: Serum SOD (U/mg protein) activity was significantly increased (p<0.001) in manic (7.44+/-3.88) and depressed (6.12+/-4.64) BD patients and SZ (9.48+/-4.51) when compared to either controls (1.81+/-0.63) or euthymic (2.75+/-1.09) BD patients. TBARS (mol/L) levels were significantly higher in the SZ group (4.95+/-1.56, p=0.016), bipolar euthymic (6.36+/-1.46, p<0.001), bipolar manic (7.54+/-1.74, p<0.001), and bipolar depressed patients (5.28+/-1.54, p=0.028) compared to controls (3.96+/-1.51). DISCUSSION: Our findings show increased SOD activity in SZ, as well as in depressed and manic bipolar patients, but not in euthymic BD subjects. This suggests a dysregulation in oxidative defenses in both disorders. It is likely that such changes reflect state changes in bipolar disorder. It is possible that this is a compensatory response to the oxidative stress that occurs in the acute phase of bipolar episodes. TBARS results show increases in lipid peroxidation in mania. TBARS levels in SZ and in euthymic as well as depressed individuals with BD were higher than in controls. This suggests persistent increases in SZ, which may reflect ongoing symptomatology or treatment, and a state dependent gradient in BD, with greatest oxidative stress in mania. These data support oxidative biology as both a key component of the pathophysiology of both BD and SZ, and the use of agents that modulate oxidative biology as a promising avenue for intervention in both disorders.

Serum levels of brain-derived neurotrophic factor in schizophrenia on a hypocaloric diet.

Dietary factors influence BDNF in animal studies, but there is no comparable data in clinical populations. We examined the effect of a dietary intervention on BDNF serum levels in 67 DSM-IV schizophrenic outpatients (51 males and 16 females). Two groups were assessed in a cross-sectional study: one on a hypocaloric diet (HD) and the other not on a hypocaloric diet. Weight, height and BMI data were collected concurrently with 5-ml blood sampling of each subject. BDNF levels were measured with a sandwich-ELISA. The blood sample was obtained a minimum of one month after the exposure to dietary intervention. Serum BDNF levels were significantly higher in patients on the HD (p=0.023). Additional research examining the interaction among patterns of nutritional food behavior and underlying physiopathology may result in insights upon which evidence-based decisions regarding dietary interventions can be made in people identified with major psychiatric disorders, such as schizophrenia.

The impact of co-morbid alcohol use disorder in bipolar patients.

Alcohol use is highly prevalent in patients with bipolar disorder (BD) and is associated with significant mortality and morbidity. The detrimental effects of each condition are compounded by the presence of the other. The objective of this study was to examine the impact of alcohol abuse and of alcohol dependence in BD in a Brazilian sample, as indicated by clinical severity, functional impairment, and quality of life (QOL). A cross-sectional survey of 186 bipolar outpatients were interviewed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders-4th Edition. The primary outcome measures were functioning, as indicated by the Global Assessment of Functioning Scale scores and QOL, as indicated by the World Health Organization Quality of Life Instrument. Secondary outcomes were clinical severity features. Alcohol abuse and dependence were associated with male gender, lower education, earlier age of onset, psychosis within first episode, depressive symptoms, and worse functioning. In addition, the presence of alcohol abuse or dependence was associated with remarkably high rates of suicide attempt. Our findings suggest that the co-occurrence of alcohol abuse/dependence with BD increases the risk for suicide attempt, which may reflect in part the greater severity of symptoms and impaired functioning. This subgroup of bipolar patients requires a treatment tailored to address both conditions.

Cognitive impairment in a Brazilian sample of patients with bipolar disorder.

OBJECTIVE: Persistent neurocognitive deficits have been described in bipolar mood disorder. As far as we are aware, no study have examined whether the cognitive impairment is presented in the same way in a Brazilian sample. METHOD: Cognitive function of 66 patients with bipolar disorder (32 with depressive symptoms and 34 euthymic) and 28 healthy subjects was examined using a complete cognitive battery. RESULTS: Patients with bipolar disorder presented a significantly poorer performance in eight of the 12 subtests when compared to healthy subjects. There was no significant difference between the subgroups of patients. These patients showed impairment in both verbal and non-verbal cognitive function. CONCLUSION: Cognitive impairment was found in both groups of patients with bipolar disorder. The findings described here suggest an overall impairment of cognitive function, independent of mood symptoms. This is in line with data showing that cognitive deficits may be a persistent characteristic of bipolar disorder.

Differences in coping strategies in adult patients with bipolar disorder and their first-degree relatives in comparison to healthy controls.

INTRODUCTION: The objective of this study was to compare patients with bipolar disorder (BD), their first-degree relatives and a group of healthy controls in terms of use of adaptive and maladaptive coping strategies, exploring differences between specific types of strategies and their correlations with clinical variables. METHODS: This was a cross-sectional study enrolling 36 euthymic patients with BD, 39 of their first-degree relatives and 44 controls. Coping strategies were assessed using the Brief COPE scale. RESULTS: Significant differences were detected in the use of adaptive and maladaptive strategies by patients, their first-degree relatives and controls. Patients used adaptive strategies less often than the patients' relatives (p<0.001) and controls (p = 0.003). There was no significant difference between first-degree relatives and controls (p=0.707). In contrast, patients (p<0.001) and their relatives (p=0.004) both exhibited higher scores for maladaptive coping than controls. There was no significant difference regarding the use of maladaptive strategies between patients and their relatives (p=0.517). CONCLUSIONS: First-degree relatives were at an intermediate level between patients with BD and controls regarding the use of coping skills. This finding supports the development of psychosocial interventions to encourage use of adaptive strategies rather than maladaptive strategies in this population.

Increased cocaine and amphetamine-regulated transcript cord blood levels in the newborns exposed to crack cocaine in utero.

BACKGROUND: Cocaine and amphetamine-regulated transcript (CART) is an endogenous antioxidant present since the embryonic period. CART is activated by high levels of dopamine and might be of interested in understanding the changes in the REDOX system associated with crack/cocaine intake. The goal of this study was to determine whether exposure to crack in utero is associated with increased CART levels. METHODS: In this cross-sectional study with consecutive sampling, we compared the umbilical cord blood (UCB) CART levels (µg/mL) of newborns exposed to crack/cocaine in utero (EN, n = 57) to levels in non-exposed newborns (NEN, n = 99). In addition, we compared serum CART levels between EN and NEN mothers, in the immediate postpartum period. Potential confounders, such as perinatal data (e.g., weight, Apgar, etc.), psychopathology (DSM-IV), and use of drugs other than crack (ASSIST) were assessed. RESULTS: According to general linear model analysis, the adjusted mean CART was significantly higher in EN (0.180, 95% CI 0.088-0.272) than in NEN (0.048, 95% CI 0.020-0.076; p < 0.002; d = 0.68). The difference in CART levels between EN and NEN mothers was not significant (p ≥ 0.05). CONCLUSION: The increase in CART levels in EN UBC suggests a response to crack/cocaine-induced oxidative stress during gestational period, as a potential attempt of neuroprotection. In adult women in puerperium, however, this endogenous antioxidant recruitment does not seem to operate.