Neurotransmitters behind pain relief with transcranial magnetic stimulation - positron emission tomography evidence for release of endogenous opioids.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) at M1/S1 cortex has been shown to alleviate neuropathic pain. OBJECTIVES: To investigate the possible neurobiological correlates of cortical neurostimulation for the pain relief. METHODS: We studied the effects of M1/S1 rTMS on nociception, brain dopamine D2 and µ-opioid receptors using a randomized, sham-controlled, double-blinded crossover study design and 3D-positron emission tomography (PET). Ten healthy subjects underwent active and sham rTMS treatments to the right M1/S1 cortex with E-field navigated device. Dopamine D2 and µ-receptor availabilities were assessed with PET radiotracers [11 C]raclopride and [11 C]carfentanil after each rTMS treatment. Thermal quantitative sensory testing (QST), contact heat evoked potential (CHEP) and blink reflex (BR) recordings were performed between the PET scans. RESULTS: µ-Opioid receptor availability was lower after active than sham rTMS (P ≤ 0.0001) suggested release of endogenous opioids in the right ventral striatum, medial orbitofrontal, prefrontal and anterior cingulate cortices, and left insula, superior temporal gyrus, dorsolateral prefrontal cortex and precentral gyrus. There were no differences in striatal dopamine D2 receptor availability between active and sham rTMS, consistent with lack of long-lasting measurable dopamine release. Active rTMS potentiated the dopamine-regulated habituation of the BR compared to sham (P = 0.02). Thermal QST and CHEP remained unchanged after active rTMS. CONCLUSIONS: rTMS given to M1/S1 activates the endogenous opioid system in a wide brain network associated with processing of pain and other salient stimuli. Direct enhancement of top-down opioid-mediated inhibition may partly explain the clinical analgesic effects of rTMS. SIGNIFICANCE: Neurobiological correlates of rTMS for the pain relief are unclear. rTMS on M1/S1 with 11 C-carfentanyl-PET activates endogenous opioids. Thermal and heat pain thresholds remain unchanged. rTMS induces top-down opioid-mediated inhibition but not change the sensory discrimination of painful stimuli.

Long-term use of benzodiazepines: Definitions, prevalence and usage patterns - a systematic review of register-based studies.

BACKGROUND: Numerous treatment guidelines recommend that long-term use of benzodiazepines (BZD) should be avoided primarily due to development of tolerance and a risk for BZD dependence. Despite this, long-term BZD use remains a controversial subject in clinical patient care with "for and against" debates. However, there is no explicit understanding of what is meant by long-term BZD use in real world. The aim of this study was to assess different definitions, usage patterns, prevalence and other characteristics of long-term BZD use based on published register-based studies. Synthesis of these characteristics is essential to derive a meaningful definition of long-term BZD. METHODS: Systematic review of register-based studies on long-term BZD use published in 1994-2014. RESULTS: Fourty-one studies met our predetermined inclusion criteria. The length of BZD use defined as "long-term" varied in these studies ranging from one month to several years. The most common definition was six months or longer during a year. The prevalence of long-term BZD use in the general population was estimated to be about 3%. The relative proportion of long-term BZD users (all definitions) in adult BZD users ranged from 6% to 76% (mean 24%; 95% CL 13-36%). The estimates were higher in studies only on the elderly (47%; 95% CL 31-64%). Long-term use involved typically steady treatment with low BZD doses. However, in elderly patients long-term BZD use and exceeding recommended doses was relatively common. Several characteristics associated with long-term use were found. CONCLUSIONS: Long-term BZD use is common and a clinical reality. Uniform definitions for "long-term", which is in line with population-based evidence, is needed to have more comparable results between studies. Our systematic review suggests that duration of BZD treatment over six months, the most common definition for long-term BZD use in the included studies. As also recommended previously, it is a useful starting point for further analyses on disadvantages but also potential advantages associated with long-term BZD use.

Attached to the web--harmful use of the Internet and its correlates.

BACKGROUND AND AIMS: The aim of this study was to test the validity of the Finnish version of the Internet Addiction Test and the correlates of harmful use of the Internet. METHODS: One thousand eight hundred and twenty-five students (45.5% men and 54.5% women, mean age 24.7 years, S.D.=5.7) filled in a web-based questionnaire including IAT, reasons for use of the Internet, distress, social support, and substance use. RESULTS: Men had a statistically significantly higher mean score on the IAT than women. Subjects with self-reported use of cannabis had higher mean score on the IAT compared to non-users (39.5 [11.3] vs 35.8 [10.8]). The total IAT score was associated with "adult entertainment" (OR=1.07, 95%CI: 1.06-1.08, P<0.001), "playing games" (OR=1.05, 95%CI: 1.04-1.06, P<0.001), "chatting" (OR=1.07, 95%CI: 1.06-1.08, P<0.001) and "discussion" (OR=1.08, 95%CI: 1.07-1.09, P<0.001) as reasons for Internet use. The IAT score had a significant negative correlation with social support (r=-0.24, P<0.001) and a significant positive correlation with the CAGE score (r=0.18, P<0.001). Using factor analysis, we found a single factor solution with a Cronbach's alpha of 0.92. CONCLUSIONS: The IAT seems to provide a valid measurement of harmful use of the Internet, as the score was significantly associated with variables tapping psychopathology.

APOE-epsilon4 predicts dementia but not other psychiatric disorders after traumatic brain injury.

The authors studied the association between APOE-epsilon4 genotype and axis I and II psychiatric disorders an average of 30 years after traumatic brain injury. Sixty patients were dichotomized into subjects with and without APOE-epsilon4 allele. Dementia and subclinical dementia were significantly more common with the presence of APOE-epsilon4. The occurrence of other psychiatric disorders did not differ between patients with and without APOE-epsilon4 allele.

Psychodynamic personality profile in first-episode severe mental disorders.

OBJECTIVE: The aim of this study was to relate measures of psychoanalytically derived personality traits to descriptive diagnosis and psychopathology in severe mental disorders. METHOD: Sixty-one consecutive first-episode patients with schizophrenia, bipolar disorder and severe major depression were interviewed. Personality traits were assessed with the Karolinska Psychodynamic Profile (KAPP) and compared with the DSM-IV diagnosis and symptom clusters derived from the BPRS. RESULTS: There were no marked differences in personality traits between the three diagnostic groups, between schizophrenia and affective disorders or between psychotic and non-psychotic illness. However, personality traits had significant associations with symptoms, especially with the emotional retardation cluster. CONCLUSION: Our findings do not support the hypothesis that severe mental disorders would differ from each other in terms of long-standing psychodynamic personality profiles. Certain dysfunctional personality traits may predict especially negative emotional symptoms and possibly also predispose a person to them.

Structural magnetic resonance imaging in patients with first-episode schizophrenia, psychotic and severe non-psychotic depression and healthy controls. Results of the schizophrenia and affective psychoses (SAP) project.

BACKGROUND: Structural brain abnormalities are prevalent in patients with schizophrenia and affective disorders. AIMS: To study how regional brain volumes and their ratios differ between patients with schizophrenia, psychotic depression, severe non-psychotic depression and healthy controls. METHOD: Magnetic resonance imaging scans of the brain on first-episode patients and on healthy controls. RESULTS: Patients with schizophrenia had a smaller left frontal grey matter volume than the other three groups. Patients with psychotic depression had larger ventricular and posterior sulcal cerebrospinal fluid (CSF) volumes than controls. Patients with depression had larger white matter volumes than the other patients. CONCLUSIONS: Left frontal lobe, especially its grey matter volume, seems to be specifically reduced in first-episode schizophrenia. Enlarged cerebral ventricles and sulcal CSF volumes are prevalent in psychotic depression. Preserved or expanded white matter is typical of non-psychotic depression.

Intense and recurrent déjà vu experiences related to amantadine and phenylpropanolamine in a healthy male.

We report a case of a 39-year-old caucasian healthy male physician who developed intense and recurrent déjà vu experiences within 24h of initiating concomitant amantadine-phenylpropanolamine treatment against influenza. Déjà vu experiences terminated on discontinuation of medication. Findings in temporal epilepsy suggest that mesial temporal structures, including hippocampus, are related to paramnesic symptoms. On the other hand, previous case reports have confirmed that both amantadine and phenylpropanolamine alone, and particularly in combination, can induce psychotic symptoms due to their dopaminergic activity. The authors suggest that déjà vu experiences may be provoked by increased dopamine activity in mesial temporal structures of the brain.

The Schizophrenia Suicide Risk Scale (SSRS): development and initial validation.

BACKGROUND: Estimations about the lifetime risk of suicide in schizophrenia vary between 4 and 10%. At present, there does not exist a suicide risk scale developed particularly for schizophrenic patients. The aims of the present study were to: (1) develop a clinically useful semi-structured scale for the estimation of short-term suicide risk among schizophrenic patients, and (2) to carry out an initial validation of the scale. METHODS: A 25-item Schizophrenia Suicide Risk Scale (SSRS) was constructed on the base of the literature. The SSRS scores of 69 living schizophrenic patients (LS group) were compared with the scores of 69 schizophrenic suicides (SS group) whose data had been collected previously from The Finnish nationwide and representative psychological autopsy study. Internal consistency of the SSRS was evaluated with Cronbach alpha. The most important SSRS items predicting suicide were identified with a logistic regression analysis. Sensitivity, specificity, positive predictive value, and negative predictive value of the SSRS in predicting suicide with various cut-off scores were calculated. RESULTS: In the final logistic regression model, the following SSRS items significantly predicted suicide: suicide plans communicated to someone during the past 3 months; one or more previous suicide attempts; loss of professional skills demanding job; depression observed during an interview; and suicide plans communicated during an interview. With high cut-off scores the specificity of the SSRS became satisfactory, but the sensitivity dropped below 32%. Internal consistency of the anamnestic history of the SSRS was low, which suggests that anamnestic risk factors for suicide in schizophrenia are multifactorial. Internal consistency of the interview-based items was high, and present state risk factors seemed to consist of two separate factors, depression-anxiety and irritability. CONCLUSIONS: The SSRS may be clinically useful in identifying schizophrenic patients with a particularly high risk for suicide. However, the SSRS seems not to be a practical screening instrument for suicide risk in schizophrenia, and it is probably impossible to construct a suicide risk scale with both high sensitivity and high specificity in this disorder.

Comparison of clinical and best-estimate research DSM-IV diagnoses in a Finnish sample of first-admission psychosis and severe affective disorder.

The purpose of this study was to investigate diagnostic agreement between clinicians and a research group in a sample of first-admission psychosis and severe affective disorder patients. Clinical DSM-IV discharge diagnoses and best-estimate DSM-IV research diagnoses were compared in 116 first-episode patients in the city of Turku, Finland. The best-estimate research diagnoses were made at consensus meetings by integrating longitudinal data; patients' medical records; and findings of a clinical interview, the structured SCAN-interview, and symptom severity ratings. Overall diagnostic agreement was moderate, with a kappa value 0.51 (95% confidence interval (CI), 0.39- 0.63). Of the diagnostic groups, schizophrenic disorders had the lowest kappa value of 0.44 (95% CI, 0.26-0.63). Clinicians had a tendency to miss depressive symptoms in psychotic patients; to overdiagnose psychotic symptoms in depressive patients; and to fail to discover earlier hypomanic or depressive episodes in depressive patients. In conclusion, hospital diagnoses were not reliable in first-episode patients. Inappropriate diagnoses may compromise both treatment and epidemiologic findings based on discharge diagnoses.

Impaired Wisconsin card sorting test performance in first-episode schizophrenia: resource or motivation deficit?

Patients with first-episode schizophrenia (n = 27) and age- and education-matched healthy controls (n = 27) were administered the standard version of the Wisconsin Card Sorting Test (WCST), the Wechsler Adult Intelligence Scale-Revised (WAIS-R), and the Rorschach according to the Comprehensive System (CS). Schizophrenic patients achieved a significantly lower full-scale IQ and made more perseverative responses and achieved fewer categories on the WCST than the healthy control group. No significant associations were observed between effort or motivation and WCST performance. Schizophrenic patients who made more perseverative responses tended to be impoverished in terms of available resources, and functioned in a simplistic way when attending to details of the stimulus field. First-episode schizophrenics are able to generate motives and initiate goal-directed activity, but some of them fail to achieve their goals because the cognitive abilities and available resources required for effective planning, purposeful action, or effective performance are impaired.

Habituation of the blink reflex in first-episode schizophrenia, psychotic depression and non-psychotic depression.

OBJECTIVE: Electrophysiological recording of the electrically elicited blink reflex is the most reliable method of investigating habituation of the startle reflex. The purpose of this study was to compare the habituation and the late R3-component of the blink reflex between control subjects (N=19) and first-episode patients with schizophrenia (N=17), psychotic depression (N=23), and severe non-psychotic depression (N=25). METHODS: The blink reflex was evoked by electrical stimulation of the supraorbital nerve, and the deficient habituation of the R2i-component was measured with a computer-assisted integral area measurement. Prefrontal executive function of the patients was assessed with the Wisconsin Card Sorting Test. Current psychiatric symptoms were assessed with the Brief Psychiatric Rating Scale, the Hamilton Depression Scale, the Positive and Negative Syndrome Scale, and the Calgary Depression Scale. RESULTS: Deficient habituation of the blink reflex and occurrence of the late R3 component were associated both with a previous diagnosis of psychotic disorder and with the presence of current psychosis. The sensitivity and specificity of the abnormal habituation of the blink reflex in detecting psychotic disorder were 0.50 and 0.80, respectively. The abnormalities of the blink reflex were not associated with psychotropic medication. In schizophrenic patients, defective habituation of the blink reflex was associated with negative and cognitive symptoms, and in depressive patients with the presence of delusions. CONCLUSIONS: The deficient habituation of the blink reflex and occurrence of the late R3 component seem to be both trait and state markers of a psychotic disorder. The results suggest that schizophrenia and psychotic depression share some common neurobiological mechanisms involved in the modulation of the startle reflex.

High levels of dopamine activity in the basal ganglia of cigarette smokers.

OBJECTIVE: The authors' goal was to study presynaptic dopamine activity in smoking and nonsmoking human subjects in vivo. METHOD: [(18)F]Fluorodopa ([(18)F]DOPA) uptake K(i) values in the basal ganglia of nine smoking and 10 nonsmoking healthy men were measured with positron emission tomography. RESULTS: Significantly higher [(18)F]DOPA uptake was observed in both the putamen (average 17.3% higher) and the caudate (average 30.4% higher) of smokers than in those of nonsmokers. CONCLUSIONS: Smoking is related to greater dopamine activity in the human basal ganglia. Nicotine-induced dopamine activity may be a relevant mechanism in dependence on cigarette smoking.

Diagnostic efficiency of the Rorschach schizophrenia and depression indices in identifying first-episode schizophrenia and severe depression

We studied the diagnostic efficiency of the Rorschach schizophrenia (SCZI) and depression (DEPI) indices for detecting first-episode schizophrenia and severe depression with and without psychotic features using DSM-IV as a gold standard measure. Twenty-seven patients with first-episode schizophrenia, 13 with bipolar I disorder, 28 with psychotic depression, 29 with non-psychotic depression, and 60 healthy controls were recruited for the study. The SCZI was highly specific with a very low false positive rate. The lowest positive value of 4, however, may yield false positives, especially among manic patients. The DEPI identified severe non-psychotic depression but not psychotic depression, suggesting that these patient groups invoke different perceptual-cognitive processes in formulating and articulating their Rorschach responses. Anyway, both the SCZI and the DEPI based on the psychological organization and functioning that are known to play a clearly formulated role in schizophrenia and depression, respectively, provide a valuable addition for diagnostics characterized by overt symptoms.

Posttraumatic stress disorder symptoms related to psychosis and acute involuntary hospitalization in schizophrenic and delusional patients.

The aims of this study were: a) to assess the prevalence of posttraumatic stress disorder (PTSD) after an acute psychotic episode in schizophrenic and delusional patients, b) to explore which psychotic symptoms and aspects of treatment were associated with traumatization, and c) to compare the extent of the traumatic impact of psychosis and involuntary hospitalization. Forty-six schizophrenic and delusional patients were assessed with the Positive and Negative Syndrome Scale (PANSS), the Impact of Event Scale-Revised (IES-R), and the Clinician-Administered PTSD Scale (CAPS) at weeks 1 and 8 after acute psychiatric admission. Traumatic symptoms related to psychosis and coercive measures were scored separately. The prevalence of PTSD was found to be 11%. Sixty-nine percent of traumatic symptoms were related to psychosis and 24% to hospitalization. High PANSS score at week 8 was the strongest risk factor for the development of PTSD. Particularly positive and depressive/anxious symptomatology were associated with psychosis-related traumatic symptoms at both weeks 1 and 8. These data suggest that, in general, schizophrenic and delusional symptoms are more traumatic than the coercive measures used to control them.

Characteristics of people with intellectual disability admitted for psychiatric inpatient treatment.

The present prospective study describes the demographic, medical and psychosocial characteristics of 40 people with intellectual disability who were referred for psychiatric inpatient treatment in the special psychiatric unit of the Special Welfare District of Southwest Finland. Three different control groups were used to study: (I) demographic variables (n = 122); (2) medical history (n = 39); and (3) psychosocial factors (n = 20). The symptoms leading to an admission to inpatient care and the connections of these clinical signs with the discharge diagnosis were evaluated. The typical inpatients were young males with mild intellectual disability, psychosis and a previous psychiatric diagnosis. They had lived in several places during their lives and their economic situation was poor. Affective and/or disruptive symptoms were the most common causes of an admission to inpatient care. The largest diagnostic group at discharge consisted of patients with psychotic disorders. The people with intellectual disability who were admitted for inpatient care formed a subgroup with certain psychiatric symptoms and social problems. Specialist psychiatric expertise is absolutely necessary for the treatment of this subgroup.

Inpatient care and its outcome in a specialist psychiatric unit for people with intellectual disability: a prospective study.

The outcome of treatment in care units has been thought to reflect the effectiveness of treatment. There have been only a few studies describing inpatient care and its outcome in patients with intellectual disability and psychiatric symptoms. The present study describes the psychiatric inpatient treatment in the specialist psychiatric unit of the Special Welfare District of Southwest Finland and the need for aftercare among people with intellectual disability and psychiatric disorders (n = 40). As an outcome measure of care, the level of psychiatric symptoms was evaluated either with the Brief Psychiatric Rating Scale (BPRS) or with the Diagnostic Assessment for the Severely Handicapped (DASH) scale; self-reports (visual analogue scale) were also used. Patients' psychotic symptoms were reduced significantly on the BPRS during inpatient care and aftercare, but non-psychotic symptoms were reduced significantly only during aftercare. For one patient, the psychiatric symptoms were reduced significantly during inpatient care on the DASH scale, while the psychiatric symptoms remained the same for three patients. Patients and their primary carers considered the patient's psychiatric condition to have improved significantly during inpatient care, but not during aftercare. The specialist unit filled the gap in the care of people with intellectual disability and psychiatric problems in Southwest Finland. It is concluded that psychotic patients particularly benefit from the inpatient care in the specialist psychiatric unit. The care in the unit should include support for primary carers. All patients' outpatient treatment should also be re-evaluated. The present study poses two important questions. Firstly, could these treatment outcomes have been achieved with other interventions? Secondly, what are the necessary services for people with intellectual disability?

Depression Scale (DEPS) in schizophrenia.

OBJECTIVE: To explore the applicability of the Depression Scale (DEPS), a screening instrument for detecting depression in primary health care, in schizophrenia. METHOD: The DEPS was compared with the Calgary Depression Scale (CDS) among 63 patients with schizophrenia. RESULTS: Using the CDS as a gold standard, the positive and negative predictive values of the DEPS for the diagnosis of depression were 41% and 97%, respectively. The correlation between the total CDS scores and the total DEPS scores was 0.73. CONCLUSION: The DEPS appears to be useful for screening depression among schizophrenic patients, but the positive diagnosis must be confirmed with a clinical interview.

Functioning in activities of daily living of psychiatric inpatients with mental retardation.

Functioning in activities of daily living of 40 psychiatric inpatients with mental retardation was compared with that of nonhospitalized control subjects matched for sex, age, and level of intellectual impairment. After excluding data for six quadriplegic control subjects from the analyses, the only difference between the groups was that the inpatients were less impaired in seeing. The findings indicate that even a major psychiatric disorder does not necessarily impair functioning in activities of daily living among individuals with mental retardation. Thus normal functioning adjusted for intellectual impairment does not necessarily indicate the absence of a major psychiatric disorder.

Smoking and cognitive deficits in schizophrenia: a pilot study.

The cross-sectional study assessed the associations among smoking status, number of cigarettes smoked per day, and psychiatric symptoms in 88 chronic schizophrenic outpatients with a stable psychic condition. Among the 49 smokers, the number of cigarettes smoked per day was associated with the severity of cognitive symptoms of the Positive and Negative Syndrome Scale. The authors suggest that smoking may alleviate cognitive deficits in schizophrenia by increasing dopaminergic neurotransmission in the prefrontal areas of the brain.