Shawn M. McClintock

Association between depression severity and neurocognitive function in major depressive disorder: a review and synthesis.

The effects of major depressive disorder (MDD) on neurocognitive function remain poorly understood. Results from published studies vary widely in terms of methodological factors, and very little is known about the effects of depression severity and other clinical characteristics on neurocognitive function. The purpose of this review was to synthesize prior research findings regarding neurocognitive functioning in patients with MDD and varying levels of depression severity and to provide recommendations for future directions. Overall, this review suggests that MDD has been inconsistently associated with neurocognitive functioning and there is limited understanding regarding the relationship between depression severity and neurocognitive sequelae. There was much heterogeneity on depression severity-related factors across studies assessing neurocognitive function in MDD, as well as substantial variability in the consideration of depression severity among studies, which suggests a need to further explore this important issue.

Bifrontal, bitemporal and right unilateral electrode placement in ECT: randomised trial

BACKGROUND Electroconvulsive therapy (ECT) is an effective treatment for major depression. Optimising efficacy and minimising cognitive impairment are goals of ongoing technical refinements. AIMS To compare the efficacy and cognitive effects of a novel electrode placement, bifrontal, with two standard electrode placements, bitemporal and right unilateral in ECT. METHOD This multicentre randomised, double-blind, controlled trial (NCT00069407) was carried out from 2001 to 2006. A total of 230 individuals with major depression, bipolar and unipolar, were randomly assigned to one of three electrode placements during a course of ECT: bifrontal at one and a half times seizure threshold, bitemporal at one and a half times seizure threshold and right unilateral at six times seizure threshold. RESULTS All three electrode placements resulted in both clinically and statistically significant antidepressant outcomes. Remission rates were 55% (95% CI 43-66%) with right unilateral, 61% with bifrontal (95% CI 50-71%) and 64% (95% CI 53-75%) with bitemporal. Bitemporal resulted in a more rapid decline in symptom ratings over the early course of treatment. Cognitive data revealed few differences between the electrode placements on a variety of neuropsychological instruments. CONCLUSIONS Each electrode placement is a very effective antidepressant treatment when given with appropriate electrical dosing. Bitemporal leads to more rapid symptom reduction and should be considered the preferred placement for urgent clinical situations. The cognitive profile of bifrontal is not substantially different from that of bitemporal.

Psychomotor retardation in depression: Biological underpinnings, measurement, and treatment

Psychomotor retardation is a long established component of depression that can have significant clinical and therapeutic implications for treatment. Due to its negative impact on overall function in depressed patients, we review its biological correlates, optimal methods of measurement, and relevance in the context of therapeutic interventions. The aim of the paper is to provide a synthesis of the literature on psychomotor retardation in depression with the goal of enhanced awareness for clinicians and researchers. Increased knowledge and understanding of psychomotor retardation in major depressive disorder may lead to further research and better informed diagnosis in regards to psychomotor retardation. Manifestations of psychomotor retardation include slowed speech, decreased movement, and impaired cognitive function. It is common in patients with melancholic depression and those with psychotic features. Biological correlates may include abnormalities in the basal ganglia and dopaminergic pathways. Neurophysiologic tools such as neuroimaging and transcranial magnetic stimulation may play a role in the study of this symptom in the future. At present, there are three objective scales to evaluate psychomotor retardation severity. Studies examining the impact of psychomotor retardation on clinical outcome have found differential results. However, available evidence suggests that depressed patients with psychomotor retardation may respond well to electroconvulsive therapy (ECT). Current literature regarding antidepressants is inconclusive, though tricyclic antidepressants may be considered for treatment of patients with psychomotor retardation. Future work examining this objective aspect of major depressive disorder (MDD) is essential. This could further elucidate the biological underpinnings of depression and optimize its treatment.

Residual symptoms in depressed outpatients who respond by 50% but do not remit to antidepressant medication.

Little is known about the quantity or quality of residual depressive symptoms in patients with major depressive disorder (MDD) who have responded but not remitted with antidepressant treatment. This report describes the residual symptom domains and individual depressive symptoms in a large representative sample of outpatients with nonpsychotic MDD who responded without remitting after up to 12 weeks of citalopram treatment in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Response was defined as 50% or greater reduction in baseline 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16) by treatment exit, and remission as a final QIDS-SR16 of less than 6. Residual symptom domains and individual symptoms were based on the QIDS-SR16 and classified as either persisting from baseline or emerging during treatment. Most responders who did not remit endorsed approximately 5 residual symptom domains and 6 to 7 residual depressive symptoms. The most common domains were insomnia (94.6%), sad mood (70.8%), and decreased concentration (69.6%). The most common individual symptoms were midnocturnal insomnia (79.0%), sad mood (70.8%), and decreased concentration/decision making (69.6%). The most common treatment-emergent symptoms were midnocturnal insomnia (51.4%) and decreased general interest (40.0%). The most common persistent symptoms were midnocturnal insomnia (81.6%), sad mood (70.8%), and decreased concentration/decision making (70.6%). Suicidal ideation was the least common treatment-emergent symptom (0.7%) and the least common persistent residual symptom (17.1%). These findings suggest that depressed outpatients who respond by 50% without remitting to citalopram treatment have a broad range of residual symptoms. Individualized treatments are warranted to specifically address each patients residual depressive symptoms.

Anesthetic Considerations for Magnetic Seizure Therapy: A Novel Therapy for Severe Depression

Electroconvulsive therapy (ECT) is a highly effective treatment for severe depression. However, its use is associated with significant posttreatment cognitive impairment. Magnetic seizure therapy (MST) was developed as an alternative therapy that could reduce postseizure side effects through the induction of more “focal” seizure activity. Using an open-parallel study design, we compared 20 case-matched patients undergoing a series of either ECT or MST procedures with respect to their anesthetic, muscle relaxant, and cardiovascular drug requirements, effects on cardiovascular and electroencephalographic bispectral index (BIS) values, and early recovery times. We found that MST was associated with a reduced time to orientation (4 ± 1 versus 18 ± 5 min; P < 0.01) compared with ECT. To minimize residual muscle paralysis after MST, a reduction in the succinylcholine dosage (38 ± 17 versus 97 ± 2 mg; P < 0.01) was required. The BIS values were higher before, and lower immediately after, the stimulus was applied in the MST (versus ECT) group. The Hamilton depression rating scale score was significantly reduced from the baseline value in both treatment groups; however, the posttreatment score was lower after the series of ECT treatments (6 ± 6 versus 14 ± 10; P < 0.05). We conclude that MST was associated with a decreased requirement for muscle relaxants, reduced variability in the BIS values after seizure induction, and a more rapid recovery of cognitive function compared with ECT. Further studies are required to evaluate the antidepressant efficacy of MST versus ECT when they are administered at comparable levels of cerebral stimulation.

Hippocampal structural and functional changes associated with electroconvulsive therapy response

Previous animal models and structural imaging investigations have linked hippocampal neuroplasticity to electroconvulsive therapy (ECT) response, but the relationship between changes in hippocampal volume and temporal coherence in the context of ECT response is unknown. We hypothesized that ECT response would increase both hippocampal resting-state functional magnetic resonance imaging connectivity and hippocampal volumes. Patients with major depressive disorder (n=19) were scanned before and after the ECT series. Healthy, demographically matched comparisons (n=20) were scanned at one-time interval. Longitudinal changes in functional connectivity of hippocampal regions and volumes of hippocampal subfields were compared with reductions in ratings of depressive symptoms. Right hippocampal connectivity increased (normalized) after the ECT series and correlated with depressive symptom reduction. Similarly, the volumes of the right hippocampal cornu ammonis (CA2/3), dentate gyrus and subiculum regions increased, but the hippocampal subfields were unchanged relative to the comparison group. Connectivity changes were not evident in the left hippocampus, and volume changes were limited to the left CA2/3 subfields. The laterality of the right hippocampal functional connectivity and volume increases may be related to stimulus delivery method, which was predominately right unilateral in this investigation. The findings suggested that increased hippocampal functional connectivity and volumes may be biomarkers for ECT response.

Electroconvulsive therapy is equally effective in unipolar and bipolar depression

Bailine S, Fink M, Knapp R, Petrides G, Husain MM, Rasmussen K, Sampson S, Mueller M, McClintock SM, Tobias KG, Kellner CH. Electroconvulsive therapy is equally effective in unipolar and bipolar depression.

Transcranial Magnetic Stimulation: A Neuroscientific Probe of Cortical Function in Schizophrenia

Transcranial magnetic stimulation (TMS) is a neuropsychiatric tool that can serve as a useful method to better understand the neurobiology of cognitive function, behavior, and emotional processing. The purpose of this article is to examine the utility of TMS as a means to measure neocortical function in neuropsychiatric disorders in general, and schizophrenia in particular, for the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia initiative. When incorporating TMS paradigms in research studies, methodologic considerations include technical aspects of TMS, cohort selection and confounding factors, and subject safety. Available evidence suggests benefits of TMS alone or in combination with neurophysiologic and neuroimaging methods, including positron emission tomography, single photon emission computed tomography, magnetic resonance imaging, functional magnetic resonance imaging, functional near infrared spectroscopy, magnetoencephalography, and electroencephalography, to explore neocortical function. With the multiple TMS techniques including single-pulse, paired-pulse, paired associative stimulation, and repetitive TMS and theta burst stimulation, combined with neurophysiologic and neuroimaging methods, there exists a plethora of TMS experimental paradigms to modulate neocortical physiologic processes. Specifically, TMS can measure cortical excitability, intracortical inhibitory and excitatory mechanisms, and local and network cortical plasticity. Coupled with functional and electrophysiologic modalities, TMS can provide insight into the mechanisms underlying healthy neurodevelopment and aging, as well as neuropsychiatric pathology. Thus, TMS could be a useful tool in the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia armamentarium of biomarker methods. Future investigations are warranted to optimize TMS methodologies for this purpose.

Age-Related Characteristics of Depression: A Preliminary STAR*D Report

OBJECTIVE Studies have shown that age is a determinant in the course of major depressive disorder. Age has been associated with depression severity; it has also been associated with varying depressive symptomatology. The authors explore the relationships between current age and depression severity, course of illness, presenting symptom features, and comorbid symptoms. METHODS Baseline clinical and sociodemographic information was collected on 1,498 participants enrolled in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study. Five age cohorts (18-25, 26-35, 36-50, 51-65, and 66-75) were compared on both sociodemographic and clinical factors. Depressive symptoms were measured with the 30-item clinician-rated Inventory of Depressive Symptomatology. RESULTS Clinically meaningful differences were found among age cohorts on several clinical and depressive symptom features. Older patients (51-65 and 66-75) endorsed longer durations of illness, more major depressive episodes, a later age at onset of their first major depressive episode, and more general medical comorbidities. Older patients had more middle and terminal insomnia, less irritability, and less hypersomnia. They were less likely to hold negative views of themselves or of their future and were less likely to report previous suicide attempts. Older patients were less likely to endorse symptoms consistent with generalized anxiety disorder, social phobia, panic disorder, and drug abuse. CONCLUSIONS These cross-sectional data indicate that different age-cohorts present with varying sociodemographic and clinical characteristics, as well as general-medical and psychiatric comorbid conditions.

Cognitive flexibility in verbal and nonverbal domains and decision making in anorexia nervosa patients: a pilot study

BackgroundThis paper aimed to investigate cognitive rigidity and decision making impairments in patients diagnosed with Anorexia Nervosa Restrictive type (AN-R), assessing also verbal components.MethodsThirty patients with AN-R were compared with thirty age-matched healthy controls (HC). All participants completed a comprehensive neuropsychological battery comprised of the Trail Making Test, Wisconsin Card Sorting Test, Hayling Sentence Completion Task, and the Iowa Gambling Task. The Beck Depression Inventory was administered to evaluate depressive symptomatology. The influence of both illness duration and neuropsychological variables was considered. Body Mass Index (BMI), years of education, and depression severity were considered as covariates in statistical analyses.ResultsThe AN-R group showed poorer performance on all neuropsychological tests. There was a positive correlation between illness duration and the Hayling Sentence Completion Task Net score, and number of completion answers in part B. There was a partial effect of years of education and BMI on neuropsychological test performance. Response inhibition processes and verbal fluency impairment were not associated with BMI and years of education, but were associated with depression severity.ConclusionsThese data provide evidence that patients with AN-R have cognitive rigidity in both verbal and non-verbal domains. The role of the impairment on verbal domains should be considered in treatment. Further research is warranted to better understand the relationship between illness state and cognitive rigidity and impaired decision-making.