Kathryn Macdonald

Course of illness, hippocampal function, and hippocampal volume in major depression

Studies have examined hippocampal function and volume in depressed subjects, but none have systematically compared never-treated first-episode patients with those who have had multiple episodes. We sought to compare hippocampal function, as assessed by performance on hippocampal-dependent recollection memory tests, and hippocampal volumes, as measured in a 1.5-T magnetic resonance imager, in depressed subjects experiencing a postpubertal onset of depression. Twenty never-treated depressed subjects in a first episode of depression were compared with matched healthy control subjects. Seventeen depressed subjects with multiple past episodes of depression were also compared with matched healthy controls and to the first-episode patients. Both first- and multiple-episode depressed groups had hippocampal dysfunction apparent on several tests of recollection memory; only depressed subjects with multiple depressive episodes had hippocampal volume reductions. Curve-fitting analysis revealed a significant logarithmic association between illness duration and hippocampal volume. Reductions in hippocampal volume may not antedate illness onset, but volume may decrease at the greatest rate in the early years after illness onset.

Bilateral Hippocampal Volume Increase in Patients with Bipolar Disorder and Short-term Lithium Treatment

Most previous magnetic resonance imaging (MRI) studies of patients with bipolar disorder (BD) report similar hippocampus (HC) volumes across patients and controls, but because patients studied were heterogeneous with respect to course of illness variables and medication status, the conclusions of these studies remain equivocal. Lithium (Li) is the reference-standard drug for BD and its role as an important agent in neuroprotection and neurogenesis has been documented in human and in animal studies. We compared the volume of the HC, hippocampal head (Hh), and body/tail (Hbt) in three groups with no history of medication use before entry into this study: (a) a group of patients treated with Li for 1–8 weeks and then scanned; (b) a group comprised of patients who were unmedicated at the time of scan; and (c) a group of patients treated with either valproic acid or lamotrigine. Healthy age- and sex-matched comparison subjects were also scanned. HC volumes did not differ between the unmedicated and healthy comparison groups. There was a bilateral increase in volumes of HC and Hh in the Li-treated group compared to the unmedicated group, an effect that was apparent even over a brief treatment period. Our study provides further confirmation that Li can exert structural effects on the HC, which are detectable in vivo. The study emphasizes the need to control for even brief exposure to medication in volumetric studies of the HC.

Anterior Cingulate Volumes in Never-Treated Patients with Major Depressive Disorder

The anterior cingulate cortex (ACC) is implicated in the cognitive and affective abnormalities observed in mood disorders. Bilateral ACC volume reductions have been reported in patients with major depressive disorder (MDD) when compared to healthy controls. We compared regional brain volumes in the subgenual prefrontal cortex (SGPFC; Brodmann area (BA) 24sg), subcallosal gyrus (BA25), and paracingulate gyrus (BA32) in 65 patients receiving a first course of treatment for MDD and 93 healthy control subjects. Patients with more than three episodes of untreated MDD had smaller subcallosal gyrus volumes than healthy controls, while those with three or fewer past untreated episodes did not differ from controls. We also found preliminary evidence that medication-exposed patients had smaller SGPFC volumes than patients with no exposure to medication and healthy controls. There was no evidence that these effects related to mood state, duration of untreated illness, or to patient age. No differences were apparent in paracingulate gyrus volumes between patients and controls. These findings confirm the presence of ACC volume reductions in untreated patients with MDD and suggest that illness burden and short-term medication exposure mediate this change.

Psychological distress in children with developmental coordination disorder and attention-deficit hyperactivity disorder.

This study explored whether or not a population-based sample of children with developmental coordination disorder (DCD), with and without comorbid attention deficit/hyperactivity disorder (ADHD), experienced higher levels of psychological distress than their peers. A two-stage procedure was used to identify 244 children: 68 with DCD only, 54 with ADHD only, 31 with comorbid DCD and ADHD, and 91 randomly selected typically developing (TD) children. Symptoms of depression and anxiety were measured by child and parent report. Child sex and caregiver ethnicity differed across groups, with a higher ratio of boys to girls in the ADHD only group and a slightly higher proportion of non-Caucasian caregivers in the TD group. After controlling for age, sex, and caregiver ethnicity, there was significant variation across groups in both anxiety (by parent report, F(3,235)=8.9, p<0.001; by child report, F(3,236)=5.6, p=0.001) and depression (parent report, F(3,236)=23.7, p<0.001; child report, F(3,238)=9.9, p<0.001). In general, children in all three disorder groups had significantly higher levels of symptoms than TD children, but most pairwise differences among those three groups were not significant. The one exception was the higher level of depressive symptoms noted by parent report in the ADHD/DCD group. In conclusion, children identified on the basis of motor coordination problems through a population-based screen showed significantly more symptoms of depression and anxiety than typically developing children. Children who have both DCD and ADHD are particularly at heightened risk of psychological distress.

Newer antiepileptic drugs in bipolar disorder: rationale for use and role in therapy.

Antiepileptic drugs (AEDS) are used regularly in the treatment of patients with bipolar disorders. Carbamazepine and valproic acid (sodium valproate) are effective as antimanic treatments, and the success of these medications has prompted investigation of other AEDs as possible treatments in patients with mood disorders.Lamotrigine appears to be the most promising of the newer AEDs with respect to effects in mood disorders. Current evidence suggests efficacy of this drug both as monotherapy and as an adjunctive agent in bipolar depression, and studies are underway to clarify its efficacy in mood stabilisation and rapid cycling, as currently available data are equivocal. Use of gabapentin is not as well supported in the literature, although data from open trials using it as an adjunctive agent suggest that it may be helpful in patients with bipolar depression. There have been some open trials and case reports supporting the use of topiramate as an adjunctive agent for the treatment of mania; however, data from controlled trials are not yet available.Further controlled trials of lamotrigine, gabapentin or topiramate as mono-therapy and adjunctive treatment are needed to clarify their potential roles in the treatment of patients with mood disorders.

Increased subgenual prefrontal cortex size in remitted patients with major depressive disorder

Bilateral reductions in the volume of the anterior cingulate cortex have been reported in patients with major depressive disorder (MDD) when compared with findings in healthy controls. We compared regional brain volumes in the subgenual prefrontal cortex (SGPFC; Brodmann area (BA) 24(sg)), subcallosal gyrus (BA25) and paracingulate gyrus (BA32) in healthy control subjects and a large and well-characterized sample of patients with recurrent MDD, all of whom had received extensive antidepressant therapy. Patients with a remitted episode of MDD had SGPFC volumes larger than those of healthy controls, while those in an active illness episode did not differ from controls. There were no differences in subcallosal gyrus and paracingulate gyrus volumes between patients with MDD and healthy controls, with the exception that women with MDD had smaller paracingulate volumes than their sex-matched controls. This effect was not related to duration of illness, number of previous episodes, age at illness onset, or age at the time of scanning. Our findings demonstrate SGPFC volume increases in association with long-term antidepressant therapy and suggest that this result may be linked to positive clinical response.

A staged approach for identifying children with developmental coordination disorder from the population.

The purpose of this study was to describe the motor, attention and intellectual characteristics of a population-based sample of children first screened for motor impairment and to discuss the recruitment and identification methods employed. A two stage cross-sectional, school-based survey was conducted to screen for children with motor coordination difficulties and to identify children with an existing diagnosis of attention deficit hyperactivity disorder/attention deficit disorder (ADHD/ADD). The identified children, and a random sample of typically developing children, were assessed to confirm or rule out the presence of developmental coordination disorder (DCD). Six thousand four hundred and seventy five children were invited to participate; 2943 children, with parental consent, completed the initial screening process. Two hundred eighty four children with possible motor impairment were identified. The parents of 113 children consented to a full assessment. Sixty eight children of the 113 children met diagnostic criteria for DCD, and 26 also had ADHD. Twenty eight of the 55 children who screened in with a diagnosis of ADHD were subsequently found to have DCD. The total number of children with confirmed characteristics of DCD was reduced after application of DCD diagnostic criteria. This study differs from others with regard to the additional screening for children with ADHD/ADD. The second stage assessment notably increased the number of children identified with both ADHD and DCD.

Increased rates of obesity in first-presentation adults with mood disorders over the course of four-year follow-up

BACKGROUND Patients with mood disorders have higher rates of obesity than the general population. With respect to this, little is known regarding how patient look like prior to treatment or the rates of change. OBJECTIVE To identify changes in the rates of obesity in never-treated patients with mood disorder over 4 years of follow-up. METHODS Sixty-six never-treated patients with mood disorders were evaluated via clinical interview, symptom assessment and body mass index (BMI). Patients were followed 4 years. Population attributable risk (PAR%) was calculated. RESULTS Patients in underweight and normal weight groups fell by nearly 29%, with a corresponding increase in patients entering overweight and obese groups. Rates of PAR% increased to 16.0, a significant 5-point increase over baseline. LIMITATIONS This study had a small sample size and the population was ethnically homogenous. BMI was used as a maker of weight and not waist circumference. CONCLUSIONS Over 4 years there was a significant increase in BMI and the risk conferred by obesity. Shift from normal weight to overweight and obese is a significant risk for patients with a mood disorder and clinical programs should consider interventions that might ameliorate risk of this shift early in the course of the illness.