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Adults with significant childhood trauma and/or serious mental illness may exhibit persistent structural brain changes within limbic structures, including the amygdala. Little is known about the structure of the amygdala prior to the onset of SMI, despite the relatively high prevalence of trauma in at-risk youth.
Data were gathered from the Canadian Psychiatric Risk and Outcome study. A total of 182 youth with a mean age of 18.3 years completed T1-weighted MRI scans along with clinical assessments that included questionnaires on symptoms of depression and anxiety. Participants also completed the Childhood Trauma and Abuse Scale. We used a novel subfield-specific amygdala segmentation workflow as a part of FreeSurfer 6.0 to examine amygdala structure.
Participants with higher trauma scores were more likely to have smaller amygdala volumes, particularly within the basal regions. Among various types of childhood trauma, sexual and physical abuse had the largest effects on amygdala subregions. Abuse-related differences in the right basal region mediated the severity of depression and anxiety symptoms, even though no participants met criteria for clinical diagnosis at the time of assessment.
The experience of physical or sexual abuse may leave detectable structural alterations in key regions of the amygdala, potentially mediating the risk of psychopathology in trauma-exposed youth.
Patients with major depressive disorder (MDD) display cognitive deficits in acutely depressed and remitted states. Childhood maltreatment is associated with cognitive dysfunction in adults, but its impact on cognition and treatment related cognitive outcomes in adult MDD has received little consideration. We investigate whether, compared to patients without maltreatment and healthy participants, adult MDD patients with childhood maltreatment display greater cognitive deficits in acute depression, lower treatment-associated cognitive improvements, and lower cognitive performance in remission.
Healthy and acutely depressed MDD participants were enrolled in a multi-center MDD predictive marker discovery trial. MDD participants received 16 weeks of standardized antidepressant treatment. Maltreatment and cognition were assessed with the Childhood Experience of Care and Abuse interview and the CNS Vital Signs battery, respectively. Cognitive scores and change from baseline to week 16 were compared amongst MDD participants with (DM+, n = 93) and without maltreatment (DM−, n = 90), and healthy participants with (HM+, n = 22) and without maltreatment (HM−, n = 80). Separate analyses in MDD participants who remitted were conducted.
DM+ had lower baseline global cognition, processing speed, and memory v. HM−, with no significant baseline differences amongst DM−, HM+, and HM− groups. There were no significant between-group differences in cognitive change over 16 weeks. Post-treatment remitted DM+, but not remitted DM−, scored significantly lower than HM− in working memory and processing speed.
Childhood maltreatment was associated with cognitive deficits in depressed and remitted adults with MDD. Maltreatment may be a risk factor for more severe and persistent cognitive deficits in adult MDD.
In an effort to optimize patient outcomes, considerable attention is being devoted to identifying patient characteristics associated with major depressive disorder (MDD) and its responsiveness to treatment. In the current study, we extend this work by evaluating whether early change in these sensitivities is associated with response to antidepressant treatment for MDD.
Participants included 210 patients with MDD who were treated with 8 weeks of escitalopram and 112 healthy comparison participants. Of the original 210 patients, 90 non-responders received adjunctive aripiprazole for an additional 8 weeks. Symptoms of depression and anhedonia were assessed at the beginning of treatment and 8 weeks later in both samples. Reward and punishment sensitivity were assessed using the BIS/BAS scales measured at the initiation of treatment and 2 weeks later.
Individuals with MDD exhibited higher punishment sensitivity and lower reward sensitivity compared with healthy comparison participants. Change in reward sensitivity during the first 2 weeks of treatment was associated with improved depressive symptoms and anhedonia following 8 weeks of treatment with escitalopram. Similarly, improvement in reward responsiveness during the first 2 weeks of adjunctive therapy with aripiprazole was associated with fewer symptoms of depression at post-treatment.
Findings highlight the predictive utility of early change in reward sensitivity during antidepressant treatment for major depression. In a clinical setting, a lack of change in early reward processing may signal a need to modify a patient's treatment plan with alternative or augmented treatment approaches.
Residual symptoms and cognitive impairment are among important sources of disability in patients with bipolar disorder. Methylene blue could improve such symptoms because of its potential neuroprotective effects.
We conducted a double-blind crossover study of a low dose (15 mg, ‘placebo’) and an active dose (195 mg) of methylene blue in patients with bipolar disorder treated with lamotrigine.
Thirty-seven participants were enrolled in a 6-month trial (trial registration: NCT00214877). The outcome measures included severity of depression, mania and anxiety, and cognitive functioning.
The active dose of methylene blue significantly improved symptoms of depression both on the Montgomery–Åsberg Depression Rating Scale and Hamilton Rating Scale for Depression (P = 0.02 and 0.05 in last-observation-carried-forward analysis). It also reduced the symptoms of anxiety measured by the Hamilton Rating Scale for Anxiety (P = 0.02). The symptoms of mania remained low and stable throughout the study. The effects of methylene blue on cognitive symptoms were not significant. The medication was well tolerated with transient and mild side-effects.
Methylene blue used as an adjunctive medication improved residual symptoms of depression and anxiety in patients with bipolar disorder.
Although people with bipolar disorder spend more time in a depressed than
manic state, little evidence is available to guide the treatment of acute
To compare the efficacy, acceptability and safety of mood stabiliser
monotherapy with combination and antidepressant treatment in adults with
acute bipolar depression.
Systematic review and meta-analysis of randomised, double-blind
Eighteen studies with a total 4105 participants were analysed. Mood
stabiliser monotherapy was associated with increased rates of response
(relative risk (RR) = 1.30, 95% CI 1.16–1.44, number needed to treat
(NNT) = 10, 95% CI 7–18) and remission (RR = 1.51, 95% CI 1.27–1.79, NNT
= 8, 95% CI 5–14) relative to placebo. Combination therapy was not
statistically superior to monotherapy. Weight gain, switching and suicide
rates did not differ between groups. No differences were found between
individual medications or drug classes for any outcome.
Mood stabilisers are moderately efficacious for acute bipolar depression.
Extant studies are few and limited by high rates of discontinuation and
short duration. Further study of existing and novel agents is
Despite increasing awareness of the extent and severity of cognitive deficits in major depressive disorder (MDD), trials of cognitive remediation have not been conducted. We conducted a 10-week course of cognitive remediation in patients with long-term MDD to probe whether deficits in four targeted cognitive domains, (i) memory, (ii) attention, (iii) executive functioning and (iv) psychomotor speed, could be improved by this intervention.
We administered a computerized cognitive retraining package (PSSCogReHab) with demonstrated efficacy to 12 stable patients with recurrent MDD. Twelve matched patients with MDD and a group of healthy control participants were included for comparison; neither comparator group received the intervention that involved stimulation of cognitive functions through targeted, repetitive exercises in each domain.
Patients who received cognitive training improved on a range of neuropsychological tests targeting attention, verbal learning and memory, psychomotor speed and executive function. This improvement exceeded that observed over the same time period in a group of matched comparisons. There was no change in depressive symptom scores over the course of the trial, thus improvement in cognitive performance occurred independent of other illness variables.
These results provide preliminary evidence that improvement of cognitive functions through targeted, repetitive exercises is a viable method of cognitive remediation in patients with recurrent MDD.