Women are at higher risk than men to develop major depressive disorder (MDD), but the mechanisms underlying the higher risk for MDD in women are unknown. There is a wealth of data showing gender differences in brain morphology and function. In addition, preclinical studies have demonstrated reciprocal relationships between ovarian hormones and serotonin neurotransmission. Thus, gender differences in brain serotonin neurotransmission are potential underlying mechanisms. In the present study, we compared normalized α-[11C]methyl-L-tryptophan brain trapping constant (α-[11C]MTrp K*; ml/g/min), an index of serotonin synthesis, between men and women with MDD.

α-[11C]MTrp K* was measured in 25 medication-free individuals with MDD (13 females and 12 males) using positron emission tomography. Comparisons of normalized α-[11C]MTrp K* values between men and women were conducted at the voxel level using Statistical Parametric Mapping 2 (SPM2) analysis.

Women with MDD displayed significantly higher (p< 0.005) normalized α-[11C]MTrp K* than men in the inferior frontal gyrus, anterior cingulate cortex (ACC), parahippocampal gyrus, precuneus and superior parietal lobule, and occipital lingual gyrus.

This finding suggests that depressive women have higher serotonin synthesis in multiple regions of the prefrontal cortex and limbic system involved with mood regulation. Gender differences in brain serotonin synthesis may be associated with higher risk for MDD in women because extra levels of tissue 5-HT could create non-physiological connections influencing changes in mood.

Current studies showed a significant association between depression and Coronary Heart Disease (CHD). Depression is a significant etiopathogenetic factor of CHD and caused with worsening of the course of the illness. The aim of this study was to asses the relationship between the intensity of depressed symptoms and the course of the illness and also demographic factors.

The group of 111 CHD patients (89 male, 22 female) aged 41-65 years (mean 55±5,6). The individuals were assessed according to the following criteria: sex, job status (working, unemployed, retired), vascular diseases in family, myocardial infarction (MI) in history, number of MI, patients with acute MI were divided according to the duration of time from the onset of MI pain (patients who passed MI within a week and above a week from the onset of MI). The intensity of depressive symptoms were assessed by subjective Beck Depression Inventory (BDI) and objective Hamilton Depression Rating Scale (HDRS).

The intensity of depressed symptoms in BDI was 9,9±7,5 and in HDRS 6,6±4,5. Females showed significant higher level of depression compared with males.In patients who passed MI within a week before the evaluation as compared with those whose term after MI was longer than a week the less level of depression was observed. Also active workers presented significantly less degree of depressive symptoms than pensioners.

The results obtained showed the association between the intensity of depression and the more severe course of the CHD, especially in female and pension patients.

This research was supported by grant 502-16-653 Medical University of Lodz

Interictal depression as a co-morbid disorder can be seen among more than 40% of patients with epilepsy. Sex, epilepsy duration, type of seizures as well as applied antiepileptic drugs can cause development of depression which influence patient's life quality.

To test relation between depressive disorders and patients sex, duration of illness, type of epileptic fits, antiepileptic therapy and life quality.

Prospectively, randomly selected, we tested 300 patients with epilepsy, with or without depressive affective disorder at the Outpatient Department for Epilepsies at the Clinical Center Sarajevo. All patients answered Beck and Hamilton depression scale.

Baseline is consisded of male patients which made 54 % with the average age of 37.7 years, as well as female patients at average age 32.83 years. Depressive disorder according to the results at the Beck scale was present in 34%, and according to the Hamilton scale in 38.9%. Duration of illnesses longer than 20 years had 56% women with the expressed depressive disorder, compared to the 42% men's with depression (p< 0.01). Partial complex seizures were more often among women (p< 0.05). Carbamazepin as monotherapy was applied for more than a half of the baseline, and combined with carbamazepin significantly more frequently among men's (p< 0.0001), while female patients had significantly more often Lamotrigil.

Depressive disorder is significantly more frequent among women with partial complex seizures, earlier epilepsy onset, and significantly more often on Phenobarbital therapy. Presence of depression with epilepsy significantly reduced patient's life quality.

To explore rearing, coping, attributional style and their relations in depression adolescents.

64 adolescents with depressive disorder and 125 normal subjects of similar age, sex were presented with self-made social demographic scale, Egna Minnen av Barndoms Uppfostran-own memories of parental rearing practices in childhood (EMBU), Children attributional style questionnaire (CASQ) and Coping style questionnaire.

1. 1. As to EMBU, there was a significant deficit in parental emotional warmth (p< 0.001) with depression adolescents, and whose parental punishment and strict (p< 0.05), rejection and denial (p< 0.001) were higher than normal ones.

2. 2. As to CASQ, the differences were significant in self-blame (p< 0.001), asking for help (p< 0.001), daydreaming (p< 0.001) and recession (p< 0.05).

3. 3. The difference of attributional pattern was significant (p< 0.001).

4. 4. Mather’ emotional warmth and rejection and denial were both related to adolescents’ coping style and attributional style.

Depressive adolescents had negative coping style and attributional style, and mother’ rearing style may has relation with them.

to describe the impact of pain on quality of life (QoL) in patients with depression

FINDER was a 6-month, european observational study to assess outcomes of QoL (SF36, EQ-5D), depression and anxiety (HADS), somatic (SSI) and pain (VAS) in a clinically diagnosed population initiating antidepressants.

606 patients enrolled in France by 57 psychiatrists and 46 general practitioners were 45.6±13.0 years old, 69% female and 39% have had a previous episode in the last 2 years. According to the patient rated HADS score greater than 11, 75% of patients were classified as cases for depression and 84% as cases for anxiety. 51% of patients rated their overall pain severity (based on VAS cut-off of 30) as moderate/severe, with 65% of them reporting no medical explanation for their pain.

During the 6-month follow-up, French patients improved on SF36 physical score (46.8±10.4 to 50.2±8.3) and mental score (20.2±8.6 to 40.5±12.3), EQ-5D Health State Index (0.38±0.28 to 0.75±0.27) and EQ-5D VAS (39.9±20.0 to 71.4±20.3). Patients with moderate/severe pain at baseline and patients defined as cases for depression or anxiety at baseline had poorer QoL scores on SF36 physical score, EQ-5D Health State Index, EQ-5D VAS and HADS both at baseline and over the 6 months of since treatment started.

Over half of French patients of this study experienced pain associated with depression. We observed that patients experiencing a moderate/severe pain at baseline had worse outcomes on QoL and depression response than those with mild or not pain at baseline.

Anhedonia, or the lack of reactivity to a pleasurable stimuli is expressed as reduced reward sensitivity in patients with major depressive disorder (MDD) (1). Reward experience might discriminate between depressed patients who respons to treatment and those who do not (2).

The purpose of this study was to test the hypothesis that patients non-responsive to treatment show reduced reward sensitivity compared to responsive patients.

A probabilistic computer task was used to measure reward sensitivity objectively (3). Twenty-eight medicated inpatients meeting DSM-IV criteria for MDD performed the reward task within the first week after submission and again after eight weeks. The response to treatment was assessed with the Hamilton Depression rating Scale (HDRS). Patients with scores less that ten or a fifty percent reduction on the HDRS after 8 weeks were considered responders to treatment. Sixteen healthy subjects were recruited as controls.

When considering reward sensitivity at baseline, the control group was significantly more sensitive to reward than the responders group and the non-responders group, who were the least reward sensitive (F = 11.88; p < 0.01). After 8 weeks, responders showed an almost similar reward dependence to controls on the task, however non-responders still preformed significantly worse compared to both responders and controls (F= 8.71; p< 0.01).

These results support the hypothesis that impairment of reward responsiveness might influence response to treatment in patients with MDD.

There is no report about the new theory of gene multiple hits. Which is identified through a MEDLINE search.

The result of new discovery: explanation of the gene multiple hits theory

We have known that cancer development is caused by the long time carcinogens' effects. The carcinogens include psychological, social, behavioral, emotional and spiritual issues factors and hereditary factors, et al. After all, the author may say in this way that before the cancer development, there are many different proto-oncogenes and tumor suppressive genes suffer from many different carcinogens' hits and damages, that is gene multiple hits. And finally, after the genes are hit many times by the environmental or chemical factors; biological factors; physical factors and hereditary factors, et al., the cancer are developed.

The major previous theory for cancer development mechanism is the gene two hits theory. It is clear that this old theory can not fully explain all the findings for cancer development mechanism. Only can the gene multiple hits theory explain fully all the scientific findings for the cancer development mechanism. Therefore, the new theory is very scientific.

The significances of the gene multiple hits theory.

The new theory not only fully explain the research findings for cancer development mechanism. But also summarizes the huge lots of different scientific research findings and using the single new theory represents the whole related scientific research findings.

Epidemiological studies have consistently shown that the risk of occurrence of depressions increases in the period between adolescent and adult ages. The current research described the most frequent subdepressive's symptoms.The aim was to analyze the importance of subclinical depressive symptoms as risk factors of the future depression.

There were 37 adolescent investigated of 13-18 years old, 9 of them were 18 years old. Symptoms of depression were measured by Beck's test. Also the frequency of separate depressive's symptoms with the Hamilton's test was considered: mood lowering, normal activity decrease, psychomotor torpidity, guilt feelings, attention deficit, fatigue, learning problems, reduction of socializing communications, sleep and appetite disorders, suicide thoughts.

The research demonstrated that 16 participants had subdepressive disorders with 9 points of Beck's test. 11 adolescent (13-17 year old) and 9 (18 year old) corresponded 19 points on Beck's test. The later were mostly predisposed to depression.

The conducted study pointed out that sudepressive symptoms which didn't meet the criteria of a big depression could be considered as a predictable factors of depressive disorders in the old year age.

The purpose of this study was to distinguish electroencephalographic possible typical features at left handed children as against to right children, and also to find out possible range aspects which can suggests the central dominance for language.

Electroencephalographic (EEG) band was recorded on an EEG device (Pegasus Digital EEG-EMS GmbH - Austria) according to the international standards.

Sample I: 8 left handed children (av. 9.38 SD 3.53 yrs); Sample II: 18 right handed children (av. 11.06 SD 2.48 yrs).

Using the data obtained by Fast Fourier Transform (FFT), we performed comparisons regarding the index, and the average frequency for delta, theta, alpha, and beta bands. The comparisons was performed for each subject, for each band, and pair of electrode between left and right hemisphere, between left and right children for every electrode, and for the two hemispheres.

We have found significant differences on EEG features between left and right children regarding both index, and frequency of the main cerebral rhythm, the most meaningful been at alpha, and beta rhythms. For instance the beta frequency was higher on the left recordings, mostly at right children, where seven of the electrode pairs presents significant differences.

In contrast with classical, and virtual analysis the Digital EEG, and FFT test is a method that can be useful to study the cerebral dominance. The advantage of this method pleads the fact that firstly it is a noninvasive method, and despite other sophisticated functional techniques remains the most inexpensive.

To explore clinical indications for, and results of, brain imaging in a department of general adult psychiatry.

We reviewed the 100 most recent episodes of brain imaging at the Department of General Adult Psychiatry, Mater Misericordiae University Hospital, Dublin.

Patients had a mean age of 55.30 years. The most common indications for scans were cognitive impairment (33%) and other neurological concerns (e.g. seizures) (30%). Forty-seven per cent of scans were abnormal. The most common abnormalities were ischaemia (17%) and atrophy (10%). Patients with abnormal scans were older than those with normal scans (61.90 and 48.70 years, respectively; p< 0.001).

Brain imaging contributes significantly to diagnosis in general adult psychiatry, especially for older patients.

To compare Magnetic Resonance Imaging (MRI) findings in Alzheimer's dementia (AD) in the general population with Down's syndrome dementia.

Background review: AD is characterised by cognitive dysfunction interfering with activities of daily living. Mild cognitive impairment (MCI) is an intermediate state between normal aging and dementia. People with Down's syndrome have an increased risk of developing AD. AD pathology initially appears in the entorhinal cortex, followed by the hippocampus and later in the temporal lobes. These areas are critical for memory functioning.

Volumetric analysis was performed on MRI brain scans using Measure software. Manual tracing was undertaken for the hippocampus, temporal lobes and lateral ventricles as well as the total brain volume of the cerebral hemispheres and cerebellum. Brain volumes were normalised as a percentage of traced intracranial volumes. Freesurfer software was used to obtain entorhinal cortical thickness measures. Statistical analysis was undertaken using SPSS15.

Subjects with AD (n=46), MCI (n=28) and controls (n=39) were compared with Down's syndrome demented subjects (DS+, n=20), non-demented subjects with Down's syndrome (DS-, n=45) and age-matched controls (n=43). Hippocampi, entorhinal cortex and temporal lobes were significantly reduced in AD and DS+ compared to controls. Lateral ventricles were significantly increased in AD and DS+ compared to controls. MCI and DS- produced findings between those of dementia and controls.

Critical memory regions atrophy in dementia corresponding to decreased cognitive functioning. DS+ morphology is comparable to AD in the general population but the atrophy is less pronounced.

To compare Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (1H-MRS) between people with Alzheimer's disease (AD) and mild cognitive impairment (MCI).

AD is characterised by cognitive impairment. 10-15% of people with MCI progress to dementia each year. The hippocampus is involved in memory functioning and is one of the brain regions first affected by AD. MRI based hippocampal volumetric measurement enables accurate quantification of atrophy. In addition, 1H-MRS can be used to measure concentrations of brain metabolites including myoinositol (mI) and N-acetylaspartate (NAA). NAA is a proxy measure of neuronal density.

Subjects with AD (n=46), MCI (n=28) and controls (n=39) were scanned using a 1.5 Tesla MR system. Manual tracing of hippocampal volumes was undertaken using Measure software. 1H-MRS voxels of interest were defined in the left and right hippocampi. A point-resolved spectroscopy pulse sequence produced spectra from each voxel and clearly resolved NAA and mI peaks. Statistical analysis was undertaken using SPSS15.

Hippocampal volumes were significantly reduced between AD and controls (p=0.003) and between AD and MCI (p=0.001). Compared to controls, individuals with AD and MCI had a significant reduction in [NAA]. MCI showed a non-significant increase in [mI]. A positive relationship was found between hippocampal volume and [NAA] and between hippocampal volume and [mI] for MCI.

AD is associated with decreased viable neuronal density/function (as measured by NAA) and a reduction in hippocampal volume associated with impaired cognitive functioning. The elevated [mI] in MCI may be a “tipping point” into dementia.

Functional studies in Autism Spectrum Disorder (ASD) have shown localised focal hypoperfusion and abnormalities in the anatomo-functional connectivity of limbic-striatal “social” brain. However, no common regional abnormalities have been found across studies.

The aim of this study was to investigate the cerebral blood flow (CBF) at rest in subjects with ASD as compared to a group of healthy controls.

In this preliminary investigation six normal intelligence patients with ASD and 5 age and sex matched healthy controls (HC) were examined using PET/CT camera and, as CBF tracer, 11C-butanol, a radiopharmaceutical produced on-site. The combination of these two methodologies reduced the whole examination time to less than 10 minutes. Statistical Parametric Mapping was implemented to analyse the data.

As compared to HC, ASD showed a highly significant CBF increase (height threshold p=0.001, p< 0.0001 at voxel-level), bilaterally, in large portions of the cerebellum, of the visual associative cortex and of the posterior parietal lobe.

This preliminary study was performed by the state-of-the-art neuroimaging methodologies that reduced considerably the examination time and resulted in less stress and more reliable investigations. The occipital and parietal associative cortex as well as the cerebellum showed an increased CBF in ASD, underscoring their involvement in the disease and raising methodological and diagnostic issues to be considered when exploring the neuroanatomy of ASD.

To examine potential similarities in neural activation during the STROOP colour word test (SCWT) in patients with Bipolar Disorder (BD) and their unaffected first degree relatives of BD patients as an expression of genetic predisposition.

39 remitted BD patients were compared to 46 of their healthy relatives and to 42 controls. fMRI data were collected on a 1.5 T GE Signa MR system using a blocked periodic design and analysed in SPM5.

There was no statistically significant group difference in the behavioural performance. At the corrected cluster level threshold of p< 0.001 controls showed more activation than:

1. a. BD patients in the caudate, the inferior (BA 47), middle and superior frontal gyri (BA 8, 6, 46), the parietal cortices (BA 7, 40), the precuneus and occipital cortices (BA 7, 19).

2. b. Relatives in the caudate and cingulate cortex (BA 24, 31!). No other contrasts were significant.

These findings suggest that changes in neural activation during response inhibition may reflect genetic predisposition to BD.

To examine the effect of a polymorphism in the Dopamine Transporter (DAT) gene on brain activation during executive function and, for the first time:

1. 1. determine the extent to which this is altered in schizophrenia and

2. 2. use a verbal fluency paradigm.

1. 1. DAT plays a key role in the regulation of dopamine, which modulates cortical activation during cognitive tasks and

2. 2. a disruption of dopamine function is a fundamental pathophysiological feature of schizophrenia.

Functional magnetic resonance imaging was used to measure whole-brain responses during overt verbal fluency in 85 subjects: 44 healthy volunteers and 41 DSM-IV schizophrenia patients. Main effects of genotype and diagnostic group on activation and their interaction were estimated using an ANOVA in SPM5.

The 10-repeat allele of the 3'UTR VNTR was associated with greater activation than the 9-repeat allele in the left (Z=4.8; FWEp=0.005) and right (Z=4.2; FWEp=0.057) anterior insula and with decreased activation in the rostral anterior cingulate (Z=4.3 FWEp=0.04) during word generation (versus baseline). These effects were irrespective of diagnostic group but generally more marked in patients. There were also strong trends for groupxgenotype interactions in the left middle frontal gyrus and the left nucleus accumbens. Analysis was controlled for task performance, IQ, antipsychotic medication, psychopathology and demographics.

Cortical function during executive tasks is normally modulated by variation in the DAT gene, effect which is dependent on the brain region. DAT's effect may be altered in schizophrenia patients, which may reflect altered central dopamine function.

Affective deficits (flat affect, a diminished expression of emotion, anhedonia, and lowered ability to experience pleasure) are very common in schizophrenia. In emotion feeling, the crucial role of the insula, rather than of the primary somatosensory cortices, strongly suggests that the neural substrate for emotions is not merely sensorial. It is more likely that the activation of the insula representation of the viscero-motor activity is responsible for feeling of disgust. A recent MRI study demonstrated specific left anterior insular volume reduction in chronic schizophrenia patients: sustainable is the suggestion that emotion of disgust or of taste may be related to the experience of pleasure, which probably is compromise in schizophrenics.We investigated fMRI brain activations in first episode schizophrenic subjects with negative symptoms and in healthy subjects elicited by pleasant and unpleasant visual stimuli.

Ten first-episode schizophrenic subjects with normal IQ were recruited from the psychiatric service “SMILE” of San Salvatore Hospital and 10 healthy volunteers matched for age and education were scanned during observation of pleasant and unpleasant visual stimuli. Functional images were acquired with a 1.5T MRI scanner. Blood oxygenation level dependent (BOLD) contrast was obtained using EPI T2* weighted images.

The most important result of the study was the demonstration that anterior insula was activated by the exposure to disgusting stimula in normal subjects but not in schizophrenic subjects.

This failure of the neural systems used to support emotional attribution is consistent with pervasive problems in experiencing emotions by schizophrenics.