Pituitary volume in pediatric obsessive-compulsive disorder.

BACKGROUND: Abnormalities in the limbic-hypothalamic-pituitary-adrenal (LHPA) axis have been implicated in the pathogenesis of obsessive-compulsive disorder (OCD). To our knowledge, however, no prior study has measured pituitary gland volume in OCD. METHODS: Volumetric magnetic resonance imaging studies were conducted in 31 psychotropic drug-na?ve children (10 boys, 21 girls) aged 8-17 years and 31 case-matched healthy comparison subjects. RESULTS: Pituitary volume was significantly smaller in patients with OCD as compared with healthy control subjects (11% smaller). Smaller pituitary volume in patients with OCD was associated with increased compulsive but not obsessive symptom severity. Boys with OCD had smaller pituitary gland volumes compared with control boys (20% smaller). No significant differences in pituitary volume were observed between girls with OCD and control girls. Boys with OCD had significantly smaller pituitary volumes than girls with OCD (31% smaller), whereas control boys also had smaller pituitary gland volumes compared with control girls (21% smaller). CONCLUSIONS: These findings provide new evidence of reduced pituitary volume in pediatric OCD that seems to be more prominent in male patients. The observed alterations in pituitary volume are consistent with neuroendocrine studies that have reported abnormalities in the LHPA axis in OCD.     

Brain maturational processes and delayed onset in schizophrenia.

The central feature of schizophrenia is its onset in adolescence. Although this clinical observation is consistent with the view that schizophrenia may be a neurodevelopmental disorder, debate has focused on when the proposed brain maturational deviations may begin and what might be the nature of such defective development. Conflicting models of this illness (e.g., the early and late neurodevelopmental models) have been proposed. In this paper, we will first review concepts from basic developmental neurobiology pertinent to these issues; we then summarize aspects of the neurobiology of schizophrenia that have a particular bearing on the adolescent onset of this illness. We propose that the schizophrenic syndrome may result from early brain adversity and late maturational processes of brain development interacting with adverse humoral, biochemical, and psychosocial factors during adolescence and early adulthood. The onset of schizophrenia in adolescence may be related to the "plasticity switch" secondary to the peripubertal brain maturational changes, perhaps involving an alteration in glutamate receptor function. This loss of plasticity could result in social and nonsocial cognitive deficits that are central to the pathophysiology of schizophrenia; the vulnerable person may therefore utilize prepubertal processing styles that are insufficient to the adaptive and "gistful" abstraction requirements of adult cognition. Schizophrenia onset might occur in the context of psychosocial developmental challenges to a delayed social cognitive capacity among neurodevelopmentally compromised individuals. We review therapeutic implications as well as testable predictions generated by this model, and discuss research strategies that might further our understanding of the brain maturational abnormalities in schizophrenia.     

Failure of clonidine treatment in benzodiazepine withdrawal

Six subjects, dependent on benzodiazepines for at least 2 years, were gradually withdrawn, using placebo substitution, while taking clonidine. After withdrawal was complete, subjects were switched to clonidine-placebo. Despite administration of clonidine at doses sufficient to produce a fall in blood pressure, an abstinence syndrome was seen in five of the subjects. In none of these cases was the withdrawal syndrome exacerbated by changing from clonidine to clonidine-placebo. Scores of depression, subjective anxiety, observed anxiety and somatic symptoms did not change throughout the study.     

Hippocampal volume in adolescent-onset alcohol use disorders

OBJECTIVE: Alcohol use disorders (defined as DSM-IV alcohol dependence or abuse) are prevalent and serious problems among adolescents. As adolescence is marked by progressive hippocampal development, this brain region may be particularly susceptible to the adverse effects of adolescent alcohol use disorders. This study compared the hippocampal volumes of adolescents and young adults with adolescent-onset alcohol use disorders to those of healthy matched comparison subjects. METHOD: Magnetic resonance imaging was used to measure the hippocampal volumes and volumes of comparison brain regions in 12 subjects with alcohol use disorders and 24 comparison subjects matched on age, sex, and handedness. RESULTS: Both left and right hippocampal volumes were significantly smaller in subjects with alcohol use disorders than in comparison subjects. Total hippocampal volume correlated positively with the age at onset and negatively with the duration of the alcohol use disorder. Intracranial, cerebral, and cortical gray and white matter volumes and measures of the mid-sagittal area of the corpus callosum did not differ between groups. CONCLUSIONS: In the mature brain, chronic alcohol use disorders are associated with graded global brain dysmorphology. Although the etiology, neuropsychological consequences, and permanence of these hippocampal findings need to be further examined, these findings suggest that, during adolescence, the hippocampus may be particularly susceptible to the adverse effects of alcohol.     

N-Acetylaspartate concentration in the anterior cingulate of maltreated children and adolescents with PTSD

OBJECTIVE: Anterior cingulate dysfunction has been implicated in the pathophysiology of posttraumatic stress disorder (PTSD). The authors hypothesized that integrity of the anterior cingulate may be affected in childhood PTSD.METHOD: Single voxel proton magnetic resonance spectroscopy (proton MRS) was used to measure the relative concentration of N-acetylaspartate and creatine, a marker of neural integrity, in the anterior cingulate of 11 children and adolescents who met DSM-IV criteria for PTSD secondary to maltreatment and 11 healthy matched comparison subjects.RESULTS: The ratio of N-acetylaspartate to creatine was significantly lower in the maltreated subjects with PTSD than in the comparison subjects. CONCLUSIONS: The lower N-acetylaspartate/creatine ratio in subjects with PTSD suggests that anterior cingulate neuronal metabolism may be altered in childhood PTSD.     

Magnetic resonance spectroscopy in schizophrenia: methodological issues and findings--part II.

Magnetic resonance spectroscopy allows investigation of in vivo neurochemical pathology of schizophrenia. "First generation" studies, focusing on phosphorus and proton magnetic resonance spectroscopy, have suggested alterations in membrane phospholipid metabolism and reductions in N-acetyl aspartate in the frontal and temporal lobes. Some discrepancies remain in the literature, perhaps related to the variations in medication status and phase of illness in the patients examined, as well as in magnetic resonance spectroscopy methodology; the pathophysiologic significance of the findings also remains unclear. Technologic advances in magnetic resonance spectroscopy in recent years have expanded the potential to measure several other metabolites of interest such as the neurotransmitters glutamate and gamma-aminobutyric acid and macromolecules such as membrane phospholipids and synaptic proteins. Issues of sensitivity, specificity, measurement reliability, and functional significance of the magnetic resonance spectroscopy findings need to be further clarified. The noninvasive nature of magnetic resonance spectroscopy allows longitudinal studies of schizophrenia both in its different phases and among individuals at genetic risk for this illness. Future studies also need to address confounds of prior treatment and illness chronicity, take advantage of current pathophysiologic models of schizophrenia, and be hypothesis driven.     

Diagnostic specificity and familiality of early versus late evoked potentials to auditory paired stimuli across the schizophrenia‐bipolar psychosis spectrum

Disrupted sensory processing is a core feature of psychotic disorders. Auditory paired stimuli (PS) evoke a complex neural response, but it is uncertain which aspects reflect shared and/or distinct liability for the most common severe psychoses, schizophrenia (SZ) and psychotic bipolar disorder (BDP). Evoked time‐voltage/time‐frequency domain responses quantified with EEG during a typical PS paradigm (S1‐S2) were compared among proband groups (SZ [n = 232], BDP [181]), their relatives (SZrel [259], BDPrel [220]), and healthy participants (H [228]). Early S1‐evoked responses were reduced in SZ and BDP, while later/S2 abnormalities showed SZ/SZrel and BDP/BDPrel specificity. Relatives' effects were absent/small despite significant familiality of the entire auditorineural response. This pattern suggests general and divergent biological pathways associated with psychosis, yet may reflect complications with conditioning solely on clinical phenomenology.     

Bullying in clinical high risk for psychosis participants from the NAPLS-3 cohort

Purpose

Bullying is associated with a heightened risk for poor outcomes, including psychosis. This study aimed to replicate previous findings on bullying prevalence in clinical high-risk (CHR) individuals, to assess the longitudinal course of clinical and functional variables between bullied and non-bullied CHR and the association of bullying with premorbid functioning, clinical outcome, transition to psychosis and risk of violence.

Methods

The sample consisted of 691 CHR participants and 96 healthy controls. Participants reported whether they had experienced bullying and how long it had lasted. Assessments included DSM-5 diagnoses, attenuated psychotic symptoms, negative symptoms, social and role functioning, depression, stress, premorbid functioning, and risk of violence. The bullied and non-bullied CHR groups were compared at baseline and further longitudinally on clinical and functioning variables and transition to psychosis.

Results

Bullying was more prevalent among CHR individuals than healthy controls. Bullied CHR had a higher prevalence of PTSD and more severe depression and stress at baseline than non-bullied CHR. There was no impact of bullying on clinical and functional variables over time. Bullying was not related to final clinical status or transition to psychosis. However, bullied participants had poorer premorbid functioning and a greater risk of violence.

Conclusion

While bullying may not impact the likelihood of CHR individuals to transition to psychosis, it may be a risk factor for development of the at-risk state and may be related to a greater risk of violence. Future studies should consider bullying perpetration among CHR individuals.

     

Anatomical measurements of the orbitofrontal cortex in child and adolescent patients with bipolar disorder

Imaging studies indicate smaller orbitofrontal cortex (OFC) volume in mood disorder patients compared with healthy subjects. We sought to determine whether child and adolescent patients with bipolar disorder have smaller OFC volumes than healthy controls. Fourteen children and adolescents meeting DSM-IV criteria for bipolar disorder (six males and eight females with a mean age+/-S.D.=15.5+/-3.2 years) and 20 healthy controls (11 males and nine females with mean age+/-S.D.=16.9+/-3.8 years) were studied. Orbitofrontal cortex volume was measured using magnetic resonance imaging. Male bipolar patients had smaller gray matter volumes in medial (p=0.044), right medial (0.037) and right (p=0.032) lateral OFC subdivisions compared to male controls. In contrast, female patients had larger gray matter volumes in left (p=0.03), lateral (p=0.012), left lateral (p=0.007), and trends for larger volumes in right lateral and left medial OFC subdivisions compared with female controls. Male patients exhibit smaller gray matter volumes, while female patients exhibit larger volumes in some OFC sub-regions. Gender differences in OFC abnormalities may be involved in illness pathophysiology among young bipolar patients.