Bulimia nervosa (BN) is a common and disabling disorder in young women. Cognitive-behavioural therapy (CBT) is the treatment of choice, yet the majority of people with the disorder do not access treatment, given the limited availability of CBT for BN. Even for those that do access treatment care may be disrupted, as this is a young mobile population. Thus, new models of service delivery for this group need to be found. Technology based treatments delivered via CD-ROM or the internet may bridge this gap. In this paper, results from two randomized controlled trials (RCTs) and one large cohort study will be presented.

All three studies evaluated the use of an interactive multi-media programme ‘Overcoming bulimia’ (Williams et al., 1998) in young people with bulimia nervosa and related disorders, delivered via CD-ROM or the internet, with different types and intensities of support and in different settings (e.g. specialist clinic, or community sample recruited via University network or a large self-help organization). Outcomes were assessed using an interview-based measure of eating disorder symptoms.

Participants’ eating disorder symptoms improved significantly compared to waiting list and improvements were maintained over time.

The findings from these studies suggest that a computerized intervention does have promise as a first step in the treatment of BN and may improve access to treatment. However, in people recruited from the community, the opportunity of having some face-to-face contact appears important.

In developing countries mental disorders are emerging as a major contributor to the Global Burden of Diseases, but mental health cares are accessible to only a minority. Psychiatric diseases do not benefit from recent dramatic progresses in terms of access to medicines seen in other fields. Thus, in the case of schizophrenia, cost effective treatment combining first generation antipsychotics and adjuvant psychosocial treatment are not widely used.

Our objective is to demonstrate that access to treatment in the field of schizophrenia could be improved by simple, assessable and adaptable programs.

In partnership with Health Authorities and local psychiatric networks, a pilot project has been elaborated in one province of Morocco (Benslimane). It will be set up early 2008 and will last 3 years. It will combine:

1. - Population awareness about mental diseases

2. - Information for patients’ families

3. - Primary care medical staff training, for diagnosis and treatment

4. - Supply of antipsychotics with a preferential pricing policy (preferential price policy).

A strict assessment of the impact of this program will be performed. The primary criterion will be: treated people each year as a proportion of the total estimated annual prevalence. Involuntary admissions as a proportion of annual admissions, clinical evolution, the potential capacity, and the burden for families will be also measured.

The present situation, the program's content, and the assessment tools will be presented.

Once the efficiency of such programs is established, the scaling-up will require commitments from international organizations and donors.

Social disability is a key outcome measure for severe mental illness, being a pivotal variable, that modulates the effectiveness of treatments and might be modified by the treatments themselves.

The aims of the studies presented were: 1) to determine changes overtime in symptoms and social disability in a 1 year treated prevalence cohort of subjects affected by psychosis vs. those affected by non psychotic disorder receiving community-based mental health care, and to explore 2) predictors of clinical and social outcome; 3) the effect of clinical course on disability and quality of life.

Three hundred fifty four patients treated in the South-Verona CMHS were followed-up over 6 years (with assessments made at baseline, at 2 and 6 years) by using a set of standardised measures exploring psychopathology (BPRS), social disability (WHO-DAS) and quality of life (LQoLP). GLLAMM models were used to explore longitudinal predictors of clinical and social outcome. The effect of clinical course on disability was explored by consulting retrospectively the clinical records.

In psychotic patients relationships with partners were more frequently severely impaired, followed by dysfunction in the occupational and parental role. Longitudinal analyses displayed a clinical and social outcome characterized by complex patterns of exacerbation and remission over time; however a clear trend towards a deteriorating course was not found, thus challenging the notion that psychotics are not fatally prone to a destiny of chronicity. Models explained 69% of the total variance for social disability. Predictors for disability were clearly differentiated from those for clinical status, but the two domains appeared entwined: the main clinical predictor of social disability was the negative component of psychotic symptoms (the higher negative symptoms, the lower social functioning) and higher disability predicted in turn a worsening of negative symptoms. Continuous course was associated with higher disability and lower quality of life.

Psychopathology and disability are distinct outcome domains only partially overlapping, which do not directly co-vary overtime and are influenced, at least in part, by separate predictors susceptible to specific interventions. However, they are entwined in a vicious cycle leading overtime to a progressive reciprocal worsening with deleterious effect on patients' daily living and independence. Modern mental health services should be capable of shaping treatments to address these patients' multifaceted problems.

Many individuals ascertained for developmental dyslexia (DD) are also diagnosed with attention-deficit hyperactivity disorder (ADHD) and approximately 20% of individuals with ADHD will have evidence for DD. The basis for this overlap is not completely understood but twin studies have provide support for common genetic influences, particularly for inattention symptoms. Genetic linkage studies have found significant evidence for linkage of DD to chromosomes 1p34-p36, 15q, 6p21.3-22, 2p15-16, 6q11.2-q12 and 18p11.2. Evidence for linkage/association to ADHD has also been found to overlap for some of these regions. The objective of this study is to identify genes contributing to both.

We examined evidence for the involvement of specific genes in these chromosomal regions using two samples of families, one ascertained through a proband with DD (n= 273 families) and the other through a proband with ADHD (n= 390 families).

Our studies of the 6p region indicate that the sample of DD families is associated to markers in this region and to ADHD but not to the same markers within the linked region. For the 15q region, we have found significant evidence for association for both the ADHD and reading phenotypes in both samples (Wigg et al., 2004; Wigg et al., 2005). We have also found evidence for the gene for the dopamine receptor D1 to be associated to the inattention symptoms in both samples

While the studies of the overlap in ADHD and DD are preliminary, they are promising in that they will ultimately help to disentangle the causal relationship.

Children with ADHD may have chronic sleeping problems, associated with circadian rhythm disturbances. Little is known about sleep in adults with ADHD.

We studied the prevalence and type of sleeping problems in 120 adults with ADHD using an interview questionnaire.

78% of the 120 adults with ADHD had difficulty to go to bed in time (between 1 and 3 am). Almost 70% reported sleep onset problems, more than 50% had difficulty sleeping through. Almost 70% had difficulty getting up in the morning and 62% felt sleepy during the day. In more than 60% these sleeping problems had been there all their lives. These results are very similar to earlier data presented by Dodson (Dodson, 1999). Several explanations for these sleeping problems may be considered (Kooij ea, 2001; Oosterloo ea, 2006; Boonstra ea, 2007). However, the frequently occurring sleeping pattern of being a ‘nightowl’, with restless sleep and difficulty getting up in the morning, may be associated with the delayed sleep phase syndrome, as was recently shown in children with ADHD and sleep onset problems (van der Heijden ea, 2006; van der Heijden ea, 2005; Weiss ea, 2006). We currently study the circadian rhytm in adults by measuring the Dim Light Melatonin Onset (DLMO) in saliva in ADHD patients with sleep onset problems (ADHD+SO), compared to ADHD patients without sleep onset problems (ADHD-SO).

About 70% of adults with ADHD have sleep onset problems compatible with a delayed sleep phase pattern. First data of DLMO in adult ADHD patients with and without sleep onset problems will be discussed.

Bipolar II disorder and ADHD share several clinical characteristics. Identifying patients with either Bipolar II or ADHD is therefore not an easy task. Little is known about the co-occurrence of both disorders and its treatment.

In a large outpatient clinic for Mood Disorders all patients with a bipolar II disorder were asked to fill in the ADHD rating scale, a screening instrument for adult ADHD. Patients who were above threshold were asked to participate in further diagnostics. This included a semi-structured interview for adult ADHD and an interview with an important other. Outcome was rated by two independent experts in adult ADHD.

The total sample consisted of 62 bipolar II patients. Forty-two participated in the first screening. The ratings of 22 patients were not above threshold. Of the 20 patients with a positive score, 6 refused further participation. Of the 14 remaining, 11 satisfied full ADHD criteria in childhood as well as adulthood.

Patients with co-occurring ADHD were significantly more often female (82%) and had more relationships in the past. All other demographic variables were not significantly different. None of the treating physicians had prior to the study been aware of the diagnosis of ADHD in the bipolar II patients.

In adults with bipolar II disorder, ADHD is a common co-occurring disorder. Almost 18% of patients with bipolar II disorder also applied for a lifetime diagnosis of ADHD. Especially female patients with bipolar II disorder had relatively often co-occurring ADHD. Since this study was carried out in a specialized centre for mood disorders, further confirmation of this high prevalence rate should be object of further study.

Population included 100 students, male and female, all aged 18 years old and above, studying in a specific center for LD. All students were diagnosed in the past as suffering from LD. No selection criteria had been administered. Methods were divided: 1) Screening questionnaire 2) ADHD assessment including: a structured interview (SCID), the Wender Utah Rating Scale (WURS), the adult ADHD self report scale (ASRS) and Test Of Variables of Attention (TOVA) with and without methylphenidate (MPH) challenge.

Results will be presented later

Despite a lot of initial enthusiasm and more than three decades of research, cognitive endophenotypes for psychiatric disorders are still to be found.

Based on a literature review and on our own research, we will analyse the reasons and consequences of this failure to find useful cognitive endophenotypes.

Several commonly held ideas that proved to be over-optimistic, over-simplistic and finally false, have limited our ability to identify cognitive endophenotypes. Among those ideas, with deleterious methodological consequences, were the beliefs that neuro-cognitive validity is sufficient to ensure genetic validity, that cognitive measures and cognitive processes are equivalent and that cognitive processes have a simpler genetic architecture than psychiatric vulnerability. The perception of these initial errors modified our definition and expectations of cognitive endophenotypes and suggested ways to improve our chances to find them.

Several aspects of the study of cognitive endophenotypes demonstrated an initial excessive optimism, followed by disillusion and, now, a time for active search for realistic solutions. We will illustrate this process by an important feature for cognitive endophenotypes: the test-retest reliability. Although cognitive measures were initially considered stable, a systematic literature review revealed that most of them had problematic test-retest reliability. The use of such measures could lead to erroneous conclusions and limit their usefulness as cognitive endophenotypes.

Taking this parameter into consideration is important in selecting cognitive tests used to detect putative endophenotypes and in suggesting new approaches in the search for cognitive endophenotypes (for example the use of cognition questionnaires).

The extent and causes of covariance between schizotypy and neurocognition is not well-known yet. Certain models conceive their association as necessary for the construct validity of schizotypy, whereas others view them as independently contributing to a multivariate endophenotype. It is also not clear whether those at increased genetic risk for schizophrenia present stronger covariance, reflecting an extra latent source of variance. We analysed their association within relatives of schizophrenia patients defined with FIGS as Presumed Carriers -PC- of the genetic risk for schizophrenia, Presumed Non Carriers -PNC-, and controls.

108 healthy relatives of schizophrenia patients and 72 healthy controls were assessed with the SCID-II and completed the SPQ-B. Neurocognitive assessment: Letter-Number Sequencing (LNS), WCST, CPT-IP, verbal fluency, and logical memory.

Partial correlations adjusting for age and education showed that within PC-relatives self-rated negative schizotypy was associated with lower LNS and CPT-IP; positive schizotypy was associated with CPT-IP, and disorganization with memory and failure to maintain set. Schizoid symptoms had an association with failure to maintain set (though not perseveration) and paranoid symptoms with memory. Within PNC-relatives, negative schizotypy was associated with lower verbal fluency and more perseverative errors. Within controls, positive schizotypy was associated with perseverative errors and both positive and negative dimensions were associated with verbal fluency.

Results indicate a wider array of covariation between relatives with presumed higher genetic liability. A consistent pattern of associations between psychotic-like dimensions and the brain functions tapped by neurocognitive tests did not emerge across groups.

Neuropsychological deficits are considered endophenotypes for schizophrenia, because they are not only found in patients but also in many of their unaffected relatives, albeit in attenuated form. It is not yet clear which of these deficits in relatives are related to genetic or to environmental causes. We tested effects of inferred genetic liability for schizophrenia on neurocognitive variables to address this problem.

Twenty-eight patients with schizophrenia, 129 non-affected biological parents and 143 matched controls were assessed with an extensive neuropsychological test battery including tests of attention, memory, executive functioning and motor soft signs. Twenty-two parents had an ancestral history of schizophrenia and therefore were hypothesized to be more likely than their spouses without such a history (n = 17) to carry a genetic risk for schizophrenia.

Unaffected parents of schizophrenic patients showed significant deficits in a wide array of neuropsychological tasks and task domains. However, comparison of more likely and less likely carriers of illness-related genes showed specifically attentional and executive functioning, but not memory, to vary with degree of inferred genetic loading.

Attentional and executive (frontal) impairments vary with genetic loading for schizophrenia and can be considered true endophenotypes for this disorder. Consequently, these functions are particularly suited to evaluate the functional impact of candidate genes for schizophrenia in future studies.