Personality disorders in hypochondriasis: prevalence and comparison with two anxiety disorders.

OBJECTIVE: Symptoms of hypochondriasis are sometimes attributed to personality psychopathology by health care providers. The goals of this study were to assess the prevalence of personality disorder (PD) comorbidity in hypochondriasis (HYP) and to compare the PD comorbidity profile of patients with HYP with that found among patients with other disorders characterized by intrusive thoughts and fears. METHODS: Structured Clinical Interview for DSM-IV Axis I and Axis II Disorders (SCID-I and SCID-II) were administered to 179 individuals: 62 with HYP, 46 with obsessive-compulsive disorder (OCD), and 71 with social anxiety disorder (SAD). For group contrasts, the samples were "purified" of the comparison comorbid disorders. General linear models were used to test the combined effect of group (HYP, OCD, SAD), age, and gender on the PD outcome variables. RESULTS: 59.7% of HYP subjects had no Axis II comorbidity. The most common PDs in HYP were paranoid (19.4%), avoidant (17.7%), and obsessive-compulsive (14.5%). HYP significantly differed from SAD in the likelihood of a cluster C disorder, whereas no significant difference was noted for HYP vs. OCD. The proportion of subjects having at least two PDs was not significantly different for HYP vs. OCD or for HYP vs. SAD. CONCLUSION: Although 40% of patients with hypochondriasis have PD comorbidity as assessed by the SCID-II, the amount of PD comorbidity is not significantly different than found among individuals with two comparison anxiety disorders. Therefore, health providers should be aware that PD may complicate the clinical profile of HYP, but they should avoid assuming that PD psychopathology is the primary source of hypochondriacal distress.

Measurement of fidgeting in patients with anorexia nervosa using a novel shoe-based monitor.

OBJECTIVE: To objectively assess seated non-exercise physical activity in patients with anorexia nervosa (AN) relative to healthy controls (HCs) and examine the associations between this physical activity, eating disorder pathology, and levels of anxiety and depression. METHOD: Eleven inpatients with AN and 10 HCs wore a shoe-based accelerometer (SmartShoe) at three time points: a) while eating lunch, b) filling out questionnaires, and c) watching television for 1h. RESULTS: Across all three tasks, patients with AN were significantly more active than HCs, thereby engaging in a greater degree of restless or fidgeting behavior. Degree of physical activity was positively correlated with eating disorder psychopathology in the sample with AN, and a trend towards a positive association between physical activity and levels of depression and anxiety was also found in this sample. Among individuals with AN, physical activity was not significantly correlated with BMI, duration of illness, or number of days since hospital admission. DISCUSSION: Use of a minimally invasive, shoe-based monitor revealed patients with AN engaged in a greater degree of fidgeting relative to HCs during quiet, seated tasks and this heightened activity was related to measures of pathology. Non-exercise physical activity, including fidgeting, may warrant further clinical attention in this patient population.

Glutamate modulators as novel interventions for mood disorders.

UNLABELLED: Recent evidence suggests that critical molecules in neurotrophic signaling cascades are long-term targets for currently available monoaminergic antidepressants. As chronic and severe mood disorders are characterized by impairments in neuronal resilience, pharmacological strategies that subserve a neuroprotective function might alter disorder pathophysiology and modify disease progression. Several promising approaches involve modulation of the glutamate neurotransmitter system, via post-synaptic receptor blockade or potentiation and presynaptic vesicular release inhibition. A focused review of the extant scientific literature was conducted, with a discussion of 3 compounds or classes of drugs currently undergoing clinical investigation: ketamine, riluzole, and AMPA receptor potentiators. Recent investigations in mood disordered patients suggest that the NMDA receptor antagonist ketamine might demonstrate rapid antidepressant properties. Riluzole has been shown to reverse glutamate-mediated impairments in neuronal plasticity and to stimulate the synthesis of brain derived neurotrophic factor. Open-label trials in treatment-resistant depression have yielded promising results. Likewise, AMPA receptor potentiators favorably impact neurotrophic factors as well as enhance cognition. CONCLUSIONS: Pharmacological approaches that modulate components of the glutamate system offer novel targets for severe, recurrent mood disorders. Controlled studies are necessary.

Treatment With Acamprosate in Patients With Schizophrenia Spectrum Disorders and Comorbid Alcohol Dependence.

OBJECTIVE: Alcohol use disorders and schizophrenia frequently co-occur with rates higher than in the general population. There is no consensus on the best treatment for patients with these comorbid conditions. Several clinical trials have shown that acamprosate is superior to placebo in reducing drinking and is particularly effective in sustaining abstinence. No study to date has examined the efficacy of acamprosate in patients with alcohol dependence and comorbid schizophrenia. The aims of this study are to assess the efficacy of acamprosate when compared to placebo in reducing drinking and to examine its effects on schizophrenic symptoms. METHODS: This was a double-blind, randomized, 12-week treatment trial of acamprosate versus placebo. Twenty-three recently abstinent patients with diagnosed alcohol dependence and comorbid schizophrenia, schizoaffective disorder, or psychosis not otherwise specified were included in this study. RESULTS: All participants significantly decreased their drinking during medication treatment, although acamprosate was not superior to placebo in increasing consecutive days of abstinence. There was a significant difference favoring the acamprosate group on obsessive thoughts of drinking but no significant group X time interaction. Overall, medication treatment significantly reduced positive symptoms of schizophrenia, but there were no group differences. CONCLUSIONS: Acamprosate was not more effective than placebo in reducing drinking or symptoms of schizophrenia. It can be safely used in patients with alcohol dependence and comorbid schizophrenia spectrum disorders.

Necessity of hippocampal neurogenesis for the therapeutic action of antidepressants in adult nonhuman primates.

BACKGROUND: Rodent studies show that neurogenesis is necessary for mediating the salutary effects of antidepressants. Nonhuman primate (NHP) studies may bridge important rodent findings to the clinical realm since NHP-depression shares significant homology with human depression and kinetics of primate neurogenesis differ from those in rodents. After demonstrating that antidepressants can stimulate neurogenesis in NHPs, our present study examines whether neurogenesis is required for antidepressant efficacy in NHPs. MATERIALS/METHODOLOGY: Adult female bonnets were randomized to three social pens (N = 6 each). Pen-1 subjects were exposed to control-conditions for 15 weeks with half receiving the antidepressant fluoxetine and the rest receiving saline-placebo. Pen-2 subjects were exposed to 15 weeks of separation-stress with half receiving fluoxetine and half receiving placebo. Pen-3 subjects 2 weeks of irradiation (N = 4) or sham-irradiation (N = 2) and then exposed to 15 weeks of stress and fluoxetine. Dependent measures were weekly behavioral observations and postmortem neurogenesis levels. RESULTS: Exposing NHPs to repeated separation stress resulted in depression-like behaviors (anhedonia and subordinance) accompanied by reduced hippocampal neurogenesis. Treatment with fluoxetine stimulated neurogenesis and prevented the emergence of depression-like behaviors. Ablation of neurogenesis with irradiation abolished the therapeutic effects of fluoxetine. Non-stressed controls had normative behaviors although the fluoxetine-treated controls had higher neurogenesis rates. Across all groups, depression-like behaviors were associated with decreased rates of neurogenesis but this inverse correlation was only significant for new neurons in the anterior dentate gyrus that were at the threshold of completing maturation. CONCLUSION: We provide evidence that induction of neurogenesis is integral to the therapeutic effects of fluoxetine in NHPs. Given the similarity between monkeys and humans, hippocampal neurogenesis likely plays a similar role in the treatment of clinical depression. Future studies will examine several outstanding questions such as whether neuro-suppression is sufficient for producing depression and whether therapeutic neuroplastic effects of fluoxetine are specific to antidepressants.

Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome compared with generalized anxiety disorder: an in vivo 3.0 T (1)H MRS imaging study.

Chronic fatigue syndrome (CFS) is a controversial diagnosis because of the lack of biomarkers for the illness and its symptom overlap with neuropsychiatric, infectious, and rheumatological disorders. We compared lateral ventricular volumes derived from tissue-segmented T(1)-weighted volumetric MRI data and cerebrospinal fluid (CSF) lactate concentrations measured by proton MRS imaging ((1)H MRSI) in 16 subjects with CFS (modified US Centers for Disease Control and Prevention criteria) with those in 14 patients with generalized anxiety disorder (GAD) and in 15 healthy volunteers, matched group-wise for age, sex, body mass index, handedness, and IQ. Mean lateral ventricular lactate concentrations measured by (1)H MRSI in CFS were increased by 297% compared with those in GAD (P < 0.001) and by 348% compared with those in healthy volunteers (P < 0.001), even after controlling for ventricular volume, which did not differ significantly between the groups. Regression analysis revealed that diagnosis accounted for 43% of the variance in ventricular lactate. CFS is associated with significantly raised concentrations of ventricular lactate, potentially consistent with recent evidence of decreased cortical blood flow, secondary mitochondrial dysfunction, and/or oxidative stress abnormalities in the disorder.

Phase I and initial phase II results from a trial investigating weekly docetaxel and carboplatin given neoadjuvantly and then concurrently with concomitant boost radiotherapy for locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND: The current Phase I/II study assessed induction docetaxel/carboplatin given weekly for 4 weeks, followed by weekly docetaxel/carboplatin and concomitant boost radiotherapy (CB-XRT) for locally advanced head and neck squamous cell carcinoma. METHODS: Twenty patients with Stage III or IV (M0) disease of the oropharynx, supraglottic larynx, or hypopharynx were enrolled. Patients initially received docetaxel 20 mg/m2 and carboplatin area under the curve (AUC) 2 weekly x 4. Patients with stable (SD) or responding disease subsequently received dose-escalated docetaxel (10-20 mg/m2 in sequential patient cohorts) and carboplatin AUC 1 weekly x 5 with CB-XRT (1.8 gray [Gy] every day x 15 days, followed by 1.8/1.5 Gy twice per day x 13 days). RESULTS: All patients were evaluable, and 15 patients (5 patients with Stage III disease, 10 patients with Stage IV disease) completed all planned therapy. The target docetaxel dose level of 20 mg/m(2) weekly with radiotherapy was achieved with no dose-limiting toxicities. The most frequent maximum toxicities during chemoradiotherapy were Grade 3 mucositis, dysphagia, and/or pain. Primary site responses after induction included 4 patients with partial responses, 11 patients with SD, and 5 patients with disease progression. Fifteen patients (75%) continued to receive chemoradiotherapy, with 14 patients attaining a complete response (CR). Overall, a clinicopathologic neck CR after chemoradiotherapy was achieved in 9 of 10 patients. One patient had persistent primary disease and underwent salvage surgery, whereas another died of unrelated causes before neck assessment. Thirteen patients remain free of any disease event, with a median follow-up of 15 months (range, 3-29 months). CONCLUSIONS: This regimen was feasible, safe, and particularly well tolerated. Early Phase II outcomes revealed promising activity in patients completing all treatment. Initial induction response results suggested that further investigation of this regimen with more aggressive induction therapy is warranted.

Glutamate modulators as novel interventions for mood disorders

Recentes evidências sugerem que as moléculas críticas nas cascatas de sinalizacão neurotrófica são alvos de longo prazo dos antidepressivos monoaminérgicos disponíveis atualmente. Na medida em que transtornos graves e crônicos são caracterizados por deficiências na resiliência neuronal, estratégias farmacológicas que sejam úteis para uma funcão neuroprotetora talvez possam alterar a fisiopatologia e modificar a progressão da doenca. Vários enfoques promissores envolvem a modulacão do sistema neurotransmissor do glutamato, via bloqueio ou potencializacão do receptor pós-sináptico e inibicão da liberacão vesicular pré-sináptica. Foi realizada uma revisão focada da literatura científica existente, com a discussão de três compostos ou classes de drogas que estão atualmente sob investigacão clínica: a ketamina, o riluzol e os potencializadores de receptores de AMPA. DISCUSSAO: Estudos recentes com pacientes com transtornos de humor sugerem que a ketamina, um antagonista do receptor NMDA, poderia ter demonstrado propriedades antidepressivas rápidas. O riluzol demonstrou reverter deficiências mediadas pelo glutamato na plasticidade neuronal e estimular a síntese de fatores neurotróficos derivados do cérebro. Ensaios abertos com depressão resistente ao tratamento produziram resultados promissores. Da mesma forma, os potencializadores de receptores de AMPA impactam favoravelmente os fatores neurotróficos, assim como melhoram a cognicão. CONCLUSÕES: Enfoques farmacológicos que modulam os componentes do sistema de glutamato oferecem novos alvos para transtornos de humor recorrentes e graves. São necessários estudos controlados.