Neurobiology of the dorsolateral prefrontal cortex in GAD: Aberrant neurometabolic correlation to hippocampus and relationship to anxiety sensitivity and IQ.

INTRODUCTION: The neurometabolism underlying the cognitive and affective symptoms associated with generalized anxiety disorder (GAD) remain poorly understood. After we have linked worry to intelligence in patients with GAD, we hypothesized that aberrant neurometabolic correlations between hippocampus and neocortical regions may underlie a shared substrate in GAD patients for both anxiety sensitivity and intelligence. METHODS: GAD patients (n = 16; F = 11) and healthy volunteers (n = 16; F = 10) were assessed using 1H-MRSI. Co-axial planes I [hippocampus (HIPP)] and co-axial plane III [dorsolateral prefrontal cortex (DLPFC), central gyrus (CG)] were examined. Using general linear models, we examined resting metabolite concentrations using HIPP as a hub to CG and DLPFC. Neocortical ROIs were related to Anxiety Sensitivity Index (ASI) and Full Scale IQ (FSIQ) in GAD patients versus controls. RESULTS: Right hippocampal Cho/Cr directly predicted left DLPFC Cho/Cr in GAD (r = 0.75), an effect distinguishable (p = 0.0004) from controls. Left HIPP Cho/Cr positively predicted left CG Cho/Cr in GAD, an effect distinguishable from controls. In patients, both left and right DLPFC Cho/Cr positively predicted ASI but only left DLPFC Cho/Cr inversely predicted IQ. By contrast, IQ in controls correlated directly with left CG Cho/Cr. LIMITATIONS: Small sample size precluded us from investigating how gender and FSIQ subscales related to neurochemical correlations in the ROIs examined. CONCLUSIONS: Aberrant resting state neurochemical correlation between left DLPFC and right HIPP may contribute to GAD symptomatology. Unlike controls, in GAD, IQ and worry may share a common yet inverse neurometabolic substrate in left DLPFC.

Effects of Acute Confinement Stress-induced Hypothalamic-Pituitary Adrenal Axis Activation and Concomitant Peripheral and Central Transforming Growth Factor-ß1 Measures in Nonhuman Primates.

Transforming growth factor-ß1 (TGF-ß1) is a multifunctional cytokine with anti-inflammatory, immunosuppressive and neuroprotective properties. The hypothalamic-pituitary-adrenal (HPA) axis and immune system exert bidirectional influences on each other, via cortisol and TGF-ß1, but the exact nature of the interaction is not well characterized. The current study examined the effects, in bonnet macaques (Macaca radiata), of two consecutive acute confinement stress periods in an unfamiliar room while mildly restrained, first without and then with dexamethasone pretreatment (0.01 mg/kg IM). Preceding the confinement studies, a non-stress control condition obtained contemporaneous levels of cortisol and TGF-ß1 in both plasma and cerebrospinal fluid (CSF) to match the confinement stress studies. Subjects were reared under either normative or variable foraging demand (VFD) conditions. Since there were no rearing effects at baseline or for any of the conditions tested -- either for cortisol or TGF-ß -- the study analyses were conducted on the combined rearing groups. The stress condition increased both plasma and CSF cortisol levels whereas dexamethasone pretreatment decreased cortisol concentrations to below baseline levels despite stress. The stress condition decreased TGF-ß1 concentrations only in CSF but not in serum. Together the data suggested that stress-induced reductions of a centrally active neuroprotective cytokine occurs in the face of HPA axis activation, potentially facilitating glucocortoid-induced neurotoxicity. Stress-induced reductions of neuroprotective cytokines prompts exploration of protective measures against glucocorticoid-induced neurotoxicity.

Diagnostic Stability of Internet Addiction in Obsessive-compulsive Disorder: Data from a Naturalistic One-year Treatment Study.

Whether internet addiction should be categorized as a primary psychiatric disorder or the result of an underlying psychiatric disorder still remains unclear. In addition, the relationship between internet addiction and obsessive-compulsive disorder remains to be explored. We hypothesized that internet addiction is a manifestation of underlying psychopathology, the treatment of which will improve internet addiction. We enrolled 34 control subjects (with or without internet addiction) and compared them to 38 patients with "pure" obsessive-compulsive disorder (with or without internet addiction). Internet addiction and obsessive-compulsive disorder were diagnosed based on Young's Diagnostic Questionnaire and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), respectively. Age and Internet Addiction Test scores were comparable in both the control (years: 26.87±6.57; scores: 43.65±11.56) and obsessive-compulsive disorder groups (years: 27.00±6.13 years, p=0.69; scores: 43.47±15.21, p=0.76). Eleven patients with obsessive-compulsive disorder (28.95%) were diagnosed with internet addiction as compared to three control subjects (p=0.039). In the obsessive-compulsive disorder group, no difference in the Yale-Brown Obsessive Compulsive Scale (24.07±3.73 non-internet addiction, 23.64±4.65 internet addiction; p=0.76) score was seen between the internet addiction/obsessive-compulsive disorder and non-internet addiction/obsessive-compulsive disorder groups. As expected, the Internet Addiction Test scores were higher in the internet addiction/obsessive-compulsive disorder group (64.09±9.63) than in the non-internet addiction/obsessive-compulsive disorder group (35.07±6.37; p=0.00). All enrolled patients with obsessive-compulsive disorder were subsequently treated for a period of one year. Treatment of obsessive-compulsive disorder improved Yale-Brown Obsessive Compulsive Scale and Internet Addiction Test scores over time. At 12 months, only two of the 11 patients with obsessive-compulsive disorder (18.18%) fulfilled the Young's Diagnostic Questionnaire criteria for internet addiction. In conclusion, treatment of the underlying disorder improved internet addiction.

A Novel Anxiety and Affective Spectrum Disorder of Mind and Body-The ALPIM (Anxiety-Laxity-Pain-Immune-Mood) Syndrome: A Preliminary Report.

The authors describe a spectrum disorder comprising a core anxiety (A) disorder and four domains: joint laxity (L), chronic pain syndromes (P), immune disorders (I), and mood disorders (M)-dubbed the ALPIM syndrome. This study examined 76 consecutive outpatients with an anxiety disorder plus at least one somatic condition from three domains. More than 80% of the patients had panic attacks, fibromyalgia, and major depressive episodes. Associations were found between joint laxity and bipolar III, headache with bipolar II, and bipolar II with chronic fatigue syndrome. Significant relationships were demonstrated within and between domains, validating ALPIM as a syndrome.

A neurobiological hypothesis of treatment-resistant depression - mechanisms for selective serotonin reuptake inhibitor non-efficacy.

First-line treatment of major depression includes administration of a selective serotonin reuptake inhibitor (SSRI), yet studies suggest that remission rates following two trials of an SSRI are <50%. The authors examine the putative biological substrates underlying "treatment resistant depression (TRD)" with the goal of elucidating novel rationales to treat TRD. We look at relevant articles from the preclinical and clinical literature combined with clinical exposure to TRD patients. A major focus was to outline pathophysiological mechanisms whereby the serotonin system becomes impervious to the desired enhancement of serotonin neurotransmission by SSRIs. A complementary focus was to dissect neurotransmitter systems, which serve to inhibit the dorsal raphe. We propose, based on a body of translational studies, TRD may not represent a simple serotonin deficit state but rather an excess of midbrain peri-raphe serotonin and subsequent deficit at key fronto-limbic projection sites, with ultimate compromise in serotonin-mediated neuroplasticity. Glutamate, serotonin, noradrenaline, and histamine are activated by stress and exert an inhibitory effect on serotonin outflow, in part by "flooding" 5-HT1A autoreceptors by serotonin itself. Certain factors putatively exacerbate this scenario - presence of the short arm of the serotonin transporter gene, early-life adversity and comorbid bipolar disorder - each of which has been associated with SSRI-treatment resistance. By utilizing an incremental approach, we provide a system for treating the TRD patient based on a strategy of rescuing serotonin neurotransmission from a state of SSRI-induced dorsal raphe stasis. This calls for "stacked" interventions, with an SSRI base, targeting, if necessary, the glutamatergic, serotonergic, noradrenergic, and histaminergic systems, thereby successively eliminating the inhibitory effects each are capable of exerting on serotonin neurons. Future studies are recommended to test this biologically based approach for treatment of TRD.

Electroconvulsive therapy for the treatment of organic catatonia due to viral encephalitis.

Catatonia is a common presentation to psychiatric services in developing countries. Medical causes of catatonia are common and are difficult to treat. A 20-year-old woman presented with an acute illness consisting of fever, delirium, perceptual abnormalities, and catatonic state. After trials with antiviral medications, benzodiazepines, and atypical antipsychotic medications, she was treated with 6 sessions of electroconvulsive therapy with complete recovery and no complications. Catatonia arising in the background of organic pathology can be treated on similar lines as in other psychiatric disorders. Electroconvulsive therapy can be a safe option that needs consideration in such cases after ruling out the contraindications.

Left behind radiological investigations: An inherent problem.

OBJECTIVES: To assess the number of investigations left behind by patients in radiology department, their cost, and the possible methods of reducing the problem. MATERIALS AND METHODS: A total of 1424 radiographs, 160 computed tomography (CT) scans, 300 ultrasonography (USG) reports, and 46 Doppler reports were left behind by patients in one financial year. The total cost of these left behind investigations was calculated and the reports were categorized into normal and abnormal for each modality. RESULTS: Of the radiographs left behind 658 were abnormal, with 211 among these being radiographs of postoperative patients. Thirty-seven percent of CT scans had positive findings. Sixty-eight percent of USG reports had positive findings while 46% of Doppler reports were abnormal. CONCLUSION: We believe that the cost and number of these left behind investigations over a period of time would definitely be significant for the health care system in a developing country. It is time to think of the possible reasons and methods for containing this problem.