Biomedical subjects

Caleb M Adler

Publications and source records attributed to Caleb M Adler.

25 records · Page 2Linked to original sources

PubMed2004

Abnormal frontal white matter tracts in bipolar disorder: a diffusion tensor imaging study.

OBJECTIVES: Prefrontal white matter has been hypothesized to be integral to the pathophysiology of bipolar disorder. Recent morphometric studies however, have not observed changes in white matter in bipolar patients. We hypothesized that changes in prefrontal function in bipolar disorder, widely reported in the literature, may be related to a loss of white matter tract integrity with a resultant dysconnectivity syndrome. In this study we utilized diffusion tensor imaging (DTI) to examine prefrontal white matter in patients with bipolar disorder. METHODS: Nine patients with bipolar disorder and nine healthy controls were recruited. DTI and localizing anatomic data were acquired, and regions of interest (ROIs) identified in the prefrontal white matter at 15, 20, 25, and 30 mm superior to the anterior commissure (AC). Fractional anisotropy (FA) and trace apparent diffusion coefficient (TADC) were compared by ROI between study groups. RESULTS: The FA of ROIs 25 and 30 mm above the AC was significantly reduced in patients with bipolar disorder; FA of all ROIs showed high-medium to large effect sizes. No significant group differences were identified in TADC. CONCLUSIONS: Our findings suggest that a loss of bundle coherence is present in prefrontal white matter. This loss of coherence may contribute to prefrontal cortical pathology in patients with bipolar disorder.

Adult↗

PubMed2004

Changes in neuronal activation in patients with bipolar disorder during performance of a working memory task.

OBJECTIVES: Several lines of evidence suggest that deficits in cognition persist in bipolar patients during periods of euthymia. Working memory impairment has been observed in euthymic bipolar patients and noted to be a significant source of functional deficits in psychiatric disorders. Functional changes associated with these cognitive deficits however, remain poorly understood. We hypothesized that patients with bipolar disorder would demonstrate changes in neuronal activation in specific regions forming part of the working memory network. METHODS: Fifteen euthymic bipolar patients and fifteen age- and gender-matched healthy controls were recruited. Subjects participated in fMRI scans during which a two-back working memory task alternated with a zero-back control/attention task using a block-design paradigm. Groups were analyzed separately, and intergroup comparisons were made using an exploratory, voxel-by-voxel analysis. RESULTS: Bipolar patients performed more poorly on the cognitive tasks than did healthy controls (F = 3.77, p = 0.04). After covarying for task performance and reaction time, bipolar patients demonstrated significantly greater activation than healthy subjects in several regions including the fronto-polar prefrontal cortex, temporal cortex, basal ganglia, thalamus, and posterior parietal cortex. No areas showed a significant decrease in activation, compared with healthy controls. CONCLUSIONS: Our findings suggest that decreased working memory performance in bipolar patients reflects specific neurofunctional deficits. These deficits may represent primary areas of neuropathology or be secondary to neuropathology elsewhere in the working memory network. Continued research utilizing other imaging modalities may further clarify the underlying neuropathology involved in these cognitive deficits.

Adult↗

PubMed2003

Boundaries of schizophrenia.

The frontiers of schizophrenia are being increasingly challenged from several directions. In addition to ongoing debate as to divisions between schizophrenia and disorders of the schizophrenic spectrum, including schizotypal personality disorder and schizophreniform disorder, it has been suggested that obsessive-compulsive disorder might overlap phenomenologically with schizophrenia. There has been a long debate around the relationship of schizophrenia to affective disorders, particularly bipolar and schizoaffective disorder. The evidence suggests that although schizotypal personality and schizophreniform disorders are not homogeneous syndromes, they are related to or represent milder forms of schizophrenia. Obsessive-compulsive disorder seems to involve pathology in many of the same regions as observed in some patients with schizophrenia, which may account for the significant incidence of obsessive-compulsive symptoms in a subset of patients with schizophrenia. Despite similarities between schizophrenia and bipolar disorder, significant differences extend across suggested causes, phenomenology, and pathophysiology. These findings support the current conceptualization that the two disorders represent distinct disorders, probably with heterogeneous causes, rather than the ends of a spectrum of symptoms comprising a single syndrome. Schizoaffective disorder likely is made up of patients from the schizophrenic and bipolar cluster of illnesses. The long-standing debate as to the boundaries of schizophrenia is ultimately must await the eventual further elaboration of the underlying causes of schizophrenia and other psychotic disorders.

Bipolar Disorder↗

PubMed2003

Atypical antipsychotics in the treatment of bipolar disorder.

Atypical antipsychotic medications are widely used for the treatment of bipolar disorder. Most empirical support suggests that these medications are efficacious in the treatment of acute mania, but there is considerably less support for the utility of these drugs in other phases of bipolar disorder. However, it is likely that several of these drugs will demonstrate efficacy in relapse prevention, and perhaps antidepressant efficacy in bipolar disorder as more studies are conducted. Atypical antipsychotics offer different side effect profiles than older antipsychotics, which may be of benefit for some patients. Consequently, atypical antipsychotics provide an important treatment option for bipolar patients.

Anticonvulsants↗

PubMed2002

Amphetamine-induced dopamine release and post-synaptic specific binding in patients with mild tardive dyskinesia.

Several lines of evidence suggest that changes in dopamine release and/or post-synaptic sensitivity may be involved in the pathogenesis of tardive dyskinesia (TD). Preclinically, increased D(2) receptor sensitivity and dopamine turnover are associated with D(2) receptor antagonism. Clinically, development of TD is associated with D(2) receptor antagonist administration. Eight patients with mild evidence of TD (AIMS ratings > or =14) and six without (AIMS = 10), underwent [(11)C]raclopride PET scans. Baseline and amphetamine-induced decrements in striatal specific binding were assessed. Baseline and amphetamine-induced decrements in specific binding did not differ between patients with and without evidence of mild TD (p =.53). AIMS ratings did not significantly correlate with baseline (p =.76) or decrements in specific binding (p =.45). This study provides evidence that TD is not associated with increased amphetamine-induced presynaptic dopamine release and/or D(2) receptor binding as measured by [(11)C]raclopride PET. More research is needed to unravel the neurobiology of this debilitating disorder.

Adult↗

PubMed2002

Volumetric MRI studies of mood disorders: do they distinguish unipolar and bipolar disorder?

The authors reviewed magnetic resonance imaging volumetric imaging results in major mood disorders, particularly comparing similarities and differences from studies of bipolar disorder and unipolar major depression. Abnormalities of cerebral brain regions appear inconsistently in mood disorders and, when present, typically consist of decreased frontal or prefrontal cortical volumes in both unipolar depression and bipolar disorder. In contrast, subcortical and medial temporal abnormalities are more commonly observed and are different between these two major classes of affective illness. Specifically, whereas structural enlargement of the basal ganglia and amygdala have been observed in bipolar disorder, in unipolar depression, these structures appear to be smaller in patients than healthy subjects. These findings suggest that affective illnesses may share in common an underdeveloped or atrophied prefrontal region, leading to loss of cortical modulation of limbic emotional networks. The effect of this loss results in unipolar depression or cycling (mania with depression) depending on the abnormalities of the subcortical structures involved. The cerebellum may also play a role in the presentation of mood disorders. This hypothesis remains speculative as much more research is needed to specifically examine how morphometric brain abnormalities translate into the neurophysiologic deficits that produce mood disorders.

Bipolar Disorder↗

PubMed2002

Ventricular and periventricular structural volumes in first- versus multiple-episode bipolar disorder.

OBJECTIVE: Ventriculomegaly has been reported in bipolar disorder, although whether it occurs at illness onset or progresses during the course of the disorder is unknown. In addition, it is unknown whether ventriculomegaly in bipolar disorder reflects acquired volume loss or underdevelopment of periventricular structures. METHOD: Magnetic resonance imaging was used to measure the volumes of the lateral and third ventricles and periventricular structures (caudate, putamen, thalamus, hippocampus). Patients with DSM-IV bipolar disorder, 18 who were having a first episode and 17 with multiple episodes, were compared with 32 healthy subjects. RESULTS: The lateral ventricles were significantly larger in the patients with multiple-episode bipolar disorder than in the first-episode patients or the healthy subjects, even after periventricular and total cerebral volumes were taken into account. Having larger lateral ventricles was associated with a higher number of prior manic episodes. The multiple-episode patients had a smaller total cerebral volume than the healthy subjects but not the first-episode patients. The putamen was significantly larger in the first-episode patients (and nearly so in the multiple-episode patients) than in the healthy subjects, although there was no difference between patient groups. CONCLUSIONS: Lateral ventriculomegaly was greater in bipolar disorder patients who had had repeated manic episodes, but it does not appear to be secondary to small critical periventricular structures. A larger than normal striatum, which has been reported in previous studies, was observed in first-episode patients. These results support the importance of prospectively studying neuroanatomic changes in bipolar disorder.

Adolescent↗