Clinical features and predictors of non-response in severe catatonic patients treated with electroconvulsive therapy.

OBJECTIVE: To explore the demographic and clinical features of severe catatonic patients, comparing responders and non-responders to ECT in order to detect possible predictors of non-response. METHODS: This naturalistic study included 59 catatonic inpatients with a diagnosis of mood disorder according to DSM-IV-TR criteria. All patients were treated with bilateral ECT and evaluated before and after ECT course. The response to ECT was defined as a Clinical Global Impression (Improvement subscale) rating 1 'very much improved' or 2 'much improved'. Clinical variables were compared between responders and non-responders; logistic regression was used to predict the probability of non-response, with regard to the symptoms presented by the patients. RESULTS: The response rate was 83.1%. Non-responders (n = 10) to ECT showed neurological comorbidities, treatments with dopamine agonists and anticholinergic drugs, waxy flexibility, and echophenomena more frequently than respondents (n = 49). Echophenomena resulted a significant predictor of non-response in the multivariate analysis. CONCLUSION: In line with previous reports, ECT resulted effective in the vast majority of severe catatonic patients. The association between ECT resistant catatonia and neurological comorbidity, use of dopamine-agonist and anticholinergic medications is consistent with the hypothesis that ECT is more effective in 'top-down' than in 'bottom-up' variant of catatonia.Key pointsCatatonic symptoms are frequently associated with severe and psychotic mood disorders.Electroconvulsive therapy is effective in treating most forms of severe catatonia.Neurological comorbidity and the presence of 'echopraxia/echolalia' could represent predictors of non-response to ECT.

High exposure to pharmacological treatments is associated with limited efficacy of electroconvulsive therapy in bipolar depression.

Episode chronicity and medication failure are considered robust predictors of poor response to electroconvulsive therapy (ECT). In this study we explored the associations between indexes of drug exposure during current episode and outcomes of ECT in 168 bipolar depressive patients. The association between response or remission and number of previous pharmacological trials, failure of treatment with antidepressants, antipsychotics or combinations, and sum of maximum Antidepressant Treatment History Form (ATHF) scores obtained in each pharmacological class were tested. 98 patients (58%) were considered responders and 21 remitters (13%). Number of trials, number of adequate trials, ATHF sum, antidepressant-antipsychotic combination therapy failure and failure of two adequate trials were significantly negatively associated with remission. The association with ATHF sum stayed significant when controlling for episode duration and manic symptoms and survived stepwise model selection. No significant associations with response were identified. In conclusion, a history of multiple drug treatments may be linked to a greater resistance to all types of therapies, including ECT. However, we could not exclude that, at least in some patients, a prolonged exposure to pharmacological treatments may be responsible for a greater chronicity and for the presence of residual symptoms, which would explain reduced remission after ECT.

Association of treatment facets, severity of manic symptoms, psychomotor disturbances and psychotic features with response to electroconvulsive therapy in bipolar depression.

OBJECTIVES: Clinically useful predictors of response to electroconvulsive therapy (ECT) are warranted, especially in the case of bipolar depression. The aim of this study was to explore the associations between response and its known and putative correlates. METHODS: Six hundred seventy bipolar depressive patients treated with ECT were included in the study. The association between response (CGI-I ≤ 2) and mean seizure duration, number of treatments, age, sex, bipolar subtype, episode duration, HAM-D and YMRS scores, psychomotor disturbances and psychotic symptoms assessed through BPRS-EV were evaluated by means of univariate and multivariate logistic regression models, including quadratic and/or linear effects of continuous variables. RESULTS: Four hundred eighty three patients (72%) were responders. Among known correlates of response, significant quadratic effects were found for seizure duration and number of treatments, while a linear association was confirmed for episode duration. Among putative correlates, severe motor retardation, tension or agitation, hyperactivity and delusions of guilt were significantly associated with response (p<.01) and a significant quadratic effect was found for YMRS score (p<.01). CONCLUSION: Bipolar depressive patients with severe psychomotor disturbances, mood-congruent delusions and severe mixed features are highly responsive to ECT. A significant improvement in response prediction is expected when considering those clinical characteristics.

Effects of substance misuse and current family history of substance use disorder on brain structure in adolescents and young adults with attention-deficit/hyperactivity disorder.

BACKGROUND: Alterations in brain structure in attention-deficit/hyperactivity disorder (ADHD) show considerable overlap with those observed in substance use disorder (SUD). These overlapping structural alterations in ADHD and SUD might be explained by family history (FH-trait) effects of SUD, and/or substance misuse (state) effects. Our aim was to investigate effects of 1) current parental SUD (SUD-FH) and 2) recent substance misuse (SM) on brain structure in a cohort of ADHD patients and controls. DESIGN: Cortical thickness and subcortical volumes were measured using structural MRI. We compared ADHD subjects and controls with or without SUD-FH (aim 1) and additionally explored differences between SUD-FH- and SUD-FH + subjects with one versus two parents with SUD. We also compared ADHD groups with and without SM (ADHD + SM and ADHD-only, respectively) and controls (aim 2). FINDINGS: There was no association between SUD-FH and brain structure. Exploratory analysis on SUD-FH showed decreased IFG thickness (p = 0.032) and nucleus accumbens (NAcc) volume (p = 0.017) in subjects with two versus one SUD parent, regardless of ADHD. ADHD + SM showed decreased inferior frontal gyrus (IFG) thickness compared to controls (pars opercularis p = 0.025, pars orbitalis p = 0.010, pars triangularis p = 0.049), while no difference was found between ADHD-only and either ADHD + SM or controls. CONCLUSIONS: Despite negative findings in the primary trait-analysis, exploratory trait-analysis on SUD-FH loading suggested potential SUD trait-effects on IFG thickness and NAcc volume. Substance misuse state effects in ADHD were linked to lower IFG thickness. Future studies should confirm these findings and investigate their clinical relevance, including the functional consequences of decreased IFG thickness.

The Role of Electroconvulsive Therapy in the Treatment of Severe Bipolar Mixed State.

Electroconvulsive therapy (ECT) results effective in two-thirds of the patients with severe and drug-resistant mixed states. The episode duration is the main predictor of nonresponse. This practice may increase the risk of mood destabilization and chronic complications and may decrease the chance of recovery in many patients. Compared with the burden of neurologic and metabolic side effects associated with long-term use of complex pharmacologic regimens, ECT should be considered a safe option with a very low incidence of severe adverse events and a long-term nondestabilizing effect.

Naturalistic follow-up in bipolar patients after successful electroconvulsive therapy.

BACKGROUND: Electroconvulsive therapy (ECT) is an effective treatment for acute depression, mania and mixed states. We evaluated the long-term outcome of patients with bipolar depression or mixed state, responsive to ECT. METHODS: this observational follow-up study was conducted in 70 patients with Bipolar Disorder: 36 patients met DSM-IV-TR criteria for a major depressive episode (MDE) and 34 for a mixed episode (MXE). During the follow-up after ECT, the relapse rates and the duration of response and remission periods were recorded. RESULTS: the mean duration of the follow-up was 57 weeks. 93% of the patients maintained at least a partial therapeutic response for more than 90% of the follow-up period. 73% of patients fulfilled the criteria for a full remission, 33% showed a depressive relapse and 10% a mixed relapse. No manic relapses occurred but almost 1/3 of the sample presented hypomanic episodes. MDE patients presented higher rates of remission compared to MXE ones. Patients with anxiety disorders reported earlier relapses than those without this comorbidity. Relapsed-patients showed higher functional impairment at baseline evaluation, compared to non-relapsed ones. LIMITATIONS: nonrandom allocation, limited sample size, possible influence of psychopharmacological treatment. CONCLUSIONS: Given several methodological limitations, this study cannot draw definite conclusions but could suggest that in treatment-resistant bipolar patients with severe depression or mixed state, ECT may represent a useful treatment option. Patients with mixed features, comorbid anxiety disorders and higher functional impairment present less favorable outcome. Future research on long-term efficacy of ECT and on clinical predictors of relapse is needed.

Adult attention-deficit hyperactivity disorder and clinical correlates of delayed sleep phase disorder.

The purpose of the study was to assess the prevalence and clinical correlates of Delayed Sleep Phase Disorder (DSPD) in adults with Attention-Deficit/Hyperactivity Disorder. Participants were 102 adults (Female= 27), aged 18-65 (mean age= 28.2 years), with ADHD diagnosed in adulthood. ADHD and DSPD diagnosis were made according to DSM-5 criteria. Assessing instruments included the Morningness-Eveningness Questionnaire, the brief Temperament Evaluation of Memphis, Pisa, Paris and San Diego Questionnaire, the Barratt Impulsiveness Scale, the Reactivity Intensity Polarity Stability Questionnaire-40 and the World Health Organization Disability Assessment Schedule 2.0. Epidemiological and Clinical features were compared in patients with and without DSPD. 34 out of 102 patients were classified as having a Delayed Sleep Phase Disorder. As expected, DSPD patients reported a more frequent evening chronotype. In the multivariate logistic regression analysis, Delayed Sleep Phase Disorder was significantly associated with young age, cannabis use, cyclothymic temperamental traits and severe global impairment. An early diagnosis with a proper treatment targeted to both disorders may be fundamental in order to improve the overall functioning and the outcome of adult ADHD patients.

Association between affective temperaments and mood features in bipolar disorder II: The role of insomnia and chronobiological rhythms desynchronization.

BACKGROUND: Bipolar disorders are complex disorders involving the interaction of multiple factors. Affective temperaments, insomnia, and chronobiological rhythms desynchronization may all contribute to bipolar disorder. Since there is a paucity of research examining this topic we aimed to study how they are interrelated and collectively associated with clinical features of bipolar disorder. METHOD: One-hundred patients with Bipolar Disorder type II depressive episode with and without mixed features were recruited and compared. Subjects were evaluated with SCID -5, the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), the Insomnia Severity Index (ISI), and the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Auto-questionnaire (TEMPS-A) while evaluating depressive (Beck Depression Inventory-BDI-II) and manic (Young Mania Rating Scale-YMRS) symptoms. Logistic regression and mediation analyses were conducted. RESULTS: Subjects with mixed features showed a higher scores in both insomnia and chronobiological rhythms scores. When considering affective temperaments not only depressive, cyclothymic and irritable temperaments predicted mood symptoms but also insomnia (depressive symptoms O.R. 4.17, p = 0.043) and chronobiological sleep de-synchronization (manic symptoms O.R. 8.69, p = 0.001). Insomnia symptoms and chronobiological alterations mediated the association between affective temperaments and mood symptoms. LIMITATIONS: the cross-sectional design limited any causal interpretation. CONCLUSION: Subjects with mixed features showed a greater severity of insomnia and chronobiological rhythm de-synchronization compared to subjects without. Insomnia and chronobiological alterations may contribute to mood disorders together with affective temperaments in a complex interplay also mediating their effect on mood. Preventive strategies for bipolars should also act on the dysregulation of sleep and circadian rhythms.

Stress-related sleep reactivity is associated with insomnia, psychopathology and suicidality in pregnant women: preliminary results.

INTRODUCTION: Depression and anxiety symptoms are commonly experienced by women during pregnancy and may have negative consequences on mothers and newborns. Deterioration of sleep quality throughout pregnancy increases insomnia, which may lead to adverse outcomes including increased psychopathology in the perinatal period. Thus, identifying women at high risk of developing insomnia may have important clinical implications on maternal-fetal outcomes. Stress-related sleep reactivity is a well-established risk factor for future insomnia, depression, and anxiety in general adult samples. However, little is known of sleep reactivity and its relations to sleep and mood pathology in pregnancy. Therefore, we explored sleep reactivity in pregnant women and its relations to prenatal symptoms of insomnia, depression, anxiety, and suicidality. METHOD: Sixty-two pregnant women (mean age 33.6 ± 3 years, 20.6 ± 0.6 weeks of pregnancy) were evaluated during their routine visit at the Gynecological Unit of the University of Pisa, Italy, using the Insomnia Severity Index (ISI) for insomnia symptoms, the Ford Insomnia Response to Stress Test for sleep reactivity (FIRST), Edinburgh Postnatal Depression Scale (EPDS) for depressive symptoms, and the Zung Self Rating Anxiety Scale (SAS) for anxiety symptoms. Item #10 of the EPDS was used to assess for suicidality. Differences in means between women with high vs low stress-related sleep reactivity were calculated using t-test or Mann-Whitney U/Wilcoxon test. Linear/multiple regression analyses have been performed to study associations between variables. RESULTS: Pregnant women with high stress-related sleep reactivity, relative to those with low reactivity, reported greater symptoms of insomnia (t = 6.5, 0.004) as well as higher rates of depression (62.0% vs 6.1%, p < 0.001), anxiety (55.1% vs 15.1%, p = 0.030), and suicidality (17.2% vs 3.0%, p = 0.025). Multivariate models revealed sleep reactivity to correlate independently with symptoms of insomnia, depression, and anxiety, when controlling for comorbid symptoms. CONCLUSIONS: In mid-pregnancy, women with high sleep reactivity report elevated symptoms of insomnia, depression, and anxiety, and are more likely to endorse suicidal ideation. As a prognostic marker of future insomnia and psychiatric illness, early detection of high prenatal sleep reactivity holds potential to prevent the development of sleep and mood pathology during pregnancy, thereby potentially improving maternal and child outcomes.

Adult insecure attachment plays a role in hyperarousal and emotion dysregulation in Insomnia Disorder.

Studies show that unhelpful cognitive processes play a role in insomnia, whereas interpersonal factors have been less studied in insomnia. Attachment theory can be used as a cognitive-interpersonal framework for understanding insomnia. Because attachment insecurity (vs security) is related to psychiatric disorders the objective was to study the attachment style in insomnia. To this aim sixty-four subjects with Insomnia Disorder (DSM-5) and 38 good sleepers were evaluate in a cross-sectional study with: Attachment Style Questionnaire (ASQ), Arousal Predisposition Scale (APS), Pre-Sleep Arousal Scale (PSAS) and Difficulties in Emotion Regulation Scale (DERS). Differences in means between groups were assessed using t-test or Mann-Whitney U/Wilcoxon test. Linear/multiple regression analyses were performed. Subjects with insomnia (mean age 47.1 + 13 yrs) presented an insecure attachment style and higher scores in all the scales (ASQ, APS, PSAS, DERS p < 0.0001) than good sleepers (mean age 48.2 + 14 yrs). After taking into account anxiety/depressive symptoms, insecure attachment was related to hyperarousal trait (p = 0.02), pre-sleep hyperarousal (p = 0.04) and emotion dysregulation (p = 0.002). In conclusion subjects with insomnia showed an insecure attachment which was related to hyperarousal trait, pre-sleep hyperarousal and emotion dysregulation. It may intervene in the trajectory of insomnia starting from predisposition to perpetuation. Clinical implications are discussed.

Lack of Resilience Is Related to Stress-Related Sleep Reactivity, Hyperarousal, and Emotion Dysregulation in Insomnia Disorder.

STUDY OBJECTIVES: According to the diathesis-stress model of insomnia, insomnia may develop in vulnerable individuals in response to stress. Resilience is a psychobiological factor that determines an individual's capacity to adapt successfully to stressful events and low resilience increases vulnerability for development of mental disorders. The aim was to explore resilience in subjects with insomnia and its relationship with the factors that contribute to its development and perpetuation. METHODS: The study consisted of 58 subjects with Insomnia Disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and 38 good sleepers. Resilience Scale for Adults (RSA), Ford Insomnia Response to Stress Test (FIRST), Pre-sleep Arousal Scale (PSAS), and Difficulties in Emotion Regulation Scale (DERS) were administered while taking into account psychiatric symptoms. Differences in means between groups were assessed using t test or Mann-Whitney U/Wilcoxon test. Linear/multivariable regression analyses and mediation analyses were performed. RESULTS: Subjects with insomnia (24 females, mean age 49 ± 2.1 years) had lower RSA and higher FIRST, DERS, and PSAS scores than good sleepers (22 females, mean age 47.2 ± 1.2 years). After controlling for anxiety/depressive symptoms, low resilience correlated with high stress-related sleep reactivity (P = .004), pre-sleep cognitive hyperarousal (P = .01) and emotion dysregulation (P = .01). Emotion dysregulation mediated the relationship between low resilience and cognitive hyperarousal (Z = 2.06, P = .03). CONCLUSIONS: Subjects with insomnia showed low resilience, which was related to high stress-related sleep reactivity, emotional dysregulation, and hyperarousal. If resilience helps to minimize the extent of pathogenesis in the developmental process, an early identification of vulnerable candidates should be useful for preventing insomnia development and maintenance. COMMENTARY: A commentary on this article appears in this issue on page 709.